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Publisher: Elsevier   (Total: 3181 journals)

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Showing 1 - 200 of 3181 Journals sorted alphabetically
Academic Pediatrics     Hybrid Journal   (Followers: 39, SJR: 1.655, CiteScore: 2)
Academic Radiology     Hybrid Journal   (Followers: 26, SJR: 1.015, CiteScore: 2)
Accident Analysis & Prevention     Partially Free   (Followers: 105, SJR: 1.462, CiteScore: 3)
Accounting Forum     Hybrid Journal   (Followers: 28, SJR: 0.932, CiteScore: 2)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 42, SJR: 1.771, CiteScore: 3)
Achievements in the Life Sciences     Open Access   (Followers: 7)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 6)
Acta Astronautica     Hybrid Journal   (Followers: 442, SJR: 0.758, CiteScore: 2)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 29, 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: 5, SJR: 0.661, CiteScore: 2)
Acta Materialia     Hybrid Journal   (Followers: 319, 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: 2, SJR: 1.793, CiteScore: 6)
Acta Poética     Open Access   (Followers: 4, SJR: 0.101, CiteScore: 0)
Acta Psychologica     Hybrid Journal   (Followers: 26, 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: 187, 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: 30, 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: 12, SJR: 0.992, CiteScore: 1)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 12, 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: 34, 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: 11, 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: 44, SJR: 2.524, CiteScore: 4)
Advances in Engineering Software     Hybrid Journal   (Followers: 29, SJR: 1.159, CiteScore: 4)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 8)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 52, 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: 67, 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: 11, 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: 26)
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: 37, 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: 15, 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: 25)
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: 19)
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: 68)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6, SJR: 0.371, CiteScore: 1)
Advances in Radiation Oncology     Open Access   (Followers: 2, 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: 423, 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: 38, 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: 6, SJR: 2.262, CiteScore: 5)
Advances in Water Resources     Hybrid Journal   (Followers: 54, SJR: 1.551, CiteScore: 3)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 1.117, CiteScore: 3)
Aerospace Science and Technology     Hybrid Journal   (Followers: 384, 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: 482, 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: 44, SJR: 1.272, CiteScore: 3)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 4)
Agriculture and Natural Resources     Open Access   (Followers: 3)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 58, SJR: 1.747, CiteScore: 4)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.589, CiteScore: 3)
Air Medical J.     Hybrid Journal   (Followers: 8, 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: 12)
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: 11, 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: 66, SJR: 1.93, CiteScore: 3)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 47, SJR: 0.604, CiteScore: 1)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 13)
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: 265, 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: 67, SJR: 0.138, CiteScore: 0)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 25, 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: 210, 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: 227, SJR: 1.58, CiteScore: 3)
Animal Feed Science and Technology     Hybrid Journal   (Followers: 7, 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: 187  
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0169-409X
Published by Elsevier Homepage  [3181 journals]
  • Sequential drug delivery for liver diseases
    • Abstract: Publication date: Available online 15 November 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Xiaozhong Huang, Fan Lee, Yao Teng, Corey Bryen Lingam, Zijian Chen, Min Sun, Ziwei Song, Gowri M. Balachander, Hwa Liang Leo, Qiongyu Guo, Imran Shah, Hanry Yu The liver performs critical physiological functions such as metabolism/detoxification and blood homeostasis/biliary excretion. A high degree of blood access means that a drug’s resident time in any cell is relatively short. This short drug exposure to cells requires local sequential delivery of multiple drugs for optimal efficacy, potency, and safety. The high metabolism and excretion of drugs also impose both technical challenges and opportunities to sequential drug delivery. This review provides an overview of the sequential events in liver regeneration and the related liver diseases. Using selected examples of liver cancer, hepatitis B viral infection, fatty liver diseases, and drug-induced liver injury, we highlight efforts made for the sequential delivery of small and macromolecular drugs through different biomaterials, cells, and microdevice-based delivery platforms that allow fast delivery kinetics and rapid drug switching. As this is a nascent area of development, we extrapolate and compare the results with other sequential drug delivery studies to suggest possible application in liver diseases, wherever appropriate.Graphical abstractUnlabelled Image
  • Nanotechnology in regenerative ophthalmology
    • Abstract: Publication date: Available online 7 November 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Fitsum Feleke Sahle, Sangyoon Kim, Kumar Kulldeep Niloy, Faiza Tahia, Cameron V. Fili, Emily Cooper, David J. Hamilton, Tao L. Lowe In recent years, regenerative medicine is gaining momentum and is giving hopes for restoring function of diseased, damaged, and aged tissues and organs and nanotechnology is serving as a catalyst. In the ophthalmology field, various types of allogenic and autologous stem cells have been investigated to treat some ocular diseases due to age-related macular degeneration, glaucoma, retinitis pigmentosa, diabetic retinopathy, and corneal and lens traumas. Nanomaterials have been utilized directly as nanoscaffolds for these stem cells to promote their adhesion, proliferation and differentiation or indirectly as vectors for various genes, tissue growth factors, cytokines and immunosuppressants to facilitate cell reprogramming or ocular tissue regeneration. In this review, we reviewed various nanomaterials used for retina, cornea, and lens regenerations, and discussed the current status and future perspectives of nanotechnology in tracking cells in the eye and personalized regenerative ophthalmology. The purpose of this review is to provide comprehensive and timely insights on the emerging field of nanotechnology for ocular tissue engineering and regeneration.Graphical abstractUnlabelled Image
  • Topical treatments for skin cancer
    • Abstract: Publication date: Available online 6 November 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Jason K. Cullen, Jacinta L. Simmons, Peter G. Parsons, Glen M. Boyle Skin cancer is a broad term used to describe a number of different malignant indications of the skin. Skin cancers mostly comprise of the keratinocyte cancers [Basal Cell Carcinoma (BCC) and cutaneous Squamous Cell Carcinoma (SCC)], and melanoma. Surgical excision of these malignancies has been the preferred treatment of patients for decades. However, the decision to perform surgery can be affected by various considerations, including co-morbidities of the patient, the anatomical site of the lesion and potential intolerance for repeated excisions. Topical treatment of skin cancer may therefore be more appropriate in certain instances. Topical treatment potentially allows for higher drug levels at the tumor site, and may result in less overall toxicity than systemic agents. This review will specifically address the current agents used in topical treatment of skin cancers, and introduce emerging treatments from the natural product field that may also find utility in these indications.Graphical abstractUnlabelled Image
  • Fibrillin microfibrils and proteases, key integrators of fibrotic pathways
