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Publisher: Elsevier   (Total: 3160 journals)

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Showing 1 - 200 of 3160 Journals sorted alphabetically
Academic Pediatrics     Hybrid Journal   (Followers: 35, SJR: 1.655, CiteScore: 2)
Academic Radiology     Hybrid Journal   (Followers: 24, SJR: 1.015, CiteScore: 2)
Accident Analysis & Prevention     Partially Free   (Followers: 96, SJR: 1.462, CiteScore: 3)
Accounting Forum     Hybrid Journal   (Followers: 27, SJR: 0.932, CiteScore: 2)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 37, SJR: 1.771, CiteScore: 3)
Achievements in the Life Sciences     Open Access   (Followers: 5)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 7)
Acta Astronautica     Hybrid Journal   (Followers: 421, SJR: 0.758, CiteScore: 2)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 28, SJR: 1.967, CiteScore: 7)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 2)
Acta de Investigación Psicológica     Open Access   (Followers: 3)
Acta Ecologica Sinica     Open Access   (Followers: 10, SJR: 0.18, CiteScore: 1)
Acta Haematologica Polonica     Free   (Followers: 1, SJR: 0.128, CiteScore: 0)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.661, CiteScore: 2)
Acta Materialia     Hybrid Journal   (Followers: 276, SJR: 3.263, CiteScore: 6)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.504, CiteScore: 1)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.542, CiteScore: 1)
Acta Oecologica     Hybrid Journal   (Followers: 12, SJR: 0.834, CiteScore: 2)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription  
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 3, SJR: 0.307, CiteScore: 0)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 1, SJR: 1.793, CiteScore: 6)
Acta Poética     Open Access   (Followers: 4, SJR: 0.101, CiteScore: 0)
Acta Psychologica     Hybrid Journal   (Followers: 27, SJR: 1.331, CiteScore: 2)
Acta Sociológica     Open Access   (Followers: 1)
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.052, CiteScore: 2)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 3, SJR: 0.374, CiteScore: 1)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 2)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 3, SJR: 0.344, CiteScore: 1)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 1)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 6, SJR: 0.19, CiteScore: 0)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 8)
Acute Pain     Full-text available via subscription   (Followers: 14, SJR: 2.671, CiteScore: 5)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.53, CiteScore: 4)
Addictive Behaviors     Hybrid Journal   (Followers: 17, SJR: 1.29, CiteScore: 3)
Addictive Behaviors Reports     Open Access   (Followers: 8, SJR: 0.755, CiteScore: 2)
Additive Manufacturing     Hybrid Journal   (Followers: 11, SJR: 2.611, CiteScore: 8)
Additives for Polymers     Full-text available via subscription   (Followers: 23)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 167, SJR: 4.09, CiteScore: 13)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 12, SJR: 1.167, CiteScore: 4)
Advanced Powder Technology     Hybrid Journal   (Followers: 17, SJR: 0.694, CiteScore: 3)
Advances in Accounting     Hybrid Journal   (Followers: 8, SJR: 0.277, CiteScore: 1)
Advances in Agronomy     Full-text available via subscription   (Followers: 15, SJR: 2.384, CiteScore: 5)
Advances in Anesthesia     Full-text available via subscription   (Followers: 28, SJR: 0.126, CiteScore: 0)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 10, SJR: 0.992, CiteScore: 1)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 11, SJR: 1.551, CiteScore: 4)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 24, SJR: 2.089, CiteScore: 5)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 14, SJR: 0.572, CiteScore: 2)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.61, CiteScore: 7)
Advances in Botanical Research     Full-text available via subscription   (Followers: 2, SJR: 0.686, CiteScore: 2)
Advances in Cancer Research     Full-text available via subscription   (Followers: 33, SJR: 3.043, CiteScore: 6)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9, SJR: 1.453, CiteScore: 2)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 1.992, CiteScore: 5)
Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 4)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 13)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 28, SJR: 0.156, CiteScore: 1)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.713, CiteScore: 1)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 10, SJR: 1.316, CiteScore: 2)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 26, SJR: 1.562, CiteScore: 3)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 20, SJR: 1.977, CiteScore: 8)
Advances in Computers     Full-text available via subscription   (Followers: 14, SJR: 0.205, CiteScore: 1)
Advances in Dermatology     Full-text available via subscription   (Followers: 15)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 12)
Advances in Digestive Medicine     Open Access   (Followers: 9)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 7)
Advances in Drug Research     Full-text available via subscription   (Followers: 25)
Advances in Ecological Research     Full-text available via subscription   (Followers: 44, SJR: 2.524, CiteScore: 4)
Advances in Engineering Software     Hybrid Journal   (Followers: 29, SJR: 1.159, CiteScore: 4)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 8)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 46, SJR: 5.39, CiteScore: 8)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 1)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 9)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 60, SJR: 0.591, CiteScore: 2)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 17)
Advances in Genetics     Full-text available via subscription   (Followers: 19, SJR: 1.354, CiteScore: 4)
Advances in Genome Biology     Full-text available via subscription   (Followers: 10, SJR: 12.74, CiteScore: 13)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 1.193, CiteScore: 3)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 24, SJR: 0.368, CiteScore: 1)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 12, SJR: 0.749, CiteScore: 3)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 23)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 2, SJR: 0.193, CiteScore: 0)
Advances in Immunology     Full-text available via subscription   (Followers: 36, SJR: 4.433, CiteScore: 6)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 10, SJR: 1.163, CiteScore: 2)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 2, SJR: 1.938, CiteScore: 3)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6, SJR: 0.176, CiteScore: 0)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 3)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.682, CiteScore: 2)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 8)
Advances in Marine Biology     Full-text available via subscription   (Followers: 18, SJR: 0.88, CiteScore: 2)
Advances in Mathematics     Full-text available via subscription   (Followers: 11, SJR: 3.027, CiteScore: 2)
Advances in Medical Sciences     Hybrid Journal   (Followers: 7, SJR: 0.694, CiteScore: 2)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4, SJR: 1.158, CiteScore: 3)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 23)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 8)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.182, CiteScore: 0)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 4)
Advances in Oncobiology     Full-text available via subscription   (Followers: 2)
Advances in Organ Biology     Full-text available via subscription   (Followers: 2)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 17, SJR: 1.875, CiteScore: 4)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 7, SJR: 0.174, CiteScore: 0)
Advances in Parasitology     Full-text available via subscription   (Followers: 5, SJR: 1.579, CiteScore: 4)
Advances in Pediatrics     Full-text available via subscription   (Followers: 25, SJR: 0.461, CiteScore: 1)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 12)
Advances in Pharmacology     Full-text available via subscription   (Followers: 16, SJR: 1.536, CiteScore: 3)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.574, CiteScore: 1)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.109, CiteScore: 1)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 10)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 5)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 19)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20, SJR: 0.791, CiteScore: 2)
Advances in Psychology     Full-text available via subscription   (Followers: 65)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6, SJR: 0.371, CiteScore: 1)
Advances in Radiation Oncology     Open Access   (Followers: 1, SJR: 0.263, CiteScore: 1)
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 3, SJR: 0.101, CiteScore: 0)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 6)
Advances in Space Research     Full-text available via subscription   (Followers: 404, SJR: 0.569, CiteScore: 2)
Advances in Structural Biology     Full-text available via subscription   (Followers: 5)
Advances in Surgery     Full-text available via subscription   (Followers: 12, SJR: 0.555, CiteScore: 2)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 34, SJR: 2.208, CiteScore: 4)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 18)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 14)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 2.262, CiteScore: 5)
Advances in Water Resources     Hybrid Journal   (Followers: 48, SJR: 1.551, CiteScore: 3)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 1.117, CiteScore: 3)
Aerospace Science and Technology     Hybrid Journal   (Followers: 359, SJR: 0.796, CiteScore: 3)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.42, CiteScore: 2)
African J. of Emergency Medicine     Open Access   (Followers: 6, SJR: 0.296, CiteScore: 0)
Ageing Research Reviews     Hybrid Journal   (Followers: 11, SJR: 3.671, CiteScore: 9)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 464, SJR: 1.238, CiteScore: 3)
Agri Gene     Hybrid Journal   (Followers: 1, SJR: 0.13, CiteScore: 0)
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 17, SJR: 1.818, CiteScore: 5)
Agricultural Systems     Hybrid Journal   (Followers: 31, SJR: 1.156, CiteScore: 4)
Agricultural Water Management     Hybrid Journal   (Followers: 42, SJR: 1.272, CiteScore: 3)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 4)
Agriculture and Natural Resources     Open Access   (Followers: 3)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 57, SJR: 1.747, CiteScore: 4)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.589, CiteScore: 3)
Air Medical J.     Hybrid Journal   (Followers: 6, SJR: 0.26, CiteScore: 0)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.19, CiteScore: 0)
Alcohol     Hybrid Journal   (Followers: 12, SJR: 1.153, CiteScore: 3)
Alcoholism and Drug Addiction     Open Access   (Followers: 11)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.604, CiteScore: 3)
Alexandria J. of Medicine     Open Access   (Followers: 1, SJR: 0.191, CiteScore: 1)
Algal Research     Partially Free   (Followers: 10, SJR: 1.142, CiteScore: 4)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.504, CiteScore: 1)
Allergology Intl.     Open Access   (Followers: 5, SJR: 1.148, CiteScore: 2)
Alpha Omegan     Full-text available via subscription   (SJR: 3.521, CiteScore: 6)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 10, SJR: 0.201, CiteScore: 1)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 52, SJR: 4.66, CiteScore: 10)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 4, SJR: 1.796, CiteScore: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 4, SJR: 1.108, CiteScore: 3)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 6)
American Heart J.     Hybrid Journal   (Followers: 56, SJR: 3.267, CiteScore: 4)
American J. of Cardiology     Hybrid Journal   (Followers: 59, SJR: 1.93, CiteScore: 3)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 44, SJR: 0.604, CiteScore: 1)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 11)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 13, SJR: 1.524, CiteScore: 3)
American J. of Human Genetics     Hybrid Journal   (Followers: 34, SJR: 7.45, CiteScore: 8)
American J. of Infection Control     Hybrid Journal   (Followers: 28, SJR: 1.062, CiteScore: 2)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 35, SJR: 2.973, CiteScore: 4)
American J. of Medicine     Hybrid Journal   (Followers: 48)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3, SJR: 1.967, CiteScore: 2)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 225, SJR: 2.7, CiteScore: 4)
American J. of Ophthalmology     Hybrid Journal   (Followers: 66, SJR: 3.184, CiteScore: 4)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 5, SJR: 0.265, CiteScore: 0)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.289, CiteScore: 1)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, CiteScore: 1)
American J. of Pathology     Hybrid Journal   (Followers: 28, SJR: 2.139, CiteScore: 4)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 29, SJR: 2.164, CiteScore: 4)
American J. of Surgery     Hybrid Journal   (Followers: 38, SJR: 1.141, CiteScore: 2)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.767, CiteScore: 1)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 7)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.144, CiteScore: 3)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 63, SJR: 0.138, CiteScore: 0)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 19, SJR: 0.411, CiteScore: 1)
Anales de Cirugia Vascular     Full-text available via subscription   (Followers: 1)
Anales de Pediatría     Full-text available via subscription   (Followers: 3, SJR: 0.277, CiteScore: 0)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription  
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 5, SJR: 4.849, CiteScore: 10)
Analytica Chimica Acta     Hybrid Journal   (Followers: 43, SJR: 1.512, CiteScore: 5)
Analytical Biochemistry     Hybrid Journal   (Followers: 188, SJR: 0.633, CiteScore: 2)
Analytical Chemistry Research     Open Access   (Followers: 12, SJR: 0.411, CiteScore: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 13)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 2)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 23, SJR: 0.683, CiteScore: 2)
Angiología     Full-text available via subscription   (SJR: 0.121, CiteScore: 0)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1, SJR: 0.111, CiteScore: 0)
Animal Behaviour     Hybrid Journal   (Followers: 204, SJR: 1.58, CiteScore: 3)
Animal Feed Science and Technology     Hybrid Journal   (Followers: 5, SJR: 0.937, CiteScore: 2)
Animal Reproduction Science     Hybrid Journal   (Followers: 7, SJR: 0.704, CiteScore: 2)

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Journal Cover
Advanced Drug Delivery Reviews
Journal Prestige (SJR): 4.09
Citation Impact (citeScore): 13
Number of Followers: 167  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0169-409X
Published by Elsevier Homepage  [3160 journals]
  • Cardiac macrotissues-on-a-plate models for phenotypic drug screens
    • Abstract: Publication date: Available online 19 March 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Tim Meyer, Malte Tiburcy, Wolfram-Hubertus Zimmermann Facilitated by the introduction of human induced pluripotent stem cells and protocols for their efficient directed differentiation at high quantity and quality, innovative human heart muscle models are being developed for applications in drug screens. Employed models range from the microscopic cardiomyocytes-on-a-chip scale to the cardiac macrotissues-on-a-plate scale. Whilst cardiomyocyte-on-a-chip models can be readily adapted to high-throughput primary screening, they are limited as to the deep phenotyping of contractility, and here in particular contractile force development. In lower throughput cardiac macrotissue-on-a-plate platforms, organotypic function, including anisotropic electrical spread of excitation and contractility, can be recapitulated at the macroscopic scale. This review serves as an overview of cardiac macrotissue-on-a-plate technologies with a focus on their application in the investigation of drug effects on heart muscle contractility and disease modeling.Graphical abstractSchematic overview of a staged approach in human cardiomyocyte based drug development, comprising 2D cardiomyocyte cultures for higher-throughput (cardiomyocytes-on-a-chip) and lower-throughput 3D models (cardiac macrotissues-on-a-plate) as primary and secondary screening platforms. The availability of patient-specific induced pluripotent stem cells, protocols for their robust cardiac differentiation, and models from the cardiomyocytes-on-a-chip to the cardiac macrotissue-on-a-plate scale may even allow for a fully personalized drug development cycle.Unlabelled Image
  • Lyophilized liposome-based parenteral drug development: Reviewing complex
           product design strategies and current regulatory environments
    • Abstract: Publication date: Available online 18 March 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Yuwei Wang, David W. Grainger Given the successful entry of several liposomal drug products into market, and some with decades of clinical efficacy, liposomal drug delivery systems have proven capabilities to overcome certain limitations of traditional drug delivery, especially for toxic and biologic drugs. This experience has helped promote new liposomal approaches to emerging drug classes and current therapeutic challenges. All approved liposomal dosage forms are parenteral formulations, a pathway demonstrating greatest safety and efficacy to date. Due to the intrinsic instability of aqueous liposomal dispersions, lyophilization is commonly applied as an important solution to improve liposomal drug stability, and facilitate transportation, storage and improve product shelf-life. While lyophilization is a mature pharmaceutical technology, liposome-specific lyophilization platforms must be developed using particular lyophilization experience and strategies. This review provides an overview of liposome formulation-specific lyophilization approaches for parenteral use, excipients used exclusively in liposomal parenteral products, lyophilized liposome formulation design and process development, long-term storage, and current regulatory guidance for liposome drug products. Readers should capture a comprehensive understanding of formulation and process variables and strategies for developing parenterally administered liposomal drugs.Graphical abstractUnlabelled Image
  • Leveraging the interplay of nanotechnology and neuroscience: Designing new
           avenues for treating central nervous system disorders
    • Abstract: Publication date: Available online 4 March 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Elizabeth Smith, Joshua E. Porterfield, Rangaramanujam M. Kannan Nanotechnology has the potential to open many novel diagnostic and treatment avenues for disorders of the central nervous system (CNS). In this review, we discuss recent developments in the applications of nanotechnology in CNS therapies, diagnosis and biology. Novel approaches for the diagnosis and treatment of neuroinflammation, brain dysfunction, psychiatric conditions, brain cancer, and nerve injury provide insights into the potential of nanomedicine. We also highlight nanotechnology-enabled neuroscience techniques such as electrophysiology and intracellular sampling to improve our understanding of the brain and its components. With nanotechnology integrally involved in the advancement of basic neuroscience and the development of novel treatments, combined diagnostic and therapeutic applications have begun to emerge. Nanotheranostics for the brain, able to achieve single-cell resolution, will hasten the rate in which we can diagnose, monitor, and treat diseases. Taken together, the recent advances highlighted in this review demonstrate the prospect for significant improvements to clinical diagnosis and treatment of a vast array of neurological diseases. However, it is apparent that a strong dialogue between the nanoscience and neuroscience communities will be critical for the development of successful nanotherapeutics that move to the clinic, benefit patients, and address unmet needs in CNS disorders.
