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Publisher: Elsevier   (Total: 3051 journals)

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Showing 1 - 200 of 3048 Journals sorted alphabetically
A Practical Logic of Cognitive Systems     Full-text available via subscription   (Followers: 7)
AASRI Procedia     Open Access   (Followers: 15)
Academic Pediatrics     Hybrid Journal   (Followers: 24, SJR: 1.402, h-index: 51)
Academic Radiology     Hybrid Journal   (Followers: 22, SJR: 1.008, h-index: 75)
Accident Analysis & Prevention     Partially Free   (Followers: 86, SJR: 1.109, h-index: 94)
Accounting Forum     Hybrid Journal   (Followers: 25, SJR: 0.612, h-index: 27)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 30, SJR: 2.515, h-index: 90)
Achievements in the Life Sciences     Open Access   (Followers: 4)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 5, SJR: 0.338, h-index: 19)
Acta Astronautica     Hybrid Journal   (Followers: 359, SJR: 0.726, h-index: 43)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 3)
Acta Biomaterialia     Hybrid Journal   (Followers: 25, SJR: 2.02, h-index: 104)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 1)
Acta de Investigación Psicológica     Open Access   (Followers: 2)
Acta Ecologica Sinica     Open Access   (Followers: 8, SJR: 0.172, h-index: 29)
Acta Haematologica Polonica     Free   (SJR: 0.123, h-index: 8)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.604, h-index: 38)
Acta Materialia     Hybrid Journal   (Followers: 226, SJR: 3.683, h-index: 202)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.615, h-index: 21)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.442, h-index: 21)
Acta Oecologica     Hybrid Journal   (Followers: 10, SJR: 0.915, h-index: 53)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription   (Followers: 1)
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 3, SJR: 0.311, h-index: 16)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 1)
Acta Poética     Open Access   (Followers: 4)
Acta Psychologica     Hybrid Journal   (Followers: 24, SJR: 1.365, h-index: 73)
Acta Sociológica     Open Access  
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.059, h-index: 77)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 4)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 3)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 4, SJR: 0.383, h-index: 19)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 2)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 5, SJR: 0.141, h-index: 3)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 4, SJR: 0.112, h-index: 2)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 4)
Acute Pain     Full-text available via subscription   (Followers: 13)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.967, h-index: 57)
Addictive Behaviors     Hybrid Journal   (Followers: 15, SJR: 1.514, h-index: 92)
Addictive Behaviors Reports     Open Access   (Followers: 6)
Additive Manufacturing     Hybrid Journal   (Followers: 7, SJR: 1.039, h-index: 5)
Additives for Polymers     Full-text available via subscription   (Followers: 21)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 132, SJR: 5.2, h-index: 222)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.265, h-index: 53)
Advanced Powder Technology     Hybrid Journal   (Followers: 17, SJR: 0.739, h-index: 33)
Advances in Accounting     Hybrid Journal   (Followers: 9, SJR: 0.299, h-index: 15)
Advances in Agronomy     Full-text available via subscription   (Followers: 15, SJR: 2.071, h-index: 82)
Advances in Anesthesia     Full-text available via subscription   (Followers: 26, SJR: 0.169, h-index: 4)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 3)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 6, SJR: 1.054, h-index: 35)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 11, SJR: 0.801, h-index: 26)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 22, SJR: 1.286, h-index: 49)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 16, SJR: 3.31, h-index: 42)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.277, h-index: 43)
Advances in Botanical Research     Full-text available via subscription   (Followers: 3, SJR: 0.619, h-index: 48)
Advances in Cancer Research     Full-text available via subscription   (Followers: 25, SJR: 2.215, h-index: 78)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9, SJR: 0.9, h-index: 30)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 2.139, h-index: 42)
Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 4)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 12)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 27, SJR: 0.183, h-index: 23)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.665, h-index: 29)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 9, SJR: 1.268, h-index: 45)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 29, SJR: 0.938, h-index: 33)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 18, SJR: 2.314, h-index: 130)
Advances in Computers     Full-text available via subscription   (Followers: 16, SJR: 0.223, h-index: 22)
Advances in Dermatology     Full-text available via subscription   (Followers: 12)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 11)
Advances in Digestive Medicine     Open Access   (Followers: 6)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 22)
Advances in Ecological Research     Full-text available via subscription   (Followers: 43, SJR: 3.25, h-index: 43)
Advances in Engineering Software     Hybrid Journal   (Followers: 25, SJR: 0.486, h-index: 10)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 7)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 42, SJR: 5.465, h-index: 64)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 3)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 8)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 50, SJR: 0.674, h-index: 38)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 16)
Advances in Genetics     Full-text available via subscription   (Followers: 15, SJR: 2.558, h-index: 54)
Advances in Genome Biology     Full-text available via subscription   (Followers: 11)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 2.325, h-index: 20)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 22, SJR: 0.906, h-index: 24)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 9, SJR: 0.497, h-index: 31)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 26)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 2, SJR: 0.396, h-index: 27)
Advances in Immunology     Full-text available via subscription   (Followers: 36, SJR: 4.152, h-index: 85)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 9, SJR: 1.132, h-index: 42)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 3, SJR: 1.274, h-index: 27)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 4)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.764, h-index: 15)
Advances in Lipobiology     Full-text available via subscription   (Followers: 2)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 9)
Advances in Marine Biology     Full-text available via subscription   (Followers: 16, SJR: 1.645, h-index: 45)
Advances in Mathematics     Full-text available via subscription   (Followers: 10, SJR: 3.261, h-index: 65)
Advances in Medical Sciences     Hybrid Journal   (Followers: 6, SJR: 0.489, h-index: 25)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4, SJR: 1.44, h-index: 51)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 22)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 10)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 8, SJR: 0.324, h-index: 8)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 4)
Advances in Oncobiology     Full-text available via subscription   (Followers: 3)
Advances in Organ Biology     Full-text available via subscription   (Followers: 2)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 15, SJR: 2.885, h-index: 45)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 7, SJR: 0.148, h-index: 11)
Advances in Parasitology     Full-text available via subscription   (Followers: 7, SJR: 2.37, h-index: 73)
Advances in Pediatrics     Full-text available via subscription   (Followers: 24, SJR: 0.4, h-index: 28)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 13)
Advances in Pharmacology     Full-text available via subscription   (Followers: 15, SJR: 1.718, h-index: 58)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.384, h-index: 26)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.248, h-index: 11)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 8)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 4)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 17)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20, SJR: 1.5, h-index: 62)
Advances in Psychology     Full-text available via subscription   (Followers: 62)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 5, SJR: 0.478, h-index: 32)
Advances in Radiation Oncology     Open Access  
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 2, SJR: 0.1, h-index: 2)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 5)
Advances in Space Research     Full-text available via subscription   (Followers: 363, SJR: 0.606, h-index: 65)
Advances in Structural Biology     Full-text available via subscription   (Followers: 8)
Advances in Surgery     Full-text available via subscription   (Followers: 7, SJR: 0.823, h-index: 27)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 30, SJR: 1.321, h-index: 56)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 16)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 1.878, h-index: 68)
Advances in Water Resources     Hybrid Journal   (Followers: 43, SJR: 2.408, h-index: 94)
Aeolian Research     Hybrid Journal   (Followers: 5, SJR: 0.973, h-index: 22)
Aerospace Science and Technology     Hybrid Journal   (Followers: 326, SJR: 0.816, h-index: 49)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.318, h-index: 36)
African J. of Emergency Medicine     Open Access   (Followers: 5, SJR: 0.344, h-index: 6)
Ageing Research Reviews     Hybrid Journal   (Followers: 8, SJR: 3.289, h-index: 78)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 412, SJR: 1.385, h-index: 72)
Agri Gene     Hybrid Journal  
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 16, SJR: 2.18, h-index: 116)
Agricultural Systems     Hybrid Journal   (Followers: 30, SJR: 1.275, h-index: 74)
Agricultural Water Management     Hybrid Journal   (Followers: 40, SJR: 1.546, h-index: 79)
Agriculture and Agricultural Science Procedia     Open Access  
Agriculture and Natural Resources     Open Access   (Followers: 1)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 54, SJR: 1.879, h-index: 120)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.434, h-index: 14)
Air Medical J.     Hybrid Journal   (Followers: 5, SJR: 0.234, h-index: 18)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.285, h-index: 3)
Alcohol     Hybrid Journal   (Followers: 11, SJR: 0.922, h-index: 66)
Alcoholism and Drug Addiction     Open Access   (Followers: 8)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.436, h-index: 12)
Alexandria J. of Medicine     Open Access   (Followers: 1)
Algal Research     Partially Free   (Followers: 8, SJR: 2.05, h-index: 20)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.46, h-index: 29)
Allergology Intl.     Open Access   (Followers: 4, SJR: 0.776, h-index: 35)
Alpha Omegan     Full-text available via subscription   (SJR: 0.121, h-index: 9)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 9, SJR: 0.158, h-index: 9)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 46, SJR: 4.289, h-index: 64)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 4)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 5)
American Heart J.     Hybrid Journal   (Followers: 49, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 47, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 40, SJR: 0.574, h-index: 65)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 9, SJR: 1.091, h-index: 45)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.653, h-index: 93)
American J. of Human Genetics     Hybrid Journal   (Followers: 32, SJR: 8.769, h-index: 256)
American J. of Infection Control     Hybrid Journal   (Followers: 26, SJR: 1.259, h-index: 81)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 32, SJR: 2.313, h-index: 172)
American J. of Medicine     Hybrid Journal   (Followers: 46, SJR: 2.023, h-index: 189)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 200, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 59, SJR: 2.803, h-index: 148)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 6)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.249, h-index: 88)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, h-index: 45)
American J. of Pathology     Hybrid Journal   (Followers: 26, SJR: 2.653, h-index: 228)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 24, SJR: 2.764, h-index: 154)
American J. of Surgery     Hybrid Journal   (Followers: 35, SJR: 1.286, h-index: 125)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.653, h-index: 70)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 5)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.066, h-index: 51)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 58, SJR: 0.124, h-index: 9)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 12)
Anales de Cirugia Vascular     Full-text available via subscription  
Anales de Pediatría     Full-text available via subscription   (Followers: 2, SJR: 0.209, h-index: 27)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription   (SJR: 0.104, h-index: 3)
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 4, SJR: 2.577, h-index: 7)
Analytica Chimica Acta     Hybrid Journal   (Followers: 37, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 166, SJR: 0.725, h-index: 154)
Analytical Chemistry Research     Open Access   (Followers: 8, SJR: 0.18, h-index: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 12)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 1)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 23, SJR: 0.421, h-index: 40)
Angiología     Full-text available via subscription   (SJR: 0.124, h-index: 9)
Angiologia e Cirurgia Vascular     Open Access  
Animal Behaviour     Hybrid Journal   (Followers: 169, SJR: 1.907, h-index: 126)

