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Publisher: Elsevier   (Total: 3042 journals)

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Showing 1 - 200 of 3042 Journals sorted alphabetically
AASRI Procedia     Open Access   (Followers: 15)
Academic Pediatrics     Hybrid Journal   (Followers: 20, SJR: 1.402, h-index: 51)
Academic Radiology     Hybrid Journal   (Followers: 17, SJR: 1.008, h-index: 75)
Accident Analysis & Prevention     Partially Free   (Followers: 82, SJR: 1.109, h-index: 94)
Accounting Forum     Hybrid Journal   (Followers: 23, SJR: 0.612, h-index: 27)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 27, 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: 327, 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  
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: 204, 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: 9, 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: 2)
Acta Poética     Open Access   (Followers: 4)
Acta Psychologica     Hybrid Journal   (Followers: 23, 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: 3)
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: 5)
Additive Manufacturing     Hybrid Journal   (Followers: 7, SJR: 1.039, h-index: 5)
Additives for Polymers     Full-text available via subscription   (Followers: 20)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 127, 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: 16, 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: 25, 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: 10, SJR: 0.801, h-index: 26)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 20, 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 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: 24, 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: 10, SJR: 1.268, h-index: 45)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 28, 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 Developmental Biology     Full-text available via subscription   (Followers: 11)
Advances in Digestive Medicine     Open Access   (Followers: 4)
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: 41, 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: 40, 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: 47, SJR: 0.674, h-index: 38)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 15)
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: 12)
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: 21, SJR: 0.906, h-index: 24)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.497, h-index: 31)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 25)
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: 35, 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: 4)
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: 7, 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 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: 7, 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: 18)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 19, SJR: 1.5, h-index: 62)
Advances in Psychology     Full-text available via subscription   (Followers: 59)
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 Research     Full-text available via subscription   (Followers: 339, 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: 6, 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: 15)
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: 308, 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: 402, SJR: 1.385, h-index: 72)
Agri Gene     Hybrid Journal  
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 15, SJR: 2.18, h-index: 116)
Agricultural Systems     Hybrid Journal   (Followers: 30, SJR: 1.275, h-index: 74)
Agricultural Water Management     Hybrid Journal   (Followers: 38, 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: 50, 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: 9, SJR: 0.922, h-index: 66)
Alcoholism and Drug Addiction     Open Access   (Followers: 6)
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  
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)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 7, SJR: 0.158, h-index: 9)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 48, SJR: 4.289, h-index: 64)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 5)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 3)
American Heart J.     Hybrid Journal   (Followers: 48, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 44, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 37, SJR: 0.574, h-index: 65)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 6, SJR: 1.091, h-index: 45)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 16, SJR: 1.653, h-index: 93)
American J. of Human Genetics     Hybrid Journal   (Followers: 31, SJR: 8.769, h-index: 256)
American J. of Infection Control     Hybrid Journal   (Followers: 24, SJR: 1.259, h-index: 81)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 34, 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: 179, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 55, SJR: 2.803, h-index: 148)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 2)
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: 23, SJR: 0.59, h-index: 45)
American J. of Pathology     Hybrid Journal   (Followers: 25, SJR: 2.653, h-index: 228)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 21, SJR: 2.764, h-index: 154)
American J. of Surgery     Hybrid Journal   (Followers: 34, 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: 55, SJR: 0.124, h-index: 9)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 10)
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: 2, SJR: 2.577, h-index: 7)
Analytica Chimica Acta     Hybrid Journal   (Followers: 38, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 158, 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: 11)
Anesthésie & Réanimation     Full-text available via subscription  
Anesthesiology Clinics     Full-text available via subscription   (Followers: 22, 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: 152, SJR: 1.907, h-index: 126)
Animal Feed Science and Technology     Hybrid Journal   (Followers: 5, SJR: 1.151, h-index: 83)
Animal Reproduction Science     Hybrid Journal   (Followers: 5, SJR: 0.711, h-index: 78)
Annales d'Endocrinologie     Full-text available via subscription   (SJR: 0.394, h-index: 30)
Annales d'Urologie     Full-text available via subscription  
Annales de Cardiologie et d'Angéiologie     Full-text available via subscription   (SJR: 0.177, h-index: 13)
Annales de Chirurgie de la Main et du Membre Supérieur     Full-text available via subscription  
Annales de Chirurgie Plastique Esthétique     Full-text available via subscription   (Followers: 2, SJR: 0.354, h-index: 22)
Annales de Chirurgie Vasculaire     Full-text available via subscription   (Followers: 1)

        1 2 3 4 5 6 7 8 | Last   [Sort by number of followers]   [Restore default list]