  • Nanoformulation properties, characterization, and behavior in complex
           biological matrices: Challenges and opportunities for brain-targeted drug
           delivery applications and enhanced translational potential
    • Abstract: Publication date: Available online 22 February 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Vibhuti Agrahari, Pierre-Alain Burnouf, Thierry Burnouf, Vivek Agrahari Nanocarriers (synthetic/cell-based) have attracted enormous interest for various therapeutic indications, including neurodegenerative disorders. A broader understanding of the impact of nanomedicines design is now required to enhance their translational potential. Nanoformulations in-vivo journey is significantly affected by their physicochemical properties including size/shape/hydrophobicity/elasticity and surface charge/chemistry/morphology, which play a role as interface with the biological environment. Understanding protein corona formation is crucial in characterizing nanocarriers and evaluating their interactions with biological systems. In this review, types and properties of the brain-targeted nanocarriers are discussed. The biological factors and nanocarriers properties affecting their in-vivo behavior are elaborated. The compositional description of cell culture and biological matrices, including proteins potentially relevant to protein corona built-up on nanoformulation especially for brain administration, is provided. Analytical techniques of characterizing nanocarriers in complex matrices, their advantages/limitations, and implementation challenges in industrial GMP environment are discussed. The uses of orthogonal complementary characterization approaches of nanocarriers are also covered.Graphical abstractUnlabelled Image
  • Technologies for intrapericardial delivery of therapeutics and cells
    • Abstract: Publication date: Available online 21 February 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Carly S. Filgueira, Stephen R. Igo, Dennis K. Wang, Matteo Hirsch, Daryl G. Schulz, Brian Bruckner, Alessandro Grattoni The pericardium, which surrounds the heart, provides a unique enclosed volume and a site for the delivery of agents to the heart and coronary arteries. While strategies for targeting the delivery of therapeutics to the heart are lacking, various technologies and nanodelivery approaches are emerging as promising methods for site specific delivery to increase therapeutic myocardial retention, efficacy, and bioactivity, while decreasing undesired systemic effects. Here, we provide a literature review of various approaches for intrapericardial delivery of agents. Emphasis is given to sustained delivery approaches (pumps and catheters) and localized release (patches, drug eluting stents, and, support devices and meshes). Further, minimally invasive access techniques, pericardial access devices, pericardial washout and fluid analysis, as well as therapeutic and cell delivery vehicles are presented. Finally, several promising new therapeutic targets to treat heart diseases are highlighted.Graphical abstractUnlabelled Image
  • Chronopharmacology of glucocorticoids
    • Abstract: Publication date: Available online 21 February 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Megerle L. Scherholz, Naomi Schlesinger, Ioannis P. Androulakis Glucocorticoids influence a wide array of metabolic, anti-inflammatory, immunosuppressive, and cognitive signaling processes, playing an important role in homeostasis and preservation of normal organ function. Synthesis is regulated by the hypothalamic-pituitary-adrenal (HPA) axis of which cortisol is the primary glucocorticoid in humans. Synthetic glucocorticoids are important pharmacological agents that augment the anti-inflammatory and immunosuppressive properties of endogenous cortisol and are widely used for the treatment of asthma, Crohn's disease, and rheumatoid arthritis, amongst other chronic conditions. The homeostatic activity of cortisol is disrupted by the administration of synthetic glucocorticoids and so there is interest in developing treatment options that minimize HPA axis disturbance while maintaining the pharmacological effects. Studies suggest that optimizing drug administration time can achieve this goal. The present review provides an overview of endogenous glucocorticoid activity and recent advances in treatment options that have further improved patient safety and efficacy with an emphasis on chronopharmacology.Graphical abstractUnlabelled Image
  • Nanoparticle technology and stem cell therapy team up against
           neurodegenerative disorders
    • Abstract: Publication date: Available online 21 February 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Caroline Vissers, Guo-li Ming, Hongjun Song The convergence of nanoparticles and stem cell therapy holds great promise for the study, diagnosis, and treatment of neurodegenerative disorders. By combining nanoparticles with stem cell therapies, researchers aim to harness the power of nanoparticles to carefully modulate their microenvironment to enhance the survival and success of stem cell transplants. Understanding the various properties of different nanoparticles is key to applying them to clinical therapies; the many distinct types of nanoparticles offer unique capacities for medical imaging, diagnosis, and treatment of neurodegeneration disorders. In this review we discuss the potentials and shortcomings of metal, silica, lipid-based, polymeric, and hydrogel nanoparticles for treatment of neurodegenerative disorders, and how they can be combined with stem cell therapies to improve clinical outcomes.Graphical abstractUnlabelled Image
  • Adenosine and lipids: A forced marriage or a love match'
    • Abstract: Publication date: Available online 21 February 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Marie Rouquette, Sinda Lepetre-Mouelhi, Patrick Couvreur Adenosine is a fascinating compound, crucial in many biochemical processes: this ubiquitous nucleoside serves as an essential building block of RNA, is also a component of ATP and regulates numerous pathophysiological mechanisms via binding to four extracellular receptors. Due to its hydrophilic nature, it belongs to a different world than lipids, and has no affinity for them. Since the 1970's, however, new discoveries have emerged and prompted the scientific community to associate adenosine with the lipid family, especially via liposomal preparations and bioconjugation. This seems to be an arranged marriage, but could it turn into a true love match? This review considered all types of unions established between adenosine and lipids. Even though exciting supramolecular structures were observed with adenosine-lipid conjugates, as well as with liposomal preparations which resulted in promising pre-clinical results, the translation of these technologies to the clinic is still limited.Graphical abstractUnlabelled Image
  • A minimalist's approach for DNA nanoconstructions
    • Abstract: Publication date: Available online 12 February 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Hua Zuo, Chengde Mao Structural DNA nanotechnology takes DNA, a biopolymer, far beyond being the molecule that stores and transmits genetic information in biological systems. DNA has been employed as building blocks for the assembly of designed, nanoscaled, supramolecular DNA architectures for applications in biophysics, structure determination, synthetic biology, diagnostics, and drug delivery. Herein, we review a symmetric approach of tile-based DNA self-assembly. This approach allows construction of DNA nanostructures from minimal numbers of different types of DNA strands based on sequence and structural symmetries. Some examples of the applications of this approach in siRNA delivery are discussed as well.Graphical abstractUnlabelled Image
  • Rationally designed DNA-based nanocarriers
    • Abstract: Publication date: Available online 12 February 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Qiao Jiang, Shuai Zhao, Jianbing Liu, Linlin Song, Zhen-Gang Wang, Baoquan Ding sNanomaterials employed for enhanced drug delivery and therapeutic effects have been extensively investigated in the past decade. The outcome of current anticancer treatments based on conventional nanoparticles is suboptimal, due to the lack of biocompatibility, the deficient tumor targeting, the limited drug accumulation in the diseased region, etc. Alternatively, DNA-based nanocarriers have emerged as a novel and versatile platform to integrate the advantages of nanotechnologies and biological sciences, which shows great promise in addressing the key issues for biomedical studies. Rather than a genetic information carrier, DNA molecules can work as building blocks to fabricate programmable and bio-functional nanostructures based on Watson Crick base-pairing rules. The DNA-based materials have demonstrated unique properties, such as uniform sizes and shapes, pre-designable and programmable nanostructures, site-specific surface functionality and excellent biocompatibility. These intrigue features allow DNA nanostructures to carry functional moieties to realize precise tumor recognition, customized therapeutic functions and stimuli-responsive drug release, making them highly attractive in many aspects of cancer treatment. In this review, we focus on the recent progress in DNA-based self-assembled materials for the biomedical applications, such as molecular imaging, drug delivery for in vitro or in vivo cancer treatments. We introduce the general strategies and essential requirements for fabricating DNA-based nanocarriers. We summarize the advances of DNA-based nanocarriers according to their functionalities and structural properties for cancer diagnosis and therapy. Finally, we discuss the challenges and future perspectives regarding the detailed in vivo parameters of DNA materials and the design of intelligent DNA nanomedicine for individualized cancer therapy.Graphical abstractOver the past decade, DNA nanocarriers have emerged as a novel and versatile platform to integrate the advantages of nanotechnologies and biological sciences. Based on Watson Crick base-pairing rules, DNA molecules can work as building blocks to fabricate programmable and bio-functional nanostructures. As a promising candidate for nanocarrier, self-assembled DNA architecture holds distinct advantages, e.g., inherent biocompatibility, precisely designed nanoscale shapes and sizes, tailored functionality, and responsive reconfiguration. These intrigue features allow DNA nanostructures to carry functional moieties to realize precise tumor recognition, customized therapeutic functions and stimuli-responsive drug release, making them highly attractive in many aspects of cancer treatment.Unlabelled Image
  • Let's get small (and smaller): Combining zebrafish and nanomedicine to
           advance neuroregenerative therapeutics
    • Abstract: Publication date: Available online 12 February 2019Source: Advanced Drug Delivery ReviewsAuthor(s): David T. White, Meera T. Saxena, Jeff S. Mumm Several key attributes of zebrafish make them an ideal model system for the discovery and development of regeneration promoting therapeutics; most notably their robust capacity for self-repair which extends to the central nervous system. Further, by enabling large-scale drug discovery directly in living vertebrate disease models, zebrafish circumvent critical bottlenecks which have driven drug development costs up. This review summarizes currently available zebrafish phenotypic screening platforms, HTS-ready neurodegenerative disease modeling strategies, zebrafish small molecule screens which have succeeded in identifying regeneration promoting compounds and explores how intravital imaging in zebrafish can facilitate comprehensive analysis of nanocarrier biodistribution and pharmacokinetics. Finally, we discuss the benefits and challenges attending the combination of zebrafish and nanoparticle-based drug optimization, highlighting inspiring proof-of-concept studies and looking toward implementation across the drug development community.Graphical abstractUnlabelled Image
  • Therapeutic gene regulation using pyrrole–imidazole polyamides
    • Abstract: Publication date: Available online 10 February 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Zutao Yu, Ganesh N. Pandian, Takuya Hidaka, Hiroshi Sugiyama Recent innovations in cutting-edge sequencing platforms have allowed the rapid identification of genes associated with communicable, noncommunicable and rare diseases. Exploitation of this collected biological information has facilitated the development of nonviral gene therapy strategies and the design of several proteins capable of editing specific DNA sequences for disease control. Small molecule-based targeted therapeutic approaches have gained increasing attention because of their suggested clinical benefits, ease of control and lower costs. Pyrrole–imidazole polyamides (PIPs) are a major class of DNA minor groove-binding small molecules that can be predesigned to recognize specific DNA sequences. This programmability of PIPs allows the on-demand design of artificial genetic switches and fluorescent probes. In this review, we detail the progress in the development of PIP-based designer ligands and their prospects as advanced DNA-based small-molecule drugs for therapeutic gene modulation.Graphical abstractUnlabelled Image
  • Nanotechnology in cell replacement therapies for type 1 diabetes
    • Abstract: Publication date: Available online 2 February 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Alexander U. Ernst, Daniel T. Bowers, Long-Hai Wang, Kaavian Shariati, Mitchell D. Plesser, Natalie K. Brown, Tigran Mehrabyan, Minglin Ma Islet transplantation is a promising long-term, compliance-free, complication-preventing treatment for type 1 diabetes. However, islet transplantation is currently limited to a narrow set of patients due to the shortage of donor islets and side effects from immunosuppression. Encapsulating cells in an immunoisolating membrane can allow for their transplantation without the need for immunosuppression. Alternatively, “open” systems may improve islet health and function by allowing vascular ingrowth at clinically attractive sites. Many processes that enable graft success in both approaches occur at the nanoscale level—in this review we thus consider nanotechnology in cell replacement therapies for type 1 diabetes. A variety of biomaterial-based strategies at the nanometer range have emerged to promote immune-isolation or modulation, proangiogenic, or insulinotropic effects. Additionally, coating islets within nano-thin polymer films has burgeoned as an islet protection modality. Materials approaches that utilize nanoscale features manipulate biology at the molecular scale, offering unique solutions to the enduring challenges of islet transplantation.Graphical abstractUnlabelled Image
  • A window into the brain: Tools to assess preclinical efficacy of
           biomaterials-based therapies on central nervous system disorders
    • Abstract: Publication date: Available online 31 January 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Juhi Samal, Ana Lucia Rebelo, Abhay Pandit Therapeutic conveyance into the brain is a cardinal requirement for treatment of diverse central nervous system (CNS) disorders and associated pathophysiology. Effectual shielding of the brain by the blood-brain barrier (BBB) sieves out major proportion of therapeutics with the exception of small lipophilic molecules. Various nano-delivery systems (NDS) provide an effective solution around this obstacle owing to their small size and targeting properties. To date, these systems have been used for several pre-clinical disease models including glioma, neurodegenerative diseases and psychotic disorders. An efficacy screen for these systems involves a test battery designed to probe into the multiple facets of therapeutic delivery. Despite their wide application in redressing various disease targets, the efficacy evaluation strategies for all can be broadly grouped into four modalities, namely: histological, bio-imaging, molecular and behavioural. This review presents a comprehensive insight into all of these modalities along with their strengths and weaknesses as well as perspectives on an ideal design for a panel of tests to screen brain nano-delivery systems.Graphical abstractUnlabelled Image
  • Cathepsin-sensitive nanoscale drug delivery systems for cancer therapy and
           other diseases
    • Abstract: Publication date: Available online 26 January 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Divya Dheer, Julien Nicolas, Ravi Shankar Cathepsins are an important category of enzymes that have attracted great attention for the delivery of drugs to improve the therapeutic outcome of a broad range of nanoscale drug delivery systems. These proteases can be utilized for instance through actuation of polymer-drug conjugates (e.g., triggering the drug release) to bypass limitations of many drug candidates. A substantial amount of work has been witnessed in the design and the evaluation of Cathepsin-sensitive drug delivery systems, especially based on the tetra-peptide sequence (Gly-Phe-Leu-Gly, GFLG) which has been extensively used as a spacer that can be cleaved in the presence of Cathepsin B. This Review Article will give an in-depth overview of the design and the biological evaluation of Cathepsin-sensitive drug delivery systems and their application in different pathologies including cancer before discussing Cathepsin B-cleavable prodrugs under clinical trials.Graphical Unlabelled Image
  • Bridging the gaps between academic research and industrial product
           developments of lipid-based formulations