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Journal Cover Advanced Drug Delivery Reviews
  [SJR: 5.2]   [H-I: 222]   [132 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0169-409X
   Published by Elsevier Homepage  [3051 journals]
  • Substrate mediated enzyme prodrug therapy
    • Authors: Betina Fejerskov; Morten T. Jarlstad Olesen; Alexander N. Zelikin
      Pages: 24 - 34
      Abstract: Publication date: 1 September 2017
      Source:Advanced Drug Delivery Reviews, Volume 118
      Author(s): Betina Fejerskov, Morten T. Jarlstad Olesen, Alexander N. Zelikin
      Substrate mediated enzyme prodrug therapy (SMEPT) is a biomedical platform developed to perform a localized synthesis of drugs mediated by implantable biomaterials. This approach combines the benefits and at the same time offers to overcome the drawbacks for traditional pill-based drug administration and site-specific, implant mediated drug delivery. Specifically, SMEPT offers the flexibility of delivering multiple drugs – individually as monotherapy, in sequence, or as a combination therapy, all of which is also accomplished in a site-specific manner. This technology is also unique for site-specific synthesis of drugs with short half-life, such as nitric oxide. This review presents historical development of SMEPT from early reports to the most recent examples, and also outlines potential avenues for subsequent development of this platform.
      Graphical abstract image

      PubDate: 2017-11-16T12:01:25Z
      DOI: 10.1016/j.addr.2017.04.013
      Issue No: Vol. 118 (2017)
       
  • Prodrugs in medicinal chemistry and enzyme prodrug therapies
    • Authors: Raoul Walther; Jarkko Rautio; Alexander N. Zelikin
      Pages: 65 - 77
      Abstract: Publication date: 1 September 2017
      Source:Advanced Drug Delivery Reviews, Volume 118
      Author(s): Raoul Walther, Jarkko Rautio, Alexander N. Zelikin
      Prodrugs are cunning derivatives of therapeutic agents designed to improve the pharmacokinetics profile of the drug. Within a prodrug, pharmacological activity of the drug is masked and is recovered within the human body upon bioconversion of the prodrug, a process that is typically mediated by enzymes. This concept is highly successful and a significant fraction of marketed therapeutic formulations is based on prodrugs. An advanced subset of prodrugs can be engineered such as to achieve site-specific bioconversion of the prodrug – to comprise the highly advantageous “enzyme prodrug therapy”, EPT. Design of prodrugs for EPT is similar to the prodrugs in general medicinal use in that the pharmacological activity of the drug is masked, but differs significantly in that site-specific bioconversion is a prime consideration, and the enzymes typically used for EPT are non-mammalian and/or with low systemic abundance in the human body. This review focuses on the design of prodrugs for EPT in terms of the choice of an enzyme and the corresponding prodrug for bioconversion. We also discuss the recent success of “self immolative linkers” which significantly empower and diversify the prodrug design, and present methodologies for the design of prodrugs with extended blood residence time. The review aims to be of specific interest for medicinal chemists, biomedical engineers, and pharmaceutical scientists.
      Graphical abstract image

      PubDate: 2017-11-16T12:01:25Z
      DOI: 10.1016/j.addr.2017.06.013
      Issue No: Vol. 118 (2017)
       
  • Designing metal-contained enzyme mimics for prodrug activation
    • Authors: Baoji Du; Dan Li; Jin Wang; Erkang Wang
      Pages: 78 - 93
      Abstract: Publication date: 1 September 2017
      Source:Advanced Drug Delivery Reviews, Volume 118
      Author(s): Baoji Du, Dan Li, Jin Wang, Erkang Wang
      Enzyme-activated prodrug therapy (EAPT) is a widely-used and effective treatment method for cancer by converting prodrugs into drugs at the demanded time and space, whose key step is prodrug activation. Traditional prodrug activations are mostly dependent on natural enzymes, which are unstable, expensive and hard to be functionalized. The emerging enzyme mimics, especially the metal-contained enzyme mimics (MEMs), provide a potential chance for improving the traditional EAPT because of their high stability, low cost and easiness of preparation and functionalization. The existing MEMs can be classified into three categories: catalytic core-scaffold MEM (csMEM), nanoparticle MEM (npMEMs) and metal-organic framework (MOF) MEM (mofMEM). These MEMs can mimic diverse functions corresponding to natural enzymes, and some of which are potentially used in prodrug activation, such as DNase, RNase, carbonate esterase, etc. In this review, we briefly summarize the MEMs according to their structure and composition, and highlight the successful and potential applications for prodrug activation mediated by hydrolase-like and oxidoreductase-like MEMs.
      Graphical abstract image

      PubDate: 2017-11-16T12:01:25Z
      DOI: 10.1016/j.addr.2017.04.002
      Issue No: Vol. 118 (2017)
       
  • Lysosomal enzyme replacement therapies: Historical development, clinical
           outcomes, and future perspectives
    • Authors: Melani Solomon; Silvia Muro
      Pages: 109 - 134
      Abstract: Publication date: 1 September 2017
      Source:Advanced Drug Delivery Reviews, Volume 118
      Author(s): Melani Solomon, Silvia Muro
      Lysosomes and lysosomal enzymes play a central role in numerous cellular processes, including cellular nutrition, recycling, signaling, defense, and cell death. Genetic deficiencies of lysosomal components, most commonly enzymes, are known as “lysosomal storage disorders” or “lysosomal diseases” (LDs) and lead to lysosomal dysfunction. LDs broadly affect peripheral organs and the central nervous system (CNS), debilitating patients and frequently causing fatality. Among other approaches, enzyme replacement therapy (ERT) has advanced to the clinic and represents a beneficial strategy for 8 out of the 50–60 known LDs. However, despite its value, current ERT suffers from several shortcomings, including various side effects, development of “resistance”, and suboptimal delivery throughout the body, particularly to the CNS, lowering the therapeutic outcome and precluding the use of this strategy for a majority of LDs. This review offers an overview of the biomedical causes of LDs, their socio-medical relevance, treatment modalities and caveats, experimental alternatives, and future treatment perspectives.
      Graphical abstract image

      PubDate: 2017-11-16T12:01:25Z
      DOI: 10.1016/j.addr.2017.05.004
      Issue No: Vol. 118 (2017)
       
  • Preface: Engineering of pharmaceutical cocrystals, salts and polymorphs:
           Advances and Challenges
    • Authors: Dennis Douroumis; Ali Nokhodchi
      Pages: 1 - 2
      Abstract: Publication date: 1 August 2017
      Source:Advanced Drug Delivery Reviews, Volume 117
      Author(s): Dennis Douroumis, Ali Nokhodchi


      PubDate: 2017-11-09T00:59:41Z
      DOI: 10.1016/j.addr.2017.10.002
      Issue No: Vol. 117 (2017)
       
  • Injectable Network Biomaterials via Molecular or Colloidal Self-Assembly
    • Authors: Jugal Kishore Sahoo; Michael A. VandenBerg; Matthew J. Webber
      Abstract: Publication date: Available online 10 November 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Jugal Kishore Sahoo, Michael A. VandenBerg, Matthew J. Webber
      Self-assembly is a powerful tool to create functional materials. A specific application for which self-assembled materials are ideally suited is in creating injectable biomaterials. Contrasting with traditional biomaterials that are implanted through surgical means, injecting biomaterials through the skin offers numerous advantages, expanding the scope and impact for biomaterials in medicine. In particular, self-assembled biomaterials prepared from molecular or colloidal interactions have been frequently explored. The strategies to create these materials are varied, taking advantage of engineered oligopeptides, proteins, and nanoparticles as well as affinity-mediated crosslinking of synthetic precursors. Self-assembled materials typically facilitate injectability through two different mechanisms: i) in situ self-assembly, whereby materials would be administered in a monomeric or oligomeric form and self-assemble in response to some physiologic stimulus, or ii) self-assembled materials that, by virtue of their dynamic, non-covalent interactions, shear-thin and self-heal to facilitate flow within a syringe and subsequent reassembly of material form at the injection site. Indeed, many classes of materials are capable of being injected using a combination of these two mechanisms. Particular utility has been noted for self-assembled biomaterials in the context of tissue engineering, regenerative medicine, drug delivery, and immunoengineering. Given the controlled and multifunctional nature of many self-assembled materials demonstrated to date, we project a future where injectable self-assembled biomaterials afford improved practice in advancing healthcare.
      Graphical abstract image