Journal Cover Advanced Drug Delivery Reviews
  [SJR: 5.2]   [H-I: 222]   [127 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0169-409X
   Published by Elsevier Homepage  [3042 journals]
  • The good and the bad collagens of fibrosis – their role in signaling
           and organ function
    • Authors: M.A. Karsdal; S.H. Nielsen; D.J. Leeming; L.L. Langholm; M.J. Nielsen; T. Manon-Jensen; A. Siebuhr; N.S. Gudmann; S. Rønnow; J.M. Sand; S.J. Daniels; J.H. Mortensen; D. Schuppan
      Abstract: Publication date: Available online 21 July 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): M.A. Karsdal, S.H. Nielsen, D.J. Leeming, L.L. Langholm, M.J. Nielsen, T. Manon-Jensen, A. Siebuhr, N.S. Gudmann, S. Rønnow, J.M. Sand, S.J. Daniels, J.H. Mortensen, D. Schuppan
      Usually the dense extracellular structure in fibrotic tissues is described as extracellular matrix (ECM) or simply as collagen. However, fibrosis is not just fibrosis, which is already exemplified by the variant morphological characteristics of fibrosis due to viral versus cholestatic, autoimmune or toxic liver injury, with reticular, chicken wire and bridging fibrosis. Importantly, the overall composition of the ECM, especially the relative amounts of the many types of collagens, which represent the most abundant ECM molecules and which centrally modulate cellular functions and physiological processes, changes dramatically during fibrosis progression. We hypothesize that there are good and bad collagens in fibrosis and that a change of location alone may change the function from good to bad. Whereas basement membrane collagen type IV anchors epithelial and other cells in a polarized manner, the interstitial fibroblast collagens type I and III do not provide directional information. In addition, feedback loops from biologically active degradation products of some collagens are examples of the importance of having the right collagen at the right place and at the right time controlling cell function, proliferation, matrix production and fate. Examples are the interstitial collagen type VI and basement membrane collagen type XVIII. Their carboxyterminal propeptides serve as an adipose tissue hormone, endotrophin, and as a regulator of angiogenesis, endostatin, respectively. We provide an overview of the 28 known collagen types and propose that the molecular composition of the ECM in fibrosis needs careful attention to assess its impact on organ function and its potential to progress or reverse. Consequently, to adequately assess fibrosis and to design optimal antifibrotic therapies, we need to dissect the molecular entity of fibrosis for the molecular composition and spatial distribution of collagens and the associated ECM.
      Graphical abstract image

      PubDate: 2017-07-24T12:41:15Z
      DOI: 10.1016/j.addr.2017.07.014
       
  • Advances in cancer stem cell targeting: How to strike the evil at its root
    • Authors: Brigitte M. Pützer; Manish Solanki; Ottmar Herchenröder
      Abstract: Publication date: Available online 21 July 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Brigitte M. Pützer, Manish Solanki, Ottmar Herchenröder
      Cancer progression to metastatic stages is still unmanageable and the promise of effective anti-metastatic therapy remains largely unmet, emphasizing the need to develop novel therapeutics. The special focus here is on cancer stem cells (CSC) as the seed of tumor initiation, epithelial-mesenchymal transition, chemoresistance and, as a consequence, drivers of metastatic dissemination. We report on targeted therapies gearing towards the CSC's internal and membrane-anchored markers using agents such as antibody derivatives, nucleic therapeutics, small molecules and genetic payloads. Another emphasis lies on novel proceedings envisaged to deliver current and prospective therapies to the target sites using newest viral and non-viral vector technologies. In this review, we summarize recent progress and remaining challenges in therapeutic strategies to combat CSC.
      Graphical abstract image

      PubDate: 2017-07-24T12:41:15Z
      DOI: 10.1016/j.addr.2017.07.013
       
  • Beyond PEGylation: alternative surface-modification of nanoparticles with
           mucus-inert biomaterials
    • Authors: Vitaliy V. Khutoryanskiy
      Abstract: Publication date: Available online 20 July 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Vitaliy V. Khutoryanskiy
      Mucus is a highly hydrated viscoelastic gel present on various moist surfaces in our body including the eyes, nasal cavity, mouth, gastrointestinal, respiratory and reproductive tracts. It serves as a very efficient barrier that prevents harmful particles, viruses and bacteria from entering the human body. However, the protective function of the mucus also hampers the diffusion of drugs and nanomedicines, which dramatically reduces their efficiency. Functionalisation of nanoparticles with low molecular weight poly(ethylene glycol) (PEGylation) is one of the strategies to enhance their penetration through mucus. Recently a number of other polymers were explored as alternatives to PEGylation. These alternatives include poly(2-alkyl-2-oxazolines), polysarcosine, poly(vinyl alcohol), other hydroxyl-containing non-ionic water-soluble polymers, zwitterionic polymers (polybetains) and mucolytic enzymes. This review discusses the studies reporting the use of these polymers or potential application to facilitate mucus permeation of nanoparticles.
      Graphical abstract image