    • Abstract: Publication date: Available online 22 January 2019Source: Advanced Drug Delivery ReviewsAuthor(s): René Holm Lipid-based formulations, including self-emulsifying drug delivery systems (SEDDS), are an interesting formulation technology that enables the clinical use of compounds for which a low aqueous solubility may be a limitation. From an academic perspective, the technology is interesting on several levels: what drives solubility, what determines bioperformance, what is the potential for solidification etc. From an industrial perspective,>35 lipid-based formulations are available and there is an unknown number of projects in the pipeline. Hence, while there is scientific interest from both academic and industrial perspectives, the agendas/needs in the two settings are different. From an industrial perspective, risks are associated with uncertainty; hence the more that is known about a technology the better – knowledge that in principle can be generated in both the academia and industry. This focuses on the development of lipid-based formulations and the knowledge gaps that could be investigated –with the hope that all stakeholders in the field of lipid-based formulations, including academia, industry, CRO's, lipid excipient manufacturers etc., would share their insight, so that this technology can be even further developed. Some of the gaps discussed include the selection of compounds suited for lipid-based formulations, which potential modifications that could be investigated, e.g., lipophilic salts, what is a relevant definition of accelerated stability studies, how best to construct an industrial development program of a lipid-based formulation, etc.Graphical abstractUnlabelled Image
  • Colloidal aspects of dispersion and digestion of self-dispersing
           lipid-based formulations for poorly water-soluble drugs
    • Abstract: Publication date: Available online 21 January 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Kapilkumar Vithani, Vincent Jannin, Colin W. Pouton, Ben J. Boyd Self-dispersing lipid-based formulations, particularly self-microemulsifying drug delivery systems (SMEDDS) have gained an increased interest in recent times as a means to enhance the oral bioavailability of poorly water-soluble lipophilic drugs. Upon dilution, SMEDDS self-emulsify in an aqueous fluid and usually form a kinetically stable oil-in-water emulsion or in some rare cases a true thermodynamically stable microemulsion. The digestion of the formulation leads to the production of amphiphilic digestion products that interact with endogenous amphiphilic components and form self-assembled colloidal phases in the aqueous environment of the intestine. The formed colloidal phases play a pivotal role in maintaining the lipophilic drug in the solubilised state during gastrointestinal transit prior to absorption. Thus, this review describes the structural characterisation techniques employed for SMEDDS and the recent literature studies that elucidated the colloidal aspects during dispersion and digestion of SMEDDS and solid SMEDDS. Possible future studies are proposed to gain better understanding on the colloidal aspects of SMEDDS and solid SMEDDS.Graphical abstractUnlabelled Image
  • Bacteriophage Interactions with Mammalian Tissue: Therapeutic Applications
    • Abstract: Publication date: Available online 17 January 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Haein Huh, Shirley Wong, Jesse St. Jean, Roderick Slavcev The human body is a large reservoir for bacterial viruses known as bacteriophages (phages), which participate in dynamic interactions with their bacterial and human hosts that ultimately affect human health. The current growing interest in human resident phages is paralleled by new uses of phages, including the design of engineered phages for therapeutic applications. Despite the increasing number of clinical trials being conducted, the understanding of the interaction of phages and mammalian cells and tissues is still largely unknown. The presence of phages in compartments within the body previously considered purely sterile, suggests that phages possess a unique capability of bypassing anatomical and physiological barriers characterized by varying degrees of selectivity and permeability. This review will discuss the direct evidence of the accumulation of bacteriophages in various tissues, focusing on the unique capability of phages to traverse relatively impermeable barriers in mammals and its relevance to its current applications in therapy.Graphical abstractUnlabelled Image
  • T-cells “à la CAR-T(e)” - Genetically engineering T-cell
           response against cancer
    • Abstract: Publication date: Available online 14 January 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Vasyl Eisenberg, Shiran Hoogi, Astar Shamul, Tilda Barliya, Cyrille J. Cohen The last decade will be remembered as the dawn of the immunotherapy era during which we have witnessed the approval by regulatory agencies of genetically engineered CAR T-cells and of checkpoint inhibitors for cancer treatment. Understandably, T-lymphocytes represent the essential player in these approaches. These cells can mediate impressive tumor regression in terminally-ill cancer patients. Moreover, they are amenable to genetic engineering to improve their function and specificity. In the present review, we will give an overview of the most recent developments in the field of T-cell genetic engineering including TCR-gene transfer and CAR T-cells strategies. We will also elaborate on the development of other types of genetic modifications to enhance their anti-tumor immune response such as the use of co-stimulatory chimeric receptors (CCRs) and unconventional CARs built on non-antibody molecules. Finally, we will discuss recent advances in genome editing and synthetic biology applied to T-cell engineering and comment on the next challenges ahead.Graphical abstractT-cells isolated from the patient are activated ex vivo and modified genetically (e.g., using a viral vector) to express new gene(s) that will endow the cell with target specificity and/or improved immunological function.Unlabelled Image
  • Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic
    • Abstract: Publication date: Available online 11 January 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Seyed Mohammadali Dadfar, Karolin Roemhild, Natascha I. Drude, Saskia von Stillfried, Ruth Knüchel, Fabian Kiessling, Twan Lammers Many different iron oxide nanoparticles have been evaluated over the years, for many different biomedical applications. We here summarize the synthesis, surface functionalization and characterization of iron oxide nanoparticles, as well as their (pre-) clinical use in diagnostic, therapeutic and theranostic settings. Diagnostic applications include liver, lymph node, inflammation and vascular imaging, employing mostly magnetic resonance imaging but recently also magnetic particle imaging. Therapeutic applications encompass iron supplementation in anemia and advanced cancer treatments, such as modulation of macrophage polarization, magnetic fluid hyperthermia and magnetic drug targeting. Because of their properties, iron oxide nanoparticles are particularly useful for theranostic purposes. Examples of such setups, in which diagnosis and therapy are intimately combined and in which iron oxide nanoparticles are used, are image-guided drug delivery, image-guided and microbubble-mediated opening of the blood-brain barrier, and theranostic tissue engineering. Together, these directions highlight the versatility and the broad applicability of iron oxide nanoparticles, and they indicate that multiple iron oxide nanoparticle-based materials will be integrated in future medical practice.Graphical abstractUnlabelled Image
  • Thermally-triggered fabrication of cell sheets for tissue engineering and
           regenerative medicine
    • Abstract: Publication date: Available online 11 January 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Hironobu Takahashi, Teruo Okano Cell transplantation is a promising approach for promoting tissue regeneration in the treatment of damaged tissues or organs. Although cells have conventionally been delivered by direct injection to damaged tissues, cell injection has limited efficiency to deliver therapeutic cells to the target sites. Progress in tissue engineering has moved scaffold-based cell/tissue delivery into the mainstream of tissue regeneration. A variety of scaffolds can be fabricated from natural or synthetic polymers to provide the appropriate culture conditions for cell growth and achieve in-vitro tissue formation. Tissue engineering has now become the primary approach for cell-based therapies. However, there are still serious limitations, particularly for engineering of cell-dense tissues. “Cell sheet engineering” is a scaffold-free tissue technology that holds even greater promise in the field of tissue engineering and regenerative medicine. Thermoresponsive poly(N-isopropylacrylamide)-grafted surfaces allow the fabrication of a tissue-like cell monolayer, a “cell sheet”, and efficiently delivers this cell-dense tissue to damaged sites without the use of scaffolds. At present, this unique approach has been applied to human clinical studies in regenerative medicine. Furthermore, this thermally triggered cell manipulation system allows us to produce a various types of 3D tissue models not only for regenerative medicine but also for tissue modeling, which can be used for drug discovery. Here, new cell sheet-based technologies are described including vascularization for scaled-up 3D tissue constructs, induced pluripotent stem (iPS) cell technology for human cell sheet fabrication and microfabrication for arranging tissue microstructures, all of which are expected to produce more complex tissues based on cell sheet tissue engineering.Graphical abstractUnlabelled Image
  • Effect of physicochemical and surface properties on in vivo fate
           of drug nanocarriers
    • Abstract: Publication date: Available online 11 January 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Zongmin Zhao, Anvay Ukidve, Vinu Krishnan, Samir Mitragotri Over the years, a plethora of materials – natural and synthetic – have been engineered at a nanoscopic level and explored for drug delivery. Nanocarriers based on such materials could improve the payload's pharmacokinetics and achieve the desired pharmacological response at the target tissue. Despite the development of rationally designed drug nanocarriers, only a handful of such formulations have been successfully translated into the clinic. The physicochemical properties (size, shape, surface chemistry, porosity, elasticity, and many others) of these nanocarriers influence its biological identity, which in presence of biological barriers in vivo, could significantly modulate the therapeutic index of its cargo and alter the desired outcome. Further, complexities associated with developing effective drug nanocarriers have led to conflicting views of its safety, permeation of biological barriers and cellular uptake. Here, in this review, we emphasize the effect of physicochemical properties of nanocarriers on their interactions with the biological milieu. The review will discuss in depth, how modulating the physicochemical properties would influence a drug nanocarrier's behavior in vivo and the mechanisms underlying these effects. The goal of this review is to summarize the design considerations based on these properties and to provide a conceptual template for achieving improved therapeutic efficacy with enhanced patient compliance.Graphical abstractUnlabelled Image
  • Nanotechnology in Peripheral Nerve Repair and Reconstruction
    • Abstract: Publication date: Available online 11 January 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Cristiana R. Carvalho, Joana Silva-Correia, Joaquim M. Oliveira, Rui L. Reis The recent progress in biomaterials science and development of tubular conduits (TCs) still fails in solving the current challenges in the treatment of peripheral nerve injuries (PNIs), in particular when disease-related and long-gap defects need to be addressed. Nanotechnology-based therapies that seemed unreachable in the past are now being considered for the repair and reconstruction of PNIs, having the power to deliver bioactive molecules in a controlled manner, to tune cellular behavior, and ultimately guide tissue regeneration in an effective manner. It also offers opportunities in the imaging field, with a degree of precision never achieved before, which is useful for diagnosis, surgery and in the patient’s follow-up. Nanotechnology approaches applied in PNI regeneration and theranostics, emphasizing the ones that are moving from the lab bench to the clinics, are herein overviewed.Graphical Unlabelled Image
  • Zebrafish as a Preclinical In Vivo Screening Model for
    • Abstract: Publication date: Available online 4 January 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Sandro Sieber, Philip Grossen, Jeroen Bussmann, Frederick Campbell, Alexander Kros, Dominik Witzigmann, Jörg Huwyler The interactions of nanomedicines with biological environments is heavily influenced by their physicochemical properties. Formulation design and optimization are therefore key steps towards successful nanomedicine development. Unfortunately, detailed assessment of nanomedicine formulations, at a macromolecular level, in rodents is severely limited by the restricted imaging possibilities within these animals. Moreover, rodent in vivo studies are time consuming and expensive, limiting the number of formulations that can be practically assessed in any one study. Consequently, screening and optimisation of nanomedicine formulations is most commonly performed in surrogate biological model systems, such as human-derived cell cultures. However, despite the time and cost advantages of classical in vitro models, these artificial systems fail to reflect and mimic the complex biological situation a nanomedicine will encounter in vivo. This has acutely hampered the selection of potentially successful nanomedicines for subsequent rodent in vivo studies. Recently, zebrafish have emerged as a promising in vivo model, within nanomedicine development pipelines, by offering opportunities to quickly screen nanomedicines under in vivo conditions and in a cost-effective manner so as to bridge the current gap between in vitro and rodent studies. In this review, we outline several advantageous features of the zebrafish model, such as biological conservation, imaging modalities, availability of genetic tools and disease models, as well as their various applications in nanomedicine development. Critical experimental parameters are discussed and the most beneficial applications of the zebrafish model, in the context of nanomedicine development, are highlighted.Graphical Unlabelled Image
  • Matrix-assisted Cell Transplantation for Tissue Vascularization
    • Abstract: Publication date: Available online 31 December 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Shane Browne, Kevin E. Healy Cell therapy offers much promise for the treatment of ischemic diseases by augmenting tissue vasculogenesis. Matrix-assisted cell transplantation (MACT) has been proposed as a solution to enhance cell survival and integration with host tissue following transplantation. By designing semi synthetic matrices (sECM) with the correct physical and biochemical signals, encapsulated cells are directed towards a more angiogenic phenotype. In this review, we describe the choice of cells suitable for pro-angiogenic therapies, the properties that should be considered when designing sECM for transplantation and their relative importance. Pre-clinical models where MACT has been successfully applied to promote angiogenesis are reviewed to show the great potential of this strategy to treat ischemic conditions.Graphical abstractUnlabelled Image
  • Advanced drug delivery systems and artificial skin grafts for skin wound
    • Abstract: Publication date: Available online 31 December 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Hye Sung Kim, Xiaoyan Sun, Jung-Hwan Lee, Hae-Won Kim, Xiaobing Fu, Kam W. Leong Cutaneous injuries, especially chronic wounds, burns, and skin wound infection, require painstakingly long-term treatment with an immense financial burden to healthcare systems worldwide. However, clinical management of chronic wounds remains unsatisfactory in many cases. Various strategies including growth factor and gene delivery as well as cell therapy have been used to enhance the healing of non-healing wounds. Drug delivery systems across the nano, micro, and macroscales can extend half-life, improve bioavailability, optimize pharmacokinetics, and decrease dosing frequency of drugs and genes. Replacement of the damaged skin tissue with substitutes comprising cell-laden scaffold can also restore the barrier and regulatory functions of skin at the wound site. This review covers comprehensively the advanced treatment strategies to improve the quality of wound healing.Graphical Unlabelled Image
  • Articular fibrocartilage - Why does hyaline cartilage fail to repair'
    • Abstract: Publication date: Available online 31 December 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Angela R. Armiento, Mauro Alini, Martin J. Stoddart Once damaged, articular cartilage has a limited potential to repair. Clinically, a repair tissue is formed yet it is often mechanically inferior fibrocartilage. The use of monolayer expanded versus naïve cells may explain one of the biggest discrepancies in mesenchymal stromal cell (MSC) based cartilage regeneration. Namely, studies utilizing monolayer expanded MSCs, as indicated by numerous in vitro studies, report the main limitation as induction of type X collagen and hypertrophy, a phenotype associated with endochondral bone formation. However, marrow stimulation and transfer studies report a mechanically inferior collagen I/ II fibrocartilage as the main outcome. Therefore, this review will highlight the collagen species produced during the different therapeutic approaches. New developments in scaffold design and delivery of therapeutic molecules will be described. Potential future directions towards clinical translation will be discussed. New delivery mechanisms are being developed and they offer new hope in targeted therapeutic delivery.This review aims to: 1. Report the challenges that still need to be addressed to achieve the goal of hyaline cartilage regeneration by focusing on the shortcoming of the repair tissue generated after traumatic injury or biological therapy; 2. Discuss the state of the art in cartilage-targeting therapeutic delivery; and 3. Highlight some of the emerging technologies and strategies that the authors believe to hold great promise.Graphical abstractUnlabelled Image