      PubDate: 2017-11-16T12:01:25Z
      DOI: 10.1016/j.addr.2017.11.005
       
  • Chemical modification of drug molecules as strategy to reduce interactions
           with mucus
    • Authors: Francisca Araújo; Cláudia Martins; Cláudia Azevedo; Bruno Sarmento
      Abstract: Publication date: Available online 28 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Francisca Araújo, Cláudia Martins, Cláudia Azevedo, Bruno Sarmento
      Many drug molecules possess inadequate physical-chemical characteristics that prevent to surpass the viscous mucus layer present in the surface of mucosal tissues. Due to mucus protective role and its fast turnover, these drug molecules end up being removed from the body before being absorbed and, thus, before exerting any physiologic affect. Envisaging a better pharmacokinetics profile, chemical modifications, to render drug a more mucopenetrating character, have been introduced to drug molecules backbone towards more effective therapies. Mucus penetration increases when drug molecules are provided with net-neutral charge, when they are conjugated with mucolytic agents and through modifications that makes them resistant to enzymes present in mucus, with the overall increase of their hydrophilicity and the decrease of their molecular weight. All of these characteristics act as a whole and influence each other so they must be well thought when drug molecules are being designed for mucosal delivery.
      Graphical abstract image

      PubDate: 2017-11-16T12:01:25Z
      DOI: 10.1016/j.addr.2017.09.020
       
  • Transflammation: Innate immune signaling in nuclear reprogramming
    • Authors: Shu Meng; Palas Chanda; Rajarajan A. Thandavarayan; John P. Cooke
      Abstract: Publication date: Available online 13 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Shu Meng, Palas Chanda, Rajarajan A. Thandavarayan, John P. Cooke
      Induction of pluripotency in somatic cells by retroviral overexpression of four transcription factors has revolutionized the field of stem cell biology and regenerative medicine. The efficient induction of pluripotency requires the activation of innate immune signaling in a process termed “transflammation” (Lee et al., 2012). Specifically, the stimulation of pattern recognition receptors (PRRs) causes global alterations in the expression and activity of epigenetic modifiers to favor an open chromatin configuration. Activation of toll-like receptors (TLR) or RIG-1-like receptors (RLR) (Sayed et al. 2017) trigger signaling cascades that result in NFκB or IRF-3 mediated changes in epigenetic plasticity that facilitate reprogramming. Another form of nuclear reprogramming is so-called direct reprogramming or transdifferentiation of one somatic cell to another lineage. We have shown that transdifferentiation of human fibroblasts to endothelial cells also involves transflammation (Sayed et al., 2015). Recently, we also identified reactive oxygen species (ROS) (Zhou et al. 2016) and reactive nitrogen species (RNS) (Meng et al., 2016) as mediators of innate immune signaling in nuclear reprogramming. Innate immune signaling plays a key role in nuclear reprogramming by regulating DNA accessibility (Fig. 1). Here, we review recent progress of innate immunity signaling in nuclear reprogramming and epigenetic plasticity.
      Graphical abstract image

      PubDate: 2017-11-16T12:01:25Z
      DOI: 10.1016/j.addr.2017.09.010
       
  • Editorial board members
    • Abstract: Publication date: 1 September 2017
      Source:Advanced Drug Delivery Reviews, Volume 118


      PubDate: 2017-11-16T12:01:25Z
       
  • MEMS devices for drug delivery
    • Authors: Hyunjoo J. Lee; Nakwon Choi; Eui-Sung Yoon; Il-Joo Cho
      Abstract: Publication date: Available online 5 November 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Hyunjoo J. Lee, Nakwon Choi, Eui-Sung Yoon, Il-Joo Cho
      Novel drug delivery systems based on microtechnology have advanced tremendously, but yet face some technological and societal hurdles to fully achieve their potential. The novel drug delivery systems aim to deliver drugs in a spatiotemporal- and dosage-controlled manner with a goal to address the unmet medical needs from oral delivery and hypodermic injection. The unmet needs include effective delivery of new types of drug candidates that are otherwise insoluble and unstable, targeted delivery to areas protected by barriers (e.g. brain and posterior eye segment), localized delivery of potent drugs, and improved patient compliance. After scrutinizing the design considerations and challenges associated with delivery to areas that cannot be efficiently targeted through standard drug delivery (e.g. brain, posterior eye segment, and gastrointestinal tract), this review provides a summary of recent advances that addressed these challenges and summarizes yet unresolved problems in each target area. The opportunities for innovation in devising the novel drug delivery systems are still high; with integration of advanced microtechnology, advanced fabrication of biomaterials, and biotechnology, the novel drug delivery is poised to be a promising alternative to the oral administration and hypodermic injection for a large spectrum of drug candidates.
      Graphical abstract image

      PubDate: 2017-11-09T00:59:41Z
      DOI: 10.1016/j.addr.2017.11.003
       
  • The role of mucus as an invisible cloak to transepithelial drug delivery
           by nanoparticles
    • Authors: María García-Díaz; Ditlev Birch; Feng Wan; Hanne Mørck Nielsen
      Abstract: Publication date: Available online 5 November 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): María García-Díaz, Ditlev Birch, Feng Wan, Hanne Mørck Nielsen
      Mucosal administration of drugs and drug delivery systems has gained increasing interest. However, nanoparticles intended to protect and deliver drugs to epithelial surfaces require transport through the surface-lining mucus. Translation from bench to bedside is particularly challenging for mucosal administration since a variety of parameters will influence the specific barrier properties of the mucus including the luminal fluids, the microbiota, the mucus composition and clearance rate, and the condition of the underlying epithelia. Besides, after administration, nanoparticles interact with the mucosal components, forming a biomolecular corona that modulates their behavior and fate after mucosal administration. These interactions are greatly influenced by the nanoparticle properties and therefore different designs and surface-engineering strategies have been proposed. Overall, it is essential to evaluate these biomolecule-nanoparticle interactions by complementary techniques using complex and relevant mucus barrier matrices.
      Graphical abstract image

      PubDate: 2017-11-09T00:59:41Z
      DOI: 10.1016/j.addr.2017.11.002
       
  • Mucus models to evaluate the diffusion of drugs and particles
    • Authors: Jaclyn Y. Lock; Taylor Carlson; Rebecca L. Carrier
      Abstract: Publication date: Available online 5 November 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Jaclyn Y. Lock, Taylor Carlson, Rebecca L. Carrier
      Mucus is a complex hydrogel that acts as a natural barrier to drug delivery at different mucosal surfaces including the respiratory, gastrointestinal, and vaginal tracts. To elucidate the role mucus plays in drug delivery, different in vitro, in vivo, and ex vivo mucus models and techniques have been utilized. Drug and drug carrier diffusion can be studied using various techniques in either isolated mucus gels or mucus present on cell cultures and tissues. The species, age, and potential disease state of the animal from which mucus is derived can all impact mucus composition and structure, and therefore impact drug and drug carrier diffusion. This review provides an overview of the techniques used to characterize drug and drug carrier diffusion, and discusses the advantages and disadvantages of the different models available to highlight the information they can afford.
      Graphical abstract image

      PubDate: 2017-11-09T00:59:41Z
      DOI: 10.1016/j.addr.2017.11.001
       
  • Animal Models of Smoke Inhalation Injury and Related Acute and Chronic
           Lung Diseases
    • Authors: Katarzyna Reczyńska; Priyanka Tharkar; Sally Yunsun Kim; Yiwei Wang; Elzbieta Pamuła; Hak-Kim Chan; Wojciech Chrzanowski
      Abstract: Publication date: Available online 3 November 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Katarzyna Reczyńska, Priyanka Tharkar, Sally Yunsun Kim, Yiwei Wang, Elzbieta Pamuła, Hak-Kim Chan, Wojciech Chrzanowski
      Smoke inhalation injury leads to various acute and chronic lung diseases and thus is the dominant cause of fire-related fatalities. In a search for an effective treatment and validation of therapies different classes of animal models have been developed, which include both small and large animals. These models have advanced our understanding of the mechanism of smoke inhalation injury, enabling a better understanding of pathogenesis and pathophysiology and development of new therapies. However, none of the animal models fully mirrors human lungs and their pathologies. All animal models have their limitations in replicating complex clinical conditions associated with smoke inhalation injury in humans. Therefore, for a correct interpretation of the results and to avoid bias, a precise understanding of similarities and differences of lungs between different animal species and humans is critical. We have reviewed and presented comprehensive comparison of different animal models and their clinical relevance. We presented an overview of methods utilized to induce smoke inhalation injuries, airway micro−/ macrostructure, advantages and disadvantages of the most commonly used small and large animal models.
      Graphical abstract image

      PubDate: 2017-11-09T00:59:41Z
      DOI: 10.1016/j.addr.2017.10.005
       
  • A slippery slope: On the origin, role and physiology of mucus
    • Authors: Farhan Taherali; Felipe Varum; Abdul W. Basit
      Abstract: Publication date: Available online 3 November 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Farhan Taherali, Felipe Varum, Abdul W. Basit
      The mucosa of the gastrointestinal tract, eyes, nose, lungs, cervix and vagina is lined by epithelium interspersed with mucus-secreting goblet cells, all of which contribute to their unique functions. This mucus provides an integral defence to the epithelium against noxious agents and pathogens. However, it can equally act as a barrier to drugs and delivery systems targeting epithelial passive and active transport mechanisms. This review highlights the various mucins expressed at different mucosal surfaces on the human body, and their role in creating a mucoid architecture to protect epithelia with specialized functions. Various factors compromising the barrier properties of mucus have been discussed, with an emphasis on how disease states and microbiota can alter the physical properties of mucus. For instance, Akkermansia muciniphila, a bacterium found in higher levels in the gut of lean individuals induces the production of a thickened gut mucus layer. The aims of this article are to elucidate the different physiological, biochemical and physical properties of bodily mucus, a keen appreciation of which will help circumvent the slippery slope of challenges faced in achieving effective mucosal drug and gene delivery.
      Graphical abstract image

