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Publisher: Elsevier   (Total: 3185 journals)

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Showing 1 - 200 of 3185 Journals sorted alphabetically
Academic Pediatrics     Hybrid Journal   (Followers: 37, SJR: 1.655, CiteScore: 2)
Academic Radiology     Hybrid Journal   (Followers: 25, SJR: 1.015, CiteScore: 2)
Accident Analysis & Prevention     Partially Free   (Followers: 100, SJR: 1.462, CiteScore: 3)
Accounting Forum     Hybrid Journal   (Followers: 28, 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: 427, 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: 3)
Acta de Investigación Psicológica     Open Access   (Followers: 3)
Acta Ecologica Sinica     Open Access   (Followers: 10, SJR: 0.18, CiteScore: 1)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.661, CiteScore: 2)
Acta Materialia     Hybrid Journal   (Followers: 293, SJR: 3.263, CiteScore: 6)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 6, 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: 2, 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: 7, 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: 15, 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: 9, 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: 179, 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: 9, SJR: 0.277, CiteScore: 1)
Advances in Agronomy     Full-text available via subscription   (Followers: 16, 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: 11, 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: 15, 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: 32, 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: 5)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 14)
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: 13)
Advances in Digestive Medicine     Open Access   (Followers: 11)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 7)
Advances in Drug Research     Full-text available via subscription   (Followers: 26)
Advances in Ecological Research     Full-text available via subscription   (Followers: 43, 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: 49, 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: 62, 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: 20, 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: 3, 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: 19, SJR: 0.88, CiteScore: 2)
Advances in Mathematics     Full-text available via subscription   (Followers: 12, 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: 17)
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: 66)
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: 414, 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: 13, SJR: 0.555, CiteScore: 2)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 36, SJR: 2.208, CiteScore: 4)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 20)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 15)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 2.262, CiteScore: 5)
Advances in Water Resources     Hybrid Journal   (Followers: 51, SJR: 1.551, CiteScore: 3)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 1.117, CiteScore: 3)
Aerospace Science and Technology     Hybrid Journal   (Followers: 364, 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: 469, 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: 44, 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: 58, 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: 2, SJR: 0.604, CiteScore: 3)
Alexandria J. of Medicine     Open Access   (Followers: 1, SJR: 0.191, CiteScore: 1)
Algal Research     Partially Free   (Followers: 11, 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: 57, SJR: 3.267, CiteScore: 4)
American J. of Cardiology     Hybrid Journal   (Followers: 62, SJR: 1.93, CiteScore: 3)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 45, 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: 29, 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: 49)
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: 232, 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: 30, SJR: 2.139, CiteScore: 4)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 28, SJR: 2.164, CiteScore: 4)
American J. of Surgery     Hybrid Journal   (Followers: 39, 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: 20, 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: 44, SJR: 1.512, CiteScore: 5)
Analytica Chimica Acta : X     Open Access  
Analytical Biochemistry     Hybrid Journal   (Followers: 201, 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: 14)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 2)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 24, 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: 207, SJR: 1.58, CiteScore: 3)
Animal Feed Science and Technology     Hybrid Journal   (Followers: 6, SJR: 0.937, CiteScore: 2)
Animal Reproduction Science     Hybrid Journal   (Followers: 7, SJR: 0.704, CiteScore: 2)

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Similar Journals
Journal Cover
Advanced Drug Delivery Reviews