  • Phage-based vaccines
    • Abstract: Publication date: Available online 27 December 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Qing Bao, Xiang Li, Gaorong Han, Ye Zhu, Chuanbin Mao, Mingying Yang Bacteriophages, or more colloquially as phages, are viruses that possess the ability to infect and replicate with bacterial cells. They are assembled from two major types of biomolecules, the nucleic acids and the proteins, with the latter forming a capsid and the former being encapsulated. In the eukaryotic hosts, phages are inert particulate antigens and cannot trigger pathogenesis. In recent years, many studies have been explored about using phages as nanomedicine platforms for developing vaccines due to their unique biological characteristics. The whole phage particles can be used for vaccine design in the form of phage-displayed vaccines or phage DNA vaccines. Phage-displayed vaccines are the phages with peptide or protein antigens genetically displayed on their surfaces as well as those with antigens chemically conjugated or biologically bound on their surfaces. The phages can then deliver the immunogenic peptides or proteins to the target cells or tissues. Phage DNA vaccines are the eukaryotic promoter-driven vaccine genes inserted in the phage genomes, which are carried by phages to the target cells to generate antigens. The antigens, either as the immunogenic peptides or proteins displayed on the phages, or as the products expressed from the vaccine genes, can serve as vaccines to elicit immune response for disease prevention and treatment. Both phage-displayed vaccines and phage DNA vaccines promise a brilliant future for developing vaccines. This review presents the recent advancements in the field of phage-based vaccines and their applications in both the prevention and treatment of various diseases. It also discusses the challenges and perspectives in moving this field forwards.Graphical abstractUnlabelled Image
  • Recent advances in Nanotherapeutic strategies for Spinal Cord Injury
    • Abstract: Publication date: Available online 22 December 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Young Hye Song, Nikunj Agrawal, Jonathan M. Griffin, Christine E. Schmidt Spinal cord injury (SCI) is a devastating and complicated condition with no cure available. The initial mechanical trauma is followed by a secondary injury characterized by inflammatory cell infiltration and inhibitory glial scar formation. Due to the limitations posed by the blood–spinal cord barrier, systemic delivery of therapeutics is challenging. Recent development of various nanoscale strategies provides exciting and promising new means of treating SCI by crossing the blood–spinal cord barrier and delivering therapeutics. As such, we discuss different nanomaterial fabrication methods and provide an overview of recent studies where nanomaterials were developed to modulate inflammatory signals, target inhibitory factors in the lesion, and promote axonal regeneration after SCI. We also review emerging areas of research such as optogenetics, immunotherapy and CRISPR-mediated genome editing where nanomaterials can provide synergistic effects in developing novel SCI therapy regimens, as well as current efforts and barriers to clinical translation of nanomaterials.Graphical Unlabelled Image
  • Influencing neuroplasticity in stroke treatment with advanced
           biomaterials-based approaches
    • Abstract: Publication date: Available online 21 December 2018Source: Advanced Drug Delivery ReviewsAuthor(s): J.M. Obermeyer, A. Gracias, E. Ho, M.S. Shoichet Since the early 1990s, we have known that the adult brain is not static and has the capacity to repair itself. The delivery of various therapeutic factors and cells have resulted in some exciting pre-clinical and clinical outcomes in stroke models by targeting post-injury plasticity to enhance recovery. Developing a deeper understanding of the pathways that modulate plasticity will enable us to optimize delivery strategies for therapeutics and achieve more robust effects. Biomaterials are a key tool for the optimization of these potential treatments, owing to their biocompatibility and tunability. In this review, we identify factors and targets that impact plastic processes known to contribute to recovery, discuss the role of biomaterials in enhancing the efficacy of treatment strategies, and suggest combinatorial approaches based on the stage of injury progression.Graphical A multi-faceted strategy of combining biomaterials with therapeutics/cell transplantation can leverage neuroplasticity for stroke recovery.Unlabelled Image
  • Photo-triggered polymer nanomedicines: From molecular mechanisms to
           therapeutic applications
    • Abstract: Publication date: Available online 13 December 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Louis Beauté, Nathan McClenaghan, Sébastien Lecommandoux The use of nanotechnology to improve treatment efficacy and reduce side effects is central to nanomedicine. In this context, stimuli-responsive drug delivery systems (DDS) such as chemical/physical gels or nanoparticles such as polymersomes, micelles or nanogels are particularly promising and are the focus of this review. Several stimuli have been considered but light as an exogenous trigger presents many advantages that are pertinent for clinical applications such as high spatial and temporal control and low cost. Underlying mechanisms required for the release of therapeutic agents in vitro and in vivo range from the molecular scale, namely photoisomerization, hydrophobicity photoswitching, photocleavage or heat generation via nanoheaters, through to the macromolecular scale. As well as these approaches, DDS destabilization, DDS permeation pore unblocking and formation are discussed.Graphical abstractUnlabelled Image
  • Design Strategies for Shape-Controlled Magnetic Iron Oxide Nanoparticles
    • Abstract: Publication date: Available online 13 December 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Alejandro G. Roca, Lucía Gutiérrez, Helena Gavilán, María Eugênia Fortes Brollo, Sabino Veintemillas-Verdaguer, María del Puerto Morales :Ferrimagnetic iron oxide nanoparticles (magnetite or maghemite) have been the subject of an intense research, not only for fundamental research but also for their potentiality in a widespread number of practical applications. Most of these studies were focused on nanoparticles with spherical morphology but recently there is an emerging interest on anisometric nanoparticles. This review is focused on the synthesis routes for the production of uniform anisometric magnetite/maghemite nanoparticles with different morphologies like cubes, rods, disks, flowers and many others, such as hollow spheres, worms, stars or tetrapods. We critically analyzed those procedures, detected the key parameters governing the production of these nanoparticles with particular emphasis in the role of the ligands in the final nanoparticle morphology. The main structural and magnetic features as well as the nanotoxicity as a function of the nanoparticle morphology are also described. Finally, the impact of each morphology on the different biomedical applications (hyperthermia, magnetic resonance imaging and drug delivery) are analysed in detail.We would like to dedicate this work to Professor Carlos J. Serna, Instituto de Ciencia de Materiales de Madrid, ICMM/CSIC, for his outstanding contribution in the field of monodispersed colloids and iron oxide nanoparticles. We would like to express our gratitude for all these years of support and inspiration on the occasion of his retirement.Graphical abstractThis review summarizes the colloidal synthetic routes leading to magnetic iron oxide nanoparticles with different morphologies and analyses the key parameters on each route that govern particle size and shape. Structural and magnetic properties for each morphology are also reviewed and related to the synthetic route as well as the advantages of using magnetic anisometric nanoparticles in biomedical applications and others.Unlabelled Image
  • Extracellular vesicles for personalized medicine: The input of physically
           triggered production, loading and theranostic properties
    • Abstract: Publication date: Available online 13 December 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Max Piffoux, Alba Nicolás-Boluda, Vladmir Mulens-Arias, Sophie Richard, Gabriel Rahmi, Florence Gazeau, Claire Wilhelm, Amanda K.A. Silva Emerging advances in extracellular vesicle (EV) research brings along new promises for tailoring clinical treatments in order to meet specific disease features of each patient in a personalized medicine concept. EVs may act as regenerative effectors conveying endogenous therapeutic factors from parent cells or constitute a bio-camouflaged delivery system for exogenous therapeutic agents. Physical stimulation may be an important tool in the field of EVs for personalized therapy by powering EV production, loading and therapeutic properties. Physically-triggered EV production is inspired by naturally occurring EV release by shear stress in blood vessels. Bioinspired physically-triggered EV production technologies may bring along high yield advantages combined to scalability assets. Physical stimulation may also provide new prospects for high-efficient EV loading. Additionally, physically-triggered EV theranostic properties brings new hopes for spatio-temporal controlled therapy combined to tracking. Technological considerations related to EV-based personalized medicine and the input of physical stimulation on EV production, loading and theranostic properties will be overviewed herein.Graphical abstractUnlabelled Image
  • Superparamagnetic Iron Oxides as MPI Tracers: A Primer and Review of early
    • Abstract: Publication date: Available online 13 December 2018Source: Advanced Drug Delivery ReviewsAuthor(s): J.W.M. Bulte Magnetic particle imaging (MPI) has recently emerged as a non-invasive, whole body imaging technique that detects superparamagnetic iron oxide (SPIO) nanoparticles similar as those used in magnetic resonance imaging (MRI). Based on tracer “hot spot” detection instead of providing contrast on MRI scans, MPI has already proven to be truly quantitative. Without the presence of endogenous background signal, MPI can also be used in certain tissues where the endogenous MRI signal is too low to provide contrast. After an introduction to the history and simplified principles of MPI, this review focuses on early MPI applications including MPI cell tracking, multiplexed MPI, perfusion and tumor MPI, lung MPI, functional MPI, and MPI-guided hyperthermia. While it is too early to tell if MPI will become a mainstay imaging technique with the (theoretical) sensitivity that it promises, and if it can successfully compete with SPIO-based 1H MRI and perfluorocarbon-based 19F MRI, it provides unprecedented opportunities for exploring new nanoparticle-based imaging applications.Graphical abstractUnlabelled Image
  • Targeting the CD40-CD40L pathway in autoimmune diseases: Humoral immunity
           and beyond
    • Abstract: Publication date: Available online 13 December 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Jodi L. Karnell, Sadiye Amcaoglu Rieder, Rachel Ettinger, Roland Kolbeck CD40 is a TNF receptor superfamily member expressed on both immune and non-immune cells. Interactions between B cell-expressed CD40 and its binding partner, CD40L, predominantly expressed on activated CD4+ T cells, play a critical role in promoting germinal center formation and the production of class-switched antibodies. Non-hematopoietic cells expressing CD40 can also engage CD40L and trigger a pro-inflammatory response. This article will highlight what is known about the biology of the CD40-CD40L axis in humans and describe the potential contribution of CD40 signaling on both hematopoietic and non-hematopoietic cells to autoimmune disease pathogenesis. Additionally, novel therapeutic approaches to target this pathway, currently being evaluated in clinical trials, are discussed.
  • Advances in Transdermal Insulin Delivery
    • Abstract: Publication date: Available online 8 December 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Yuqi Zhang, Jicheng Yu, Anna R. Kahkoska, Jinqiang Wang, John B. Buse, Zhen Gu :Insulin therapy is necessary to regulate blood glucose levels for people with type 1 diabetes and commonly used in advanced type 2 diabetes. Although subcutaneous insulin administration via hypodermic injection or pump-mediated infusion is the standard route of insulin delivery, it may be associated with pain, needle phobia, and decreased adherence, as well as the risk of infection. Therefore, transdermal insulin delivery has been widely investigated as an attractive alternative to subcutaneous approaches for diabetes management in recent years. Transdermal systems designed to prevent insulin degradation and offer controlled, sustained release of insulin may be desirable for patients and lead to increased adherence and glycemic outcomes. A challenge for transdermal insulin delivery is the inefficient passive insulin absorption through the skin due to the large molecular weight of the protein drug. In this review, we focus on the different transdermal insulin delivery techniques and their respective advantages and limitations, including chemical enhancers-promoted, electrically enhanced, mechanical force-triggered, and microneedle-assisted methods.Graphical abstractUnlabelled Image
  • Advances in Immunotherapy of Type I Diabetes
    • Abstract: Publication date: Available online 7 December 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Qianqian Ni, Ngoc B. Pham, Wilson S. Meng, Guizhi Zhu, Xiaoyuan Chen Type 1 diabetes mellitus (T1DM) is an autoimmune disease affecting 3 million individuals in the U.S. The pathogenesis of T1DM is driven by immune-mediated destruction of pancreatic β cells, the source of glucose regulator insulin. While T1DM can be successfully managed with insulin replacement therapy, approaches that can modify the underlying immuno-pathology of β cell destruction has been long sought after. Immunotherapy can attenuate T cell responses against β cell antigens. Given the detailed cellular and molecular definitions of T1DM immune responses, rational immunomodulation can be and have been developed in mouse models, and in some instances, tested in humans. The possibility of identifying individuals who are predisposed to T1DM through genotyping lend to the possibility of preventive vaccines. While much has been accomplished in delineating the mechanisms of immunotherapies, some of which are being tested in humans, long-term preservation of β cells and insulin independency has not been achieved. In this regard, the drug delivery field has much to offer in maximizing the benefits of immune modulators by optimizing spatiotemporal presentation of antigens and costimulatory signals. In this review, we attempt to capture the current state of T1DM immunotherapy by highlighting representative studies.Graphical Unlabelled Image
  • Aggregation-induced emission (AIE) fluorophores as imaging tools to trace
           the biological fate of nano-based drug delivery systems
    • Abstract: Publication date: Available online 6 December 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Yufei Wang, Yuxuan Zhang, Jinjin Wang, Xing-Jie Liang The vigorous development of nanotechnology has been accompanied by an equally strong interest and research efforts in nano-based drug delivery systems (NDDSs). However, only a few NDDSs have been translated into clinic thus far. One of the important hurdles is the lack of tools to comprehensively and directly trace the biological fate of NDDSs. Recently, aggregation-induced emission (AIE) fluorophores have emerged as attractive bioimaging tools due to flexible controllability, negligible toxicity and superior photostability. Herein, we recapitulate the current advances in the application of AIE fluorophores to monitor NDDSs both in vitro and in vivo. Particularly, we discuss the cellular fates of self-indicating and stimuli-responsive NDDSs with AIE fluorophores. Moreover, we highlight the in vivo application of AIE agents on the long-term tracking of therapeutics and the multi-modal monitoring of diagnostics in NDDSs. Challenges and opportunities in AIE-guided exploration of NDDSs are also discussed in detail.Graphical Unlabelled Image
  • Engineering Lymphocytes with RNAi
    • Abstract: Publication date: Available online 6 December 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Srinivas Ramishetti, Dan Peer Lymphocytes are the gatekeepers of the body's immune system and are involved in pathogenesis if their surveillance is stalled by inhibitory molecules or when they act as mediators for viral entry. Engineering lymphocytes in order to restore their functions is an unmet need in immunological disorders, cancer and in lymphotropic viral infections. Recently, the FDA approved several therapeutic antibodies for blocking inhibitory signals on T cells. This has revolutionized the field of solid tumor care, together with chimeric antigen receptor T cell (CAR-T) therapy that did the same for hematological malignancies. RNA interference (RNAi) is a promising approach where gene function can be inhibited in almost all types of cells. However, manipulation of genes in lymphocyte subsets are difficult due to their hard-to-transfect nature and in vivo targeting remains challenging as they are dispersed throughout the body. The ability of RNAi molecules to gain entry into cells is almost impossible without delivery strategy. Nanotechnology approaches are rapidly growing and their impact in the field of drug and gene delivery applications to transport payloads inside cells have been extensively studied. Here we discuss various technologies available for RNAi delivery to lymphocytes. We shed light on the importance of targeting molecules in order to target lymphocytes in vivo. In addition, we discuss recent developments of RNAi delivery to lymphocyte subsets, and detail the potential implication for the future of molecular medicine in leukocytes implicated diseases.Graphical Unlabelled Image
