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Publisher: Elsevier   (Total: 3184 journals)

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Showing 1 - 200 of 3184 Journals sorted alphabetically
Academic Pediatrics     Hybrid Journal   (Followers: 37, SJR: 1.655, CiteScore: 2)
Academic Radiology     Hybrid Journal   (Followers: 26, 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: 40, SJR: 1.771, CiteScore: 3)
Achievements in the Life Sciences     Open Access   (Followers: 6)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 7)
Acta Astronautica     Hybrid Journal   (Followers: 433, 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: 11, SJR: 0.18, CiteScore: 1)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.661, CiteScore: 2)
Acta Materialia     Hybrid Journal   (Followers: 305, SJR: 3.263, CiteScore: 6)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.504, CiteScore: 1)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.542, CiteScore: 1)
Acta Oecologica     Hybrid Journal   (Followers: 12, SJR: 0.834, CiteScore: 2)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription  
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 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: 25, 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: 18, 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: 181, 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: 17, SJR: 2.384, CiteScore: 5)
Advances in Anesthesia     Full-text available via subscription   (Followers: 29, 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: 33, SJR: 3.043, CiteScore: 6)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9, SJR: 1.453, CiteScore: 2)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 1.992, CiteScore: 5)
Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 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: 29, 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: 12)
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: 51, 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: 65, 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: 21, 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: 7, SJR: 1.193, CiteScore: 3)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 26, SJR: 0.368, CiteScore: 1)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 11, SJR: 0.749, CiteScore: 3)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 24)
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: 9, 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: 21, 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: 8, SJR: 0.694, CiteScore: 2)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 6)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 5, SJR: 1.158, CiteScore: 3)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 24)
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: 5)
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: 18, 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: 27, SJR: 0.461, CiteScore: 1)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 18)
Advances in Pharmacology     Full-text available via subscription   (Followers: 17, SJR: 1.536, CiteScore: 3)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 9, 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: 6)
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: 418, 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: 37, 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: 53, SJR: 1.551, CiteScore: 3)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 1.117, CiteScore: 3)
Aerospace Science and Technology     Hybrid Journal   (Followers: 380, 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: 12, SJR: 3.671, CiteScore: 9)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 471, SJR: 1.238, CiteScore: 3)
Agri Gene     Hybrid Journal   (Followers: 1, SJR: 0.13, CiteScore: 0)
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 18, SJR: 1.818, CiteScore: 5)
Agricultural Systems     Hybrid Journal   (Followers: 31, SJR: 1.156, CiteScore: 4)
Agricultural Water Management     Hybrid Journal   (Followers: 45, 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: 7, 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: 54, SJR: 4.66, CiteScore: 10)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 6, SJR: 1.796, CiteScore: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 6, SJR: 1.108, CiteScore: 3)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 5)
American Heart J.     Hybrid Journal   (Followers: 58, SJR: 3.267, CiteScore: 4)
American J. of Cardiology     Hybrid Journal   (Followers: 63, SJR: 1.93, CiteScore: 3)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 46, SJR: 0.604, CiteScore: 1)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 12)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.524, CiteScore: 3)
American J. of Human Genetics     Hybrid Journal   (Followers: 37, 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: 36, SJR: 2.973, CiteScore: 4)
American J. of Medicine     Hybrid Journal   (Followers: 50)
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: 247, 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: 32, 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: 66, SJR: 0.138, CiteScore: 0)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 24, 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: 207, SJR: 0.633, CiteScore: 2)
Analytical Chemistry Research     Open Access   (Followers: 13, 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: 25, 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: 217, 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: 181  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0169-409X
Published by Elsevier Homepage  [3184 journals]
  • Carbohydrate-based nanocarriers and their application to target
           macrophages and deliver antimicrobial agents
    • Abstract: Publication date: Available online 10 September 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Tamim Mosaiab, Dylan Farr, Milton J. Kiefel, Todd A. HoustonMany deadly infections are produced by microorganisms capable of sustained survival in macrophages. This reduces exposure to chemotherapy, prevents immune detection, and is akin to criminals hiding in police stations. Therefore, the use of glyco-nanoparticles (GNPs) as carriers of therapeutic agents is a burgeoning field. Such an approach can enhance the penetration of drugs into macrophages with specific carbohydrate targeting molecules on the nanocarrier to interact with macrophage lectins. Carbohydrates are natural biological molecules and the key constituents in a large variety of biological events such as cellular communication, infection, inflammation, enzyme trafficking, cellular migration, cancer metastasis and immune functions. The prominent characteristics of carbohydrates including biodegradability, biocompatibility, hydrophilicity and the highly specific interaction of targeting cell-surface receptors support their potential application to drug delivery system (DDS). This review presents the 21st century development of carbohydrate-based nanocarriers for drug targeting of therapeutic agents for diseases localized in macrophages. The significance of natural carbohydrate derived nanoparticles (GNPs) as anti-microbial drug carriers is highlighted in several areas of treatment including tuberculosis, salmonellosis, leishmaniasis, candidiasis, and HIV/AIDS.Graphical abstractUnlabelled Image
       