      PubDate: 2017-07-24T12:41:15Z
      DOI: 10.1016/j.addr.2017.07.015
       
  • Molecular Imaging in stem cell-based therapies of cardiac diseases
    • Authors: Xiang Li; Marcus Hacker
      Abstract: Publication date: Available online 19 July 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Xiang Li, Marcus Hacker
      In the past 15years, despite regenerative medicine has shown great potential for cardiovascular diseases, the outcome and safety of stem cell transplantation has shown controversial results in the published literature. Medical imaging might be useful for monitoring and quantification transplanted cells within the heart and to serially characterize the effects of stem cell therapy of the myocardium. From the multiple available noninvasive imaging techniques, magnetic resonance imaging and nuclear imaging by positron (PET) or single photon emission computer tomography (SPECT) are the most used clinical approaches to follow the fate of transplanted stem cells in vivo. In this article, we provide a review on the role of different noninvasive imaging modalities and discuss their advantages and disadvantages. We focus on the different in-vivo labeling and reporter gene imaging strategies for stem cell tracking as well as the concept and reliability to use imaging parameters as noninvasive surrogate endpoints for the evaluation of the post-therapeutic outcome.
      Graphical abstract image

      PubDate: 2017-07-24T12:41:15Z
      DOI: 10.1016/j.addr.2017.07.012
       
  • Strategies to develop endogenous stem cell recruiting bioactive materials
           for tissue repair and regeneration
    • Authors: Settimio Pacelli; Sayantani Basu; Jonathan Whitlow; Aparna R. Chakravarti; Francisca Acosta; Arushi Varshney; Saman Modaresi; Cory Berkland; Arghya Paul
      Abstract: Publication date: Available online 19 July 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Settimio Pacelli, Sayantani Basu, Jonathan Whitlow, Aparna R. Chakravarti, Francisca Acosta, Arushi Varshney, Saman Modaresi, Cory Berkland, Arghya Paul
      A leading strategy in tissue engineering is the design of biomimetic scaffolds that stimulate the body's repair mechanisms through the recruitment of endogenous stem cells to sites of injury. Approaches that employ the use of chemoattractant gradients to guide tissue regeneration without external cell sources are favored over traditional cell-based therapies that have limited potential for clinical translation. Following this concept, bioactive scaffolds can be engineered to provide a temporally and spatially controlled release of biological cues, with the possibility to mimic the complex signaling patterns of endogenous tissue regeneration. Another effective way to regulate stem cell activity is to leverage the inherent chemotactic properties of extracellular matrix (ECM)-based materials to build versatile cell-instructive platforms. This review introduces the concept of endogenous stem cell recruitment, and provides a comprehensive overview of the strategies available to achieve effective cardiovascular and bone tissue regeneration.
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      PubDate: 2017-07-24T12:41:15Z
      DOI: 10.1016/j.addr.2017.07.011
       
  • Drug Targeting to Myofibroblasts: Implications for Fibrosis and Cancer
    • Authors: Saleh Yazdani; Ruchi Bansal; Jai Prakash
      Abstract: Publication date: Available online 16 July 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Saleh Yazdani, Ruchi Bansal, Jai Prakash
      Myofibroblasts are the key players in extracellular matrix remodeling, a core phenomenon in numerous devastating fibrotic diseases. Not only in organ fibrosis, but also the pivotal role of myofibroblasts in tumor progression, invasion and metastasis has recently been highlighted. Myofibroblast targeting has gained tremendous attention in order to inhibit the progression of incurable fibrotic diseases, or to limit the myofibroblast-induced tumor progression and metastasis. In this review, we outline the origin of myofibroblasts, their general characteristics and functions during fibrosis progression in three major organs: liver, kidneys and lungs as well as in cancer. We will then discuss the state-of-the art drug targeting technologies to myofibroblasts in context of the above-mentioned organs and tumor microenvironment. The overall objective of this review is therefore to advance our understanding in drug targeting to myofibroblasts, and concurrently identify opportunities and challenges for designing new strategies to develop novel diagnostics and therapeutics against fibrosis and cancer.
      Graphical abstract image