    • Abstract: Publication date: June 2019Source: Advanced Drug Delivery Reviews, Volume 146Author(s): Paola Zigrino, Gerhard Sengle Supramolecular networks composed of multi-domain ECM proteins represent intricate cellular microenvironments which are required to balance tissue homeostasis and direct remodeling. Structural deficiency in ECM proteins results in imbalances in ECM-cell communication resulting often times in fibrotic reactions. To understand how individual components of the ECM integrate communication with the cell surface by presenting growth factors or providing fine-tuned biomechanical properties is mandatory for gaining a better understanding of disease mechanisms in the quest for new therapeutic approaches. Here we provide an overview about what we can learn from inherited connective tissue disorders caused primarily by mutations in fibrillin-1 and binding partners as well as by altered ECM processing leading to defined structural changes and similar functional knock-in mouse models. We will utilize this knowledge to propose new molecular hypotheses which should be tested in future studies.Graphical abstractUnlabelled Image
  • Wound healing and fibrosis – State of play
    • Abstract: Publication date: June 2019Source: Advanced Drug Delivery Reviews, Volume 146Author(s): Stefanie Korntner, Dimitrios I. Zeugolis
  • Scarless wound healing: From development to senescence
    • Abstract: Publication date: June 2019Source: Advanced Drug Delivery Reviews, Volume 146Author(s): Harris Pratsinis, Eleni Mavrogonatou, Dimitris Kletsas An essential element of tissue homeostasis is the response to injuries, cutaneous wound healing being the most studied example. In the adults, wound healing aims at quickly restoring the barrier function of the skin, leading however to scar, a dysfunctional fibrotic tissue. On the other hand, in fetuses a scarless tissue regeneration takes place. During ageing, the wound healing capacity declines; however, in the absence of comorbidities a higher quality in tissue repair is observed. Senescent cells have been found to accumulate in chronic unhealed wounds, but more recent reports indicate that their transient presence may be beneficial for tissue repair. In this review data on skin wound healing and scarring are presented, covering the whole spectrum from early embryonic development to adulthood, and furthermore until ageing of the organism.Graphical abstractUnlabelled Image
  • Intervertebral disc regeneration: From cell therapy to the development of
           novel bioinspired endogenous repair strategies
    • Abstract: Publication date: June 2019Source: Advanced Drug Delivery Reviews, Volume 146Author(s): Johann Clouet, Marion Fusellier, Anne Camus, Catherine Le Visage, Jérôme Guicheux Low back pain (LBP), frequently associated with intervertebral disc (IVD) degeneration, is a major public health concern. LBP is currently managed by pharmacological treatments and, if unsuccessful, by invasive surgical procedures, which do not counteract the degenerative process.Considering that IVD cell depletion is critical in the degenerative process, the supplementation of IVD with reparative cells, associated or not with biomaterials, has been contemplated. Recently, the discovery of reparative stem/progenitor cells in the IVD has led to increased interest in the potential of endogenous repair strategies. Recruitment of these cells by specific signals might constitute an alternative strategy to cell transplantation. Here, we review the status of cell-based therapies for treating IVD degeneration and emphasize the current concept of endogenous repair as well as future perspectives. This review also highlights the challenges of the mobilization/differentiation of reparative progenitor cells through the delivery of biologics factors to stimulate IVD regeneration.Graphical abstractUnlabelled Image
  • Re-epithelialization of adult skin wounds: Cellular mechanisms and
           therapeutic strategies
    • Abstract: Publication date: June 2019Source: Advanced Drug Delivery Reviews, Volume 146Author(s): Patricia Rousselle, Fabienne Braye, Guila Dayan Cutaneous wound healing in adult mammals is a complex multi-step process involving overlapping stages of blood clot formation, inflammation, re-epithelialization, granulation tissue formation, neovascularization, and remodelling. Re-epithelialization describes the resurfacing of a wound with new epithelium. The cellular and molecular processes involved in the initiation, maintenance, and completion of epithelialization are essential for successful wound closure. A variety of modulators are involved, including growth factors, cytokines, matrix metalloproteinases, cellular receptors, and extracellular matrix components. Here, we focus on cellular mechanisms underlying keratinocyte migration and proliferation during epidermal closure. Inability to re-epithelialize is a clear indicator of chronic non-healing wounds, which fail to proceed through the normal phases of wound healing in an orderly and timely manner. This review summarizes the current knowledge regarding the management and treatment of acute and chronic wounds, with a focus on re-epithelialization, offering some insights into novel future therapies.Graphical Unlabelled Image
  • Articular fibrocartilage - Why does hyaline cartilage fail to repair'
    • Abstract: Publication date: June 2019Source: Advanced Drug Delivery Reviews, Volume 146Author(s): Angela R. Armiento, Mauro Alini, Martin J. Stoddart Once damaged, articular cartilage has a limited potential to repair. Clinically, a repair tissue is formed, yet, it is often mechanically inferior fibrocartilage. The use of monolayer expanded versus naïve cells may explain one of the biggest discrepancies in mesenchymal stromal/stem cell (MSC) based cartilage regeneration. Namely, studies utilizing monolayer expanded MSCs, as indicated by numerous in vitro studies, report as a main limitation the induction of type X collagen and hypertrophy, a phenotype associated with endochondral bone formation. However, marrow stimulation and transfer studies report a mechanically inferior collagen I/II fibrocartilage as the main outcome. Therefore, this review will highlight the collagen species produced during the different therapeutic approaches. New developments in scaffold design and delivery of therapeutic molecules will be described. Potential future directions towards clinical translation will be discussed. New delivery mechanisms are being developed and they offer new hope in targeted therapeutic delivery.Graphical abstractUnlabelled Image
  • Acellular and cellular approaches to improve diabetic wound healing
    • Abstract: Publication date: June 2019Source: Advanced Drug Delivery Reviews, Volume 146Author(s): Hongkwan Cho, Michael R. Blatchley, Elia J. Duh, Sharon Gerecht Chronic diabetic wounds represent a huge socioeconomic burden for both affected individuals and the entire healthcare system. Although the number of available treatment options as well as our understanding of wound healing mechanisms associated with diabetes has vastly improved over the past decades, there still remains a great need for additional therapeutic options. Tissue engineering and regenerative medicine approaches provide great advantages over conventional treatment options, which are mainly aimed at wound closure rather than addressing the underlying pathophysiology of diabetic wounds. Recent advances in biomaterials and stem cell research presented in this review provide novel ways to tackle different molecular and cellular culprits responsible for chronic and nonhealing wounds by delivering therapeutic agents in direct or indirect ways. Careful integration of different approaches presented in the current article could lead to the development of new therapeutic platforms that can address multiple pathophysiologic abnormalities and facilitate wound healing in patients with diabetes.Graphical abstractUnlabelled Image
  • Bioresponsive drug delivery systems in intestinal inflammation:
           State-of-the-art and future perspectives