  • Modified nucleobase-specific gene regulation using engineered
           transcription activator-like effectors
    • Abstract: Publication date: Available online 9 September 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Shogo Tsuji, Miki ImanishiEpigenetic modification, as typified by cytosine methylation, is a key aspect of gene regulation that affects many biological processes. However, the biological roles of individual methylated cytosines are poorly understood. Sequence-specific DNA recognition tools can be used to investigate the roles of individual instances of DNA methylation. Transcription activator-like effectors (TALEs), which are DNA-binding proteins, are promising candidate tools with designable sequence specificity and sensitivity to DNA methylation. In this review, we describe the bases of DNA recognition of TALEs, including methylated cytosine recognition, and the applications of TALEs for the study of methylated DNA. In addition, we discuss TALE-based epigenome editing and oxidized methylated cytosine recognition.Graphical abstractUnlabelled Image
       
  • NanoDDS 2018: Engineering the next wave of nanomedicine and drug delivery
           systems
    • Abstract: Publication date: April 2019Source: Advanced Drug Delivery Reviews, Volume 144Author(s): Gaurav Sahay
       
  • Aggregation-induced emission (AIE) fluorophores as imaging tools to trace
           the biological fate of nano-based drug delivery systems
    • Abstract: Publication date: 15 March 2019Source: Advanced Drug Delivery Reviews, Volume 143Author(s): Yufei Wang, Yuxuan Zhang, Jinjin Wang, Xing-Jie LiangThe vigorous development of nanotechnology has been accompanied by an equally strong interest and research efforts in nano-based drug delivery systems (NDDSs). However, only a few NDDSs have been translated into clinic thus far. One of the important hurdles is the lack of tools to comprehensively and directly trace the biological fate of NDDSs. Recently, aggregation-induced emission (AIE) fluorophores have emerged as attractive bioimaging tools due to flexible controllability, negligible toxicity and superior photostability. Herein, we recapitulate the current advances in the application of AIE fluorophores to monitor NDDSs both in vitro and in vivo. Particularly, we discuss the cellular fates of self-indicating and stimuli-responsive NDDSs with AIE fluorophores. Moreover, we highlight the in vivo application of AIE agents on the long-term tracking of therapeutics and the multi-modal monitoring of diagnostics in NDDSs. Challenges and opportunities in AIE-guided exploration of NDDSs are also discussed in detail.Graphical abstractUnlabelled Image
       
  • Unraveling the in vivo fate and cellular pharmacokinetics of drug
           nanocarriers
    • Abstract: Publication date: 15 March 2019Source: Advanced Drug Delivery Reviews, Volume 143Author(s): Wei Wu, Tonglei Li
       
  • Editorial
    • Abstract: Publication date: Available online 21 January 2012Source: Advanced Drug Delivery ReviewsAuthor(s): Raphaël Lévy, Mathias Brust
       
  • Pharmacokinetics of nanotechnology-based formulations in pediatric
           populations
    • Abstract: Publication date: Available online 5 September 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Venkata Yellepeddi, Andrea Joseph, Elizabeth NanceThe development of therapeutics for pediatric use has advanced in the last few decades. However, off-label use of adult medications in pediatrics remains a significant clinical problem. Furthermore, the development of therapeutics for pediatrics is challenged by the lack of pharmacokinetic (PK) data in the pediatric population. To promote the development of therapeutics for pediatrics, the United States Pediatric Formulation Initiative recommended the investigation of nanotechnology-based delivery systems. Therefore, in this review, we provided comprehensive information on the PK of nanotechnology-based formulations from preclinical and clinical studies in pediatrics. Specifically, we discuss the relationship between formulation parameters of nanoformulations and PK of the encapsulated drug in the context of pediatrics. We review nanoformulations that include dendrimers, liposomes, polymeric long-acting injectables (LAIs), nanocrystals, inorganic nanoparticles, polymeric micelles, and protein nanoparticles. In addition, we describe the importance and need of PK modeling and simulation approaches used in predicting PK of nanoformulations for pediatric applications.Graphical abstractUnlabelled Image
       