      PubDate: 2017-07-24T12:41:15Z
      DOI: 10.1016/j.addr.2017.07.010
       
  • Advanced methodologies for cocrystal synthesis
    • Authors: Dennis Douroumis; Steven A. Ross; Ali Nokhodchi
      Abstract: Publication date: Available online 14 July 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Dennis Douroumis, Steven A. Ross, Ali Nokhodchi
      Pharmaceutical cocrystals are multicomponent systems composed of two or more molecules and held together by H-bonding. Currently, cocrystals provide exciting opportunities in the pharmaceutical industry for the development and manufacturing of new medicines by improving poor physical properties of Active Pharmaceutical Ingredients (APIs) such as processability, solubility, stability and bioavailability. According to the recent reclassification, cocrystals are considered as drug polymorph rather a new API which has a significant impact on drug development, regulatory submissions and intellectual property protection. This review summarises recent trends and advances in synthesis, manufacturing and scale – up of cocrystals. The operational principles of several cocrystals manufacturing technologies are discussed including their advantages and disadvantages in terms of crystal quality, purity stability, throughput and limitations in large scale production.
      Graphical abstract image

      PubDate: 2017-07-24T12:41:15Z
      DOI: 10.1016/j.addr.2017.07.008
       
  • Key players in the immune response to biomaterial scaffolds for
           regenerative medicine
    • Authors: Liam Chung; David R. Maestas; Franck Housseau; Jennifer H. Elisseeff
      Abstract: Publication date: Available online 13 July 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Liam Chung, David R. Maestas, Franck Housseau, Jennifer H. Elisseeff
      The compatibility of biomaterials is critical to their structural and biological function in medical applications. The immune system is the first responder to tissue trauma and to a biomaterial implant. The innate immune effector cells, most notably the macrophage, play a significant role in the defense against foreign bodies and formation of a fibrous capsule around synthetic implants. Alternatively, macrophages participate in the pro-regenerative capacity of tissue-derived biological scaffolds. Research is now elucidating the role of the adaptive immune system, and T cells in particular, in directing macrophage response to synthetic and biological materials. Here, we review basic immune cell types and discuss recent research on the role of the immune system in tissue repair and its potential relevance to scaffold design. We will also discuss new emerging immune cell types relevant to biomaterial responses and tissue repair. Prospects for specifically targeting and modulating the immune response to biomaterial scaffolds for enhancing tissue repair and regeneration will be presented.
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      PubDate: 2017-07-14T13:49:34Z
      DOI: 10.1016/j.addr.2017.07.006
       
  • Effects of Klotho on fibrosis and cancer: A renal focus on mechanisms and
           therapeutic strategies
    • Authors: Rik Mencke; Hannes Olauson; Jan-Luuk Hillebrands
      Abstract: Publication date: Available online 12 July 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Rik Mencke, Hannes Olauson, Jan-Luuk Hillebrands
      Klotho is a membrane-bound protein predominantly expressed in the kidney, where it acts as a permissive co-receptor for Fibroblast Growth Factor 23. In its shed form, Klotho exerts anti-fibrotic effects in several tissues. Klotho-deficient mice spontaneously develop fibrosis and Klotho deficiency exacerbates the disease progression in fibrotic animal models. Furthermore, Klotho overexpression or supplementation protects against fibrosis in various models of renal and cardiac fibrotic disease. These effects are mediated at least partially by the direct inhibitory effects of soluble Klotho on TGFβ1 signaling, Wnt signaling, and FGF2 signaling. Soluble Klotho, as present in the circulation, appears to be the primary mediator of anti-fibrotic effects. Similarly, through inhibition of the TGFβ1, Wnt, FGF2, and IGF1 signaling pathways, Klotho also inhibits tumorigenesis. The Klotho promoter gene is generally hypermethylated in cancer, and overexpression or supplementation of Klotho has been found to inhibit tumor growth in various animal models. This review focuses on the protective effects of soluble Klotho in inhibiting renal fibrosis and fibrosis in distant organs secondary to renal Klotho deficiency. We also discuss the structure-function relationships of Klotho domains and biological effects in the context of potential targeted treatment strategies.
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      PubDate: 2017-07-14T13:49:34Z
      DOI: 10.1016/j.addr.2017.07.009
       