  • Strategies for improving diabetic therapy via alternative administration
           routes that involve stimuli-responsive insulin-delivering systems
    • Abstract: Publication date: Available online 6 December 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Yu-Jung Lin, Fwu-Long Mi, Po-Yen Lin, Yang-Bao Miao, Tringyo Huang, Kuan-Hung Chen, Chiung-Tong Chen, Yen Chang, Hsing-Wen Sung The encapsulation of insulin in micro- or nanodelivery systems may eliminate the need for frequent subcutaneous injections, improving the quality of life of diabetic patients. Formulations for oral, intranasal, pulmonary, subcutaneous, and transdermal administration have been developed. The use of stimuli-responsive polymeric carriers that can release the encapsulated drug in response to changes of the environmental stimuli or external activation enables the design of less invasive or non-invasive systems for smart insulin delivery from depots in the body. This article will look at strategies for the development of responsive delivery systems and the future meeting of the demands of new modes of insulin delivery.Graphical Unlabelled Image
  • Molecular imaging of diabetes and diabetic complications: beyond
           pancreatic β-cell targeting
    • Abstract: Publication date: Available online 5 December 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Jichun Yang, Long Jiang Zhang, Fan Wang, Tianpei Hong, Zhaofei LiuABSTRACTDiabetes is a chronic non-communicable disease affecting over 400 million people worldwide. Diabetic patients are at a high risk of various complications, such as cardiovascular, renal, and other diseases. The pathogenesis of diabetes (both type 1 and type 2 diabetes) is associated with a functional impairment of pancreatic β-cells. Consequently, most efforts to manage and prevent diabetes have focused on preserving β-cells and their function. Advances in imaging techniques, such as magnetic resonance imaging, magnetic resonance spectroscopy, positron emission tomography, and single-photon-emission computed tomography, have enabled noninvasive and quantitative detection and characterization of the population and function of β-cells in vivo. These advantages aid the defining and monitoring of the progress of diabetes and determination of the efficacy of anti-diabetic therapies. Beyond β-cell targeting, molecular imaging of biomarkers associated with the development of diabetes, e.g., lymphocyte infiltration, insulitis, and metabolic changes, may also be a promising strategy for early detection of diabetes, monitoring its progression, and occurrence of complications, as well as facilitating exploration of new therapeutic interventions. Moreover, molecular imaging of glucose uptake, production and excretion in specified tissues is critical for understanding the pathogenesis of diabetes. In the current review, we summarize and discuss recent advances in noninvasive imaging technologies for imaging of biomarkers beyond β-cells for early diagnosis of diabetes, investigation of glucose metabolism, and precise diagnosis and monitoring of diabetic complications for better management of diabetic patients.Graphical Unlabelled Image
  • Therapeutic medications against diabetes: What we have and what we expect
    • Abstract: Publication date: Available online 5 December 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Cheng Hu, Weiping Jia Diabetes has become one of the largest global health and economic burdens, with its increased prevalence and high complication ratio. Stable and satisfactory blood glucose control are vital to reduce diabetes-related complications. Therefore, continuous attempts have been made in antidiabetic drugs, treatment routes, and traditional Chinese medicine to achieve better disease control. New antidiabetic drugs and appropriate combinations of these drugs have increased diabetes control significantly. Besides, novel treatment routes including oral antidiabetic peptide delivery, nanocarrier delivery system, implantable drug delivery system are also pivotal for diabetes control, with its greater efficiency, increased bioavailability, decreased toxicity and reduced dosing frequency. Among these new routes, nanotechnology, artificial pancreas and islet cell implantation have shown great potential in diabetes therapy. Traditional Chinese medicine also offer new options for diabetes treatment. Our paper aim to overview these therapeutic methods for diabetes therapy. Proper combinations of these existing anti-diabetic medications and searching for novel routes are both necessary for better diabetes control.Graphical abstractUnlabelled Image
  • Solidification to Improve the Biopharmaceutical Performance of SEDDS:
           Opportunities and Challenges
    • Abstract: Publication date: Available online 4 December 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Paul Joyce, Tahnee J. Dening, Tahlia Meola, Hayley Schultz, René Holm, Nicky Thomas, Clive A. Prestidge Self-emulsifying drug delivery systems (SEDDS) offer potential for overcoming the inherent slow dissolution and poor oral absorption of hydrophobic drugs by retaining them in a solubilised state during gastrointestinal transit. However, the promising biopharmaceutical benefits of liquid lipid formulations has not translated into widespread commercial success, due to their susceptibility to long term storage and in vivo precipitation issues. One strategy that has emerged to overcome such limitations, is to combine the solubilisation and dissolution enhancing properties of lipids with the stabilising effects of solid carrier materials. The development of intelligent hybrid drug formulations has presented new opportunities to harness the potential of emulsified lipids in optimising oral bioavailability for lipophilic therapeutics. Specific emphasis of this review is placed on the impact of solidification approaches and excipients on the biopharmaceutical performance of self-emulsifying lipids, with findings highlighting the key design considerations that should be implemented when developing hybrid lipid-based formulations.Graphical Unlabelled Image
  • Bench-to-bedside translation of dendrimers: Reality or utopia' A
           concise analysis
    • Abstract: Publication date: November–December 2018Source: Advanced Drug Delivery Reviews, Volumes 136–137Author(s): Serge Mignani, João Rodrigues, Helena Tomas, René Roy, Xiangyang Shi, Jean-Pierre Majoral Nanomedicine, which is an application of nanotechnologies in healthcare is developed to improve the treatments and lives of patients suffering from a range of disorders and to increase the successes of drug candidates. Within the nanotechnology universe, the remarkable unique and tunable properties of dendrimers have made them promising tools for diverse biomedical applications such as drug delivery, gene therapy and diagnostic. Up-to-date, very few dendrimers has yet gained regulatory approval for systemic administration, why? In this critical review, we briefly focus on the list of desired basic dendrimer requirements for decision-making purpose by the scientists (go/no-go decision), in early development stages, to become clinical candidates, and to move towards Investigational New Drugs (IND) application submission. In addition, the successful translation between research and clinic should be performed by the implementation of a simple roadmap to jump the ‘valley of death’ successfully.Graphical abstractImage 1
  • Nanomaterials and molecular transporters to overcome the bacterial
           envelope barrier: Towards advanced delivery of antibiotics
    • Abstract: Publication date: November–December 2018Source: Advanced Drug Delivery Reviews, Volumes 136–137Author(s): Rita S. Santos, Céu Figueiredo, Nuno F. Azevedo, Kevin Braeckmans, Stefaan C. De Smedt With the dramatic consequences of bacterial resistance to antibiotics, nanomaterials and molecular transporters have started to be investigated as alternative antibacterials or anti-infective carrier systems to improve the internalization of bactericidal drugs. However, the capability of nanomaterials/molecular transporters to overcome the bacterial cell envelope is poorly understood. It is critical to consider the sophisticated architecture of bacterial envelopes and reflect how nanomaterials/molecular transporters can interact with these envelopes, being the major aim of this review. The first part of this manuscript overviews the permeability of bacterial envelopes and how it limits the internalization of common antibiotic and novel oligonucleotide drugs. Subsequently we critically discuss the mechanisms that allow nanomaterials/molecular transporters to overcome the bacterial envelopes, focusing on the most promising ones to this end – siderophores, cyclodextrins, metal nanoparticles, antimicrobial/cell-penetrating peptides and fusogenic liposomes. This review may stimulate drug delivery and microbiology scientists in designing effective nanomaterials/molecular transporters against bacterial infections.Graphical abstractUnlabelled Image
  • ADDR Editor’s Collection 2018
    • Abstract: Publication date: November–December 2018Source: Advanced Drug Delivery Reviews, Volumes 136–137Author(s): Hamidreza Ghandehari
  • Editorial: Drug delivery in older people – unique challenges and
           important opportunities
    • Abstract: Publication date: October 2018Source: Advanced Drug Delivery Reviews, Volume 135Author(s): Andrew J. McLachlan, Victoria C. Cogger
  • Physiologically based pharmacokinetic modelling to guide drug delivery in
           older people
    • Abstract: Publication date: October 2018Source: Advanced Drug Delivery Reviews, Volume 135Author(s): Manoranjenni Chetty, Trevor N. Johnson, Sebastian Polak, Farzaneh Salem, Kosuke Doki, Amin Rostami-Hodjegan Older patients are generally not included in Phase 1 clinical trials despite being the population group who use the largest number of prescription medicines. Physiologically based pharmacokinetic (PBPK) modelling provides an understanding of the absorption and disposition of drugs in older patients. In this review, PBPK models used for the prediction of absorption and exposure of drugs after parenteral, oral and transdermal administration are discussed. Comparisons between predicted drug pharmacokinetics (PK) and observed PK are presented to illustrate the accuracy of the predictions by the PBPK models and their potential use in informing clinical trial design and dosage adjustments in older patients. In addition, a case of PBPK modelling of a bioequivalence study on two controlled release products is described, where PBPK predictions reproduced the study showing bioequivalence in healthy volunteers but not in older subjects with achlorhydria, indicating further utility in prospectively identifying challenges in bioequivalence studies.Graphical abstractUnlabelled Image
  • Dosage form modification and oral drug delivery in older people
    • Abstract: Publication date: October 2018Source: Advanced Drug Delivery Reviews, Volume 135Author(s): Esther T.L. Lau, Kathryn J. Steadman, Julie A.Y. Cichero, Lisa M. Nissen Many people cannot swallow whole tablets and capsules. The cause ranges from difficulties overriding the natural instinct to chew solids/foodstuff before swallowing, to a complex disorder of swallowing function affecting the ability to manage all food and fluid intake. Older people can experience swallowing difficulties because of co-morbidities, age-related physiological changes, and polypharmacy. To make medicines easier to swallow, many people will modify the medication dosage form e.g. split or crush tablets, and open capsules. Some of the challenges associated with administering medicines to older people, and issues with dosage form modification will be reviewed. Novel dosage forms in development are promising and may help overcome some of the issues. However, until these are more readily available, effective interdisciplinary teams, and improving patient health literacy will help reduce the risk of medication misadventures in older people.Graphical abstractUnlabelled Image
  • Challenges and innovations of drug delivery in older age
    • Abstract: Publication date: October 2018Source: Advanced Drug Delivery Reviews, Volume 135Author(s): Muhammad Suleman Khan, Michael S. Roberts Both drug delivery performance and various age-related physical, mental and physiological changes can affect drug effectiveness and safety in elderly patients. The many drug delivery systems developed over the years include recent novel transdermal, nasal, pulmonary and orally disintegrating tablets that provide consistent, precise, timely and more targeted drug delivery. Certain drug delivery systems may be associated with suboptimal outcomes in the elderly because of the nature of drug present, a lack of appreciation of the impact of age-related changes in drug absorption, distribution and clearance, the limited availability of pharmacokinetic, safety and clinical data. Polypharmacy, patient morbidity and poor adherence can also contribute to sub-optimal drug delivery systems outcomes in the elderly. The development of drug delivery systems for the elderly is a poorly realised opportunity, with each system having specific advantages and limitations. A key challenge is to provide the innovation that best meets the specific physiological, psychological and multiple drug requirements of individual elderly patients.Graphical abstractUnlabelled Image
  • Novel targets for delaying aging: The importance of the liver and advances
           in drug delivery
    • Abstract: Publication date: October 2018Source: Advanced Drug Delivery Reviews, Volume 135Author(s): Nicholas J. Hunt, Peter A.G. McCourt, David G. Le Couteur, Victoria C. Cogger Age-related changes in liver function have a significant impact on systemic aging and susceptibility to age-related diseases. Nutrient sensing pathways have emerged as important targets for the development of drugs that delay aging and the onset age-related diseases. This supports a central role for the hepatic regulation of metabolism in the association between nutrition and aging. Recently, a role for liver sinusoidal endothelial cells (LSECs) in the relationship between aging and metabolism has also been proposed. Age-related loss of fenestrations within LSECs impairs the transfer of substrates (such as lipoproteins and insulin) between sinusoidal blood and hepatocytes, resulting in post-prandial hyperlipidemia and insulin resistance. Targeted drug delivery methods such as nanoparticles and quantum dots will facilitate the direct delivery of drugs that regulate fenestrations in LSECs, providing an innovative approach to ameliorating age-related diseases and increasing healthspan.Graphical abstractUnlabelled Image
  • Pulmonary drug delivery to older people
    • Abstract: Publication date: October 2018Source: Advanced Drug Delivery Reviews, Volume 135Author(s): Martin Wallin, Tatsuaki Tagami, Lan Chen, Mingshi Yang, Hak-Kim Chan Pulmonary diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are common in older people. Treatment principles are well established in this group of patients; however, inadequate training and improper inhaler techniques often results in poor treatment outcomes. Healthcare professionals often do not have the required knowledge about the most common inhaler devices. Age-related conditions like cognitive ability and physical strength would also impact on the inhaler usage. Pharmacokinetics and pharmacodynamics may be affected by physiological changes, like impaired renal and hepatic functions and reduced lung functions. Adjusting and optimizing the inhaler device to the patient preferences, improvement of the drug formulation and inhalers, and using different adherence strategies might improve the treatment outcomes in elderly patients.Graphical abstractImage 1
  • Impact of aging, Alzheimer's disease and Parkinson's disease on the
           blood-brain barrier transport of therapeutics
    • Abstract: Publication date: October 2018Source: Advanced Drug Delivery Reviews, Volume 135Author(s): Yijun Pan, Joseph A. Nicolazzo Older people are at a greater risk of medicine-induced toxicity resulting from either increased drug sensitivity or age-related pharmacokinetic changes. The scenario is further complicated with the two most prevalent age-related neurodegenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD). With aging, AD and PD, there is growing evidence of altered structure and function of the blood-brain barrier (BBB), including modifications to tight junctions and efflux transporters, such as P-glycoprotein. The subsequent impact on CNS drug exposure and risk of neurotoxicity from systemically-acting medicines is less well characterized. The purpose of this review, therefore, is to provide an overview of the multiple changes that occur to the BBB as a result of aging, AD and PD, and the impact that such changes have on CNS exposure of drugs, based on studies conducted in aged rodents or rodent models of disease, and in elderly people with and without AD or PD.Graphical abstractUnlabelled Image
  • Challenges and innovations of delivering medicines to older adults
    • Abstract: Publication date: October 2018Source: Advanced Drug Delivery Reviews, Volume 135Author(s): Danijela Gnjidic, Andy Husband, Adam Todd Older adults with multimorbidity, polypharmacy, and complex health needs are the major consumer of health care. Ensuring that medicines are used safely, effectively, and delivered efficiently in this population is challenging. In this context, the approach to medicines delivery should seek to overcome some of the difficulties of delivering medicines to older people, and ensure each medication is delivered by the optimal and most convenient route for the patient in question. However, this poses significant obstacles, as the development of medicines suitable for use in older populations does not often account for complex health needs, potential challenges in relation to drug disposition, safety of excipients and limitations with practical usability of dosage forms. The objective of this review is to summarise and discuss current challenges and novel approaches to delivering medications to older adults.