  • Domesticating the foreign body response: Recent advances and applications
    • Abstract: Publication date: Available online 3 September 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Omid Veiseh, Arturo J. VegasThe foreign body response is an immunological process that leads to the rejection of implanted devices and presents a fundamental challenge to their performance, durability, and therapeutic utility. Recent advances in materials development and device design are now providing strategies to overcome this immune-mediated reaction. Here, we briefly review our current mechanistic understanding of the foreign body response and highlight new anti-FBR technologies from this decade that have been applied successfully in biomedical applications relevant to implants, devices, and cell-based therapies. Further development of these important technologies promises to enable new therapies, diagnostics, and revolutionize the management of patient care for many intractable diseases.Graphical abstractUnlabelled Image
       
  • Lymphatic changes in cancer and drug delivery to the lymphatics in solid
           tumors
    • Abstract: Publication date: Available online 25 August 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Brianna Cote, Deepa Rao, Raid G. Alany, Glen S. Kwon, Adam W.G. AlaniAlthough many solid tumors use the lymphatic system to metastasize, there are few treatment options that directly target cancer present in the lymphatic system, and those that do are highly invasive, uncomfortable, and/or have limitations. This review gives a brief overview of lymphatic function and anatomy, discusses changes that befall the lymphatics in cancer and the mechanisms by which these changes occur, and presents limitations for drug delivery to the lymphatic system. We then go on to summarize relevant techniques and new research for targeting cancer populations in the lymphatics and enhancing drug delivery intralymphatically, including intralymphatic injections, isolated limb perfusion, passive nano drug delivery systems, and actively targeted nanomedicine.Graphical abstractUnlabelled Image
       
  • Lessons learned from intervertebral disc pathophysiology to guide rational
           design of sequential delivery systems for therapeutic biological factors
    • Abstract: Publication date: Available online 21 August 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Leslie Frapin, Johann Clouet, Vianney Delplace, Marion Fusellier, Jérôme Guicheux, Catherine Le VisageIntervertebral disc (IVD) degeneration has been associated with low back pain, which is a major musculoskeletal disorder and socio-economic problem that affects as many as 600 million patients worldwide. Here, we first review the current knowledge of IVD physiology and physiopathological processes in terms of homeostasis regulation and consecutive events that lead to tissue degeneration. Recent progress with IVD restoration by anti-catabolic or pro-anabolic approaches are then analyzed, as are the design of macro-, micro-, and nano-platforms to control the delivery of such therapeutic agents. Finally, we hypothesize that a sequential delivery strategy that i) firstly targets the inflammatory, pro-catabolic microenvironment with release of anti-inflammatory or anti-catabolic cytokines; ii) secondly increases cell density in the less hostile microenvironment by endogenous cell recruitment or exogenous cell injection, and finally iii) enhances cellular synthesis of extracellular matrix with release of pro-anabolic factors, would constitute an innovative yet challenging approach to IVD regeneration.Graphical abstractUnlabelled Image
       
  • Hyaluronan as tunable drug delivery system
    • Abstract: Publication date: Available online 14 August 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Alberto Passi, Davide VigettiThe hyaluronan (HA) polymer is an important macromolecule of extracellular matrix with remarkable structure and functions: it is a linear and unbranched polymer without sulphate or phosphate groups and has key role in several biological processes in mammals. It is ubiquitous in mammalian tissues with several and specific functions, influencing cell proliferation and migration as well as angiogenesis and inflammation. To exert these important functions in tissues HA modifies the concentration and size. Considering this HA content in tissues is carefully controlled by different mechanisms including covalent modification of the synthetic enzymes and epigenetic control of their gene expression. The function of HA is also critical in several pathologies including cancer, diabetes and chronic inflammation. Among these biological roles, the structural properties of HA allow to use this polymer in regenerative medicine including cosmetics and drug delivery. HA takes advantage from its capacity to form gels even at concentration of 1% producing scaffolds with very intriguing mechanical properties. These hydrogels are useful in regenerative medicine as biocompatible material for advanced therapeutic uses. In this review we highlight the biological aspects of HA addressing the mechanisms controlling the HA content in tissues and its role as drug delivery system.Graphical abstractUnlabelled Image
       