Journal Prestige (SJR): 4.09
Citation Impact (citeScore): 13
Number of Followers: 179  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0169-409X
Published by Elsevier Homepage  [3185 journals]
  • Application of Förster Resonance Energy Transfer (FRET) technique to
           elucidate intracellular and In Vivo biofate of nanomedicines
    • Abstract: Publication date: Available online 12 June 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Tongkai Chen, Bing He, Jingsong Tao, Yuan He, Hailiang Deng, Xueqing Wang, Ying Zheng Extensive studies on nanomedicines have been conducted for drug delivery and disease diagnosis (especially for cancer therapy). However, the intracellular and in vivo biofate of nanomedicines, which is significantly associated with their clinical therapeutic effect, is poorly understood at present. This is because of the technical challenges to quantify the disassembly and behaviour of nanomedicines. As a fluorescence- and distance-based approach, the Förster Resonance Energy Transfer (FRET) technique is very successful to study the interaction of nanomedicines with biological systems. In this review, principles on how to select a FRET pair and construct FRET-based nanomedicines have been described first, followed by their application to study structural integrity, biodistribution, disassembly kinetics, and elimination of nanomedicines at intracellular and in vivo levels, especially with drug nanocarriers including polymeric micelles, polymeric nanoparticles, and lipid-based nanoparticles. FRET is a powerful tool to reveal changes and interaction of nanoparticles after delivery, which will be very useful to guide future developments of nanomedicine.Graphical abstractUnlabelled Image
  • Electrically conductive nanomaterials for cardiac tissue engineering
    • Abstract: Publication date: Available online 6 June 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Khadijeh Ashtari, Hojjatollah Nazari, Hyojin Ko, Peyton Tebon, Masoud Akhshik, Mohsen Akbari, Sanaz Naghavi Alhosseini, Masoud Mozafari, Bita Mehravi, Masoud Soleimani, Reza Ardehali, Majid Ebrahimi Warkiani, Samad Ahadian, Ali Khademhosseini Patient deaths resulting from cardiovascular diseases are increasing across the globe, posing the greatest risk to patients in developed countries. Myocardial infarction, as a result of inadequate blood flow to the myocardium, results in irreversible loss of cardiomyocytes which can lead to heart failure. A sequela of myocardial infarction is scar formation that can alter the normal myocardial architecture and result in arrhythmias. Over the past decade, a myriad of tissue engineering approaches has been developed to fabricate engineered scaffolds for repairing cardiac tissue. This paper highlights the recent application of electrically conductive nanomaterials (carbon and gold-based nanomaterials, electroactive polymers) to the development of scaffolds for cardiac tissue engineering. Moreover, this work summarizes the effects of these nanomaterials on cardiac cell behavior such as proliferation and migration, as well as cardiomyogenic differentiation in stem cells.Graphical abstractUnlabelled Image
  • Nuclear imaging of liposomal drug delivery systems: A critical review of
           radiolabelling methods and applications in nanomedicine
    • Abstract: Publication date: Available online 3 June 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Francis Man, Peter J. Gawne, Rafael T.M. de Rosales The integration of nuclear imaging with nanomedicine is a powerful tool for efficient development and clinical translation of liposomal drug delivery systems. Furthermore, it may allow highly efficient imaging-guided personalised treatments. In this article, we critically review methods available for radiolabelling liposomes. We discuss the influence that the radiolabelling methods can have on their biodistribution and highlight the often-overlooked possibility of misinterpretation of results due to decomposition in vivo. We stress the need for knowing the biodistribution/pharmacokinetics of both the radiolabelled liposomal components and free radionuclides in order to confidently evaluate the images, as they often share excretion pathways with intact liposomes (e.g. phospholipids, metallic radionuclides) and even show significant tumour uptake by themselves (e.g. some radionuclides). Finally, we describe preclinical and clinical studies using radiolabelled liposomes and discuss their impact in supporting liposomal drug development and clinical translation in several diseases, including personalised nanomedicine approaches.Graphical abstractUnlabelled Image
  • Cardiac fibrosis – A short review of causes and therapeutic