      PubDate: 2017-11-09T00:59:41Z
      DOI: 10.1016/j.addr.2017.10.014
       
  • Stem Cells, Niches and Scaffolds: Applications to Burns and Wound Care
    • Authors: Suzanne M. Watt; Jonathan M. Pleat
      Abstract: Publication date: Available online 26 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Suzanne M. Watt, Jonathan M. Pleat
      The importance of skin to survival, and the devastating physical and psychological consequences of scarring following reparative healing of extensive or difficult to heal human wounds, cannot be disputed. We discuss the significant challenges faced by patients and healthcare providers alike in treating these wounds. New state of the art technologies have provided remarkable insights into the role of skin stem and progenitor cells and their niches in maintaining skin homeostasis and in reparative wound healing. Based on this knowledge, we examine different approaches to repair extensive burn injury and chronic wounds, including full and split thickness skin grafts, temporising matrices and scaffolds and composite cultured skin products. Notable developments include next generation skin substitutes to replace split thickness skin autografts and next generation gene editing coupled with cell therapies to treat genodermatoses. Further refinements are predicted with the advent of bioprinting technologies, and newly defined biomaterials and autologous cell sources that can be engineered to more accurately replicate human skin architecture, function and cosmesis. These advances will undoubtedly improve quality of life for patients with extensive burns and difficult to heal wounds.
      Graphical abstract image

      PubDate: 2017-11-02T00:40:33Z
      DOI: 10.1016/j.addr.2017.10.012
       
  • The role of mucus on drug transport and its potential to affect
           therapeutic outcomes
    • Authors: Xabier Murgia; Brigitta Loretz; Olga Hartwig; Marius Hittinger; Claus-Michael Lehr
      Abstract: Publication date: Available online 26 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Xabier Murgia, Brigitta Loretz, Olga Hartwig, Marius Hittinger, Claus-Michael Lehr
      A layer of mucus covers the surface of all wet epithelia throughout the human body. Mucus is a hydrogel mainly composed of water, mucins (glycoproteins), DNA, proteins, lipids, and cell debris. This complex composition yields a tenacious viscoelastic hydrogel that lubricates and protects the exposed epithelia from external threats and enzymatic degradation. The natural protective role of mucus is nowadays acknowledged as a major barrier to be overcome in non-invasive drug delivery. The heterogeneity of mucus components offers a wide range of potential chemical interaction sites for macromolecules, while the mesh-like architecture given to mucus by the intermolecular cross-linking of mucin molecules results in a dense network that physically, and in a size-dependent manner, hinders the diffusion of nanoparticles through mucus. Consequently, drug diffusion, epithelial absorption, drug bioavailability, and ultimately therapeutic outcomes of mucosal drug delivery can be attenuated.
      Graphical abstract image

      PubDate: 2017-11-02T00:40:33Z
      DOI: 10.1016/j.addr.2017.10.009
       
  • Epigenetic reprogramming in liver fibrosis and cancer
    • Authors: Caroline L. Wilson; Derek A. Mann; Lee A. Borthwick
      Abstract: Publication date: Available online 25 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Caroline L. Wilson, Derek A. Mann, Lee A. Borthwick
      Novel insights into the epigenetic control of chronic liver diseases are now emerging. Recent advances in our understanding of the critical roles of DNA methylation, histone modifications and ncRNA may now be exploited to improve management of fibrosis/cirrhosis and cancer. Furthermore, improved technologies for the detection of epigenetic markers from patients' blood and tissues will vastly improve diagnosis, treatment options and prognostic tracking. The aim of this review is to present recent findings from the field of liver epigenetics and to explore their potential for translation into therapeutics to prevent disease promoting epigenome reprogramming and reverse epigenetic changes.
      Graphical abstract image

      PubDate: 2017-10-26T01:44:14Z
      DOI: 10.1016/j.addr.2017.10.011
       
  • Enzyme decorated drug carriers: Targeted swords to cleave and overcome the
           mucus barrier
    • Authors: Claudia Menzel; Andreas Bernkop-Schnürch
      Abstract: Publication date: Available online 24 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Claudia Menzel, Andreas Bernkop-Schnürch
      The use of mucus permeating drug carrier systems being able to overcome the mucus barrier can lead to a remarkable enhancement in bioavailability. One promising approach is the design of mucolytic enzyme decorated carrier systems (MECS). These systems include micro- and nanoparticles as well as self-emulsifying drug delivery systems (SEDDS) decorated with mucin cleaving enzymes such as papain (PAP) or bromelain (BRO). MECS are able to cross the mucus barrier in a comparatively efficient manner by cleaving mucus substructures in front of them on their way to the epithelium. Thereby these enzymes hydrolyze peptide bonds of mucus glycoproteins forming tiny holes or passages through the mucus. In various in vitro and in vivo studies MECS proved to be superior in their mucus permeating properties over nanocarriers without enzyme decoration. PAP decorated nanoparticles, for instance, remained 3h after oral administration to an even 2.5-fold higher extend in rat small intestine than the corresponding undecorated nanoparticles permeating the intestinal mucus gel layer to a much lower degree. As MECS break up the mucus network only locally without destroying its overall protective barrier function, even long term treatments with such systems seem feasible. Within this review article we address different drug carrier systems decorated with various types of enzymes, their particular pros and cons and potential applications.
      Graphical abstract image

      PubDate: 2017-10-26T01:44:14Z
      DOI: 10.1016/j.addr.2017.10.004
       
  • Restoration of skin pigmentation after deep partial or full-thickness burn
           injury
    • Authors: Niann-Tzyy Dai; Hsin-I Chang; Yi-Wen Wang; Keng-Yen Fu; Tai-Chun Huang; Nien-Chi Huang; Jhen-Kai Li; Pai-Shan Hsieh; Lien-Guo Dai; Chao-Kuei Hsu; Peter K. Maitz
      Abstract: Publication date: Available online 24 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Niann-Tzyy Dai, Hsin-I Chang, Yi-Wen Wang, Keng-Yen Fu, Tai-Chun Huang, Nien-Chi Huang, Jhen-Kai Li, Pai-Shan Hsieh, Lien-Guo Dai, Chao-Kuei Hsu, Peter K. Maitz
      Significant skin pigmentation changes occur when patients suffer deep burn injuries. These pigmentation disorders may cause not only cosmetic and psychological issues, but more importantly it increases the risk of skin cancer or photoaging. Severe burns significantly effect on the process of repigmentation as the pigmentation is tightly regulated by cell proliferation and differentiation of melanocytes and melanocyte stem cells which are housing in the epidermis and hair follicles of the skin. In the present review, we discuss the possible mechanisms to replenish the melanocytes from the healthy epidermis and hair follicles surrounding burn wounds. The molecular mechanisms of skin repigmentation following healing of burn injuries includes the differentiation of melanoblasts into melanocytes, the distribution and responses of melanocytes and melanocyte stem cells after burn injury, and the regulation of melanin production. We also reviewed advanced therapeutic strategies to treat pigmentation disorders, such as convectional surgery, laser, UV treatment and emerging concepts in skin tissue-engineering.
      Graphical abstract image

      PubDate: 2017-10-26T01:44:14Z
      DOI: 10.1016/j.addr.2017.10.010
       
  • Insights into the key roles of epigenetics in matrix
           macromolecules-associated wound healing
    • Authors: Zoi Piperigkou; Martin Götte; Achilleas D. Theocharis; Nikos K. Karamanos
      Abstract: Publication date: Available online 24 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Zoi Piperigkou, Martin Götte, Achilleas D. Theocharis, Nikos K. Karamanos
      Extracellular matrix (ECM) is a dynamic network of macromolecules, playing a regulatory role in cell functions, tissue regeneration and remodeling. Wound healing is a tissue repair process necessary for the maintenance of the functionality of tissues and organs. This highly orchestrated process is divided into four temporally overlapping phases, including hemostasis, inflammation, proliferation and tissue remodeling. The dynamic interplay between ECM and resident cells exerts its critical role in many aspects of wound healing, including cell proliferation, migration, differentiation, survival, matrix degradation and biosynthesis. Several epigenetic regulatory factors, such as the endogenous non-coding microRNAs (miRNAs), are the drivers of the wound healing response. microRNAs have pivotal roles in regulating ECM composition during wound healing and dermal regeneration.Their expression is associated with the distinct phases of wound healing, and they serve as target biomarkers and targets for systematic regulation of wound repair. In this article we critically present the importance of epigenetics with particular emphasis on miRNAs regulating ECM components (i.e. glycoproteins, proteoglycans and matrix proteases) that are key players in wound healing. The clinical relevance of miRNA targeting as well as the delivery strategies designed for clinical applications are also presented and discussed.