  • 3D in vitro models of liver fibrosis
    • Authors: Leo A. van Grunsven
      Abstract: Publication date: Available online 8 July 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Leo A. van Grunsven
      Animal testing is still the most popular preclinical assesment model for liver fibrosis. To develop efficient anti-fibrotic therapies, robust and representative in vitro models are urgently needed. The most widely used in vitro fibrosis model is the culture-induced activation of primary rodent hepatic stellate cells. While these cultures have contributed greatly to the current understanding of hepatic stellate cell activation, they seem to be inadequate to cover the complexity of this regenerative response. This review summarizes recent progress towards the development of 3D culture models of liver fibrosis. Thusfar, only a few hepatic culture systems have successfully implemented hepatic stellate cells (or other non-parenchymal cells) into hepatocyte cultures. Recent advances in bioprinting, spheroid- and precision-cut liver slice cultures and the use of microfluidic bioreactors will surely lead to valid 3D in vitro models of liver fibrosis in the near future.
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      PubDate: 2017-07-14T13:49:34Z
      DOI: 10.1016/j.addr.2017.07.004
       
  • Exploiting lymphatic vessels for immunomodulation: Rationale,
           opportunities, and challenges
    • Authors: Katharina Maisel; Maria Stella Sasso; Lambert Potin; Melody A. Swartz
      Abstract: Publication date: Available online 8 July 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Katharina Maisel, Maria Stella Sasso, Lambert Potin, Melody A. Swartz
      Lymphatic vessels are the primary route of communication from peripheral tissues to the immune system; as such, they represent an important component of local immunity. In addition to their transport functions, new immunomodulatory roles for lymphatic vessels and lymphatic endothelial cells have come to light in recent years, demonstrating that lymphatic vessels help shape immune responses in a variety of ways: promoting tolerance to self-antigens, archiving antigen for later presentation, dampening effector immune responses, and resolving inflammation, among others. In addition to these new biological insights, the growing field of immunoengineering has begun to explore therapeutic approaches to utilize or exploit the lymphatic system for immunotherapy.
      Graphical abstract image

      PubDate: 2017-07-14T13:49:34Z
      DOI: 10.1016/j.addr.2017.07.005
       
  • Pharmacological and Physical Vessel Modulation Strategies to Improve
           EPR-mediated Drug Targeting to Tumors
    • Authors: Tarun Ojha; Vertika Pathak; Yang Shi; Wim Hennink; Chrit Moonen; Gert Storm; Fabian Kiessling; Twan Lammers
      Abstract: Publication date: Available online 8 July 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Tarun Ojha, Vertika Pathak, Yang Shi, Wim Hennink, Chrit Moonen, Gert Storm, Fabian Kiessling, Twan Lammers
      . The performance of nanomedicine formulations depends on the Enhanced Permeability and Retention (EPR) effect. Prototypic nanomedicine-based drug delivery systems, such as liposomes, polymers and micelles, aim to exploit the EPR effect to accumulate at pathological sites, to thereby improve the balance between drug efficacy and toxicity. Thus far, however, tumor-targeted nanomedicines have not yet managed to achieve convincing therapeutic results, at least not in large cohorts of patients. This is likely mostly due to high inter- and intra-patient heterogeneity in EPR. Besides developing (imaging) biomarkers to monitor and predict EPR, another strategy to address this heterogeneity is the establishment of vessel modulation strategies to homogenize and improve EPR. Over the years, several pharmacological and physical co-treatments have been evaluated to improve EPR-mediated tumor targeting. These include pharmacological strategies, such as vessel permeabilization, normalization, disruption and promotion, as well as physical EPR enhancement via hyperthermia, radiotherapy, sonoporation and phototherapy. In the present manuscript, we summarize exemplary studies showing that pharmacological and physical vessel modulation strategies can be used to improve tumor-targeted drug delivery, and we discuss how these advanced combination regimens can be optimally employed to enhance the (pre-) clinical performance of tumor-targeted nanomedicines.
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      PubDate: 2017-07-14T13:49:34Z
      DOI: 10.1016/j.addr.2017.07.007
       