    • Abstract: Publication date: Available online 31 May 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Svenja Hinderer, Katja Schenke-Layland Fibrotic diseases cause annually more than 800,000 deaths worldwide, whereof the majority accounts for lung and cardiac fibrosis. A pathological remodeling of the extracellular matrix either due to ageing or as a result of an injury or disease leads to fibrotic scars. In the heart, these scars cause several cardiac dysfunctions either by reducing the ejection fraction due to a stiffened myocardial matrix, or by impairing electric conductance, or they can even lead to death. Today it is known that there are several different types of cardiac scars depending on the underlying cause of fibrosis. In this review, we will present an overview of what is known about cardiac fibrosis including the role of cardiac cells and extracellular matrix in this disease. We will further summarize current diagnostic tools and highlight clinical or pre-clinical therapeutic strategies to address cardiac fibrosis.Graphical abstractUnlabelled Image
  • Towards more accurate bioimaging of drug nanocarriers: turning
           aggregation-caused quenching into a useful tool
    • Abstract: Publication date: Available online 31 May 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Jianping Qi, Xiongwei Hu, Xiaochun Dong, Yi Lu, Huiping Lu, Weili Zhao, Wei Wu One of the current challenges in the monitoring of drug nanocarriers lies in the difficulties in discriminating the carrier-bound signals from the bulk signals of probes. Environment-responsive probes that enable signal switching are making steps towards a solution to this problem. Aggregation-caused quenching (ACQ), a phenomenon generally regarded as unfavorable in bioimaging, has turned out to be a promising characteristic for achieving environment-responsiveness and eliminating free-probe interference. So-called ACQ probes emit fluorescence when dispersed molecularly within the carrier matrix but quench immediately and absolutely once they are released into the ambient aqueous environment upon the degradation of the nanocarriers. Therefore, the fluorescence observed represents integral nanocarriers. Based on this rationale, the in vivo fates of various nanocarriers have been explored using live imaging equipment, with very interesting findings revealing the role of the particles. The current applications are however restricted to nanocarriers with highly hydrophobic matrices (lipid or polyester nanoparticles) or with a hydrophobic core-hydrophilic shell structure (micelles). The ACQ-based bioimaging strategy is emerging as a promising tool to achieve more accurate bioimaging of drug nanocarriers. This review article provides an overview of the ACQ phenomenon and the rationale for and examples of applications, as well as the limitations of the ACQ-based strategy, with a focus on improving the accuracy of bioimaging of nanoparticles.Graphical abstractUnlabelled Image
  • Ligand density on nanoparticles: A parameter with critical impact on
    • Abstract: Publication date: Available online 31 May 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Alaaldin M. Alkilany, Lin Zhu, Horst Weller, Alf Mews, Wolfgang Parak, Matthias Barz, Neus Feliu Nanoparticles modified with ligands for specific targeting towards receptors expressed on the surface of target cells are discussed in literature towards improved delivery strategies. In such concepts the ligand density on the surface of the nanoparticles plays an important role. How many ligands per nanoparticle are best for the most efficient delivery?. Importantly, this number may be different for in vitro and in vivo scenarios. In this review first viruses as “biological” nanoparticles are analyzed towards their ligand density, which is then compared to the ligand density of engineered nanoparticles. Then, experiments are reviewed in which in vitro and in vivo nanoparticle delivery has been analyzed in terms of ligand density. These results help to understand which ligand densities should be attempted for better targeting. Finally synthetic methods for controlling the ligand density of nanoparticles are described.Graphical abstractUnlabelled Image
  • Unlocking the full potential of lipid-based formulations using lipophilic
           salt/ionic liquid forms
    • Abstract: Publication date: Available online 29 May 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Hywel D. Williams, Leigh Ford, Annabel Igonin, Zhenhua Shan, Paolo Botti, Michael M. Morgen, Guixian Hu, Colin W. Pouton, Peter J. Scammells, Christopher J.H. Porter, Hassan Benameur Lipid-based formulations (LBF) are widely used by industry and accepted by the regulatory authorities for oral drug delivery in the pharmaceutical and consumer healthcare market. Innovation in the LBF field is however needed in order to meet the demands of modern drugs, their more challenging problem statements and growing needs for achieving optimal pharmacokinetics (i.e., no food-effects, low variability) on approval. This review describes a new lipophilic salt / ionic liquid approach in combination with LBF, and how this salt strategy can be used to better tailor the properties of a drug to LBFs. The potential advantages of lipophilic salts are discussed in the context of dose escalation studies during toxicological evaluation, reducing the pill burden, increasing drug absorption of new drugs and in life-cycle management. Commentary on lipophilic salt synthesis, scale-up, LBF design and the regulatory aspects are also provided. These topics are discussed in the broad context of bringing the widely recognized advantages of LBFs to a broader spectrum of drugs.Graphical abstractUnlabelled Image