      PubDate: 2017-10-26T01:44:14Z
      DOI: 10.1016/j.addr.2017.10.008
       
  • Enzyme prodrug therapies and therapeutic enzymes
    • Authors: Brigitte Städler; Alexander N. Zelikin
      Abstract: Publication date: Available online 18 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Brigitte Städler, Alexander N. Zelikin


      PubDate: 2017-10-26T01:44:14Z
      DOI: 10.1016/j.addr.2017.10.006
       
  • Stem cells and heart disease - brake or accelerator'
    • Authors: Gustav Steinhoff; Julia Nesteruk; Markus Wolfien; Jana Große; Ulrike Ruch; Praveen Vasudevan; Paula Müller
      Abstract: Publication date: Available online 18 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Gustav Steinhoff, Julia Nesteruk, Markus Wolfien, Jana Große, Ulrike Ruch, Praveen Vasudevan, Paula Müller
      After two decades of intensive research and attempts of clinical translation, stem cell based therapies for cardiac diseases are not getting closer to clinical success. This review tries to unravel the obstacles and focuses on underlying mechanisms as the target for regenerative therapies. At present, the principal outcome in clinical therapy does not reflect experimental evidence. It seems that the scientific obstacle is a lack of integration of knowledge from tissue repair and disease mechanisms. Recent insights from clinical trials delineate mechanisms of stem cell dysfunction and gene defects in repair mechanisms as cause of atherosclerosis and heart disease. These findings require a redirection of current practice of stem cell therapy and a reset using more detailed analysis of stem cell function interfering with disease mechanisms. To accelerate scientific development the authors suggest intensifying unified computational data analysis and shared data knowledge by using open-access data platforms
      Graphical abstract image

      PubDate: 2017-10-26T01:44:14Z
      DOI: 10.1016/j.addr.2017.10.007
       
  • The application of mesenchymal stem cells to treat thermal and radiation
           burns
    • Authors: Kathleen Rodgers; Sachin S. Jadhav
      Abstract: Publication date: Available online 12 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Kathleen Rodgers, Sachin S. Jadhav
      Mesenchymal stem cells (MSCs) have been developed for a number of indications due to their regenerative and anti-inflammatory phenotypes and their utility is enhanced by the fact that allogeneic transplant is feasible with this cell type. Animal studies and early human cases indicate that this has the potential to be an exciting new therapy for treating chronic non-healing wounds such as diabetic ulcers, burns and cutaneous radiation burns. This review will focus on the use of MSCs to treat thermal and radiation burns. Large, severe burns are difficult to treat and pose a major public health burden worldwide. They are characterized by an extensive loss of the outer protective barrier, delayed wound healing, increased oxidative stress and a heightened inflammatory state. The breakdown of the protective barrier results in increased susceptibility to fluid loss and bacterial sepsis. In the case of radiation burns, chronic inflammation can result in subsequent waves of tissue injury leading to skin breakdown and necrosis. The aim of this review is to summarize the current knowledge on MSCs in treating thermal and radiation burns along with the specific scope of characterizing the biologic function of MSCs that help enhance wound healing in these chronic injuries.
      Graphical abstract image

      PubDate: 2017-10-18T00:26:56Z
      DOI: 10.1016/j.addr.2017.10.003
       
  • Engineering nanomaterials to overcome the mucosal barrier by modulating
           surface properties
    • Authors: Lei Wu; Wei Shan; Zhirong Zhang; Yuan Huang
      Abstract: Publication date: Available online 5 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Lei Wu, Wei Shan, Zhirong Zhang, Yuan Huang
      Although nanotechnology has been investigated during recent years to increase the bioavailability and therapeutic effects of mucosal administrated drugs, numerous barriers (e.g., pH environment, enzymes and mucus) still limit the delivery efficiency. And the epithelium would also affect the systemic mucosal drug delivery. Amongst all the barriers, the protective mucus has drawn more and more attention, which strongly hinders the accessibility of nanovehicles to epithelium. Therefore, trials to conquer the mucus barrier have been designed using two controversial strategies: mucoadhesion and mucus-penetration. This review summarizes the influence of mucus layer on nanomaterials and introduces the modification strategies by modulating surface properties (i.e., hydrophilicity/hydrophobicity and surface charge) to overcome mucus barriers. Furthermore, it also reviews advanced modification methods to meet the different surface requirements of nanovehicles to overcome mucus and epithelium barriers in systemic mucosal delivery.
      Graphical abstract image

      PubDate: 2017-10-18T00:26:56Z
      DOI: 10.1016/j.addr.2017.10.001
       
  • The biology of mucus: Composition, synthesis and organization
    • Authors: Rama Bansil; Bradley S. Turner
      Abstract: Publication date: Available online 29 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Rama Bansil, Bradley S. Turner
      In this review we discuss mucus, the viscoelastic secretion from goblet or mucous producing cells that lines the epithelial surfaces of all organs exposed to the external world. Mucus is a complex aqueous fluid that owes its viscoelastic, lubricating and hydration properties to the glycoprotein mucin combined with electrolytes, lipids and other smaller proteins. Electron microscopy of mucosal surfaces reveals a highly convoluted surface with a network of fibers and pores of varying sizes. The major structural and functional component, mucin is a complex glycoprotein coded by about 20 mucin genes which produce a protein backbone having multiple tandem repeats of Serine, Threonine (ST repeats) where oligosaccharides are covalently O-linked. The N- and C-terminals of this apoprotein contain other domains with little or no glycosylation but rich in cysteines leading to dimerization and further multimerization via S-S bonds. The synthesis of this complex protein starts in the endoplasmic reticulum with the formation of the apoprotein and is further modified via glycosylation in the cis and medial golgi and packaged into mucin granules via Ca2+ bridging of the negative charges on the oligosaccharide brush in the trans golgi. The mucin granules fuse with the plasma membrane of the secretory cells and following activation by signaling molecules release Ca2+ and undergo a dramatic change in volume due to hydration of the highly negatively charged polymer brush leading to exocytosis from the cells and forming the mucus layer. The rheological properties of mucus and its active component mucin and its mucoadhesivity are briefly discussed in light of their importance to mucosal drug delivery.
      Graphical abstract image

      PubDate: 2017-10-05T01:44:45Z
      DOI: 10.1016/j.addr.2017.09.023
       
  • PDGF receptors in tumor stroma: Biological effects and associations with
           prognosis and response to treatment
    • Authors: Arne
      Abstract: Publication date: Available online 29 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Arne Östman
      Platelet-derived growth factor (PDGF) ligands and their receptors (PDGFRα and PDGFRβ) regulate mesenchymal cells, such as fibroblasts and pericytes. These cells are important constituents of tumor stroma where they impact on tumor growth, metastasis and drug response. Studies in model systems have demonstrated ability of the PDGF system to regulate the tumor-stimulatory effects of fibroblasts, as well as their ability to promote cancer cell migration and invasion. Animal studies imply PDGFR-signaling as a regulator of tumor drug uptake. Emerging correlative analyses of different tumor collections are identifying clinically relevant variations in stromal PDGFR status, and associations between PDGFR status in tumor stroma and survival. These associations could either relate to effects of stromal PDGFR signaling on the natural course of the disease or response to treatment. The availability of clinically approved PDGFR-inhibitory drugs suggest interesting possibilities for novel clinical studies, performed on selected patient sub-groups, which further exploits tumor stroma-derived PDGFR signaling.
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      PubDate: 2017-10-05T01:44:45Z
       
  • Clinical translation of stem cell based interventions for spinal cord
           injury- Are we there yet'
    • Authors: Harvinder S. Chhabra; Kanchan Sarda
      Abstract: Publication date: Available online 28 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Harvinder S. Chhabra, Kanchan Sarda
      Recent advances in basic science in research related to spinal cord injury (SCI) and regeneration have led to a variety of novel experimental therapeutics designed to promote functionally effective axonal regrowth and sprouting. Stem cell and other cellular interventions have gained lot of attention due to their immense potential of regeneration. These interventions have been tested for their efficacy in case of SCI both at the pre-clinical and clinical level. In this review we critically discuss the published literature on the cellular interventions for SCI and their clinical applications with respect to the strength of evidence established by these studies. The need to curb unethical practice of offering unproven stem cell “therapies” for SCI at a global level is also discussed.
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      PubDate: 2017-10-05T01:44:45Z
      DOI: 10.1016/j.addr.2017.09.021
       
  • The effects of major burn related pathophysiological changes on the
           pharmacokinetics and pharmacodynamics of drug use: An appraisal utilizing
           antibiotics
    • Authors: Andrew A. Udy; Jason A. Roberts; Jeffrey Lipman; Stijn Blot
      Abstract: Publication date: Available online 28 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Andrew A. Udy, Jason A. Roberts, Jeffrey Lipman, Stijn Blot
      Patients suffering major burn injury represent a unique population of critically ill patients. Widespread skin and tissue damage causes release of systemic inflammatory mediators that promote endothelial leak, extravascular fluid shifts, and cardiovascular derangement. This phase is characterized by relative intra-vascular hypovolaemia and poor peripheral perfusion. Large volume intravenous fluid resuscitation is generally required. The patients' clinical course is then typically complicated by ongoing inflammation, protein catabolism, and marked haemodynamic perturbation. At all times, drug distribution, metabolism, and elimination are grossly distorted. For hydrophilic agents, changes in volume of distribution and clearance are marked, resulting in potentially sub-optimal drug exposure. In the case of antibiotics, this may then promote treatment failure, or the development of bacterial drug resistance. As such, empirical dose selection and pharmaceutical development must consider these features, with the application of strategies that attempt to counter the unique pharmacokinetic changes encountered in this setting.
      Graphical abstract image