    • Abstract: Publication date: June 2019Source: Advanced Drug Delivery Reviews, Volume 146Author(s): Niranjan G. Kotla, Shubhasmin Rana, Gandhi Sivaraman, Omprakash Sunnapu, Praveen K. Vemula, Abhay Pandit, Yury Rochev Oral colon-specific delivery systems emerged as the main therapeutic cargos by making a significant impact in the field of modern medicine for local drug delivery in intestinal inflammation. The site-specific delivery of therapeutics (aminosalicylates, glucocorticoids, biologics) to the ulcerative mucus tissue can provide prominent advantages in mucosal healing (MH). Attaining gut mucosal healing and anti-fibrosis are main treatment outcomes in inflammatory bowel disease (IBD). The pharmaceutical strategies that are commonly used to achieve a colon-specific drug delivery system include time, pH-dependent polymer coating, prodrug, colonic microbiota-activated delivery systems and a combination of these approaches. Amongst the different approaches reported, the use of biodegradable polysaccharide coated systems holds great promise in delivering drugs to the ulcerative regions. The present review focuses on major physiological gastro-intestinal tract challenges involved in altering the pharmacokinetics of delivery systems, pathophysiology of MH and fibrosis, reported drug-polysaccharide cargos and focusing on conventional to advanced disease responsive delivery strategies, highlighting their limitations and future perspectives in intestinal inflammation therapy.Graphical abstractUnlabelled Image
  • Local delivery of adenosine receptor agonists to promote bone regeneration
           and defect healing
    • Abstract: Publication date: June 2019Source: Advanced Drug Delivery Reviews, Volume 146Author(s): Christopher D. Lopez, Jonathan M. Bekisz, Carmen Corciulo, Aranzazu Mediero, Paulo G. Coelho, Lukasz Witek, Roberto L. Flores, Bruce N. Cronstein Adenosine receptor activation has been investigated as a potential therapeutic approach to heal bone. Bone has enhanced regenerative potential when influenced by either direct or indirect adenosine receptor agonism. As investigators continue to elucidate how adenosine influences bone cell homeostasis at the cellular and molecular levels, a small but growing body of literature has reported successful in vivo applications of adenosine delivery. This review summarizes the role adenosine receptor ligation plays in osteoblast and osteoclast biology and remodeling/regeneration. It also reports on all the modalities described in the literature at this point for delivery of adenosine through in vivo models for bone healing and regeneration.Graphical abstractUnlabelled Image
  • Advanced drug delivery systems and artificial skin grafts for skin wound
    • Abstract: Publication date: June 2019Source: Advanced Drug Delivery Reviews, Volume 146Author(s): Hye Sung Kim, Xiaoyan Sun, Jung-Hwan Lee, Hae-Won Kim, Xiaobing Fu, Kam W. Leong Cutaneous injuries, especially chronic wounds, burns, and skin wound infection, require painstakingly long-term treatment with an immense financial burden to healthcare systems worldwide. However, clinical management of chronic wounds remains unsatisfactory in many cases. Various strategies including growth factor and gene delivery as well as cell therapy have been used to enhance the healing of non-healing wounds. Drug delivery systems across the nano, micro, and macroscales can extend half-life, improve bioavailability, optimize pharmacokinetics, and decrease dosing frequency of drugs and genes. Replacement of the damaged skin tissue with substitutes comprising cell-laden scaffold can also restore the barrier and regulatory functions of skin at the wound site. This review covers comprehensively the advanced treatment strategies to improve the quality of wound healing.Graphical abstractUnlabelled Image
  • Engineered delivery strategies for enhanced control of growth factor
           activities in wound healing
    • Abstract: Publication date: June 2019Source: Advanced Drug Delivery Reviews, Volume 146Author(s): Yiming Niu, Qiu Li, Ya Ding, Lei Dong, Chunming Wang Growth factors (GFs) are versatile signalling molecules that orchestrate the dynamic, multi-stage process of wound healing. Delivery of exogenous GFs to the wound milieu to mediate healing in an active, physiologically-relevant manner has shown great promise in laboratories; however, the inherent instability of GFs, accompanied with numerous safety, efficacy and cost concerns, has hindered the clinical success of GF delivery. In this article, we highlight that the key to overcoming these challenges is to enhance the control of the activities of GFs throughout the delivering process. We summarise the recent strategies based on biomaterials matrices and molecular engineering, which aim to improve the conditions of GFs for delivery (at the ‘supply’ end of the delivery), increase the stability and functions of GFs in extracellular matrix (in transportation to target cells), as well as enhance the GFs/receptor interaction on the cell membrane (at the ‘destination’ end of the delivery). Many of these investigations have led to encouraging outcomes in various in vitro and in vivo regenerative models with considerable translational potential.Graphical abstractUnlabelled Image
  • Limiting angiogenesis to modulate scar formation
    • Abstract: Publication date: June 2019Source: Advanced Drug Delivery Reviews, Volume 146Author(s): Stefanie Korntner, Christine Lehner, Renate Gehwolf, Andrea Wagner, Moritz Grütz, Nadja Kunkel, Herbert Tempfer, Andreas Traweger Angiogenesis, the process of new blood vessel formation from existing blood vessels, is a key aspect of virtually every repair process. During wound healing an extensive, but immature and leaky vascular plexus forms which is subsequently reduced by regression of non-functional vessels. More recent studies indicate that uncontrolled vessel growth or impaired vessel regression as a consequence of an excessive inflammatory response can impair wound healing, resulting in scarring and dysfunction. However, in order to elucidate targetable factors to promote functional tissue regeneration we need to understand the molecular and cellular underpinnings of physiological angiogenesis, ranging from induction to resolution of blood vessels. Especially for avascular tissues (e.g. cornea, tendon, ligament, cartilage, etc.), limiting rather than boosting vessel growth during wound repair potentially is beneficial to restore full tissue function and may result in favourable long-term healing outcomes.Graphical abstractUnlabelled Image
  • Matrix-assisted cell transplantation for tissue vascularization
    • Abstract: Publication date: June 2019Source: Advanced Drug Delivery Reviews, Volume 146Author(s): Shane Browne, Kevin E. Healy Cell therapy offers much promise for the treatment of ischemic diseases by augmenting tissue vasculogenesis. Matrix-assisted cell transplantation (MACT) has been proposed as a solution to enhance cell survival and integration with host tissue following transplantation. By designing semi synthetic matrices (sECM) with the correct physical and biochemical signals, encapsulated cells are directed towards a more angiogenic phenotype. In this review, we describe the choice of cells suitable for pro-angiogenic therapies, the properties that should be considered when designing sECM for transplantation and their relative importance. Pre-clinical models where MACT has been successfully applied to promote angiogenesis are reviewed to show the great potential of this strategy to treat ischemic conditions.Graphical abstractUnlabelled Image
  • Therapeutic strategies for enhancing angiogenesis in wound healing
    • Abstract: Publication date: June 2019Source: Advanced Drug Delivery Reviews, Volume 146Author(s): Austin P. Veith, Kayla Henderson, Adrianne Spencer, Andrew D. Sligar, Aaron B. Baker The enhancement of wound healing has been a goal of medical practitioners for thousands of years. The development of chronic, non-healing wounds is a persistent medical problem that drives patient morbidity and increases healthcare costs. A key aspect of many non-healing wounds is the reduced presence of vessel growth through the process of angiogenesis. This review surveys the creation of new treatments for healing cutaneous wounds through therapeutic angiogenesis. In particular, we discuss the challenges and advancement that have been made in delivering biologic, pharmaceutical and cell-based therapies as enhancers of wound vascularity and healing.Graphical abstractUnlabelled Image
  • Muscle fibrosis in the soft palate: Delivery of cells, growth factors and
    • Abstract: Publication date: June 2019Source: Advanced Drug Delivery Reviews, Volume 146Author(s): Johannes W. Von den Hoff, Paola L. Carvajal Monroy, Edwin M. Ongkosuwito, Toin H. van Kuppevelt, Willeke F. Daamen The healing of skeletal muscle injuries after major trauma or surgical reconstruction is often complicated by the development of fibrosis leading to impaired function. Research in the field of muscle regeneration is mainly focused on the restoration of muscle mass while far less attention is paid to the prevention of fibrosis. In this review, we take as an example the reconstruction of the muscles in the soft palate of cleft palate patients. After surgical closure of the soft palate, muscle function during speech is often impaired by a shortage of muscle tissue as well as the development of fibrosis. We will give a short overview of the most common approaches to generate muscle mass and then focus on strategies to prevent fibrosis. These include anti-fibrotic strategies that have been developed for muscle and other organs by the delivery of small molecules, decorin and miRNAs. Anti-fibrotic compounds should be delivered in aligned constructs in order to obtain the organized architecture of muscle tissue. The available techniques for the preparation of aligned muscle constructs will be discussed. The combination of approaches to generate muscle mass with anti-fibrotic components in an aligned muscle construct may greatly improve the functional outcome of regenerative therapies for muscle injuries.Graphical abstractUnlabelled Image