  • Intrinsic cancer vaccination
    • Abstract: Publication date: Available online 24 May 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Yoosoo Yang, Gi-Hoon Nam, Gi Beom Kim, Yoon Kyoung Kim, In-San Kim Immunotherapy is revolutionizing the treatment of cancer, and the current immunotherapeutics have remarkably improved the outcomes for some cancer patients. However, we still need answers for patients with immunologically cold tumors that do not benefit from the current immunotherapy treatments. Here, we suggest a novel strategy that is based on using a very old and sophisticated system for cancer immunotherapy, namely “intrinsic cancer vaccination”, which seeks to awaken our own immune system to activate tumor-specific T cells. To do this, we must take advantage of the genetic instability of cancer cells and the expression of cancer cell neoantigens to trigger immunity against cancer cells. It will be necessary to not only enhance the phagocytosis of cancer cells by antigen presenting cells but also induce immunogenic cancer cell death and the subsequent immunogenic clearance, cross-priming and generation of tumor-specific T cells. This strategy will allow us to avoid using known tumor-specific antigens, ex vivo manipulation or adoptive cell therapy; rather, we will efficiently present cancer cell neoantigens to our immune system and propagate the cancer-immunity cycle. This strategy simply follows the natural cycle of cancer-immunity from its very first step, and therefore could be combined with any other treatment modality to yield enhanced efficacy.Graphical abstractUnlabelled Image
  • Corrigendum to “Overcoming ocular drug delivery barriers through the use
           of physical forces” [Advanced Drug Delivery Reviews 126 (2018) 96–112]
    • Abstract: Publication date: Available online 24 May 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Di Huang, Ying-Shan Chen, Ilva D. Rupenthal
  • Sequential drug delivery to modulate macrophage behavior and enhance
           implant integration
    • Abstract: Publication date: Available online 16 May 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Erin M. O'Brien, Gregory E. Risser, Kara L. Spiller Macrophages are major upstream regulators of the inflammatory response to implanted biomaterials. Sequential functions of distinct macrophage phenotypes are essential to the normal tissue repair process, which ideally results in vascularization and integration of implants. Improper timing of M1 or M2 macrophage activation results in dysfunctional healing in the form of chronic inflammation or fibrous encapsulation of the implant. Thus, biphasic drug delivery systems that modulate macrophage behavior are an appealing approach to promoting implant integration. In this review, we describe the timing and roles of macrophage phenotypes in healing, then highlight current drug delivery systems designed to sequentially modulate macrophage behavior.Graphical abstractUnlabelled Image
  • Translational challenges in advancing regenerative therapy for treating
           neurological disorders using nanotechnology
    • Abstract: Publication date: Available online 14 May 2019Source: Advanced Drug Delivery ReviewsAuthor(s): C.L. Nemeth, A.S. Fine, A. Fatemi The focus of regenerative therapies is to replace or enrich diseased or injured cells and tissue in an attempt to replenish the local environment and function, while slowing or halting further degeneration. Targeting neurological diseases specifically is difficult, due to the complex nature of the central nervous system, including the difficulty of bypassing the brain's natural defense systems. While cell-based regenerative therapies show promise in select tissues, preclinical and clinical studies have been largely unable to transfer these successes to the brain. Advancements in nanotechnologies have provided new methods of central nervous system access, drug and cell delivery, as well as new systems of cell maintenance and support that may bridge the gap between regenerative therapies and the brain. In this review, we discuss current regenerative therapies for neurological diseases, nanotechnology as nanocarriers, and the technical, manufacturing, and regulatory challenges that arise from inception to formulation of nanoparticle-regenerative therapies.Graphical abstractUnlabelled Image
  • Oxygenation strategies for encapsulated islet and beta cell transplants