      PubDate: 2017-10-05T01:44:45Z
      DOI: 10.1016/j.addr.2017.09.019
       
  • Burn injury: Challenges and advances in burn wound healing, infection,
           pain and scarring
    • Authors: Yiwei Wang; Joanneke Beekman; Jonathan Hew; Stuart Jackson; Andrea C. Issler-Fisher; Roxanne Parungao; Sepher S. Lajevardi; Zhe Li; Peter K.M. Maitz
      Abstract: Publication date: Available online 20 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Yiwei Wang, Joanneke Beekman, Jonathan Hew, Stuart Jackson, Andrea C. Issler-Fisher, Roxanne Parungao, Sepher S. Lajevardi, Zhe Li, Peter K.M. Maitz
      Severe burn injuries are the most traumatic and physically debilitating injuries affecting nearly every organ system and leading to significant morbidity and mortality. Early burn wound excision and skin grafting are common clinical practices that have significantly improved the outcomes for severe burn injured patients by reducing mortality rate and days of hospital stay. However, slow wound healing, infection, pain, and hypertrophic scarring continue to remain a major challenge in burn research and management. In the present article, we review and discuss issues in the current treatment of burn injuries; the advances and novel strategies developed in the past decade that have improved burn management; and also, pioneer ideas and studies in burn research which aims to enhance burn wound care with a focus on burn wound infection, pain management, treatments for scarring and skin tissue engineering.
      Graphical abstract image

      PubDate: 2017-09-22T16:08:27Z
      DOI: 10.1016/j.addr.2017.09.018
       
  • Nanoparticle-based local antimicrobial drug delivery
    • Authors: Weiwei Gao; Yijie Chen; Yue Zhang; Qiangzhe Zhang; Liangfang Zhang
      Abstract: Publication date: Available online 20 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Weiwei Gao, Yijie Chen, Yue Zhang, Qiangzhe Zhang, Liangfang Zhang
      Despite the wide success of antibiotics in modern medicine, the treatment of bacterial infections still faces critical challenges, especially due to the rapid emergence of antibiotic resistance. As a result, local antimicrobial treatment aimed at enhancing drug concentration at the site of infection while avoiding systemic exposure is becoming increasingly attractive, as it may alleviate resistance development. Meanwhile, therapeutic nanoparticles, especially liposomes, polymeric nanoparticles, dendrimers, and inorganic nanoparticles, are gaining traction to improve the therapeutic efficacy with many applications specifically focused on local antimicrobial treatment. This review highlights topics where nanoparticle-based strategies hold significant potential to advance treatment against local bacterial infections, including (1) promoting antibiotic localization to the pathogen, (2) modulating drug-pathogen interaction against antibiotic resistance, and (3) enabling novel anti-virulence approaches for ‘drug-free’ antimicrobial activity. In each area, we highlight the innovative antimicrobial strategies tailored for local applications and review the progress made for the treatment of bacterial infections.
      Graphical abstract image

      PubDate: 2017-09-22T16:08:27Z
      DOI: 10.1016/j.addr.2017.09.015
       
  • In vitro and ex vivo models to study drug delivery barriers in the
           posterior segment of the eye
    • Authors: Karen Peynshaert; Joke Devoldere; Stefaan C. De Smedt; Katrien Remaut
      Abstract: Publication date: Available online 19 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Karen Peynshaert, Joke Devoldere, Stefaan C. De Smedt, Katrien Remaut
      Many ocular disorders leading to blindness could benefit from efficient delivery of therapeutics to the retina. However, despite extensive research into drug delivery vehicles and administration techniques, efficacy remains limited because of the many static and dynamic barriers present in the eye. Comprehension of the various barriers and especially how to overcome them can improve our ability to estimate the potential of existent drug delivery vectors and support the design of new ones. To this end, this review gives an overview of the most important ocular barriers for each administration route to the back of the eye. For each barrier, its biological composition and its role as an obstacle towards macromolecules, nanoparticles and viral vectors will be discussed; special attention will be paid to the influence of size, charge and lipophilicity of drug(s) (carrier) on their ability to overcome each barrier. Finally, the most significant available in vitro and ex vivo methods and models to test the potential of a therapeutic to cross each barrier are listed.
      Graphical abstract image

      PubDate: 2017-09-22T16:08:27Z
      DOI: 10.1016/j.addr.2017.09.007
       
  • Targeted Drug Delivery to Melanoma
    • Authors: Qi Liu; Manisit Das; Yun Liu; Leaf Huang
      Abstract: Publication date: Available online 19 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Qi Liu, Manisit Das, Yun Liu, Leaf Huang
      Melanoma derived from melanocytes is the most aggressive genre of skin cancer. Although the considerable advancement in the study of human cancer biology and drug discovery, most advanced melanoma patients are inevitably unable to be cured. With the emergence of nanotechnology, the use of nano-carriers is widely expected to alter the landscape of melanoma treatment. In this review, we will discuss melanoma biology, current treatment options, mechanisms behind drug resistance, and nano-based solutions for effective anti-cancer therapy, followed by challenges and perspectives in both pre-clinical and clinical settings.
      Graphical abstract image

      PubDate: 2017-09-22T16:08:27Z
      DOI: 10.1016/j.addr.2017.09.016
       
  • Recent advances of controlled drug delivery using microfluidic platforms
    • Authors: Sharma T. Sanjay; Wan Zhou; Maowei Dou; Hamed Tavakoli; Lei Ma; Feng Xu; XiuJun Li
      Abstract: Publication date: Available online 15 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Sharma T. Sanjay, Wan Zhou, Maowei Dou, Hamed Tavakoli, Lei Ma, Feng Xu, XiuJun Li
      Conventional systematically-administered drugs distribute evenly throughout the body, get degraded and excreted rapidly while crossing many biological barriers, leaving minimum amounts of the drugs at pathological sites. Controlled drug delivery aims to deliver drugs to the target sites at desired rates and time, thus enhancing the drug efficacy, pharmacokinetics, and bioavailability while maintaining minimal side effects. Due to a number of unique advantages of the recent microfluidic lab-on-a-chip technology, microfluidic lab-on-a-chip has provided unprecedented opportunities for controlled drug delivery. Drugs can be efficiently delivered to the target sites at desired rates in a well-controlled manner by microfluidic platforms via integration, implantation, localization, automation, and precise control of various microdevice parameters. These features accordingly make reproducible, on-demand, and tunable drug delivery become feasible. On-demand self-tuning dynamic drug delivery systems have shown great potential for personalized drug delivery. This review presents an overview of recent advances in controlled drug delivery using microfluidic platforms. The review first briefly introduces microfabrication techniques of microfluidic platforms, followed by detailed descriptions of numerous microfluidic drug delivery systems that have significantly advanced the field of controlled drug delivery. Those microfluidic systems can be separated into four major categories, namely drug carrier-free micro-reservoir-based drug delivery systems, highly integrated carrier-free microfluidic lab-on-a-chip systems, drug carrier-integrated microfluidic systems, and microneedles. Microneedles can be further categorized into five different types, i.e. solid, porous, hollow, coated, and biodegradable microneedles, for controlled transdermal drug delivery. At the end, we discuss current limitations and future prospects of microfluidic platforms for controlled drug delivery.
      Graphical abstract image

      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.013
       
  • Cell-Mediated Enzyme Prodrug Cancer Therapies
    • Authors: Rachael Mooney; Asma Abdul Majid; Jennifer Batalla; Alexander J. Annala; Karen S. Aboody
      Abstract: Publication date: Available online 13 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Rachael Mooney, Asma Abdul Majid, Jennifer Batalla, Alexander J. Annala, Karen S. Aboody
      Cell-directed gene therapy is a promising new frontier for the field of targeted cancer therapies. Here we discuss the current pre-clinical and clinical use of cell-mediated enzyme prodrug therapy (EPT) directed against solid tumors and avenues for further development. We also discuss some of the challenges encountered upon translating these therapies to clinical trials. Upon sufficient development, cell-mediated enzyme prodrug therapy has the potential to maximize the distribution of therapeutic enzymes within the tumor environment, localizing conversion of prodrug to active drug at the tumor sites thereby decreasing off-target toxicities. New combinatorial possibilities are also promising. For example, when combined with viral gene-delivery vehicles, this may result in new hybrid vehicles that attain heretofore unmatched levels of therapeutic gene expression within the tumor.
      Graphical abstract image

      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.003
       
  • Genome stability of programmed stem cell products
    • Authors: Ulrich Martin
      Abstract: Publication date: Available online 13 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Ulrich Martin
      Inherited and acquired genomic abnormalities are known to cause genetic diseases and contribute to cancer formation. Recent studies demonstrated a substantial mutational load in mouse and human embryonic and induced pluripotent stem cells (ESCs and iPSCs). Single nucleotide variants, copy number variations, and larger chromosomal abnormalities may influence the differentiation capacity of pluripotent stem cells and the functionality of their derivatives in disease modelling and drug screening, and are considered a serious risk for cellular therapies based on ESC or iPSC derivatives. This review discusses the types and origins of different genetic abnormalities in pluripotent stem cells, methods for their detection, and the mechanisms of development and enrichment during reprogramming and culture expansion.
      Graphical abstract image

      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.004
       
  • Enzymes as Key Features in Therapeutic Cell Mimicry
    • Authors: Fabian Itel; Philipp S. Schattling; Yan Zhang; Brigitte Städler
      Abstract: Publication date: Available online 12 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Fabian Itel, Philipp S. Schattling, Yan Zhang, Brigitte Städler
      Cell mimicry is a nature inspired concept that aims to substitute for missing or lost (sub)cellular function. This review focuses on the latest advancements in the use of enzymes in cell mimicry for encapsulated catalysis and artificial motility in synthetic bottom-up assemblies with emphasis on the biological response in cell culture or more rarely in animal models. Entities across the length scale from nano-sized enzyme mimics, sub-micron sized artificial organelles and self-propelled particles (swimmers) to micron-sized artificial cells are discussed. Although the field remains in its infancy, the primary aim of this review is to illustrate the advent of nature-mimicking artificial molecules and assemblies on their way to become a complementary alternative to their role models for diverse biomedical purposes.
      Graphical abstract image

      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.006
       
  • Antibody Directed Enzyme Prodrug Therapy (ADEPT): Trials and Tribulations
    • Authors: Surinder K. Sharma; Kenneth D. Bagshawe
      Abstract: Publication date: Available online 12 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Surinder K. Sharma, Kenneth D. Bagshawe
      Antibody directed enzyme prodrug therapy has the potential to be an effective therapy for most common solid cancers. Clinical studies with CPG2 system have shown the feasibility of this approach. The key limitation has been immunogenicity of the enzyme. Technologies now exist to eliminate this problem. Non-immunogenic enzymes in combination with prodrugs that generate potent cytotoxic drugs can provide a powerful approach to cancer therapy. ADEPT has the potential to be non -toxic to normal tissue and can therefore be combined with other modalities including immunotherapy for greater clinical benefit.