  • Hydrogel vehicles for sequential delivery of protein drugs to promote
           vascular regeneration
    • Abstract: Publication date: Available online 14 August 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Zhao Wei, Eugenia Volkova, Michael R. Blatchley, Sharon GerechtIn recent years, as the mechanisms of vasculogenesis and angiogenesis have been uncovered, the functions of various pro-angiogenic growth factors (GFs) and cytokines have been identified. Therefore, therapeutic angiogenesis, by delivery of GFs, has been sought as a treatment for many vascular diseases. However, direct injection of these protein drugs has proven to have limited clinical success due to their short half-lives and systemic off-target effects. To overcome this, hydrogel carriers have been developed to conjugate single or multiple GFs with controllable, sustained, and localized delivery. However, these attempts have failed to account for the temporal complexity of natural angiogenic pathways, resulting in limited therapeutic effects. Recently, the emerging ideas of optimal sequential delivery of multiple GFs have been suggested to better mimic the biological processes and to enhance therapeutic angiogenesis. Incorporating sequential release into drug delivery platforms will likely promote the formation of neovasculature and generate vast therapeutic potential.Graphical abstractUnlabelled Image
       
  • Brief update on endocytosis of nanomedicines
    • Abstract: Publication date: Available online 13 August 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Siddharth Patel, Jeonghwan Kim, Marco Herrera, Anindit Mukherjee, Alexander Kabanov, Gaurav SahayThe complexity of nanoscale interactions between biomaterials and cells has limited the realization of the ultimate vision of nanotechnology in diagnostics and therapeutics. As such, significant effort has been devoted to advancing our understanding of the biophysical interactions of the myriad nanoparticles. Endocytosis of nanomedicine has drawn tremendous interest in the last decade. Here, we highlight the ever-present barriers to efficient intracellular delivery of nanoparticles as well as the current advances and strategies deployed to breach these barriers. We also introduce new barriers that have been largely overlooked such as the glycocalyx and macromolecular crowding. Additionally, we draw attention to the potential complications arising from the disruption of the newly discovered functions of the lysosomes. Novel strategies of exploiting the inherent intracellular defects in disease states to enhance delivery and the use of exosomes for bioanalytics and drug delivery are explored. Furthermore, we discuss the advances in imaging techniques like electron microscopy, super resolution fluorescence microscopy, and single particle tracking which have been instrumental in our growing understanding of intracellular pathways and nanoparticle trafficking. Finally, we advocate for the push towards more intravital analysis of nanoparticle transport phenomena using the multitude of techniques available to us. Unraveling the underlying mechanisms governing the cellular barriers to delivery and biological interactions of nanoparticles will guide the innovations capable of breaching these barriers.Graphical abstractUnlabelled Image
       
  • Nanocarrier-based systems for targeted and site specific therapeutic
           delivery
    • Abstract: Publication date: Available online 7 August 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Joydeb Majumder, Oleh Taratula, Tamara MinkoSystemic drug delivery methods such as oral or parenteral administration of free drugs possess relatively low treatment efficiency and marked adverse side effects. The use of nanoparticles for drug delivery in most cases substantially enhances drug efficacy, improves pharmacokinetics and drug release and limits their side effects. However, further enhancement in drug efficacy and significant limitation of adverse side effects can be achieved by specific targeting of nanocarrier-based delivery systems especially in combination with local administration. The present review describes major advantages and limitations of organic and inorganic nanocarriers or living cell-based drug and nucleic acid delivery systems. Among these, different nanoparticles, supramolecular gels, therapeutic cells as living drug carriers etc. have emerged as a new frontier in modern medicine.Graphical abstractUnlabelled Image
       
  • RNA imaging by chemical probes
    • Abstract: Publication date: Available online 6 August 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Fumiaki Tomoike, Hiroshi AbeSequence-specific detection of intracellular RNA is one of the most important approaches to understand life phenomena. However, it is difficult to detect RNA in living cells because of its variety and scarcity. In the last three decades, several chemical probes have been developed for RNA detection in living cells. These probes are composed of DNA or artificial nucleic acid and hybridize with the target RNA in a sequence-specific manner. This hybridization triggers a change of fluorescence or a chemical reaction. In this review, we classify the probes according to the associated fluorogenic mechanism, that is, interaction between fluorophore and quencher, environmental change of fluorophore, and template reaction with/without ligation. In addition, we introduce examples of RNA imaging in living cells.Graphical abstractUnlabelled Image
       