    • Abstract: Publication date: Available online 8 May 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Klearchos K. Papas, Hector De Leon, Thomas M. Suszynski, Robert C. Johnson Human allogeneic islet transplantation (ITx) is emerging as a promising treatment option for qualified patients with T1D. However, widespread clinical application of allogeneic ITx is hindered by two critical barriers: the need for systemic immunosuppression and the limited supply of human islet tissue. Biocompatible, retrievable immunoisolation devices containing glucose-responsive insulin-secreting tissue may address both critical barriers by enabling the more effective and efficient use of allogeneic islets without immunosuppression in the near-term, and ultimately the use of a cell source with a virtually unlimited supply, such as human stem cell derived β-cells or xenogeneic (porcine) islets with minimal or no immunosuppression. However, even though encapsulation have been developed and immunoprotection has been successfully tested in small and large animal models and to a limited extent in proof of concept clinical studies, the effective use of encapsulation approaches to convincingly and consistently treat diabetes in humans has yet to be demonstrated. There is increasing consensus that inadequate oxygen supply is a major factor limiting their clinical translation and routine implementation. Poor oxygenation negatively affects cell viability and β-cell function, and the problem is exacerbated with the high-density seeding required for reasonably-sized clinical encapsulation devices. Approaches for enhanced oxygen delivery to encapsulated tissues in implantable devices are therefore being actively developed and tested. This review summarizes fundamental aspects of islet microarchitecture and β-cell physiology as well as encapsulation approaches highlighting the need for adequate oxygenation; it also evaluates existing and emerging approaches for enhanced oxygen delivery to encapsulation devices, particularly with the advent of β-cell sources from stem cells that may enable large-scale application of this approach.Graphical abstractUnlabelled Image
  • The significance of artificial intelligence in drug delivery system design
    • Abstract: Publication date: Available online 6 May 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Parichehr Hassanzadeh, Fatemeh Atyabi, Rassoul Dinarvand Over the last decade, increasing interest has been attracted towards the application of artificial intelligence (AI) technology for analyzing and interpreting the biological or genetic information, accelerated drug discovery, and identification of the selective small-molecule modulators or rare molecules and prediction of their behavior. Application of the automated workflows and databases for rapid analysis of the huge amounts of data and artificial neural networks (ANNs) for development of the novel hypotheses and treatment strategies, prediction of disease progression, and evaluation of the pharmacological profiles of drug candidates may significantly improve treatment outcomes. Target fishing (TF) by rapid prediction or identification of the biological targets might be of great help for linking targets to the novel compounds. AI and TF methods in association with human expertise may indeed revolutionize the current theranostic strategies, meanwhile, validation approaches are necessary to overcome the potential challenges and ensure higher accuracy. In this review, the significance of AI and TF in the development of drugs and delivery systems and the potential challenging issues have been highlighted.Graphical abstractUnlabelled Image
  • Thiolated polymers: Bioinspired polymers utilizing one of the most
           important bridging structures in nature
    • Abstract: Publication date: Available online 25 April 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Christina Leichner, Max Jelkmann, Andreas Bernkop-Schnürch Thiolated polymers designated “thiomers” are obtained by covalent attachment of thiol functionalities on the polymeric backbone of polymers. In 1998 these polymers were first described as mucoadhesive and in situ gelling compounds forming disulfide bonds with cysteine-rich substructures of mucus glycoproteins and crosslinking through inter- and intrachain disulfide bond formation. In the following, it was shown that thiomers are able to form disulfides with keratins and membrane-associated proteins exhibiting also cysteine-rich substructures. Furthermore, permeation enhancing, enzyme inhibiting and efflux pump inhibiting properties were demonstrated. Because of these capabilities thiomers are promising tools for drug delivery guaranteeing a strongly prolonged residence time as well as sustained release on mucosal membranes. Apart from that, thiomers are used as drugs per se. In particular, for treatment of dry eye syndrome various thiolated polymers are in development and a first product has already reached the market. Within this review an overview about the thiomer-technology and its potential for different applications is provided discussing especially the outcome of studies in non-rodent animal models and that of numerous clinical trials. Moreover, an overview on product developments is given.Graphical abstractThe great potential of thiolated polymers for life sciences might be described in the best way by the simple imagination of protein chemistry with and without cysteineUnlabelled Image
  • Concepts of nanoparticle cellular uptake, intracellular trafficking, and