      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.009
       
  • Designer Bacteria as Intratumoural Enzyme Biofactories
    • Authors: Panos Lehouritis; Glenn Hogan; Mark Tangney
      Abstract: Publication date: Available online 12 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Panos Lehouritis, Glenn Hogan, Mark Tangney
      Bacterial-directed enzyme prodrug therapy (BDEPT) is an emerging form of treatment for cancer. It is a biphasic variant of gene therapy in which a bacterium, armed with an enzyme that can convert an inert prodrug into a cytotoxic compound, induces tumour cell death following tumour-specific prodrug activation. BDEPT combines the innate ability of bacteria to selectively proliferate in tumours, with the capacity of prodrugs to undergo contained, compartmentalised conversion into active metabolites in vivo. Although BDEPT has undergone clinical testing, it has received limited clinical exposure, and has yet to achieve regulatory approval. In this article, we review BDEPT from the system designer's perspective, and provide detailed commentary on how the designer should strategize its development de novo. We report on contemporary advancements in this field which aim to enhance BDEPT in terms of safety and efficacy. Finally, we discuss clinical and regulatory barriers facing BDEPT, and propose promising approaches through which these hurdles may best be tackled.
      Graphical abstract image

      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.012
       
  • Overcoming ocular drug delivery barriers through the use of pHysical
           forces
    • Authors: Di Huang; Ying-Shan Chen; Ilva D. Rupenthal
      Abstract: Publication date: Available online 12 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Di Huang, Ying-Shan Chen, Ilva D. Rupenthal
      Overcoming the physiological barriers in the eye remains a key obstacle in the field of ocular drug delivery. While ocular barriers naturally have a protective function, they also limit drug entry into the eye. Various pharmaceutical strategies, such as novel formulations and physical force-based techniques, have been investigated to weaken these barriers and transport therapeutic agents effectively to both the anterior and the posterior segments of the eye. This review summarizes and discusses the recent research progress in the field of ocular drug delivery with a focus on the application of physical methods, including electrical fields, sonophoresis, and microneedles, which can enhance penetration efficiency by transiently disrupting the ocular barriers in a minimally or non-invasive manner.
      Graphical abstract image

      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.008
       
  • Two-step polymer- and liposome- enzyme prodrug therapies for cancer: PDEPT
           and PELT concepts and future perspectives
    • Authors: Anna Scomparin; Helena F. Florindo; Galia Tiram; Elaine L. Ferguson; Ronit Satchi-Fainaro
      Abstract: Publication date: Available online 12 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Anna Scomparin, Helena F. Florindo, Galia Tiram, Elaine L. Ferguson, Ronit Satchi-Fainaro
      Polymer-directed enzyme prodrug therapy (PDEPT) and polymer enzyme liposome therapy (PELT) are two-step therapies developed to provide anticancer drugs site-selective intratumoral accumulation and release. Nanomedicines, such as polymer-drug conjugates and liposomal drugs, accumulate in the tumor site due to extravasation-dependent mechanism (enhanced permeability and retention – EPR – effect), and further need to cross the cellular membrane and release their payload in the intracellular compartment. The subsequent administration of a polymer-enzyme conjugate able to accumulate in the tumor tissue and to trigger the extracellular release of the active drug showed promising preclinical results. The development of polymer-enzyme, polymer-drug conjugates and liposomal drugs had undergone a vast advancement over the past decades. Several examples of enzyme mimics for in vivo therapy can be found in the literature. Moreover, polymer therapeutics often present an enzyme-sensitive mechanism of drug release. These nanomedicines can thus be optimal substrates for PDEPT and this review aims to provide new insights and stimuli towards the future perspectives of this promising combination.
      Graphical abstract image

      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.011
       
  • (Re-)programming of subtype specific cardiomyocytes
    • Authors: Frauke Hausburg; Julia Jeannine Jung; Matti Hoch; Markus Wolfien; Arash Yavari; Christian Rimmbach; Robert David
      Abstract: Publication date: Available online 12 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Frauke Hausburg, Julia Jeannine Jung, Matti Hoch, Markus Wolfien, Arash Yavari, Christian Rimmbach, Robert David
      Adult cardiomyocytes (CMs) possess a highly restricted intrinsic regenerative potential — a major barrier to the effective treatment of a range of chronic degenerative cardiac disorders characterized by cellular loss and/or irreversible dysfunction and which underlies the majority of deaths in developed countries. Both stem cell programming and direct cell reprogramming hold promise as novel, potentially curative approaches to address this therapeutic challenge. The advent of induced pluripotent stem cells (iPSCs) has introduced a second pluripotent stem cell source besides embryonic stem cells (ESCs), enabling even autologous cardiomyocyte production. In addition, the recent achievement of directly reprogramming somatic cells into cardiomyocytes is likely to become of great importance. In either case, different clinical scenarios will require the generation of highly pure, specific cardiac cellular-subtypes. In this review, we discuss these themes as related to the cardiovascular stem cell and programming field, including a focus on the emergent topic of pacemaker cell generation for the development of biological pacemakers and in vitro drug testing.
      Graphical abstract image

      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.005
       
  • Stem cell-based peripheral vascular regeneration
    • Authors: Yasuyuki Fujita; Atsuhiko Kawamoto
      Abstract: Publication date: Available online 11 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Yasuyuki Fujita, Atsuhiko Kawamoto
      Chronic critical limb ischemia (CLI) represents an end-stage manifestation of peripheral arterial disease (PAD). CLI patients are at very high risk of amputation and cardiovascular complications, leading to severe morbidity and mortality. Because many patients with CLI are ineligible for conventional revascularization procedures, it is urgently needed to explore alternative strategies to improve blood supply in the ischemic tissue. Although researchers initially focused on gene/protein therapy using proangiogenic growth factors/cytokines, recent discovery of somatic stem/progenitor cells including bone marrow (BM)-derived endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) has drastically developed the field of therapeutic angiogenesis for CLI. Overall, early phase clinical trials demonstrated that stem/progenitor cell therapies may be safe, feasible and potentially effective. However, only few late-phase clinical trials have been conducted. This review provides an overview of the preclinical and clinical reports to demonstrate the usefulness and the current limitations of the cell-based therapies.
      Graphical abstract image

      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.001
       
  • Targeting and Isolation of Cancer Cells Using Micro/Nanomotors
    • Authors: Weiwei Gao; Berta Esteban-Fernández de Ávila; Liangfang Zhang; Joseph Wang
      Abstract: Publication date: Available online 9 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Weiwei Gao, Berta Esteban-Fernández de Ávila, Liangfang Zhang, Joseph Wang
      Micro/nanomotors distinguish themselves with in situ energy conversion capability for autonomous movement, a feature that confers remarkable potential to improve cancer treatment. In this review article, three areas are highlighted where micro/nanomotors have established themselves with unique contributions, including propelled navigation to promote cancer cell targeting, powered cell membrane penetration to enhance intracellular delivery, and steered isolation of circulating cancer cells for detection. Progress made in these areas has offered promising inspiration and opportunities aimed for enhancing the efficiency and precision of drug targeting to cancer cells, improving the capability of delivering anticancer drug into cytoplasm for bioactivity, and enabling more rapid and sensitive cancer cell detection. Herein, we review each area with highlights of the current and forthcoming micro/nanomotor techniques in advancing cancer diagnosis and treatment.
      Graphical abstract image

      PubDate: 2017-09-11T03:30:42Z
      DOI: 10.1016/j.addr.2017.09.002
       
  • PEGylation for enhancing nanoparticle diffusion in mucus
    • Authors: Justin T. Huckaby; Samuel K. Lai
      Abstract: Publication date: Available online 4 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Justin T. Huckaby, Samuel K. Lai
      The viscoelastic mucus secretions coating exposed organs such as the lung airways and the female reproductive tract can trap and quickly eliminate not only foreign pathogens and ultrafine particles but also particle-based drug delivery systems, thus limiting sustained and targeted drug delivery at mucosal surfaces. To improve particle distribution across the mucosa and enhance delivery to the underlying epithelium, many investigators have sought to develop nanoparticles capable of readily traversing mucus. The first synthetic nanoparticles shown capable of rapidly penetrating physiological mucus secretions utilized a dense coating of polyethylene glycol (PEG) covalently grafted onto the surface of preformed polymeric nanoparticles. In the decade since, PEG has become the gold standard in engineering mucus-penetrating drug carriers for sustained and targeted drug delivery to the lungs, gastrointestinal tract, eyes, and female reproductive tract. This review summarizes the history of the development of various PEG-based mucus-penetrating particles, and highlights the key physicochemical properties of PEG coatings and PEGylation strategies to achieve muco-inert PEG coatings on nanoparticle drug carriers for improved drug and gene delivery at mucosal surfaces.
      Graphical abstract image