  • Current and upcoming therapies to modulate skin scarring and fibrosis
    • Abstract: Publication date: June 2019Source: Advanced Drug Delivery Reviews, Volume 146Author(s): João Q. Coentro, Eugenia Pugliese, Geoffrey Hanley, Michael Raghunath, Dimitrios I. Zeugolis Skin is the largest organ of the human body. Being the interface between the body and the outer environment, makes it susceptible to physical injury. To maintain life, nature has endowed skin with a fast healing response that invariably ends in the formation of scar at the wounded dermal area. In many cases, skin remodelling may be impaired, leading to local hypertrophic scars or keloids. One should also consider that the scarring process is part of the wound healing response, which always starts with inflammation. Thus, scarring can also be induced in the dermis, in the absence of an actual wound, during chronic inflammatory processes. Considering the significant portion of the population that is subject to abnormal scarring, this review critically discusses the state-of-the-art and upcoming therapies in skin scarring and fibrosis.Graphical abstractUnlabelled Image
  • Use of plant viruses and virus-like particles for the creation of novel
    • Abstract: Publication date: May 2019Source: Advanced Drug Delivery Reviews, Volume 145Author(s): Ina Balke, Andris Zeltins In recent decades, the development of plant virology and genetic engineering techniques has resulted in the construction of plant virus-based vaccines for protection against different infectious agents, cancers and autoimmune diseases in both humans and animals. Interaction studies between plant viruses and mammalian organisms have suggested that plant viruses and virus-like particles (VLPs) are safe and noninfectious to humans and animals. Plant viruses with introduced antigens are powerful vaccine components due to their strongly organized, repetitive spatial structure; they can elicit strong immune responses similar to those observed with infectious mammalian viruses. The analysis of published data demonstrated that at least 73 experimental vaccines, including 61 prophylactic and 12 therapeutic vaccines, have been constructed using plant viruses as a carrier structure for presentation of different antigens. This information clearly demonstrates that noninfectious viruses are also applicable as vaccine carriers. Moreover, several plant viruses have been used for platform development, and corresponding vaccines are currently being tested in human and veterinary clinical trials. This review therefore discusses the main principles of plant VLP vaccine construction, emphasizing the physical, chemical, genetic and immunological aspects. Results of the latest studies suggest that several plant virus-based vaccines will join the list of approved human and animal vaccines in the near future.Graphical abstractUnlabelled Image
  • Plant virus-based materials for biomedical applications: Trends and
    • Abstract: Publication date: May 2019Source: Advanced Drug Delivery Reviews, Volume 145Author(s): Sabine Eiben, Claudia Koch, Klara Altintoprak, Alexander Southan, Günter Tovar, Sabine Laschat, Ingrid M. Weiss, Christina Wege Nanomaterials composed of plant viral components are finding their way into medical technology and health care, as they offer singular properties. Precisely shaped, tailored virus nanoparticles (VNPs) with multivalent protein surfaces are efficiently loaded with functional compounds such as contrast agents and drugs, and serve as carrier templates and targeting vehicles displaying e.g. peptides and synthetic molecules. Multiple modifications enable uses including vaccination, biosensing, tissue engineering, intravital delivery and theranostics. Novel concepts exploit self-organization capacities of viral building blocks into hierarchical 2D and 3D structures, and their conversion into biocompatible, biodegradable units. High yields of VNPs and proteins can be harvested from plants after a few days so that various products have reached or are close to commercialization. The article delineates potentials and limitations of biomedical plant VNP uses, integrating perspectives of chemistry, biomaterials sciences, molecular plant virology and process engineering.Graphical abstractUnlabelled Image
  • Bacteriophage-based biomaterials for tissue regeneration
    • Abstract: Publication date: May 2019Source: Advanced Drug Delivery Reviews, Volume 145Author(s): Binrui Cao, Yan Li, Tao Yang, Qing Bao, Mingying Yang, Chuanbin Mao Bacteriophage, also called phage, is a human-safe bacteria-specific virus. It is a monodisperse biological nanostructure made of proteins (forming the outside surface) and nucleic acids (encased in the protein capsid). Among different types of phages, filamentous phages have received great attention in tissue regeneration research due to their unique nanofiber-like morphology. They can be produced in an error-free format, self-assemble into ordered scaffolds, display multiple signaling peptides site-specifically, and serve as a platform for identifying novel signaling or homing peptides. They can direct stem cell differentiation into specific cell types when they are organized into proper patterns or display suitable peptides. These unusual features have allowed scientists to employ them to regenerate a variety of tissues, including bone, nerves, cartilage, skin, and heart. This review will summarize the progress in the field of phage-based tissue regeneration and the future directions in this field.Graphical abstractUnlabelled Image
  • Bacteriophage T4 nanoparticles for vaccine delivery against infectious
    • Abstract: Publication date: May 2019Source: Advanced Drug Delivery Reviews, Volume 145Author(s): Pan Tao, Jingen Zhu, Marthandan Mahalingam, Himanshu Batra, Venigalla B. Rao Subunit vaccines containing one or more target antigens from pathogenic organisms represent safer alternatives to whole pathogen vaccines. However, the antigens by themselves are not sufficiently immunogenic and require additives known as adjuvants to enhance immunogenicity and protective efficacy. Assembly of the antigens into virus-like nanoparticles (VLPs) is a better approach as it allows presentation of the epitopes in a more native context. The repetitive, symmetrical, and high density display of antigens on the VLPs mimic pathogen-associated molecular patterns seen on bacteria and viruses. The antigens, thus, might be better presented to stimulate host's innate as well as adaptive immune systems thereby eliciting both humoral and cellular immune responses. Bacteriophages such as phage T4 provide excellent platforms to generate the nanoparticle vaccines. The T4 capsid containing two non-essential outer proteins Soc and Hoc allow high density array of antigen epitopes in the form of peptides, domains, full-length proteins, or even multi-subunit complexes. Co-delivery of DNAs, targeting molecules, and/or molecular adjuvants provides additional advantages. Recent studies demonstrate that the phage T4 VLPs are highly immunogenic, do not need an adjuvant, and provide complete protection against bacterial and viral pathogens. Thus, phage T4 could potentially be developed as a “universal” VLP platform to design future multivalent vaccines against complex and emerging pathogens.Graphical abstractUnlabelled Image
  • Phage-based vaccines