           kinetics in nanomedicine
    • Abstract: Publication date: Available online 22 April 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Nathan D. Donahue, Handan Acar, Stefan Wilhelm Nanoparticle-based therapeutics and diagnostics are commonly referred to as nanomedicine and may significantly impact the future of healthcare. However, the clinical translation of these technologies is challenging. One of these challenges is the efficient delivery of nanoparticles to specific cell populations and subcellular targets in the body to elicit desired biological and therapeutic responses. It is critical for researchers to understand the fundamental concepts of how nanoparticles interact with biological systems to predict and control in vivo nanoparticle transport for improved clinical benefit. In this overview article, we review and discuss cellular internalization pathways, summarize the field`s understanding of how nanoparticle physicochemical properties affect cellular interactions, and explore and discuss intracellular nanoparticle trafficking and kinetics. Our overview may provide a valuable resource for researchers and may inspire new studies to expand our current understanding of nanotechnology-biology interactions at cellular and subcellular levels with the goal to improve clinical translation of nanomedicines.Graphical abstractUnlabelled Image
  • Cowpea mosaic virus nanoparticles for cancer imaging and therapy
    • Abstract: Publication date: Available online 17 April 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Perrin H. Beatty, John D. Lewis Nanoparticle platforms are particularly attractive for theranostic applications due to their capacity for multifunctionality and multivalency. Some of the most promising nano-scale scaffold systems have been co-opted from nature including plant viruses such as cowpea mosaic virus (CPMV). The use of plant viruses like CPMV as viral nanoparticles is advantageous for many reasons; they are non-infectious and nontoxic to humans and safe for use in intravital imaging and drug delivery. The CPMV capsid icosahedral shape allows for enhanced multifunctional group display and the ability to carry specific cargoes. The native tropism of CPMV for cell-surface displayed vimentin and the enhanced permeability and retention effect allow them to preferentially extravasate from tumor neovasculature and efficiently penetrate tumors. Furthermore, CPMVs can be engineered via several straightforward chemistries to display targeting and imaging moieties on external, addressable residues and they can be loaded internally with therapeutic drug cargoes. These qualities make them highly effective as biocompatible platforms for tumor targeting, intravital imaging and cancer therapy.Graphical abstractDepiction of CPMV as a theranostic tool for cancer cell imaging and therapy. Multifunctional CPMV nanoparticles (green circle) with externally-coupled fluorophore dye moieties (yellow spikes) carrying drug molecules as cargo (red star) home towards cancer cells over-expressing cell membrane-bound vimentin (+). The targeting and then retention of the functionalized nanoparticles to the tumor cells is theorized to be due to the efficiency of CPMV extravasation (purple arrows) into the stroma of the tumor by the EPR effect.Unlabelled Image
  • Tissue engineered models of healthy and malignant human bone marrow
    • Abstract: Publication date: Available online 17 April 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Alan Chramiec, Gordana Vunjak-Novakovic Tissue engineering is becoming increasingly successful in providing in vitro models of human tissues that can be used for ex vivo recapitulation of functional tissues as well as predictive testing of drug efficacy and safety. From simple tissue models to microphysiological platforms comprising multiple tissue types connected by vascular perfusion, these “tissues on a chip” are emerging as a fast track application for tissue engineering, with great potential for modeling diseases and supporting the development of new drugs and therapeutic targets. We focus here on tissue engineering of the hematopoietic stem and progenitor cell compartment and the malignancies that develop in the human bone and bone marrow. Our overall goal is to demonstrate the utility and interconnectedness of improvements in bioengineering methods developed in one area of bone marrow studies for the remaining, seemingly disparate, bone marrow fields.Graphical abstractUnlabelled Image
  • CAR T-cell bioengineering: Single variable domain of heavy chain antibody
           targeted CARs