      PubDate: 2017-09-06T17:10:31Z
      DOI: 10.1016/j.addr.2017.08.010
       
  • Device-assisted transdermal drug delivery
    • Authors: Hyunjae Lee; Changyeong Song; Seungmin Baik; Dokyoon Kim; Taeghwan Hyeon; Dae-Hyeong Kim
      Abstract: Publication date: Available online 1 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Hyunjae Lee, Changyeong Song, Seungmin Baik, Dokyoon Kim, Taeghwan Hyeon, Dae-Hyeong Kim
      Transdermal drug delivery is a prospective drug delivery strategy to complement the limitations of conventional drug delivery systems including oral and injectable methods. This delivery route allows both convenient and painless drug delivery and a sustained release profile with reduced side effects. However, physiological barriers in the skin undermine the delivery efficiency of conventional patches, limiting drug candidates to small-molecules and lipophilic drugs. Recently, transdermal drug delivery technology has advanced from unsophisticated methods simply relying on natural diffusion to drug releasing systems that dynamically respond to external stimuli. Furthermore, physical barriers in the skin have been overcome using microneedles, and controlled delivery by wearable biosensors has been enabled ultimately. In this review, we classify the evolution of advanced drug delivery strategies based on generations and provide a comprehensive overview. Finally, the recent progress in advanced diagnosis and therapy through customized drug delivery systems based on real-time analysis of physiological cues is highlighted.
      Graphical abstract image

      PubDate: 2017-09-06T17:10:31Z
      DOI: 10.1016/j.addr.2017.08.009
       
  • Nano-sized and other improved reporters for Magnetic Resonance Imaging of
           angiogenesis
    • Authors: Simonetta Geninatti Crich; Enzo Terreno; Silvio Aime
      Abstract: Publication date: Available online 9 August 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Simonetta Geninatti Crich, Enzo Terreno, Silvio Aime
      Magnetic Resonance Imaging (MRI) enables to provide anatomical, functional and molecular information of pathological angiogenesis when used with properly tailored imaging probes. Functional studies have been the domain of Dynamic Contrast Enhancement (DCE) -MRI protocols from which it is possible to extract quantitative estimations on key parameters such as the volumes of vascular and extracellular compartments and the rates of the bidirectional exchange of the imaging reporters across the endothelial barrier. Whereas paramagnetic Gd-complexes able to reversibly bind to serum albumin act better than the clinically used small-sized, hydrophilic species, new findings suggest that an accurate assessment of the vascular volume is possible by analyzing images acquired upon the i.v. administration of Gd-labelled Red Blood Cells (RBCs). As far as it concerns molecular MRI, among the many available biomarkers, αvβ3 integrins are the most investigated ones. The low expression of these targets makes mandatory the use of nano-sized systems endowed with the proper signal enhancing capabilities. A number of targeted nano-particles have been investigated including micelles, liposomes, iron oxides and perfluorocarbon containing systems. Finally, a growing attention is devoted to the design and testing of “theranostic” agents based on the exploitation of MRI to monitor drug delivery processes and therapeutic outcome.
      Graphical abstract image

      PubDate: 2017-08-10T14:52:05Z
      DOI: 10.1016/j.addr.2017.08.004
       
  • Current developments and applications of microfluidic technology toward
           clinical translation of nanomedicines
    • Authors: Dongfei Liu; Hongbo Zhang; Flavia Fontana; Jouni T. Hirvonen; Hélder A. Santos
      Abstract: Publication date: Available online 8 August 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Dongfei Liu, Hongbo Zhang, Flavia Fontana, Jouni T. Hirvonen, Hélder A. Santos
      Nanoparticulate drug delivery systems hold great potential for the therapy of many diseases, especially cancer. However, the translation of nanoparticulate drug delivery systems from academic research to the industrial and clinical practice has been slow. This slow translation can be ascribed to the high batch-to-batch variations and insufficient production rate of the conventional methods, and the lack of technologies for rapid screening of nanoparticulate drug delivery systems with high correlation to the in vivo tests. These issues can be addressed by the microfluidic technologies. For example, microfluidics can not only produce nanoparticles in a well-controlled, reproducible, and high-throughput manner, but also create 3D environments with continuous flow to mimic the physiological and/or pathological processes. This review provides an overview of the microfluidic devices developed to prepare nanoparticulate drug delivery systems, including drug nanosuspensions, polymer nanoparticles, polyplexes, structured nanoparticles and theranostic nanoparticles. We also highlight the recent advances of microfluidic systems in fabricating the increasingly realistic models of the in vivo milieu for rapid screening of nanoparticles. Overall, the microfluidic technologies offer a promise approach to accelerate the clinical translation of nanoparticulate drug delivery systems.
      Graphical abstract image

      PubDate: 2017-08-10T14:52:05Z
      DOI: 10.1016/j.addr.2017.08.003
       
  • Nanomedicine and advanced technologies for burns: Preventing infection and
           facilitating wound healing
    • Authors: Mirza Ali Mofazzal Jahromi; Parham Sahandi Zangabad; Seyed Masoud Moosavi Basri; Keyvan Sahandi Zangabad; Ameneh Ghamarypour; Amir R. Aref; Mahdi Karimi; Michael R. Hamblin
      Abstract: Publication date: Available online 4 August 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Mirza Ali Mofazzal Jahromi, Parham Sahandi Zangabad, Seyed Masoud Moosavi Basri, Keyvan Sahandi Zangabad, Ameneh Ghamarypour, Amir R. Aref, Mahdi Karimi, Michael R. Hamblin
      According to the latest report from the World Health Organization, an estimated 265,000 deaths still occur every year as a direct result of burn injuries. A widespread range of these deaths induced by burn wound happens in low- and middle-income countries, where survivors face a lifetime of morbidity. Most of the deaths occur due to infections when a high percentage of the external regions of the body area is affected. Microbial nutrient availability, skin barrier disruption, and vascular supply destruction in burn injuries as well as systemic immunosuppression are important parameters that cause burns to be susceptible to infections. Topical antimicrobials and dressings are generally employed to inhibit burn infections followed by a burn wound therapy, because systemic antibiotics have problems in reaching the infected site, coupled with increasing microbial drug resistance. Nanotechnology has provided a range of molecular designed nanostructures (NS) that can be used in both therapeutic and diagnostic applications in burns. These NSs can be divided into organic and non-organic (such as polymeric nanoparticles (NPs) and silver NPs, respectively), and many have been designed to display multifunctional activity. The present review covers the physiology of skin, burn classification, burn wound pathogenesis, animal models of burn wound infection, and various topical therapeutic approaches designed to combat infection and stimulate healing. These include biological based approaches (e.g. immune-based antimicrobial molecules, therapeutic microorganisms, antimicrobial agents, etc.), antimicrobial photo- and ultrasound-therapy, as well as nanotechnology-based wound healing approaches as a revolutionizing area. Thus, we focus on organic and non-organic NSs designed to deliver growth factors to burned skin, and scaffolds, dressings, etc. for exogenous stem cells to aid skin regeneration. Eventually, recent breakthroughs and technologies with substantial potentials in tissue regeneration and skin wound therapy (that are as the basis of burn wound therapies) are briefly taken into consideration including 3D–printing, cell-imprinted substrates, nano-architectured surfaces, and novel gene-editing tools such as CRISPR-Cas.
      Graphical abstract image

      PubDate: 2017-08-10T14:52:05Z
      DOI: 10.1016/j.addr.2017.08.001
       
  • Understanding the neurovascular unit at multiple scales: advantages and
           limitations of multi-photon and functional ultrasound imaging
    • Authors: Alan Urban; Lior Golgher; Clément Brunner; Amos Gdalyahu; Hagai Har-Gil; David Kain; Gabriel Montaldo; Laura Sironi; Pablo Blinder
      Abstract: Publication date: Available online 2 August 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Alan Urban, Lior Golgher, Clément Brunner, Amos Gdalyahu, Hagai Har-Gil, David Kain, Gabriel Montaldo, Laura Sironi, Pablo Blinder
      Developing efficient brain imaging technologies by combining a high spatiotemporal resolution and a large penetration depth is a key step for better understanding the neurovascular interface that emerges as a main pathway to neurodegeneration in many pathologies such as dementia. This review focuses on the advances in two complementary techniques: multi-photon laser scanning microscopy (MPLSM) and functional ultrasound imaging (fUSi). MPLSM has become the gold standard for in vivo imaging of cellular dynamics and morphology, together with cerebral blood flow. fUSi is an innovative imaging modality based on Doppler ultrasound, capable of recording vascular brain activity over large scales (i.e., tens of cubic millimeters) at unprecedented spatial and temporal resolution for such volumes (up to 10 μm pixel size at 10 kHz). By merging these two technologies, researchers may have access to a more detailed view of the various processes taking place at the neurovascular interface. TPLSM and fUSi are also good candidates for addressing the major challenge of real-time delivery, monitoring, and in vivo evaluation of drugs in neuronal tissue.
      Graphical abstract image

      PubDate: 2017-08-10T14:52:05Z
      DOI: 10.1016/j.addr.2017.07.018
       
 
 
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