    • Abstract: Publication date: May 2019Source: Advanced Drug Delivery Reviews, Volume 145Author(s): Qing Bao, Xiang Li, Gaorong Han, Ye Zhu, Chuanbin Mao, Mingying Yang Bacteriophages, or more colloquially as phages, are viruses that possess the ability to infect and replicate with bacterial cells. They are assembled from two major types of biomolecules, the nucleic acids and the proteins, with the latter forming a capsid and the former being encapsulated. In the eukaryotic hosts, phages are inert particulate antigens and cannot trigger pathogenesis. In recent years, many studies have been explored about using phages as nanomedicine platforms for developing vaccines due to their unique biological characteristics. The whole phage particles can be used for vaccine design in the form of phage-displayed vaccines or phage DNA vaccines. Phage-displayed vaccines are the phages with peptide or protein antigens genetically displayed on their surfaces as well as those with antigens chemically conjugated or biologically bound on their surfaces. The phages can then deliver the immunogenic peptides or proteins to the target cells or tissues. Phage DNA vaccines are the eukaryotic promoter-driven vaccine genes inserted in the phage genomes, which are carried by phages to the target cells to generate antigens. The antigens, either as the immunogenic peptides or proteins displayed on the phages, or as the products expressed from the vaccine genes, can serve as vaccines to elicit immune responses for disease prevention and treatment. Both phage-displayed vaccines and phage DNA vaccines promise a brilliant future for developing vaccines. This review presents the recent advancements in the field of phage-based vaccines and their applications in both the prevention and treatment of various diseases. It also discusses the challenges and perspectives in moving this field forwards.Graphical abstractUnlabelled Image
  • Use of phage therapy to treat long-standing, persistent, or chronic
           bacterial infections
    • Abstract: Publication date: May 2019Source: Advanced Drug Delivery Reviews, Volume 145Author(s): Stephen T. Abedon Viruses of bacteria – known as bacteriophages or phages – have been used clinically as antibacterial agents for nearly 100 years. Often this phage therapy is of long-standing, persistent, or chronic bacterial infections, and this can be particularly so given prior but insufficiently effective infection treatment using standard antibiotics. Such infections, in turn, often have a biofilm component. Phages in modern medicine thus are envisaged to serve especially as anti-biofilm/anti-persistent infection agents. Here I review the English-language literature concerning in vivo experimental and clinical phage treatment of longer-lived bacterial infections. Overall, published data appears to be supportive of a relatively high potential for phages to cure infections which are long standing and which otherwise have resisted treatment with antibieiotics.Graphical abstractUnlabelled Image
  • Bacteriophage interactions with mammalian tissue: Therapeutic applications
    • Abstract: Publication date: May 2019Source: Advanced Drug Delivery Reviews, Volume 145Author(s): Haein Huh, Shirley Wong, Jesse St. Jean, Roderick Slavcev The human body is a large reservoir for bacterial viruses known as bacteriophages (phages), which participate in dynamic interactions with their bacterial and human hosts that ultimately affect human health. The current growing interest in human resident phages is paralleled by new uses of phages, including the design of engineered phages for therapeutic applications. Despite the increasing number of clinical trials being conducted, the understanding of the interaction of phages and mammalian cells and tissues is still largely unknown. The presence of phages in compartments within the body previously considered purely sterile, suggests that phages possess a unique capability of bypassing anatomical and physiological barriers characterized by varying degrees of selectivity and permeability. This review will discuss the direct evidence of the accumulation of bacteriophages in various tissues, focusing on the unique capability of phages to traverse relatively impermeable barriers in mammals and its relevance to its current applications in therapy.Graphical abstractUnlabelled Image
  • Biomaterials based on phages and other viruses
    • Abstract: Publication date: May 2019Source: Advanced Drug Delivery Reviews, Volume 145Author(s): Mingying Yang, Chuanbin Mao
  • Nanoformulation properties, characterization, and behavior in complex
           biological matrices: Challenges and opportunities for brain-targeted drug
           delivery applications and enhanced translational potential
    • Abstract: Publication date: Available online 22 February 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Vibhuti Agrahari, Pierre-Alain Burnouf, Thierry Burnouf, Vivek Agrahari Nanocarriers (synthetic/cell-based have attracted enormous interest for various therapeutic indications, including neurodegenerative disorders. A broader understanding of the impact of nanomedicines design is now required to enhance their translational potential. Nanoformulations in vivo journey is significantly affected by their physicochemical properties including the size, shape, hydrophobicity, elasticity, and surface charge/chemistry/morphology, which play a role as an interface with the biological environment. Understanding protein corona formation is crucial in characterizing nanocarriers and evaluating their interactions with biological systems. In this review, the 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
  • Adenosine and lipids: A forced marriage or a love match'
    • Abstract: Publication date: Available online 21 February 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Marie Rouquette, Sinda Lepetre-Mouelhi, Patrick Couvreur Adenosine is a fascinating compound, crucial in many biochemical processes: this ubiquitous nucleoside serves as an essential building block of RNA, is also a component of ATP and regulates numerous pathophysiological mechanisms via binding to four extracellular receptors. Due to its hydrophilic nature, it belongs to a different world than lipids, and has no affinity for them. Since the 1970's, however, new discoveries have emerged and prompted the scientific community to associate adenosine with the lipid family, especially via liposomal preparations and bioconjugation. This seems to be an arranged marriage, but could it turn into a true love match? This review considered all types of unions established between adenosine and lipids. Even though exciting supramolecular structures were observed with adenosine-lipid conjugates, as well as with liposomal preparations which resulted in promising pre-clinical results, the translation of these technologies to the clinic is still limited.Graphical abstractUnlabelled Image
  • Silk fibroin for skin injury repair: Where do things stand'
    • Abstract: Publication date: Available online 31 October 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Mazaher Gholipourmalekabadi, Sunaina Sapru, Ali Samadikuchaksaraei, Rui L. Reis, David L. Kaplan, Subhas C. Kundu Several synthetic and natural materials are used in soft tissue engineering and regenerative medicine with varying degrees of success. Among them, silkworm silk protein fibroin, a naturally occurring protein-based biomaterial, exhibits many promising characteristics such as biocompatibility, controllable biodegradability, tunable mechanical properties, aqueous preparation, minimal inflammation in host tissue, low cost and ease of use. Silk fibroin is often used alone or in combination with other materials in various formats and is also a promising delivery system for bioactive compounds as part of such repair scenarios. These properties make silk fibroin an excellent biomaterial for skin tissue engineering and repair applications. This review focuses on the promising characteristics and recent advances in the use of silk fibroin for skin wound healing and/or soft-tissue repair applications. The benefits and limitations of silk fibroin as a scaffolding biomaterial in this context are also discussed.Statement of significanceSilk protein fibroin is a natural biomaterial with important biological and mechanical properties for soft tissue engineering applications. Silk fibroin is obtained from silkworms and can be purified using alkali or enzyme based degumming (removal of glue protein sericin) procedures. Fibroin is used alone or in combination with other materials in different scaffold forms, such as nanofibrous mats, hydrogels, sponges or films tailored for specific applications. The investigations carried out using silk fibroin or its blends in skin tissue engineering have increased dramatically in recent years due to the advantages of this unique biomaterial. This review focuses on the promising characteristics of silk fibroin for skin wound healing and/or soft-tissue repair applications.Graphical abstractSilkworm silk fibroin is a well-established natural protein in the realm of biomaterials with an array of matrices in its repository. These range from primary bio coating to state of the art, bioprinting en route for creating an advanced graft for diversified biomedical applications. Augmenting these matrices by incorporating functional traits like delivery of bioactive molecules/compounds (growth factor, drug, antibiotic, gene or cell) or conductivity make them smart matrices for skin tissue regeneration and skin repair.Unlabelled Image