  • Biologically Targeted Photo-Crosslinkable Nanopatch to Prevent
           Postsurgical Peritoneal Adhesion
    • Abstract: Publication date: Available online 19 July 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Yu Mi, Feifei Yang, Cameron Bloomquist, Youli Xia, Bo Sun, Yanfei Qi, Kyle Wagner, Stephanie Montgomery, Tian Zhang, Andrew Z. WangCancer immunotherapy is one of the fastest growing and most promising fields in clinical oncology. T-cell checkpoint inhibitors are revolutionizing the management of advanced cancers including non-small cell lung cancer and melanoma. Unfortunately, many common cancers are not responsive to these drugs and resistance remains problematic. A growing number of novel cancer immunotherapies have been discovered but their clinical translation has been limited by shortcomings of conventional drug delivery. Immune signaling is tightly-regulated and often requires simultaneous or near-simultaneous activation of multiple signals in specific subpopulations of immune cells. Nucleic acid therapies, which require intact intracellular delivery, are among the most promising approaches to modulate the tumor microenvironment to a pro-immunogenic phenotype. Advanced nanomedicines can be precisely engineered to overcome many of these limitations and appear well-poised to enable the clinical translation of promising cancer immunotherapies.Graphical abstractUnlabelled Image
       
  • A toll-like receptor 3 (TLR3) agonist ARNAX for therapeutic immunotherapy
    • Abstract: Publication date: Available online 11 July 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Tsukasa Seya, Yohei Takeda, Misako MatsumotoSummaryVaccine immunotherapy consisting of tumor antigens combined with an immune-enhancing adjuvant fosters cytotoxic T cell (CTL) proliferation. Clinically, polyI:C has been used as an adjuvant to enhance cancer vaccine protocols. However, according to its long history, polyI:C promotes inflammation that causes cytokine toxicity. Although checkpoint inhibitor immunotherapy has improved the prognoses of patients with progressive cancer, over 75% of patients continue to experience resistance to antibody (Ab) against anti-programmed cell death-protein 1 (PD-1) or its ligand, PD-L1 therapy. In most cases, patients suffer from adverse events resulting from inflammation during anti-PD-1/L1 Ab therapy, which is a serious obstacle to patients' quality of life. We have studied the functional properties of double-stranded (ds)RNA and polyI:C, and developed a nucleic acid adjuvant that barely induces a significant increase in the level of serum inflammatory cytokines in mouse models. This adjuvant, termed ARNAX, consists of DNA-capped dsRNA that specifies the endosomal target for Toll-like receptor 3 (TLR3) in dendritic cells (DCs). We expect that this adjuvant is safe for administration in elderly patients with cancer receiving immunotherapy. Here, we summarize the properties of ARNAX for immunotherapy in mice. We suggest that DC-priming is essential to induce anti-tumor immunity; neither exogenous inflammation nor the administration of tumor antigens is always a prerequisite for DC-mediated CTL proliferation. If our mouse data can be extrapolated to humans, ARNAX and the liberated endogenous tumor antigens may facilitate effect of current therapies on patients with therapy-resistant tumors.Graphical abstractUnlabelled Image
       
  • Fibrosis in tissue engineering and regenerative medicine: treat or
           trigger'
    • Abstract: Publication date: Available online 8 July 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Alicia Fernández-Colino, Laura Iop, Mónica S. Ventura Ferreira, Petra MelaFibrosis is a life-threatening pathological condition resulting from a dysfunctional tissue repair process. There is no efficient treatment and organ transplantation is in many cases the only therapeutic option.Here we review tissue engineering and regenerative medicine (TERM) approaches to address fibrosis in the cardiovascular system, the kidney, the lung and the liver. These strategies have great potential to achieve repair or replacement of diseased organs by cell- and material-based therapies. However, paradoxically, they might also trigger fibrosis. Cases of TERM interventions with adverse outcome are also included in this review. Furthermore, we emphasize the fact that, although organ engineering is still in its infancy, the advances in the field are leading to biomedically relevant in vitro models with tremendous potential for disease recapitulation and development of therapies. These human tissue models might have increased predictive power for human drug responses thereby reducing the need for animal testing.Graphical abstractUnlabelled Image
       