  • Nano-technology based carriers for nitrogen-containing bisphosphonates
           delivery as sensitisers of γδ T cells for anticancer immunotherapy
    • Authors: Naomi O. Hodgins; Julie Tzu-Wen Wang; Khuloud T. Al-Jamal
      Abstract: Publication date: Available online 8 July 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Naomi O. Hodgins, Julie Tzu-Wen Wang, Khuloud T. Al-Jamal
      Nitrogen containing bisphosphonates (N-BPs) including zoledronate (ZOL) and alendronate (ALD) inhibit farnesyl diphosphate synthase, and have been shown to have a cytotoxic affect against cancer cells as a monotherapy and to also sensitise tumour cells to destruction by γδ T cells. γδ T cells are a subset of human T lymphocytes and have a diverse range of roles in the immune system including the recognition and destruction of cancer cells. This property of γδ T cells can be harnessed for use in cancer immunotherapy through in vivo expansion or the adoptive transfer of ex vivo activated γδ T cells. The use of N-BPs with γδ T cells has been shown to have a synergistic effect in in vitro, animal and clinical studies. N-BPs have limited in vivo activity due to rapid clearance from the circulation. By encapsulating N-BPs in liposomes (L) it is possible to increase the levels of N-BPs at non-osseous tumour sites. L-ZOL and L-ALD have been shown to have different toxicological profiles than free ZOL or ALD. Both L-ALD and L-ZOL led to increased spleen weight, leucocytosis, neutrophilia and lymphocytopenia in mice after intravenous injection. L-ALD was shown to be better tolerated than L-ZOL in murine studies. Biodistribution studies have been performed in order to better understand the interaction of N-BPs and γδ T cells in vivo. Additionally, in vivo therapy studies have shown that mice treated with both L-ALD and γδ T cells had a significant reduction in tumour growth compared to mice treated with L-ALD or γδ T cells alone. The use of ligand-targeted liposomes may further increase the efficacy of this combinatory immunotherapy. Liposomes targeting the αvβ6 integrin receptor using the peptide A20FMDV2 had a greater ability than untargeted liposomes in sensitising cancer cells to destruction by γδ T cells in αvβ6 positive cancer cell lines.
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      PubDate: 2017-07-14T13:49:34Z
      DOI: 10.1016/j.addr.2017.07.003
       
  • Drug delivery devices for retinal diseases
    • Authors: Hirokazu Kaji; Nobuhiro Nagai; Matsuhiko Nishizawa; Toshiaki Abe
      Abstract: Publication date: Available online 6 July 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Hirokazu Kaji, Nobuhiro Nagai, Matsuhiko Nishizawa, Toshiaki Abe
      Retinal degenerative diseases are a leading cause of irreversible blindness and visual impairment, affecting millions of people worldwide. Although intravitreal injection can directly deliver drugs to the posterior segment of the eye, it is invasive and associated with serious side effects. The design of drug delivery systems targeting the posterior segment of the eye in a less invasive manner has still been challenging because of various anatomical and physiological barriers. In this review, we provide an overview of the current implant device-based approaches used for treating retinal degenerative diseases. We then offer our perspectives on future directions and challenges that remain for developing more effective device-based therapies for retinal diseases.
      Graphical abstract image

      PubDate: 2017-07-14T13:49:34Z
      DOI: 10.1016/j.addr.2017.07.002
       
  • Pharmaceutical aspects of salt and cocrystal forms of APIs and
           characterization challenges
    • Authors: Paolo Cerreia Vioglio; Michele R. Chierotti; Roberto Gobetto
      Abstract: Publication date: Available online 5 July 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Paolo Cerreia Vioglio, Michele R. Chierotti, Roberto Gobetto
      In recent years many efforts have been devoted to the screening and the study of new solid-state forms of old active pharmaceutical ingredients (APIs) with salification or co-crystallization processes, thus modulating final properties without changing the pharmacological nature. Salts, hydrates/solvates, and cocrystals are the common solid-state forms employed. They offer the intriguing possibility of exploring different pharmaceutical properties for a single API in the quest of enhancing the final drug product. New synthetic strategies and advanced characterization techniques have been recently proposed in this hot topic for pharmaceutical companies. This paper reviews the recent progresses in the field particularly focusing on the characterization challenges encountered when the nature of the solid-state form must be determined. The aim of this article is to offer the state-of-the-art on this subject in order to develop new insights and to promote cooperative efforts in the fascinating field of API salt and cocrystal forms.
      Graphical abstract image

      PubDate: 2017-07-06T07:37:28Z
      DOI: 10.1016/j.addr.2017.07.001
       
  • Prodrugs in medicinal chemistry and enzyme prodrug therapies
    • Authors: Raoul Walther; Jarkko Rautio; Alexander N. Zelikin
      Abstract: Publication date: Available online 1 July 2017
      Source:Advanced Drug Delivery Reviews
      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.
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      PubDate: 2017-07-06T07:37:28Z
      DOI: 10.1016/j.addr.2017.06.013
       
  • Advances in keratinocyte delivery in burn wound care
    • Authors: Britt ter Horst; Gurpreet Chouhan; Naiem S. Moiemen; Liam M. Grover
      Abstract: Publication date: Available online 28 June 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Britt ter Horst, Gurpreet Chouhan, Naiem S. Moiemen, Liam M. Grover
      This review gives an updated overview on keratinocyte transplantation in burn wounds concentrating on application methods and future therapeutic cell delivery options with a special interest in hydrogels and spray devices for cell delivery. To achieve faster re-epithelialisation of burn wounds, the original autologous keratinocyte culture and transplantation technique was introduced over 3 decades ago. Application types of keratinocytes transplantation have improved from cell sheets to single-cell solutions delivered with a spray system. However, further enhancement of cell culture, cell viability and function in vivo, cell carrier and cell delivery systems remain themes of interest. Hydrogels such as chitosan, alginate, fibrin and collagen are frequently used in burn wound care and have advantageous characteristics as cell carriers. Future approaches of keratinocyte transplantation involve spray devices, but optimisation of application technique and carrier type is necessary.
      Graphical abstract image