  • Advanced nanotherapies to promote neuroregeneration in the injured newborn
    • Abstract: Publication date: Available online 31 October 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Olatz Arteaga Cabeza, Alkisti Mikrogeorgiou, Sujatha Kannan, Donna M. Ferriero Neonatal brain injury affects thousands of babies each year and may lead to long-term and permanent physical and neurological problems. Currently, therapeutic hypothermia is standard clinical care for term newborns with moderate to severe neonatal encephalopathy. Nevertheless, it is not completely protective, and additional strategies to restore and promote regeneration are urgently needed. One way to ensure recovery following injury to the immature brain is to augment endogenous regenerative pathways. However, novel strategies such as stem cell therapy, gene therapies and nanotechnology have not been adequately explored in this unique age group. In this perspective review, we describe current efforts that promote neuroprotection and potential targets that are unique to the developing brain, which can be leveraged to facilitate neuroregeneration.Graphical abstractUnlabelled Image
  • Intradermal and transdermal drug delivery using microneedles –
    • Abstract: Publication date: Available online 18 October 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Akmal H. Sabri, Yujin Kim, Maria Marlow, David J. Scurr, Joel Segal, Ajay K. Banga, Leonid Kagan, Jong Bong Lee The progress in microneedle research is evidenced by the transition from simple ‘poke and patch’ solid microneedles fabricated from silicon and stainless steel to the development of bioresponsive systems such as hydrogel-forming and dissolving microneedles. In this review, we provide an outline on various microneedle fabrication techniques which are currently employed. As a range of factors, including materials, geometry and design of the microneedles, affect the performance, it is important to understand the relationships between them and the resulting delivery of therapeutics. Accordingly, there is a need for appropriate methodologies and techniques for characterization and evaluation of microneedle performance, which will also be discussed. As the research expands, it has been observed that therapeutics delivered via microneedles has gained expedited access to the lymphatics, which makes them a favorable delivery method for targeting the lymphatic system. Such opportunity is valuable in the area of vaccination and treatment of lymphatic disorders, which is the final focus of the review.Graphical abstractUnlabelled Image
  • Fundamentals of fractional laser-assisted drug delivery: An in-depth guide
           to experimental methodology and data interpretation
    • Abstract: Publication date: Available online 16 October 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Emily Wenande, R. Rox Anderson, Merete Haedersdal In the decade since their advent, ablative fractional lasers have emerged as powerful tools to enhance drug delivery to and through the skin. Effective and highly customizable, laser-assisted drug delivery (LADD) has led to improved therapeutic outcomes for several medical indications. However, for LADD to reach maturity as a standard treatment technique, a greater appreciation of its underlying science is needed. This work aims to provide an in-depth guide to the technology's fundamental principles, experimental methodology and unique aspects of LADD data interpretation. We show that drug's physicochemical properties including solubility, molecular weight and tissue binding behavior, are crucial determinants of how laser channel morphology influences topical delivery. Furthermore, we identify strengths and limitations of experimental models and drug detection techniques, interrogating the usefulness of in vitro data in predicting LADD in vivo. By compiling insights from over 75 studies, we ultimately devise an approach for intelligent application of LADD, supporting its implementation in the clinical setting.Graphical abstractUnlabelled Image
  • Physical and chemical profiles of nanoparticles for lymphatic targeting
    • Abstract: Publication date: Available online 15 October 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Xiyu Ke, Gregory P. Howard, Haoyu Tang, Bei Cheng, May Tun Saung, José L. Santos, Hai-Quan Mao Nanoparticles (NPs) have been gaining prominence as delivery vehicles for modulating immune responses to improve treatments against cancer and autoimmune diseases, enhancing tissue regeneration capacity, and potentiating vaccination efficacy. Various engineering approaches have been extensively explored to control the NP physical and chemical properties including particle size, shape, surface charge, hydrophobicity, rigidity and surface targeting ligands to modulate immune responses. This review examines a specific set of physical and chemical characteristics of NPs that enable efficient delivery targeted to secondary lymphoid tissues, specifically the lymph nodes and immune cells. A critical analysis of the structure-property-function relationship will facilitate further efforts to engineer new NPs with unique functionalities, identify novel utilities, and improve the clinical translation of NP formulations for immunotherapy.Graphical abstractUnlabelled Image
  • Nanostructured DNA for the delivery of therapeutic agents
    • Abstract: Publication date: Available online 12 October 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Makiya Nishikawa, Mengmeng Tan, Wenqing Liao, Kosuke Kusamori DNA and RNA, the nucleic acids found in every living organism, are quite crucial, because not only do they store the genetic information, but also they are used as signals through interaction with various molecules within the body. The nature of nucleic acids, especially DNA, to form double-helix makes it possible to design nucleic acid-based nanostructures with various shapes. Because the shapes as well as the physicochemical properties determine their interaction with proteins or cells, nanostructured DNAs will have different features in the interaction compared with single- or double-stranded DNA. Some of these unique features of nanostructured DNA make ways for efficient delivery of therapeutic agents to specific targets. In this review, we begin with the factors affecting the properties of nanostructured DNA, followed by summarizing the methods for the development of nanostructured DNA. Further, we discuss the characteristics of nanostructured DNA and their applications for the delivery of bioactive compounds.Graphical abstractUnlabelled Image
  • 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. Houston Many 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 Imanishi Epigenetic 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
  • Pharmacokinetics of nanotechnology-based formulations in pediatric
    • Abstract: Publication date: Available online 5 September 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Venkata Yellepeddi, Andrea Joseph, Elizabeth Nance The 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
  • 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 Visage Intervertebral 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 Vigetti The 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 Gerecht In 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
  • RNA imaging by chemical probes
    • Abstract: Publication date: Available online 6 August 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Fumiaki Tomoike, Hiroshi Abe Sequence-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
  • 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
    • Abstract: Publication date: Available online 8 July 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Alicia Fernández-Colino, Laura Iop, Mónica S. Ventura Ferreira, Petra Mela Fibrosis 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
  • 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 Yang An 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 Raghunath The 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. Wacker After 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
  • Cardiac fibrosis – A short review of causes and therapeutic