  • Subchronic and Chronic Toxicity Evaluation of Inorganic Nanoparticles for
           Delivery Applications
    • Abstract: Publication date: Available online 8 July 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Raziye Mohammadpour, Marina A. Dobrovolskaia, Darwin L. Cheney, Khaled F. Greish, Hamidreza GhandehariInorganic nanoparticles provide the opportunity to localize bioactive agents to the target sites and protect them from degradation. In many cases, acute toxicities of inorganic nanoparticles used for delivery applications have been investigated. However, little information is available regarding the long-term toxicity of such materials. This review focuses on the importance of subchronic and chronic toxicity assessment of inorganic nanoparticles investigated for delivery applications. We have attempted to provide a comprehensive review of the available literature for chronic toxicity assessment of inorganic nanoparticles. Where possible correlations are made between particle composition, physiochemical properties, duration, frequency and route of administration, as well as the sex of animals, with tissue and blood toxicity, immunotoxicity and genotoxicity. A critical gap analysis is provided and important factors that need to be considered for long-term toxicology of inorganic nanoparticles are discussed.Graphical abstractUnlabelled Image
       
  • Listening for the therapeutic window: Advances in drug delivery utilizing
           photoacoustic imaging
    • Abstract: Publication date: Available online 8 July 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Colman Moore, Fang Chen, Junxin Wang, Jesse V. JokerstThe preclinical landscape of photoacoustic imaging has experienced tremendous growth in the past decade. This non-invasive imaging modality augments the spatiotemporal capabilities of ultrasound with optical contrast. While it has principally been investigated for diagnostic applications, many recent reports have described theranostic delivery systems and drug monitoring strategies using photoacoustics. Here, we provide an overview of the of the progress to date while highlighting work in three specific areas: theranostic nanoparticles, real-time drug monitoring, and stem cell (“living drug”) tracking. Additionally, we discuss the challenges that remain to be addressed in this burgeoning field.Graphical abstractUnlabelled Image
       
  • Integrating nanomedicine into clinical radiotherapy regimens
    • Abstract: Publication date: Available online 4 July 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Allison N. DuRoss, Megan J. Neufeld, Shushan Rana, Charles R. Thomas, Conroy SunWhile the advancement of clinical radiotherapy was driven by technological innovations throughout the 20th century, continued improvement relies on rational combination therapies derived from biological insights. In this review, we highlight the importance of combination radiotherapy in the era of precision medicine. Specifically, we survey and summarize the areas of research where improved understanding in cancer biology will propel the field of radiotherapy forward by allowing integration of novel nanotechnology-based treatments.Graphical abstractUnlabelled Image
       
  • Intratumoral fate of functional nanoparticles in response to
           microenvironment factor: Implications on cancer diagnosis and therapy
    • Abstract: Publication date: Available online 2 July 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Jinrong Peng, Qian Yang, Kun Shi, Yao Xiao, Xiawei Wei, Zhiyong QianThe extraordinary growth and progression of tumor require enormous nutrient and energy. Unregulated behaviors of cancer cell progressing and persistently change of tumor microenvironment (TME) which acts as the soil for cancer growth and metastasis are the ubiquitous features. The tumor microenvironment exhibits some unique features which differ with the normal tissues. While the nanoparticles get through the blood vessel leakage, they encounter immediately and interact directly with these microenvironment factors. These factors may inhibit the diffusion of nanoparticles from penetrating through the tumor, or induce the dissociation of nanoparticles. Different nanoparticles encountered with different intratumoral microenvironment factors end up in different way. Therefore, in this review, we first briefly introduced the formations, distributions, features of some intratumoral microenvironment, and their effects on the tumor progression. They include extracellular matrix (ECM), matrix metalloproteinases (MMPs), acidic/hypoxia environment, redox environment, and tumor associated macrophages (TAMs). We then exemplified how these factors interact with nanoparticles and emphasized the potentials and challenges of nanoparticle-based strategies facing in enhancing intratumoral penetration and tumor microenvironment remodeling. We hope to give a simple understanding of the interaction between these microenvironment factors and the nanoparticles, thus, favors the designing and constructing of more ideal functional nanoparticles.Graphical abstractUnlabelled Image
       