    • Abstract: Publication date: Available online 17 April 2019Source: Advanced Drug Delivery ReviewsAuthor(s): F. Rahbarizadeh, D. Ahmadvand, S.M. Moghimi Redirecting the recognition specificity of T lymphocytes to designated tumour cell surface antigens by transferring chimeric antigen receptor (CAR) genes is becoming an effective strategy to combat cancer. Today, CAR T-cell therapy has proven successful in the treatment of haematological malignancies and the first CD19 CAR T-cell products has already entered the market. This success is expanding CAR design for broader malignancies including solid tumours. Nevertheless, CARs such as those built on antigen-specific single chain antibody variable fragment (scFv) may induce some adverse effects. Here, we briefly review CAR T-cell bioengineering and discuss selected important initiatives for improved T-cell reprogramming, function and safety. In this respect, we further elaborate on unconventional CARs structured on single variable domain of heavy chain (VHH) antibodies (single-domain antibodies) as an alternative to scFv, because of their interesting immunological and physicochemical characteristics and unique structure, which shows a high degree of homology with human VH3 gene family.Graphical abstractUnlabelled Image
  • Neuronanotechnology for brain regeneration
    • Abstract: Publication date: Available online 17 April 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Kevin Liaw, Zhi Zhang, Sujatha Kannan Identifying and harnessing regenerative pathways while suppressing the growth-inhibiting processes of the biological response to injury is the central goal of stimulating neurogenesis after central nervous system (CNS) injury. However, due to the complexity of the mature CNS involving a plethora of cellular pathways and extracellular cues, as well as difficulties in accessibility without highly invasive procedures, clinical successes of regenerative medicine for CNS injuries have been extremely limited. Current interventions primarily focus on stabilization and mitigation of further neuronal death rather than direct stimulation of neurogenesis. In the past few decades, nanotechnology has offered substantial innovations to the field of regenerative medicine. Their nanoscale features allow for the fine tuning of biological interactions for enhancing drug delivery and stimulating cellular processes. This review gives an overview of nanotechnology applications in CNS regeneration organized according to cellular and extracellular targets and discuss future directions for the field.Graphical abstractUnlabelled Image
  • Synthetic T cell receptor-based lymphocytes for cancer therapy
    • Abstract: Publication date: Available online 12 April 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Daniel Getts, Robert Hoffmeister, Alfonso Quintás-Cardama Chimeric antigen receptor (CAR) T cells have been remarkably successful in patients with hematological malignancies expressing the CD19 surface antigen, but such level of success is far from being replicated in solid tumors. Engineered T cell receptor (TCR) T cells targeting cancer antigens were first developed over two decades ago and represent an alternative adoptive T cell approach that has produced provocative clinical data in solid cancers. However, several factors may hinder this technology from realizing its full potential, including the need for HLA matching, HLA downregulation by cancer cells, the suppressive tumor microenvironment, and tissue liabilities resulting from targeting antigens shared with normal tissues. Efforts therefore continue to engineer enhanced versions of CAR T and TCR T therapies that can overcome current barriers. Furthermore, emergent novel TCR-based, HLA-unrestricted platforms may also provide unique tools that integrate the complexity of the TCR signaling cascade that can be applied to treat solid tumors. This article reviews the current state of development of TCR T cell approaches and discusses next generation improvements to overcome their current limitations.Graphical abstractUnlabelled Image
  • Self-emulsifying drug delivery system: Mucus permeation and innovative
           quantification technologies
    • Abstract: Publication date: Available online 8 April 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Muthanna Abdulkarim, Peeyush Kumar Sharma, Mark Gumbleton Mucus is a dynamic barrier which covers and protects the underlying mucosal epithelial membrane against bacteria and foreign particles. This protection mechanism extends to include therapeutic macromolecules and nanoparticles (NPs) through trapping of these particles. Mucus is not only a physical barrier that limiting particles movements based on their sizes but it selectively binds with particles through both hydrophilic and lipophilic interactions. Therefore, nano-carriers for mucosal delivery should be designed to eliminate entrapment by the mucus barrier. For this reason, different strategies have been approached for both solid nano-carriers and liquid core nano-carriers to synthesise muco-diffusive nano-carrier. Among these nano-strategies, Self-Emulsifying Drug Delivery System (SEDDS) was recognised as very promising nano-carrier for mucus delivery. The system was introduced to enhance the dissolution and bioavailability of orally administered insoluble drugs. SEDDS has shown high stability against intestinal enzymatic activity and more importantly, relatively rapid permeation characteristics across mucus barrier. The high diffusivity of SEDDS has been tested using various in vitro measurement techniques including both bulk and individual measurement of droplets diffusion within mucus. The selection and processing of an optimum in vitro technique is of great importance to avoid misinterpretation of the diffusivity of SEDDS through mucus barrier. In conclusion, SEDDS is a system with high capacity to diffuse through intestinal mucus even though this system has not been studied to the same extent as solid nano-carriers.Graphical abstractUnlabelled Image