  • Bacteriophage-based biomaterials for tissue regeneration
    • Abstract: Publication date: Available online 16 November 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Binrui Cao, Yan Li, Tao Yang, Qing Bao, Mingying Yang, Chuanbin Mao Bacteriophage, also called phage, is a human-safe bacteria-specific virus. It is a monodisperse biological nanostructure made of proteins (forming the outside surface) and nucleic acids (encased in the protein capsid). Among different types of phages, filamentous phages have received great attention in tissue regeneration research due to their unique nanofiber-like morphology. They can be produced in an error-free format, self-assemble into ordered scaffolds, display multiple signaling peptides site-specifically, and serve as a platform for identifying novel signaling or homing peptides. They can direct stem cell differentiation into specific cell types when they are organized into proper patterns or display suitable peptides. These unusual features have allowed scientists to employ them to regenerate a variety of tissues, including bone, nerves, cartilage, skin, and heart. This review will summarize the progress in the field of phage-based tissue regeneration and the future directions in this field.Graphical abstractUnlabelled Image
  • Drug supersaturation during formulation digestion, including real-time
           analytical approaches
    • Abstract: Publication date: Available online 13 November 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Martin Kuentz Self-emulsifying and other lipid-based drug delivery systems have drawn considerable interest from pharmaceutical scientists for managing oral delivery of poorly water-soluble compounds. Following administration, self-emulsifying systems exhibit complex aqueous dispersion and digestion in the gastro-intestinal tract. These processes generally result in drug supersaturation, which leads to enhanced absorption or the high drug concentrations may cause precipitation with erratic and variable oral bioavailability. This review briefly outlines drug supersaturation obtained from self-emulsifying and other lipid-based formulations; recent advancements of in vitro lipolysis testing are also discussed. Further, a main focus is mechanisms by which supersaturation is triggered from gastro-intestinal processes, as well as analytical techniques that are promising from a research and development perspective. Comparatively simple approaches are presented together with more sophisticated process analytics to enable direct examination of kinetic changes. The analytical methods together with their sensor probes are discussed in detail to clarify opportunities as well as technical limitations. Some of the more sophisticated methods, including those based on synchrotron radiation, are primarily research oriented despite interesting experimental findings from an industrial viewpoint. The availability of kinetic data further opens the door to mathematical modeling of supersaturation and precipitation versus permeation, which lays the groundwork for better in vitro to in vivo correlations as well as for physiologically-based modeling of lipid-based systems.Graphical Unlabelled Image
  • Successful development of oral SEDDS: Screening of excipients from the
           industrial point of view
    • Abstract: Publication date: Available online 7 November 2018Source: Advanced Drug Delivery ReviewsAuthor(s): I. Nardin, S. Köllner Oral administration is the most accepted and favored route as various side effects such as fear, pain and risk of infections can be avoided resulting in a comparatively high patient compliance. However, from the industrial point of view the development of oral delivery systems is still challenging as various drugs are poorly soluble as well as slightly permeable leading to low bioavailability. As self-emulsifying drug delivery systems are able to incorporate both hydrophobic and hydrophilic drugs, these carrier systems have received more and more attention within the last years. Based on the broad range of currently available excipients, this review provides a kind of guideline for the selection of excipients useful to improve bioavailability of the drug on the one hand. As the regulatory status of potential excipients are highly important to introduce the formulation on the market, the review is focused on the other hand on excipients listed in the IIG database of the FDA by taking their corresponding maximum concentration into account. Furthermore, the issue of oral sensation and taste masking is discussed useful for the development of intraoral SEDDS.Graphical abstractUnlabelled Image
  • Imaging and therapeutic applications of persistent luminescence
    • Abstract: Publication date: Available online 7 November 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Jianhua Liu, Thomas Lécuyer, Johanne Séguin, Nathalie Mignet, Daniel Scherman, Bruno Viana, Cyrille Richard The development of probes for biomolecular imaging and diagnostics is a very active research area. Among the different imaging modalities, optics emerged since it is a noninvasive and cheap imaging technique allowing real time imaging. In vitro, this technique is very useful however in vivo, fluorescence suffers from low signal-to-noise ratio due to tissue autofluorescence under constant excitation. To address this limitation, novel types of optical nanoprobes are actually being developed and among them, persistent luminescence nanoparticles (PLNPs), with long lasting near-infrared (NIR) luminescence capability, allows doing optical imaging without constant excitation and so without autofluorescence. This review will begin by introducing the physical phenomenon associated to the long luminescence decay of such nanoprobes, from minutes to hours after ceasing the excitation. Then we will show how this property can be used to develop in vivo imaging probes and also more recently nanotheranostic agents. Finally, preliminary data on their biocompatibility will be mentioned and we will conclude by envisioning on the future applications and improvements of such nanomaterials.Graphical abstractUnlabelled Image
  • Recent insights in magnetic hyperthermia: From the “hot-spot” effect
           for local delivery to combined magneto-photo-thermia using
           magneto-plasmonic hybrids
    • Abstract: Publication date: Available online 7 November 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Esther Cazares-Cortes, Sonia Cabana-Montenegro, Charlotte Boitard, Emilie Nehling, Nebewia Griffete, Jérôme Fresnais, Claire Wilhelm, Ali Abou-Hassan, Christine Ménager Magnetic hyperthermia which exploits the heat generated by magnetic nanoparticles (MNPs) when exposed to an alternative magnetic field (AMF) is now in clinical trials for the treatment of cancers. However, this thermal therapy requires a high amount of MNPs in the tumor to be efficient. On the contrary the hot spot local effect refers to the use of specific temperature profile at the vicinity of nanoparticles for heating with minor to no long-range effect. This magneto-thermal effect can be exploited as a relevant external stimulus to temporally and spatially trigger a drug release.In this review, we focus on recent advances in magnetic hyperthermia. Indirect experimental proofs of the local temperature increase are first discussed leading to a good estimation of the temperature at the surface (from 0.5 to 6 nm) of superparamagnetic NPs. Then we highlight recent studies illustrating the hot-spot effect for drug-release. Finally, we present another recent strategy to enhance the efficacity of thermal treatment by combining photothermal therapy with magnetic hyperthermia mediated by magneto-plasmonic nanoplatforms.Graphical abstractUnlabelled Image
  • Electric field-responsive nanoparticles and electric fields: Physical,
           chemical, biological mechanisms and therapeutic prospects
    • Abstract: Publication date: Available online 7 November 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Jelena Kolosnjaj-Tabi, Laure Gibot, Isabelle Fourquaux, Muriel Golzio, Marie-Pierre Rols Electric fields are among physical stimuli that have revolutionized therapy. Occurring endogenously or exogenously, the electric field can be used as a trigger for controlled drug release from electroresponsive drug delivery systems, can stimulate wound healing and cell proliferation, may enhance endocytosis or guide stem cell differentiation. Electric field pulses may be applied to induce cell fusion, can increase the penetration of therapeutic agents into cells, or can be applied as a standalone therapy to ablate tumors. This review describes the main therapeutic trends and overviews the main physical, chemical and biological mechanisms underlying the actions of electric fields. Overall, the electric field can be used in therapeutic approaches in several ways. The electric field can act on drug carriers, cells and tissues. Understanding the multiple effects of this powerful tool will help harnessing its full therapeutic potential in an efficient and safe way.Graphical abstractUnlabelled Image
  • Approaches to physical stimulation of metallic nanoparticles for
           glioblastoma treatment
    • Abstract: Publication date: Available online 7 November 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Sophie Pinel, Noémie Thomas, Cédric Boura, Muriel Barberi-Heyob Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor. Despite new knowledges on the genetic characteristics, conventional therapy for GBM, tumor resection followed by radiotherapy and chemotherapy using temozolomide is limited in efficacy due to high rate of recurrence. GBM is indeed one of the most complex and difficult to treat of any cancer mainly due to its highly invasive properties and the standard treatments are thus rarely curative. Major challenges in the treatment of GBM are the limitation of irreversible brain damage, the infiltrative part of the tumor which is the ultimate cause of recurrence, the difficulty of identifying tumor margins and disseminated tumor cells, and the transport across the blood-brain barrier in order to obtain a sufficient therapeutic effect. Considering these limitations, this review explores the in vivo potential of metal-based nanoparticles for hyperthermia, radiotherapy and photodynamic therapy. This article describes and clearly outlines the recent in vivo advances using innovative therapeutic metallic nanoparticles such as iron oxide, silver, gadolinium and gold nanoparticles.Graphical abstractUnlabelled Image
  • Enhancing patient-level clinical data access to promote evidence-based
           practice and incentivize therapeutic innovation
    • Abstract: Publication date: Available online 31 January 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Alice Fortunato, David W. Grainger, Mohamed Abou-El-Enein Clinical trials are crucial to determining the human safety and efficacy of new therapeutic innovations. Extraordinary amounts of human experiential data are generated over the course of any clinical trial, however, much of these data is never made publicly accessible. Improved, reliable data sharing is essential to inform clinical decisions and incentivize further therapeutic improvements; this need, and the call and concept to enhance patient-level clinical trial data accessibility is not new. Several recent public and private shifts in clinical data sharing policies and procedures promise to improve access and data utility to reduce waste in research and increase efficiency of evidence synthesis. Nonetheless, pharmaceutical industry remain reluctant to share full clinical data sets at some level to protect their commercial interests and avoid misuse of their data. Here, we review the landscape of emerging regulations related to the sharing of patient level data and current clinical data access models of major pharmaceutical companies. We also summarize the different measures that could satisfy both clinical data producers and users in achieving the benefits of accessing patient-level data while mitigating any associated risks.Graphical abstractResponsible data sharing model would facilitate the access to clinical trial data to make informed decisions critical to advancing new therapeutics for patient benefit.Unlabelled Image
  • Neurotheranostics as personalized medicines
    • Abstract: Publication date: Available online 26 October 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Bhavesh D. Kevadiya, Brendan M. Ottemann, Midhun Ben Thomas, Insiya Mukadam, Saumya Nigam, JoEllyn McMillan, Santhi Gorantla, Tatiana K. Bronich, Benson Edagwa, Howard E. Gendelman The discipline of neurotheranostics was forged to improve diagnostic and therapeutic clinical outcomes for neurological disorders. Research was facilitated, in largest measure, by the creation of pharmacologically effective multimodal pharmaceutical formulations. Deployment of neurotheranostic agents could revolutionize staging and improve nervous system disease therapeutic outcomes. However, obstacles in formulation design, drug loading and payload delivery still remain. These will certainly be aided by multidisciplinary basic research and clinical teams with pharmacology, nanotechnology, neuroscience and pharmaceutic expertise. When successful the end results will provide “optimal” therapeutic delivery platforms. The current report reviews an extensive body of knowledge of the natural history, epidemiology, pathogenesis and therapeutics of neurologic disease with an eye on how, when and under what circumstances neurotheranostics will soon be used as personalized medicines for a broad range of neurodegenerative, neuroinflammatory and neuroinfectious diseases.Graphical abstractUnlabelled Image
  • Physical stimuli-responsive vesicles in drug delivery: Beyond liposomes
           and polymersomes
    • Abstract: Publication date: Available online 25 October 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Ulrike Kauscher, Margaret N. Holme, Mattias Björnmalm, Molly M. StevensABSTRACTOver the past few decades, a range of vesicle-based drug delivery systems have entered clinical practice and several others are in various stages of clinical translation. While most of these vesicle constructs are lipid-based (liposomes), or polymer-based (polymersomes), recently new classes of vesicles have emerged that defy easy classification. Examples include assemblies with small molecule amphiphiles, biologically derived membranes, hybrid vesicles with two or more classes of amphiphiles, or more complex hierarchical structures such as vesicles incorporating gas bubbles or nanoparticulates in the lumen or membrane. In this review, we explore these recent advances and emerging trends at the edge and just beyond the research fields of conventional liposomes and polymersomes. A focus of this review is the distinct behaviors observed for these classes of vesicles when exposed to physical stimuli - such as ultrasound, heat, light and mechanical triggers - and we discuss the resulting potential for new types of drug delivery, with a special emphasis on current challenges and opportunities.Graphical abstractUnlabelled Image
  • Local delivery of macromolecules to treat diseases associated with the
    • Abstract: Publication date: Available online 22 October 2018Source: Advanced Drug Delivery ReviewsAuthor(s): A. Bak, M. Ashford, D.J. Brayden Current treatments for intestinal diseases including inflammatory bowel diseases, irritable bowel syndrome, and colonic bacterial infections are typically small molecule oral dosage forms designed for systemic delivery. The intestinal permeability hurdle to achieve systemic delivery from oral formulations of macromolecules is challenging, but this drawback can be advantageous if an intestinal region is associated with the disease. There are some promising formulation approaches to release peptides, proteins, antibodies, antisense oligonucleotides, RNA, and probiotics in the colon to enable local delivery and efficacy. We briefly review colonic physiology in relation to the main colon-associated diseases (inflammatory bowel disease, irritable bowel syndrome, infection, and colorectal cancer), along with the impact of colon physiology on dosage form design of macromolecules. We then assess formulation strategies designed to achieve colonic delivery of small molecules and concluded that they can also be applied some extent to macromolecules. We describe examples of formulation strategies in preclinical research aimed at colonic delivery of macromolecules to achieve high local concentration in the lumen, epithelial-, or sub-epithelial tissue, depending on the target, but with the benefit of reduced systemic exposure and toxicity. Finally, the industrial challenges in developing macromolecule formulations for colon-associated diseases are presented, along with a framework for selecting appropriate delivery technologies.Graphical abstractUnlabelled Image
  • Stem-cell based organ-on-a-chip models for diabetes research
    • Abstract: Publication date: Available online 22 October 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Julia Rogal, Aline Zbinden, Katja Schenke-Layland, Peter Loskill Diabetes mellitus (DM) ranks among the severest global health concerns of the 21st century. It encompasses a group of chronic disorders characterized by a dysregulated glucose metabolism, which arises as a consequence of progressive autoimmune destruction of pancreatic beta-cells (type 1 DM), or as a result of beta-cell dysfunction combined with systemic insulin resistance (type 2 DM). Human cohort studies have provided evidence of genetic and environmental contributions to DM; yet, these studies are mostly restricted to investigating statistical correlations between DM and certain risk factors. Mechanistic studies, on the other hand, aimed at re-creating the clinical picture of human DM in animal models. A translation to human biology is, however, often inadequate owing to significant differences between animal and human physiology, including the species-specific glucose regulation. Thus, there is an urgent need for the development of advanced human in vitro models with the potential to identify novel treatment options for DM. This review provides an overview of the technological advances in research on DM-relevant stem cells and their integration into microphysiological environments as provided by the organ-on-a-chip technology.Graphical abstractUnlabelled Image
  • Triggering antitumoural drug release and gene expression by magnetic
    • Abstract: Publication date: Available online 17 October 2018Source: Advanced Drug Delivery ReviewsAuthor(s): María Moros, Javier Idiago-López, Laura Asín, Eduardo Moreno-Antolín, Lilianne Beola, Valeria Grazú, Raluca M. Fratila, Lucía Gutiérrez, Jesús Martínez de la Fuente Magnetic nanoparticles (MNPs) are promising tools for a wide array of biomedical applications. One of their most outstanding properties is the ability to generate heat when exposed to alternating magnetic fields, usually exploited in magnetic hyperthermia therapy of cancer. In this contribution, we provide a critical review of the use of MNPs and magnetic hyperthermia as drug release and gene expression triggers for cancer therapy. Several strategies for the release of chemotherapeutic drugs from thermo-responsive matrices are discussed, providing representative examples of their application at different levels (from proof of concept to in vivo applications). The potential of magnetic hyperthermia to promote in situ expression of therapeutic genes using vectors that contain heat-responsive promoters is also reviewed in the context of cancer gene therapy.Graphical abstractUnlabelled Image
  • Advances on non-invasive physically triggered Nucleic Acid delivery from
    • Abstract: Publication date: Available online 12 October 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Hai Doan Do, Brice Martin Couillaud, Bich-Thuy Doan, Yohann Corvis, Nathalie Mignet Nucleic acids (NAs) have been considered as promising therapeutic agents for various types of diseases. However, their clinical applications still face many limitations due to their charge, high molecular weight, instability in biological environment and low levels of transfection. To overcome these drawbacks, therapeutic NAs should be carried in a stable nanocarrier, which can be viral or non-viral vectors, and released at specific target site. Various controllable gene release strategies are currently being evaluated with interesting results. Endogenous stimuli-responsive systems, for example pH-, redox reaction-, enzymatic-triggered approaches have been widely studied based on the physiological differences between pathological and normal tissues. Meanwhile, exogenous triggered release strategies require the use of externally non-invasive physical triggering signals such as light, heat, magnetic field and ultrasound. Compared to internal triggered strategies, external triggered gene release is time and site specifically controllable through active management of outside stimuli. The signal induces changes in the stability of the delivery system or some specific reactions which lead to endosomal escape and/or gene release. In the present review, the mechanisms and examples of exogenous triggered gene release approaches are detailed. Challenges and perspectives of such gene delivery systems are also discussed.Graphical abstractUnlabelled Image
  • Light-Responsive Nanomedicine for Biophotonic Imaging and Targeted Therapy