      PubDate: 2017-07-06T07:37:28Z
      DOI: 10.1016/j.addr.2017.06.012
       
  • Emerging Strategies for Delivering Antiangiogenic Therapies to Primary and
           Metastatic Brain Tumors
    • Authors: Vasileios Askoxylakis; Costas D. Arvanitis; Christina S.F. Wong; Gino B. Ferraro; Rakesh K. Jain
      Abstract: Publication date: Available online 22 June 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Vasileios Askoxylakis, Costas D. Arvanitis, Christina S.F. Wong, Gino B. Ferraro, Rakesh K. Jain
      Five-years survival rates have not increased appreciably for patients with primary and metastatic brain tumors. Nearly 17,000 patients die from primary brain tumors, whereas approximately 200,000 cases are diagnosed with brain metastasis every year in the US alone. At the same time, with improved control of systemic disease, the incidence of brain metastasis is increasing. Thus novel approaches for improving the treatment outcome for these uniformly fatal diseases are needed urgently. In the review, we summarize the challenges in the treatment of these diseases using antiangiogenic therapies alone or in combination with radio-, chemo- and immuno-therapies. We also discuss the emerging strategies to improve the treatment outcome using both pharmacological approaches to normalize the tumor microenvironment and physical approaches (e.g., focused ultrasound) to modulate the blood-tumor-barrier, along with limitations of each approach. Finally, we offer some new avenues of future research.
      Graphical abstract image

      PubDate: 2017-06-27T01:27:52Z
      DOI: 10.1016/j.addr.2017.06.011
       
  • Nanoformulations for Combination or Cascade Anticancer Therapy
    • Authors: Lei Miao; Shutao Guo; C. Michael Lin; Qi Liu; Leaf Huang
      Abstract: Publication date: Available online 15 June 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Lei Miao, Shutao Guo, C. Michael Lin, Qi Liu, Leaf Huang
      Nanoparticle drug formulations have been extensively investigated, developed, and in some cases, approved by the Food and Drug Administration (FDA). Synergistic combinations of drugs having distinct tumor-inhibiting mechanisms and non-overlapping toxicity can circumvent the issue of treatment resistance and may be essential for effective anti-cancer therapy. At the same time, co-delivery of a combined regimen by a single nanocarrier presents a challenge due to differences in solubility, molecular weight, functional groups and encapsulation conditions between the two drugs. This review discusses cellular and microenvironment mechanisms behind treatment resistance and nanotechnology-based solutions for effective anti-cancer therapy. Co-loading or cascade delivery of multiple drugs using of polymeric nanoparticles, polymer-drug conjugates and lipid nanoparticles will be discussed along with lipid-coated drug nanoparticles developed by our lab and perspectives on combination therapy.
      Graphical abstract image

      PubDate: 2017-06-19T13:29:10Z
      DOI: 10.1016/j.addr.2017.06.003
       
  • Cells as Advanced Therapeutics: State-of-the-art, Challenges, and
           Opportunities in Large Scale Biomanufacturing of High-Quality Cells for
           Adoptive Immunotherapies
    • Authors: Nate J. Dwarshuis; Kirsten Parratt; Adriana Santiago-Miranda; Krishnendu Roy
      Abstract: Publication date: Available online 15 June 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Nate J. Dwarshuis, Kirsten Parratt, Adriana Santiago-Miranda, Krishnendu Roy
      Therapeutic cells hold tremendous promise in treating currently incurable, chronic diseases since they perform multiple, integrated, complex functions in vivo compared to traditional small-molecule drugs or biologics. However, they also pose significant challenges as therapeutic products because (a) their complex mechanisms of actions are difficult to understand and (b) low-cost bioprocesses for large-scale, reproducible manufacturing of cells have yet to be developed. Immunotherapies using T cells and dendritic cells (DCs) have already shown great promise in treating several types of cancers, and human mesenchymal stromal cells (hMSCs) are now extensively being evaluated in clinical trials as immune-modulatory cells. Despite these exciting developments, the full potential of cell-based therapeutics cannot be realized unless new engineering technologies enable cost-effective, consistent manufacturing of high-quality therapeutic cells at large-scale. Here we review cell-based immunotherapy concepts focused on the state-of-the-art in manufacturing processes including cell sourcing, isolation, expansion, modification, quality control (QC), and culture media requirements. We also offer insights into how current technologies could be significantly improved and augmented by new technologies, and how disciplines must converge to meet the long-term needs for large-scale production of cell-based immunotherapies.
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      PubDate: 2017-06-19T13:29:10Z
      DOI: 10.1016/j.addr.2017.06.005
       