  • Drug therapies and delivery mechanisms to treat perturbed skin wound
    • Abstract: Publication date: Available online 6 April 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Jiah Shin Chin, Leigh Madden, Sing Yian Chew, David L. Becker Acute wound healing is an orderly process of four overlapping events: haemostasis, inflammation, proliferation and remodelling. A drug delivery system with a temporal control of release could promote each of these events sequentially. However, acute wound healing normally proceeds very well in healthy individuals and there is little need to promote it. In the elderly and diabetics however, healing is often slow and wounds can become chronic and we need to promote their healing. Targeting the events of acute wound healing would not be appropriate for a chronic wound, which have stalled in the proinflammatory phase. They also have many additional problems such as poor circulation, low oxygen, high levels of leukocytes, high reactive oxygen species, high levels of proteolytic enzymes, high levels of proinflammatory cytokines, bacterial infection and high pH. The future challenge will be to tackle each of these negative factors to create a wound environment conducive to healing.Graphical abstractUnlabelled Image
  • Physically-triggered nanosystems for therapy and diagnosis
    • Abstract: Publication date: 1 January 2019Source: Advanced Drug Delivery Reviews, Volume 138Author(s): Claire Wilhelm, Florence Gazeau, Amanda K.A. Silva
  • Variations in gastrointestinal lipases, pH and bile acid levels with food
           intake, age and diseases: Possible impact on oral lipid-based drug
           delivery systems
    • Abstract: Publication date: Available online 26 March 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Sawsan Amara, Claire Bourlieu, Lydie Humbert, Dominique Rainteau, Frédéric Carrière The lipids and some surfactants present in oral lipid-based drug delivery systems are potential substrates for the various lipases involved in gastrointestinal (GI) lipolysis. The levels of these enzymes, together with pH and biliairy secretion, are important parameters that condition the fate of lipid-based formulations (LBF) and the dispersion, solubilization and absorption of lipophilic drugs in the GI tract. Since in vitro methods of digestion are now combined with dissolution assays for a better assessment of LBF performance, it is essential to have a basic knowledge on lipase, pH and bile acid (BA) levels in vivo to develop relevant in vitro models. While these parameters and their variations in healthy subjects are today well documented, in vivo data on specific populations (age groups, patients with various diseases, patients with treatment affecting GI tract parameters, …) are scarce and obtaining them from clinical studies is sometimes difficult due to ethical limitations. Here we collected some in vivo data already available on the levels of digestive lipases, gastric and intestinal pH, and BAs at various ages and in patients with exocrine pancreatic insufficiency, a pathological situation that leads to drastic changes in GI tract parameters and impacts pharmacological treatments.Graphical abstractUnlabelled Image
  • Scaffold-mediated sequential drug/gene delivery to promote nerve
           regeneration and remyelination following traumatic nerve injuries
    • Abstract: Publication date: Available online 22 March 2019Source: Advanced Drug Delivery ReviewsAuthor(s): William Ong, Coline Pinese, Sing Yian Chew Neural tissue regeneration following traumatic injuries is often subpar. As a result, the field of neural tissue engineering has evolved to find therapeutic interventions and has seen promising outcomes. However, robust nerve and myelin regeneration remain elusive. One possible reason may be the fact that tissue regeneration often follows a complex sequence of events in a temporally-controlled manner. Although several other fields of tissue engineering have begun to recognise the importance of delivering two or more biomolecules sequentially for more complete tissue regeneration, such serial delivery of biomolecules in neural tissue engineering remains limited. This review aims to highlight the need for sequential delivery to enhance nerve regeneration and remyelination after traumatic injuries in the central nervous system, using spinal cord injuries as an example. In addition, possible methods to attain temporally-controlled drug/gene delivery are also discussed for effective neural tissue regeneration.Graphical abstractUnlabelled Image
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
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