    • Abstract: Publication date: Available online 31 May 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Svenja Hinderer, Katja Schenke-Layland Fibrotic diseases cause annually more than 800,000 deaths worldwide, whereof the majority accounts for lung and cardiac fibrosis. A pathological remodeling of the extracellular matrix either due to ageing or as a result of an injury or disease leads to fibrotic scars. In the heart, these scars cause several cardiac dysfunctions either by reducing the ejection fraction due to a stiffened myocardial matrix, or by impairing electric conductance, or they can even lead to death. Today it is known that there are several different types of cardiac scars depending on the underlying cause of fibrosis. In this review, we will present an overview of what is known about cardiac fibrosis including the role of cardiac cells and extracellular matrix in this disease. We will further summarize current diagnostic tools and highlight clinical or pre-clinical therapeutic strategies to address cardiac fibrosis.Graphical abstractUnlabelled Image
  • Intrinsic cancer vaccination
    • Abstract: Publication date: Available online 24 May 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Yoosoo Yang, Gi-Hoon Nam, Gi Beom Kim, Yoon Kyoung Kim, In-San Kim Immunotherapy is revolutionizing the treatment of cancer, and the current immunotherapeutics have remarkably improved the outcomes for some cancer patients. However, we still need answers for patients with immunologically cold tumors that do not benefit from the current immunotherapy treatments. Here, we suggest a novel strategy that is based on using a very old and sophisticated system for cancer immunotherapy, namely “intrinsic cancer vaccination”, which seeks to awaken our own immune system to activate tumor-specific T cells. To do this, we must take advantage of the genetic instability of cancer cells and the expression of cancer cell neoantigens to trigger immunity against cancer cells. It will be necessary to not only enhance the phagocytosis of cancer cells by antigen presenting cells but also induce immunogenic cancer cell death and the subsequent immunogenic clearance, cross-priming and generation of tumor-specific T cells. This strategy will allow us to avoid using known tumor-specific antigens, ex vivo manipulation or adoptive cell therapy; rather, we will efficiently present cancer cell neoantigens to our immune system and propagate the cancer-immunity cycle. This strategy simply follows the natural cycle of cancer-immunity from its very first step, and therefore could be combined with any other treatment modality to yield enhanced efficacy.Graphical abstractUnlabelled Image
  • Sequential drug delivery to modulate macrophage behavior and enhance
           implant integration
    • Abstract: Publication date: Available online 16 May 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Erin M. O'Brien, Gregory E. Risser, Kara L. Spiller Macrophages are major upstream regulators of the inflammatory response to implanted biomaterials. Sequential functions of distinct macrophage phenotypes are essential to the normal tissue repair process, which ideally results in vascularization and integration of implants. Improper timing of M1 or M2 macrophage activation results in dysfunctional healing in the form of chronic inflammation or fibrous encapsulation of the implant. Thus, biphasic drug delivery systems that modulate macrophage behavior are an appealing approach to promoting implant integration. In this review, we describe the timing and roles of macrophage phenotypes in healing, then highlight current drug delivery systems designed to sequentially modulate macrophage behavior.Graphical abstractUnlabelled Image
  • Translational challenges in advancing regenerative therapy for treating
           neurological disorders using nanotechnology
    • Abstract: Publication date: Available online 14 May 2019Source: Advanced Drug Delivery ReviewsAuthor(s): C.L. Nemeth, A.S. Fine, A. Fatemi The focus of regenerative therapies is to replace or enrich diseased or injured cells and tissue in an attempt to replenish the local environment and function, while slowing or halting further degeneration. Targeting neurological diseases specifically is difficult, due to the complex nature of the central nervous system, including the difficulty of bypassing the brain's natural defense systems. While cell-based regenerative therapies show promise in select tissues, preclinical and clinical studies have been largely unable to transfer these successes to the brain. Advancements in nanotechnologies have provided new methods of central nervous system access, drug and cell delivery, as well as new systems of cell maintenance and support that may bridge the gap between regenerative therapies and the brain. In this review, we discuss current regenerative therapies for neurological diseases, nanotechnology as nanocarriers, and the technical, manufacturing, and regulatory challenges that arise from inception to formulation of nanoparticle-regenerative therapies.Graphical abstractUnlabelled Image
  • The significance of artificial intelligence in drug delivery system design
    • Abstract: Publication date: Available online 6 May 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Parichehr Hassanzadeh, Fatemeh Atyabi, Rassoul Dinarvand Over the last decade, increasing interest has been attracted towards the application of artificial intelligence (AI) technology for analyzing and interpreting the biological or genetic information, accelerated drug discovery, and identification of the selective small-molecule modulators or rare molecules and prediction of their behavior. Application of the automated workflows and databases for rapid analysis of the huge amounts of data and artificial neural networks (ANNs) for development of the novel hypotheses and treatment strategies, prediction of disease progression, and evaluation of the pharmacological profiles of drug candidates may significantly improve treatment outcomes. Target fishing (TF) by rapid prediction or identification of the biological targets might be of great help for linking targets to the novel compounds. AI and TF methods in association with human expertise may indeed revolutionize the current theranostic strategies, meanwhile, validation approaches are necessary to overcome the potential challenges and ensure higher accuracy. In this review, the significance of AI and TF in the development of drugs and delivery systems and the potential challenging issues have been highlighted.Graphical abstractUnlabelled Image
  • Thiolated polymers: Bioinspired polymers utilizing one of the most
           important bridging structures in nature
    • Abstract: Publication date: Available online 25 April 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Christina Leichner, Max Jelkmann, Andreas Bernkop-Schnürch Thiolated polymers designated “thiomers” are obtained by covalent attachment of thiol functionalities on the polymeric backbone of polymers. In 1998 these polymers were first described as mucoadhesive and in situ gelling compounds forming disulfide bonds with cysteine-rich substructures of mucus glycoproteins and crosslinking through inter- and intrachain disulfide bond formation. In the following, it was shown that thiomers are able to form disulfides with keratins and membrane-associated proteins exhibiting also cysteine-rich substructures. Furthermore, permeation enhancing, enzyme inhibiting and efflux pump inhibiting properties were demonstrated. Because of these capabilities thiomers are promising tools for drug delivery guaranteeing a strongly prolonged residence time as well as sustained release on mucosal membranes. Apart from that, thiomers are used as drugs per se. In particular, for treatment of dry eye syndrome various thiolated polymers are in development and a first product has already reached the market. Within this review an overview about the thiomer-technology and its potential for different applications is provided discussing especially the outcome of studies in non-rodent animal models and that of numerous clinical trials. Moreover, an overview on product developments is given.Graphical abstractThe great potential of thiolated polymers for life sciences might be described in the best way by the simple imagination of protein chemistry with and without cysteineUnlabelled Image
  • Cowpea mosaic virus nanoparticles for cancer imaging and therapy