    • Abstract: Publication date: Available online 12 October 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Jihwan Son, Gawon Yi, Jihye Yoo, Changhee Park, Heebeom Koo, Hak Soo Choi Nanoparticles (NPs) play a key role in nanomedicine in multimodal imaging, drug delivery and targeted therapy of human diseases. Consequently, due to the attractive properties of NPs including high stability, high payload, multifunctionality, design flexibility, and efficient delivery to target tissues, nanomedicine employs various types of NPs to enhance targeting and treatment efficacy. In this review, we primarily focus on light-responsive materials, such as fluorophores, photosensitizers, semiconducting polymers, carbon structures, gold particles, quantum dots, and upconversion crystals, for their biomedical applications. Armed with these nanomaterials, NPs represent a growing potential in biophotonic imaging (luminescence, photoacoustic, surface enhanced Raman scattering, and optical coherence tomography) as well as targeted therapy (photodynamic therapy, photothermal therapy, and light-responsive drug release).Graphical abstractUnlabelled Image
  • External Stimulus Responsive Inorganic Nanomaterials for Cancer
    • Abstract: Publication date: Available online 12 October 2018Source: Advanced Drug Delivery ReviewsAuthor(s): M. Sheikh Mohamed, Srivani Veeranarayanan, Toru Maekawa, D. Sakthi Kumar Cancer is a highly intelligent system of cells, that works together with the body to thrive and subsequently overwhelm the host in order for its survival. Therefore, treatment regimens should be equally competent to outsmart these cells. Unfortunately, it is not the case with current therapeutic practices, the reason why it is still one of the most deadly adversaries and an imposing challenge to healthcare practitioners and researchers alike. With rapid nanotechnological interventions in the medical arena, the amalgamation of diagnostic and therapeutic functionalities into a single platform, theranostics provides a never before experienced hope of enhancing diagnostic accuracy and therapeutic efficiency. Additionally, the ability of these nanotheranostic agents to perform their actions on-demand, i.e. can be controlled by external stimulus such as light, magnetic field, sound waves and radiation has cemented their position as next generation anti-cancer candidates. Numerous reports exist of such stimuli-responsive theranostic nanomaterials against cancer, but few have broken through to clinical trials, let alone clinical practice. This review sheds light on the pros and cons of a few such theranostic nanomaterials, especially inorganic nanomaterials which do not require any additional chemical moieties to initiate the stimulus. The review will primarily focus on preclinical and clinical trial approved theranostic agents alone, describing their success or failure in the respective stages.Graphical abstractUnlabelled Image
  • Thermoresponsive polymer nanocarriers for biomedical applications
    • Abstract: Publication date: Available online 11 October 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Alexandre Bordat, Tanguy Boissenot, Julien Nicolas, Nicolas Tsapis Polymer nanocarriers allow drug encapsulation leading to fragile molecule protection from early degradation/metabolization, increased solubility of poorly soluble drugs and improved plasmatic half-life. However, efficiently controlling the drug release from nanocarriers is still challenging. Thermoresponsive polymers exhibiting either a lower critical solubility temperature (LCST) or an upper critical solubility temperature (UCST) in aqueous medium may be the key to build spatially and temporally controlled drug delivery systems. In this review, we provide an overview of LCST and UCST polymers used as building blocks for thermoresponsive nanocarriers for biomedical applications. Recent nanocarriers based on thermoresponsive polymer exhibiting unprecedented features useful for biomedical applications are also discussed. While LCST nanocarriers have been studied for over two decades, UCST nanocarriers have recently emerged and already show great potential for effective thermoresponsive drug release.Graphical abstractUnlabelled Image
  • Remotely controlled opening of delivery vehicles and release of cargo by
           external triggers
    • Abstract: Publication date: Available online 11 October 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Dingcheng Zhu, Sathi Roy, Ziyao Liu, Horst Weller, Wolfgang Parak, Neus Feliu Tremendous efforts have been devoted to the development of future nanomedicines that can be specifically designed to incorporate responsive elements that undergo modification in structural properties upon external triggers. One potential use of such stimuli-responsive materials is to release encapsulated cargo upon excitation by an external trigger. Today, such stimuli-response materials allow for spatial and temporal tunability, which enables the controlled delivery of compounds in a specific and dose-dependent manner. This potentially is of great interest for medicine (e.g. allowing for remotely controlled drug delivery to cells, etc.). Among the different external exogenous and endogenous stimuli used to control the desired release, light and magnetic fields offer interesting possibilities, allowing defined, real time control of intracellular releases. In this review we highlight the use of stimuli-responsive controlled release systems that are able to respond to light and magnetic field triggers for controlling the release of encapsulated cargo inside cells. We discuss established approaches and technologies and describe prominent examples. Special attention is devoted towards polymer capsules and polymer vesicles as containers for encapsulated cargo molecules. The advantages and disadvantages of this methodology in both, in vitro and in vivo models are discussed. An overview of challenges associate with the successful translation of those stimuli-responsive materials towards future applications in the direction of potential clinical use is given.Graphical abstractRelease of encapsulated molecular cargo upon (external) triggers.Unlabelled Image
  • The potential for remodelling the tumour vasculature in glioblastoma
    • Abstract: Publication date: Available online 9 October 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Caterina Brighi, Simon Puttick, Stephen Rose, Andrew K. Whittaker Despite significant improvements in the clinical management of glioblastoma, poor delivery of systemic therapies to the entire population of tumour cells remains one of the biggest challenges in the achievement of more effective treatments. On the one hand, the abnormal and dysfunctional tumour vascular network largely limits blood perfusion, resulting in an inhomogeneous delivery of drugs to the tumour. On the other hand, the presence of an intact blood-brain barrier (BBB) in certain regions of the tumour prevents chemotherapeutic drugs from permeating through the tumour vessels and reaching the diseased cells. In this review we analyse in detail the implications of the presence of a dysfunctional vascular network and the impenetrable BBB on drug transport. We discuss advantages and limitations of the currently available strategies for remodelling the tumour vasculature aiming to ameliorate the above mentioned limitations. Finally we review research methods for visualising vascular dysfunction and highlight the power of DCE- and DSC-MRI imaging to assess changes in blood perfusion and BBB permeability.Graphical abstractUnlabelled Image
  • Animal models for analysis of immunological responses to nanomaterials:
           Challenges and considerations
    • Abstract: Publication date: Available online 29 September 2018Source: Advanced Drug Delivery ReviewsAuthor(s): William C. Zamboni, Janos Szebeni, Serguei V. Kozlov, Andrew T. Lucas, Joseph A. Piscitelli, Marina A. Dobrovolskaia Nanotechnology provides many solutions to improve conventional drug delivery and has a unique niche in the areas related to the specific targeting of the immune system, such as immunotherapies and vaccines. Preclinical studies in this field rely heavily on the combination of in vitro and in vivo methods to assess the safety and efficacy of nanotechnology platforms, nanoparticle-formulated drugs, and vaccines. While certain types of toxicities can be evaluated in vitro and good in vitro–in vivo correlation has been demonstrated for such tests, animal studies are still needed to address complex biological questions and, therefore, provide a unique contribution to establishing nanoparticle safety and efficacy profiles. The genetic, metabolic, mechanistic, and phenotypic diversity of currently available animal models often complicates both the animal choice and the interpretation of the results. This review summarizes current knowledge about differences in the immune system function and immunological responses of animals commonly used in preclinical studies of nanomaterials. We discuss challenges, highlight current gaps, and propose recommendations for animal model selection to streamline preclinical analysis of nanotechnology formulations.Graphical abstractUnlabelled Image
  • Therapeutic strategies for enhancing angiogenesis in wound healing
    • Abstract: Publication date: Available online 26 September 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Austin P. Veith, Kayla Henderson, Adrianne Spencer, Andrew D. Sligar, Aaron B. Baker The enhancement of wound healing has been a goal of medical practitioners for thousands of years. The development of chronic, non-healing wounds is a persistent medical problem that drives patient morbidity and increases healthcare costs. A key aspect of many non-healing wounds is the reduced presence of vessel growth through the process of angiogenesis. This review surveys the creation of new treatments for healing cutaneous wounds through therapeutic angiogenesis. In particular, we discuss the challenges and advancement that have been made in delivering biologic, pharmaceutical and cell-based therapies as enhancers of wound vascularity and healing.Graphical abstractUnlabelled Image
  • Utilizing microphysiological systems and induced pluripotent stem cells
           for disease modeling: a case study for blood brain barrier research in a
           pharmaceutical setting
    • Abstract: Publication date: Available online 22 September 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Kristin M. Fabre, Louise Delsing, Ryan Hicks, Nicola Colclough, Damian Crowther, Lorna Ewart Microphysiological systems (MPS) may be able to provide the pharmaceutical industry models that can reflect human physiological responses to improve drug discovery and translational outcomes. With lack of efficacy being the primary cause for drug attrition, developing MPS disease models would help researchers identify novel targets, study mechanisms in more physiologically-relevant depth, screen for novel biomarkers and test/optimize various therapeutics (small molecules, nanoparticles and biologics). Furthermore, with advances in inducible pluripotent stem cell technology (iPSC), pharmaceutical companies can access cells from patients to help recreate specific disease phenotypes in MPS platforms. Combining iPSC and MPS technologies will contribute to our understanding of the complexities of neurodegenerative diseases and of the blood brain barrier (BBB) leading to development of enhanced therapeutics.Graphical abstractUnlabelled Image
  • Micromotors for drug delivery in vivo: The road ahead
    • Abstract: Publication date: Available online 17 September 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Sarvesh Kumar Srivastava, Gael Clergeaud, Thomas L. Andresen, Anja Boisen Autonomously propelled/externally guided micromotors overcome current drug delivery challenges by providing (a) higher drug loading capacity, (b) localized delivery (less toxicity), (c) enhanced tissue penetration and (d) active maneuvering in vivo. These microscale drug delivery systems can exploit biological fluids as well as exogenous stimuli, like light-NIR, ultrasound and magnetic fields (or a combination of these) towards propulsion/drug release. Ability of these wireless drug carriers towards localized targeting and controlled drug release, makes them a lucrative candidate for drug administration in complex microenvironments (like solid tumors or gastrointestinal tract). In this report, we discuss these microscale drug delivery systems for their therapeutic benefits under in vivo setting and provide a design-application rationale towards greater clinical significance.Graphical abstractUnlabelled Image
  • The effect of Low- and High-Penetration Light on Localized Cancer Therapy
    • Abstract: Publication date: Available online 12 September 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Daniel F. Costa, Lívia P. Mendes, Vladimir P. Torchilin The design of a delivery system allowing targeted and controlled drug release has been considered one of the main strategies used to provide individualized cancer therapy, to improve survival statistics, and to enhance quality-of-life. External stimuli including low- and high-penetration light have been shown to have the ability to turn drug delivery on and off in a non-invasive remotely-controlled fashion. The success of this approach has been closely related to the development of a variety of drug delivery systems – from photosensitive liposomes to gold nanocages – and relies on multiple mechanisms of drug release activation. In this review, we make reference to the two extremes of the light spectrum and their potential as triggers for the delivery of antitumor drugs, along with the most recent achievements in preclinical trials and the challenges to an efficient translation of this technology to the clinical setting.Graphical abstractUnlabelled Image
  • Antibody-cytokine fusion proteins: Biopharmaceuticals with
           immunomodulatory properties for cancer therapy
    • Abstract: Publication date: Available online 7 September 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Cornelia Hutmacher, Dario Neri Cytokines have long been used for therapeutic applications in cancer patients. Substantial side effects and unfavorable pharmacokinetics limit their application and may prevent dose escalation to therapeutically active regimens. Antibody-cytokine fusion proteins (often referred to as immunocytokines) may help localize immunomodulatory cytokine payloads to the tumor, thereby activating anticancer immune responses. A variety of formats (e.g., intact IgGs or antibody fragments), molecular targets (e.g., extracellular matrix components and cell membrane antigens) and cytokine payloads have been considered for the development of this novel class of biopharmaceuticals. This review presents the basic concepts on the design and engineering of immunocytokines, reviews their potential limitations, points out emerging opportunities and summarizes key features of preclinical and clinical-stage products.Graphical abstractUnlabelled Image
  • Corrigendum to ‘Current state and challenges in developing oral
           vaccines’ [Adv. Drug Deliv. Rev. 114 (2017) 116-131]
    • Abstract: Publication date: Available online 3 September 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Julia E. Vela Ramirez, Lindsey A. Sharpe, Nicholas A. Peppas
  • Plant virus-based materials for biomedical applications: trends and
    • Abstract: Publication date: Available online 31 August 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Sabine Eiben, Claudia Koch, Klara Altintoprak, Alexander Southan, Günter Tovar, Sabine Laschat, Ingrid M. Weiss, Christina Wege Nanomaterials composed of plant viral components are finding their way into medical technology and health care, as they offer singular properties. Precisely shaped, tailored virus nanoparticles (VNPs) with multivalent protein surfaces are efficiently loaded with functional compounds such as contrast agents and drugs, and serve as carrier templates and targeting vehicles displaying e.g. peptides and synthetic molecules. Multiple modifications enable uses including vaccination, biosensing, tissue engineering, intravital delivery and theranostics. Novel concepts exploit self-organization capacities of viral building blocks into hierarchical 2D and 3D structures, and their conversion into biocompatible, biodegradable units. High yields of VNPs and proteins can be harvested from plants after a few days so that various products have reached or are close to commercialization. The article delineates potentials and limitations of biomedical plant VNP uses, integrating perspectives of chemistry, biomaterials sciences, molecular plant virology and process engineering.Graphical abstractUnlabelled Image
  • Physically-triggered nanosystems based on two-dimensional materials for
           cancer theranostics
    • Abstract: Publication date: Available online 31 August 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Ding-Kun Ji, Cécilia Ménard-Moyon, Alberto Bianco There is an increasing demand to develop effective methods for treating malignant diseases to improve healthcare in our society. Stimuli-responsive nanosystems, which can respond to internal or external stimuli are promising in cancer therapy and diagnosis due to their functionality and versatility. As a newly emerging class of nanomaterials, two-dimensional (2D) nanomaterials have attracted huge interest in many different fields including biomedicine due to their unique physical and chemical properties. In the past decade, stimuli-responsive nanosystems based on 2D nanomaterials have been widely studied, showing promising applications in cancer therapy and diagnosis, including phototherapies, magnetic therapy, drug and gene delivery, and non-invasive imaging. Here, we will focus our attention on the state-of-the-art of physically-triggered nanosystems based on graphene and two-dimensional nanomaterials for cancer therapy and diagnosis. The physical triggers include light, temperature, magnetic and electric fields.Graphical abstractUnlabelled Image
  • Current and upcoming therapies to modulate skin scarring and fibrosis
    • Abstract: Publication date: Available online 30 August 2018Source: Advanced Drug Delivery ReviewsAuthor(s): João Q. Coentro, Eugenia Pugliese, Geoffrey Hanley, Michael Raghunath, Dimitrios I. Zeugolis Skin is the largest organ of the human body. Being the interface between the body and the outer environment, makes it susceptible to physical injury. To maintain life, nature has endowed skin with a fast healing response that invariably ends in the formation of scar at the wounded dermal area. In many cases, skin remodelling may be impaired, leading to local hypertrophic scars or keloids. One should also consider that the scarring process is part of the wound healing response, which always starts with inflammation. Thus, scarring can also be induced in the dermis, in the absence of an actual wound, during chronic inflammatory processes. Considering the significant portion of the population that is subject to abnormal scarring, this review critically discusses the state-of-the-art and upcoming therapies in skin scarring and fibrosis.Graphical abstractUnlabelled Image
  • Use of plant viruses and virus-like particles for the creation of novel
    • Abstract: Publication date: Available online 30 August 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Ina Balke, Andris Zeltins In recent decades, the development of plant virology and genetic engineering techniques has resulted in the construction of plant virus-based vaccines for protection against different infectious agents, cancers and autoimmune diseases in both humans and animals. Interaction studies between plant viruses and mammalian organisms have suggested that plant viruses and virus-like particles (VLPs) are safe and noninfectious to humans and animals. Plant viruses with introduced antigens are powerful vaccine components due to their strongly organized, repetitive spatial structure; they can elicit strong immune responses similar to those observed with infectious mammalian viruses. The analysis of published data demonstrated that at least 73 experimental vaccines, including 61 prophylactic and 12 therapeutic vaccines, have been constructed using plant viruses as a carrier structure for presentation of different antigens. This information clearly demonstrates that noninfectious viruses are also applicable as vaccine carriers. Moreover, several plant viruses have been used for platform development, and corresponding vaccines are currently being tested in human and veterinary clinical trials. This review therefore discusses the main principles of plant VLP vaccine construction, emphasizing the physical, chemical, genetic and immunological aspects. Results of the latest studies suggest that several plant virus-based vaccines will join the list of approved human and animal vaccines in the near future.Graphical abstractUnlabelled Image
  • Muscle fibrosis in the soft palate: Delivery of cells, growth factors and