  • Absorption, distribution, metabolism and excretion of the biomaterials
           used in Nanocarrier drug delivery systems
    • Abstract: Publication date: Available online 28 June 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Chong Su, Yingze Liu, Runzhi Li, Wei Wu, John Paul Fawcett, Jingkai GuNanocarriers (NCs) are a type of drug delivery system commonly used to regulate the pharmacokinetic and pharmacodynamic properties of drugs. Although a wide variety of NCs has been developed, relatively few have been registered for clinical trials and even fewer are clinically approved. Overt or potential toxicity, indistinct mechanisms of drug release and unsatisfactory pharmacokinetic behavior all contribute to their high failure rate during preclinical and clinical testing. These negative characteristics are not only due to the NCs themselves but also to the materials of the drug nanocarrier system (MDNS) that are released in vivo. In this article, we review the main analytical techniques used for bioassay of NCs and MDNS and their pharmacokinetics after administration by various routes. We anticipate our review will serve to improve the understanding of MDNS pharmacokinetics and facilitate the development of NC drug delivery systems.Graphical abstractUnlabelled Image
       
  • Careers in nanomedicine and drug delivery
    • Abstract: Publication date: Available online 28 June 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Elizabeth NanceNanomedicine continues to be a rapidly growing and increasingly interdisciplinary field. The career opportunities available in nanomedicine are also numerous, yet not always obvious to the early-career scientist determining their individual track for maximal impact. This perspective provides a brief overview of the field of nanomedicine, then delves into the many career trajectories one could take in this field. The article concludes with thoughts on how to provide diverse training to increase supply for the variety of career paths, and the role that mentors can play in young scientists' development and exploration of these career paths.Graphical abstractUnlabelled Image
       
  • Hybrid drug nanocrystals
    • Abstract: Publication date: Available online 26 June 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Yi Lu, Yongjiu Lv, Tonglei LiNanocrystals show promise to deliver poorly water-soluble drugs to yield systemic exposure. However, our knowledge regarding the in vivo fate of nanocrystals is in its infancy, as nanocrystallization is simply viewed as an approach to enhance the dissolution of drug crystals. The dying crystal phenomenon inspired the development of hybrid nanocrystals by physically embedding fluorophores into the crystal lattice. This approach achieved concurrent therapy and bioimaging and is well-established to study pharmacokinetics and nanocrystal dissolution in vivo. Nanocrystals also offer the advantage of long-term durability in the body for interacting with biological tissues and cells. This review introduces the hybrid nanocrystal technique, including the theoretical concepts, preparation, and applications. We also discuss the latest development in self-discriminative hybrid nanocrystals utilizing environment-responsive probes. This review will stimulate further development and application of nanocrystal-based drug delivery systems for theranostic strategies.Graphical abstractUnlabelled Image
       
  • Enabling biodegradable functional biomaterials for the management of
           neurological disorders
    • Abstract: Publication date: Available online 20 June 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Dingying Shan, Chuying Ma, Jian YangAn increasing number of patients are being diagnosed with neurological diseases, but are rarely cured because of the lack of curative therapeutic approaches. This situation creates an urgent clinical need to develop effective diagnosis and treatment strategies for repair and regeneration of injured or diseased neural tissues. In this regard, biodegradable functional biomaterials provide promising solutions to meet this demand owing to their unique responsiveness to external stimulation fields, which enable neuro-imaging, neuro-sensing, specific targeting, hyperthermia treatment, controlled drug delivery, and nerve regeneration. This review discusses recent progress in the research and development of biodegradable functional biomaterials including electroactive biomaterials, magnetic materials and photoactive biomaterials for the management of neurological disorders with emphasis on their applications in bioimaging (photoacoustic imaging, MRI and fluorescence imaging), biosensing (electrochemical sensing, magnetic sensing and opical sensing), and therapy strategies (drug delivery, hyperthermia treatment, and tissue engineering). It is expected that this review will provide an insightful discussion on the roles of biodegradable functional biomaterials in the diagnosis and treatment of neurological diseases, and lead to innovations for the design and development of the next generation biodegradable functional biomaterials.Graphical abstractUnlabelled Image
       