    • Abstract: Publication date: Available online 17 April 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Perrin H. Beatty, John D. Lewis Nanoparticle platforms are particularly attractive for theranostic applications due to their capacity for multifunctionality and multivalency. Some of the most promising nano-scale scaffold systems have been co-opted from nature including plant viruses such as cowpea mosaic virus (CPMV). The use of plant viruses like CPMV as viral nanoparticles is advantageous for many reasons; they are non-infectious and nontoxic to humans and safe for use in intravital imaging and drug delivery. The CPMV capsid icosahedral shape allows for enhanced multifunctional group display and the ability to carry specific cargoes. The native tropism of CPMV for cell-surface displayed vimentin and the enhanced permeability and retention effect allow them to preferentially extravasate from tumor neovasculature and efficiently penetrate tumors. Furthermore, CPMVs can be engineered via several straightforward chemistries to display targeting and imaging moieties on external, addressable residues and they can be loaded internally with therapeutic drug cargoes. These qualities make them highly effective as biocompatible platforms for tumor targeting, intravital imaging and cancer therapy.Graphical abstractDepiction of CPMV as a theranostic tool for cancer cell imaging and therapy. Multifunctional CPMV nanoparticles (green circle) with externally-coupled fluorophore dye moieties (yellow spikes) carrying drug molecules as cargo (red star) home towards cancer cells over-expressing cell membrane-bound vimentin (+). The targeting and then retention of the functionalized nanoparticles to the tumor cells is theorized to be due to the efficiency of CPMV extravasation (purple arrows) into the stroma of the tumor by the EPR effect.Unlabelled Image
  • Neuronanotechnology for brain regeneration
    • Abstract: Publication date: Available online 17 April 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Kevin Liaw, Zhi Zhang, Sujatha Kannan Identifying and harnessing regenerative pathways while suppressing the growth-inhibiting processes of the biological response to injury is the central goal of stimulating neurogenesis after central nervous system (CNS) injury. However, due to the complexity of the mature CNS involving a plethora of cellular pathways and extracellular cues, as well as difficulties in accessibility without highly invasive procedures, clinical successes of regenerative medicine for CNS injuries have been extremely limited. Current interventions primarily focus on stabilization and mitigation of further neuronal death rather than direct stimulation of neurogenesis. In the past few decades, nanotechnology has offered substantial innovations to the field of regenerative medicine. Their nanoscale features allow for the fine tuning of biological interactions for enhancing drug delivery and stimulating cellular processes. This review gives an overview of nanotechnology applications in CNS regeneration organized according to cellular and extracellular targets and discuss future directions for the field.Graphical abstractUnlabelled Image
  • Drug therapies and delivery mechanisms to treat perturbed skin wound
    • Abstract: Publication date: Available online 6 April 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Jiah Shin Chin, Leigh Madden, Sing Yian Chew, David L. Becker Acute wound healing is an orderly process of four overlapping events: haemostasis, inflammation, proliferation and remodelling. A drug delivery system with a temporal control of release could promote each of these events sequentially. However, acute wound healing normally proceeds very well in healthy individuals and there is little need to promote it. In the elderly and diabetics however, healing is often slow and wounds can become chronic and we need to promote their healing. Targeting the events of acute wound healing would not be appropriate for a chronic wound, which have stalled in the proinflammatory phase. They also have many additional problems such as poor circulation, low oxygen, high levels of leukocytes, high reactive oxygen species, high levels of proteolytic enzymes, high levels of proinflammatory cytokines, bacterial infection and high pH. The future challenge will be to tackle each of these negative factors to create a wound environment conducive to healing.Graphical abstractUnlabelled Image
  • Scaffold-mediated sequential drug/gene delivery to promote nerve
           regeneration and remyelination following traumatic nerve injuries
    • Abstract: Publication date: Available online 22 March 2019Source: Advanced Drug Delivery ReviewsAuthor(s): William Ong, Coline Pinese, Sing Yian Chew Neural tissue regeneration following traumatic injuries is often subpar. As a result, the field of neural tissue engineering has evolved to find therapeutic interventions and has seen promising outcomes. However, robust nerve and myelin regeneration remain elusive. One possible reason may be the fact that tissue regeneration often follows a complex sequence of events in a temporally-controlled manner. Although several other fields of tissue engineering have begun to recognise the importance of delivering two or more biomolecules sequentially for more complete tissue regeneration, such serial delivery of biomolecules in neural tissue engineering remains limited. This review aims to highlight the need for sequential delivery to enhance nerve regeneration and remyelination after traumatic injuries in the central nervous system, using spinal cord injuries as an example. In addition, possible methods to attain temporally-controlled drug/gene delivery are also discussed for effective neural tissue regeneration.Graphical abstractUnlabelled Image
  • Lyophilized liposome-based parenteral drug development: Reviewing complex
           product design strategies and current regulatory environments
    • Abstract: Publication date: Available online 18 March 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Yuwei Wang, David W. Grainger Given the successful entry of several liposomal drug products into market, and some with decades of clinical efficacy, liposomal drug delivery systems have proven capabilities to overcome certain limitations of traditional drug delivery, especially for toxic and biologic drugs. This experience has helped promote new liposomal approaches to emerging drug classes and current therapeutic challenges. All approved liposomal dosage forms are parenteral formulations, a pathway demonstrating greatest safety and efficacy to date. Due to the intrinsic instability of aqueous liposomal dispersions, lyophilization is commonly applied as an important solution to improve liposomal drug stability, and facilitate transportation, storage and improve product shelf-life. While lyophilization is a mature pharmaceutical technology, liposome-specific lyophilization platforms must be developed using particular lyophilization experience and strategies. This review provides an overview of liposome formulation-specific lyophilization approaches for parenteral use, excipients used exclusively in liposomal parenteral products, lyophilized liposome formulation design and process development, long-term storage, and current regulatory guidance for liposome drug products. Readers should capture a comprehensive understanding of formulation and process variables and strategies for developing parenterally administered liposomal drugs.Graphical abstractUnlabelled Image
  • Leveraging the interplay of nanotechnology and neuroscience: Designing new
           avenues for treating central nervous system disorders
    • Abstract: Publication date: Available online 4 March 2019Source: Advanced Drug Delivery ReviewsAuthor(s): Elizabeth Smith, Joshua E. Porterfield, Rangaramanujam M. Kannan Nanotechnology has the potential to open many novel diagnostic and treatment avenues for disorders of the central nervous system (CNS). In this review, we discuss recent developments in the applications of nanotechnology in CNS therapies, diagnosis and biology. Novel approaches for the diagnosis and treatment of neuroinflammation, brain dysfunction, psychiatric conditions, brain cancer, and nerve injury provide insights into the potential of nanomedicine. We also highlight nanotechnology-enabled neuroscience techniques such as electrophysiology and intracellular sampling to improve our understanding of the brain and its components. With nanotechnology integrally involved in the advancement of basic neuroscience and the development of novel treatments, combined diagnostic and therapeutic applications have begun to emerge. Nanotheranostics for the brain, able to achieve single-cell resolution, will hasten the rate in which we can diagnose, monitor, and treat diseases. Taken together, the recent advances highlighted in this review demonstrate the prospect for significant improvements to clinical diagnosis and treatment of a vast array of neurological diseases. However, it is apparent that a strong dialogue between the nanoscience and neuroscience communities will be critical for the development of successful nanotherapeutics that move to the clinic, benefit patients, and address unmet needs in CNS disorders.
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