    • Abstract: Publication date: Available online 11 August 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Johannes W. Von den Hoff, Paola L. Carvajal Monroy, Edwin M. Ongkosuwito, Toin H. van Kuppevelt, Willeke F. Daamen The healing of skeletal muscle injuries after major trauma or surgical reconstruction is often complicated by the development of fibrosis leading to impaired function. Research in the field of muscle regeneration is mainly focused on the restoration of muscle mass while far less attention is paid to the prevention of fibrosis. In this review, we take as an example the reconstruction of the muscles in the soft palate of cleft palate patients. After surgical closure of the soft palate, muscle function during speech is often impaired by a shortage of muscle tissue as well as the development of fibrosis. We will give a short overview of the most common approaches to generate muscle mass and then focus on strategies to prevent fibrosis. These include anti-fibrotic strategies that have been developed for muscle and other organs by the delivery of small molecules, decorin and miRNAs. Anti-fibrotic compounds should be delivered in aligned constructs in order to obtain the organized architecture of muscle tissue. The available techniques for the preparation of aligned muscle constructs will be discussed. The combination of approaches to generate muscle mass with anti-fibrotic components in an aligned muscle construct may greatly improve the functional outcome of regenerative therapies for muscle injuries.Graphical abstractUnlabelled Image
  • Acellular and cellular approaches to improve diabetic wound healing
    • Abstract: Publication date: Available online 1 August 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Hongkwan Cho, Michael R. Blatchley, Elia J. Duh, Sharon Gerecht Chronic diabetic wounds represent a huge socioeconomic burden for both affected individuals and the entire healthcare system. Although the number of available treatment options as well as our understanding of wound healing mechanisms associated with diabetes has vastly improved over the past decades, there still remains a great need for additional therapeutic options. Tissue engineering and regenerative medicine approaches provide great advantages over conventional treatment options, which are mainly aimed at wound closure rather than addressing the underlying pathophysiology of diabetic wounds. Recent advances in biomaterials and stem cell research presented in this review provide novel ways to tackle different molecular and cellular culprits responsible for chronic and nonhealing wounds by delivering therapeutic agents in direct or indirect ways. Careful integration of different approaches presented in the current article could lead to the development of new therapeutic platforms that can address multiple pathophysiologic abnormalities and facilitate wound healing in patients with diabetes.Graphical abstractUnlabelled Image
  • Strategies to overcome the polycation dilemma in drug delivery
    • Abstract: Publication date: Available online 29 July 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Andreas Bernkop-Schnürch Because of polycationic auxiliary agents such as chitosan, polyethyleneimine and cell penetrating peptides as well as cationic lipids assembling to polycationic systems, drug carriers can tightly interact with cell membranes exhibiting a high-density anionic charge. Because of these interactions the cell membrane is depolarized and becomes vulnerable to various uptake mechanisms. On their way to the target site, however, the polycationic character of all these drug carriers is eliminated by polyanionic macromolecules such as mucus glycoproteins, serum proteins, proteoglycans of the extracellular matrix (ECM) and polyanionic surface substructures of non-target cells such as red blood cells. Strategies to overcome this polycation dilemma are focusing on a pH-, redox- or enzyme-triggered charge conversion at the target site. The pH-triggered systems are making use of a slight acidic environment at the target site such as in case of solid tumors, inflammatory tissue and ischemic tissue. Due to a pH shift from 7.2 to slightly acidic mainly amino substructures of polymeric excipients are protonated or shielding groups such as 2,3 dimethylmaleic acid are cleaved off unleashing the underlying cationic character. Redox-triggered systems are utilizing disulfide linkages to bulky side chains such as PEGs masking the polycationic character. Under mild reducing conditions such as in the tumor microenvironment these disulfide bonds are cleaved. Enzyme-triggered systems are targeting enzymes such as alkaline phosphatase, matrix metalloproteinases or hyaluronidase in order to eliminate anionic moieties via enzymatic cleavage resulting in a charge conversion from negative to positive. Within this review an overview about the pros and cons of these systems is provided.Graphical abstractUnlabelled Image
  • Stem cell-based Lung-on-Chips: The best of both worlds'
    • Abstract: Publication date: Available online 25 July 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Janna C. Nawroth, Riccardo Barrile, David Conegliano, Sander van Riet, Pieter S. Hiemstra, Remi Villenave Pathologies of the respiratory system such as lung infections, chronic inflammatory lung diseases, and lung cancer are among the leading causes of morbidity and mortality, killing one in six people worldwide. Development of more effective treatments is hindered by the lack of preclinical models of the human lung that can capture the disease complexity, highly heterogeneous disease phenotypes, and pharmacokinetics and pharmacodynamics observed in patients. The merger of two novel technologies, Organs-on-Chips and human stem cell engineering, has the potential to deliver such urgently needed models. Organs-on-Chips, which are microengineered bioinspired tissue systems, recapitulate the mechanochemical environment and physiological functions of human organs while concurrent advances in generating and differentiating human stem cells promise a renewable supply of patient-specific cells for personalized and precision medicine. Here, we discuss the challenges of modeling human lung pathophysiology in vitro, evaluate past and current models including Organs-on-Chips, review the current status of lung tissue modeling using human pluripotent stem cells, explore in depth how stem-cell based Lung-on-Chips may advance disease modeling and drug testing, and summarize practical consideration for the design of Lung-on-Chips for academic and industry applications.Graphical abstractUnlabelled Image
  • Bacteriophage T4 nanoparticles for vaccine delivery against infectious
    • Abstract: Publication date: Available online 6 July 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Pan Tao, Jingen Zhu, Marthandan Mahalingam, Himanshu Batra, Venigalla B. Rao Subunit vaccines containing one or more target antigens from pathogenic organisms represent safer alternatives to whole pathogen vaccines. However, the antigens by themselves are not sufficiently immunogenic and require additives known as adjuvants to enhance immunogenicity and protective efficacy. Assembly of the antigens into virus-like nanoparticles (VLPs) is a better approach as it allows presentation of the epitopes in a more native context. The repetitive, symmetrical, and high density display of antigens on the VLPs mimic pathogen-associated molecular patterns seen on bacteria and viruses. The antigens, thus, might be better presented to stimulate host's innate as well as adaptive immune systems thereby eliciting both humoral and cellular immune responses. Bacteriophages such as phage T4 provide excellent platforms to generate the nanoparticle vaccines. The T4 capsid containing two non-essential outer proteins Soc and Hoc allow high density array of antigen epitopes in the form of peptides, domains, full-length proteins, or even multi-subunit complexes. Co-delivery of DNAs, targeting molecules, and/or molecular adjuvants provides additional advantages. Recent studies demonstrate that the phage T4 VLPs are highly immunogenic, do not need an adjuvant, and provide complete protection against bacterial and viral pathogens. Thus, phage T4 could potentially be developed as a “universal” VLP platform to design future multivalent vaccines against complex and emerging pathogens.Graphical abstractUnlabelled Image
  • Re-epithelialization of adult skin wounds: Cellular mechanisms and
           therapeutic strategies
    • Abstract: Publication date: Available online 5 July 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Patricia Rousselle, Fabienne Braye, Guila Dayan Cutaneous wound healing in adult mammals is a complex multi-step process involving overlapping stages of blood clot formation, inflammation, re-epithelialization, granulation tissue formation, neovascularization, and remodelling. Re-epithelialization describes the resurfacing of a wound with new epithelium. The cellular and molecular processes involved in the initiation, maintenance, and completion of epithelialization are essential for successful wound closure. A variety of modulators are involved, including growth factors, cytokines, matrix metalloproteinases, cellular receptors, and extracellular matrix components. Here, we focus on cellular mechanisms underlying keratinocyte migration and proliferation during epidermal closure. Inability to re-epithelialize is a clear indicator of chronic non-healing wounds, which fail to proceed through the normal phases of wound healing in an orderly and timely manner. This review summarizes the current knowledge regarding the management and treatment of acute and chronic wounds, with a focus on re-epithelialization, offering some insights into novel future therapies.Graphical Unlabelled Image
  • Bioresponsive drug delivery systems in intestinal inflammation:
           State-of-the-art and future perspectives
    • Abstract: Publication date: Available online 5 July 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Niranjan G. Kotla, Shubhasmin Rana, Gandhi Sivaraman, Omprakash Sunnapu, Praveen K. Vemula, Abhay Pandit, Yury Rochev Oral colon-specific delivery systems emerged as the main therapeutic cargos by making a significant impact in the field of modern medicine for local drug delivery in intestinal inflammation. The site-specific delivery of therapeutics (aminosalicylates, glucocorticoids, biologics) to the ulcerative mucus tissue can provide prominent advantages in mucosal healing (MH). Attaining gut mucosal healing and anti-fibrosis are main treatment outcomes in inflammatory bowel disease (IBD). The pharmaceutical strategies that are commonly used to achieve a colon-specific drug delivery system include time, pH-dependent polymer coating, prodrug, colonic microbiota-activated delivery systems and a combination of these approaches. Amongst the different approaches reported, the use of biodegradable polysaccharide coated systems holds great promise in delivering drugs to the ulcerative regions. The present review focuses on major physiological gastro-intestinal tract challenges involved in altering the pharmacokinetics of delivery systems, pathophysiology of MH and fibrosis, reported drug-polysaccharide cargos and focusing on conventional to advanced disease responsive delivery strategies, highlighting their limitations and future perspectives in intestinal inflammation therapy.Graphical abstractUnlabelled Image
  • SEDDS: A game changing approach for the oral administration of hydrophilic
           macromolecular drugs
    • Abstract: Publication date: Available online 4 July 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Arshad Mahmood, Andreas Bernkop-Schnürch Since the development of self-emulsifying drug delivery systems (SEDDS) in 1980's, they attract the attention of researchers in order to confront the challenge of poor water-solubility of orally given drugs. Within recent years, SEDDS were also discovered for oral administration of hydrophilic macromolecular drugs such as peptides, proteins, polysaccharides and pDNA. Due to hydrophobic ion pairing (HIP) with oppositely charged lipophilic auxiliary agents the resulting complexes can be incorporated in the lipophilic phase of SEDDS. Depending on the solubility of the complex in the SEDDS pre-concentrate and in the release medium drug release can be adjusted on purpose by choosing more or less lipophilic auxiliary agents in appropriate quantities for HIP. Within the oily droplets formed in the GI-tract drugs are protected towards degradation by proteases and nucleases and thiol-disulfide exchange reactions with dietary proteins. The oily droplets can be made mucoadhesive or highly mucus permeating depending on their target site. Furthermore, even their cellular uptake properties can be tuned by adjusting their zeta potential or decorating them with cell penetrating peptides. The potential of SEDDS for oral administration of hydrophilic macromolecular drugs could meanwhile be demonstrated via various in vivo studies showing a bioavailability at least in the single digit percentage range. Owing to these properties advanced SEDDS turned out to be a game changing approach for the oral administration of hydrophilic macromolecular drugs.Graphical abstractUnlabelled Image
  • Use of phage therapy to treat long-standing, persistent, or chronic
           bacterial infections
    • Abstract: Publication date: Available online 3 July 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Stephen T. Abedon Viruses of bacteria – known as bacteriophages or phages – have been used clinically as antibacterial agents for nearly 100 years. Often this phage therapy is of long-standing, persistent, or chronic bacterial infections, and this can be particularly so given prior but insufficiently effective infection treatment using standard antibiotics. Such infections, in turn, often have a biofilm component. Phages in modern medicine thus are envisaged to serve especially as anti-biofilm/anti-persistent infection agents. Here I review the English-language literature concerning in vivo experimental and clinical phage treatment of longer-lived bacterial infections. Overall, published data appears to be supportive of a relatively high potential for phages to cure infections which are long standing and which otherwise have resisted treatment with antibieiotics.Graphical abstractUnlabelled Image
  • Molecular imaging of β-cells: diabetes and beyond
    • Abstract: Publication date: Available online 3 July 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Weijun Wei, Emily B. Ehlerding, Xiaoli Lan, Quan-Yong Luo, Weibo Cai Since diabetes is becoming a global epidemic, there is a great need to develop early β-cell specific diagnostic techniques for this disorder. There are two types of diabetes (i.e., type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM)). In T1DM, the destruction of pancreatic β-cells leads to reduced insulin production or even absolute insulin deficiency, which consequently results in hyperglycemia. Actually, a central issue in the pathophysiology of all types of diabetes is the relative reduction of β-cell mass (BCM) and/or impairment of the function of individual β-cells. In the past two decades, scientists have been trying to develop imaging techniques for noninvasive measurement of the viability and mass of pancreatic β-cells. Despite intense scientific efforts, only two tracers for positron emission tomography (PET) and one contrast agent for magnetic resonance (MR) imaging are currently under clinical evaluation. β-cell specific imaging probes may also allow us to precisely and specifically visualize transplanted β-cells and to improve transplantation outcomes, as transplantation of pancreatic islets has shown promise in treating T1DM. In addition, some of these probes can be applied to the preoperative detection of hidden insulinomas as well. In the present review, we primarily summarize potential tracers under development for imaging β-cells with a focus on tracers for PET, SPECT, MRI, and optical imaging. We will discuss the advantages and limitations of the various imaging probes and extend an outlook on future developments in the field.Graphical abstractUnlabelled Image
  • Advanced in vitro models of vascular biology: Human induced pluripotent
           stem cells and organ-on-chip technology
    • Abstract: Publication date: Available online 23 June 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Amy Cochrane, Hugo J. Albers, Robert Passier, Christine L. Mummery, Albert van den Berg, Valeria V. Orlova, Andries D. van der Meer The vascular system is one of the first to develop during embryogenesis and is essential for all organs and tissues in our body to develop and function. It has many essential roles including controlling the absorption, distribution and excretion of compounds and therefore determines the pharmacokinetics of drugs and therapeutics. Vascular homeostasis is under tight physiological control which is essential for maintaining tissues in a healthy state. Consequently, disruption of vascular homeostasis plays an integral role in many disease processes, making cells of the vessel wall attractive targets for therapeutic intervention. Experimental models of blood vessels can therefore contribute significantly to drug development and aid in predicting the biological effects of new drug entities. The increasing availability of human induced pluripotent stem cells (hiPSC) derived from healthy individuals and patients have accelerated advances in developing experimental in vitro models of the vasculature: human endothelial cells (ECs), pericytes and vascular smooth muscle cells (VSMCs), can now be generated with high efficiency from hiPSC and used in ‘microfluidic chips’ (also known as ‘organ-on-chip’ technology) as a basis for in vitro models of blood vessels. These near physiological scaffolds allow the controlled integration of fluid flow and three-dimensional (3D) co-cultures with perivascular cells to mimic tissue- or organ-level physiology and dysfunction in vitro. Here, we review recent multidisciplinary developments in these advanced experimental models of blood vessels that combine hiPSC with microfluidic organ-on-chip technology. We provide examples of their utility in various research areas and discuss steps necessary for further integration in biomedical applications so that they can be contribute effectively to the evaluation and development of new drugs and other therapeutics as well as personalized (patient-specific) treatments.Graphical abstractUnlabelled Image
  • Local delivery of adenosine receptor agonists to promote bone regeneration
           and defect healing
    • Abstract: Publication date: Available online 18 June 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Christopher D. Lopez, Jonathan M. Bekisz, Carmen Corciulo, Aranzazu Mediero, Paulo G. Coelho, Lukasz Witek, Roberto L. Flores, Bruce N. Cronstein Adenosine receptor activation has been investigated as a potential therapeutic approach to heal bone. Bone has enhanced regenerative potential when influenced by either direct or indirect adenosine receptor agonism. As investigators continue to elucidate how adenosine influences bone cell homeostasis at the cellular and molecular levels, a small but growing body of literature has reported successful in vivo applications of adenosine delivery. This review summarizes the role adenosine receptor ligation plays in osteoblast and osteoclast biology and remodeling/regeneration. It also reports on all the modalities described in the literature at this point for delivery of adenosine through in vivo models for bone healing and regeneration.Graphical abstractUnlabelled Image
  • Microphysiological systems meet hiPSC technology – New tools for disease
           modeling of liver infections in basic research and drug development
    • Abstract: Publication date: Available online 15 June 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Martin Raasch, Enrico Fritsche, Andreas Kurtz, Michael Bauer, Alexander S. Mosig Complex cell culture models such as microphysiological models (MPS) mimicking human liver functionality in vitro are in the spotlight as alternative to conventional cell culture and animal models. Promising techniques like microfluidic cell culture or micropatterning by 3D bioprinting are gaining increasing importance for the development of MPS to address the needs for more predictivity and cost efficiency. In this context, human induced pluripotent stem cells (hiPSCs) offer new perspectives for the development of advanced liver-on-chip systems by recreating an in vivo like microenvironment that supports the reliable differentiation of hiPSCs to hepatocyte-like cells (HLC). In this review we will summarize current protocols of HLC generation and highlight recently established MPS suitable to resemble physiological hepatocyte function in vitro. In addition, we are discussing potential applications of liver MPS for disease modeling related to systemic or direct liver infections and the use of MPS in testing of new drug candidates.Graphical abstractUnlabelled Image
  • Progress, obstacles, and limitations in the use of stem cells in
           organ-on-a-chip models
    • Abstract: Publication date: Available online 6 June 2018Source: Advanced Drug Delivery ReviewsAuthor(s): Alexa Wnorowski, Huaxiao Yang, Joseph C. Wu In recent years, drug development costs have soared, primarily due to the failure of preclinical animal and cell culture models, which do not directly translate to human physiology. Organ-on-a-chip (OOC) is a burgeoning technology with the potential to revolutionize disease modeling, drug discovery, and toxicology research by strengthening the relevance of culture-based models while reducing costly animal studies. Although OOC models can incorporate a variety of tissue sources, the most robust and relevant OOC models going forward will include stem cells. In this review, we will highlight the benefits of stem cells as a tissue source while considering current limitations to their complete and effective implementation into OOC models.Graphical abstractUnlabelled Image
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