  • Local pharmacological induction of angiogenesis: Drugs for cells and cells
           as drugs
    • Abstract: Publication date: Available online 19 June 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Diana Gaspar, Rita Peixoto, Andrea De Pieri, Britta Striegl, Dimitrios I. Zeugolis, Michael RaghunathThe past decades have seen significant advances in pro-angiogenic strategies based on delivery of molecules and cells for conditions such as coronary artery disease, critical limb ischemia and stroke. Currently, three major strategies are evolving. Firstly, various pharmacological agents (growth factors, interleukins, small molecules, DNA/RNA) are locally applied at the ischemic region. Secondly, preparations of living cells with considerable bandwidth of tissue origin, differentiation state and preconditioning are delivered locally, rarely systemically. Thirdly, based on the notion, that cellular effects can be attributed mostly to factors secreted in situ, the cellular secretome (conditioned media, exosomes) has come into the spotlight. We review these three strategies to achieve (neo)angiogenesis in ischemic tissue with focus on the angiogenic mechanisms they tackle, such as transcription cascades, specific signalling steps and cellular gases. We also include cancer-therapy relevant lymphangiogenesis, and shall seek to explain why there are often conflicting data between in vitro and in vivo. The lion's share of data encompassing all three approaches comes from experimental animal work and we shall highlight common technical obstacles in the delivery of therapeutic molecules, cells, and secretome. This plethora of preclinical data contrasts with a dearth of clinical studies. A lack of adequate delivery vehicles and standardised assessment of clinical outcomes might play a role here, as well as regulatory, IP, and manufacturing constraints of candidate compounds; in addition, completed clinical trials have yet to reveal a successful and efficacious strategy. As the biology of angiogenesis is understood well enough for clinical purposes, it will be a matter of time to achieve success for well-stratified patients, and most probably with a combination of compounds.Graphical abstractUnlabelled Image
       
  • Nanomedicines - Tiny particles and big challenges
    • Abstract: Publication date: Available online 19 June 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Margareth R.C. Marques, Qiuyi Choo, Mukul Ashtikar, Thais Correa Rocha, Susanne Bremer-Hoffmann, Matthias G. WackerAfter decades of research, nanotechnology has been used in a broad array of biomedical products including medical devices, drug products, drug substances, and pharmaceutical-grade excipients. But like many great achievements in science, there is a fine balance between the risks and opportunities of this new technology. Some materials and surface structures in the nanosize range can exert unexpected toxicities and merit a more detailed safety assessment. Regulatory agencies such as the United States Food and Drug Administration or the European Medicines Agency have started dealing with the potential risks posed by nanomaterials. Considering that a thorough characterization is one of the key aspects of controlling such risks this review presents the regulatory background of nanosafety assessment and provides some practical advice on how to characterize nanomaterials and drug formulations. Further, the challenges of how to maintain and monitor pharmaceutical quality through a highly complex production processes will be discussed.Graphical abstractUnlabelled Image
       
  • 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 ZhengExtensive 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 KhademhosseiniPatient 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 RosalesThe 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
           strategies
    • Abstract: Publication date: Available online 31 May 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Svenja Hinderer, Katja Schenke-LaylandFibrotic 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 WuOne 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
           nanomedicine
    • 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 FeliuNanoparticles 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
       
  • 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 KimImmunotherapy 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
       
  • 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. SpillerMacrophages 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. FatemiThe 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
       
  • 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 DinarvandOver 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-SchnürchThiolated 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 WilhelmNanoparticle-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. LewisNanoparticle 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
       
  • Neuronanotechnology for brain regeneration
    • Abstract: Publication date: Available online 17 April 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Kevin Liaw, Zhi Zhang, Sujatha KannanIdentifying 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
       
  • Drug therapies and delivery mechanisms to treat perturbed skin wound
           healing
    • Abstract: Publication date: Available online 6 April 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Jiah Shin Chin, Leigh Madden, Sing Yian Chew, David L. BeckerAcute 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
       
  • 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 ChewNeural 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
       
  • 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. GraingerGiven 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. KannanAbstractNanotechnology 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 AgrahariNanocarriers (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 GrattoniThe 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. AndroulakisGlucocorticoids 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 SongThe 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 CouvreurAdenosine 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 MaoStructural 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 DingsNanomaterials 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. MummSeveral 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 SugiyamaRecent 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
       
  • 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 PanditTherapeutic 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 ShankarAbstractCathepsins 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 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 SlavcevThe 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
       
  • 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 MitragotriOver 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. ReisAbstractThe 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 AbstractUnlabelled Image
       
  • Zebrafish as a Preclinical In Vivo Screening Model for
           Nanomedicines
    • 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 HuwylerAbstractThe 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 AbstractUnlabelled Image
       
 
 
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