  • Combinatorial immunotherapy and nanoparticle mediated hyperthermia
    • Authors: Austin J. Moy; James W. Tunnell
      Abstract: Publication date: Available online 15 June 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Austin J. Moy, James W. Tunnell
      Immune checkpoint therapy has become the first widely adopted immunotherapy for patients with late stage malignant melanoma, with potential for a wide range of cancers. While some patients can experience long term disease remission, this is limited only to a subset of patients and tumor types. The path forward to expand this therapy to more patients and tumor types is currently thought to be combinatorial treatments, the combination of immunotherapy with other treatments. In this review, the combinatorial approach of immune checkpoint therapy combined with nanoparticle-assisted localized hyperthermia is discussed, starting with an overview of the different nanoparticle hyperthermia approaches in development, an overview of the state of immune checkpoint therapy, recent reports of immune checkpoint therapy and nanoparticle-assisted hyperthermia in a combinatorial approach, and finally a discussion of future research topics and areas to be explored in this new combinatorial approach to cancer treatment.
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      PubDate: 2017-06-19T13:29:10Z
      DOI: 10.1016/j.addr.2017.06.008
       
  • Engineering Challenges for Brain Tumor Immunotherapy
    • Authors: Johnathan G. Lyon; Nassir Mokarram; Tarun Saxena; Sheridan L. Carroll; Ravi V. Bellamkonda
      Abstract: Publication date: Available online 15 June 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Johnathan G. Lyon, Nassir Mokarram, Tarun Saxena, Sheridan L. Carroll, Ravi V. Bellamkonda
      Malignant brain tumors represent one of the most devastating forms of cancer with abject survival rates that have not changed in the past 60years. This is partly because the brain is a critical organ, and poses unique anatomical, physiological, and immunological barriers. The unique interplay of these barriers also provides an opportunity for creative engineering solutions. Cancer immunotherapy, a means of harnessing the host immune system for anti-tumor efficacy, is becoming a standard approach for treating many cancers. However, its use in brain tumors is not widespread. This review discusses the current approaches, and hurdles to these approaches in treating brain tumors, with a focus on immunotherapies. We identify critical barriers to immunoengineering brain tumor therapies and discuss possible solutions to these challenges.
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      PubDate: 2017-06-19T13:29:10Z
      DOI: 10.1016/j.addr.2017.06.006
       
  • Nanomedicine-based combination anticancer therapy between nucleic acids
           and small-molecular drugs
    • Authors: Wei Huang; Liqing Chen; Lin Kang; Mingji Jin; Ping Sun; Xin Xin; Zhonggao Gao; You Han Bae
      Abstract: Publication date: Available online 15 June 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Wei Huang, Liqing Chen, Lin Kang, Mingji Jin, Ping Sun, Xin Xin, Zhonggao Gao, You Han Bae
      Anticancer therapy has always been a vital challenge for the development of nanomedicine. Repeated single therapeutic agent may lead to undesirable and severe side effects, unbearable toxicity and multidrug resistance due to complex nature of tumor. Nanomedicine-based combination anticancer therapy can synergistically improve antitumor outcomes through multiple-target therapy, decreasing the dose of each therapeutic agent and reducing side effects. There are versatile combinational anticancer strategies such as chemotherapeutic combination, nucleic acid-based co-delivery, intrinsic sensitive and extrinsic stimulus combinational patterns. Based on these combination strategies, various nanocarriers and drug delivery systems were engineered to carry out the efficient co-delivery of combined therapeutic agents for combination anticancer therapy. This review focused on illustrating nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs for synergistically improving anticancer efficacy.
      Graphical abstract image

      PubDate: 2017-06-19T13:29:10Z
      DOI: 10.1016/j.addr.2017.06.004
       
  • Drug Discovery and Therapeutic Delivery for the Treatment of B and T cell
           Tumors
    • Authors: Regan Stephenson; Ankur Singh
      Abstract: Publication date: Available online 15 June 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Regan Stephenson, Ankur Singh
      Hematological malignancies manifest as lymphoma, leukemia, and myeloma, and remain a burden on society. From initial therapy to endless relapse-related treatment, societal burden is felt not only in the context of healthcare cost, but also in the compromised quality of life of patients. Long-term therapeutic strategies have become the standard in keeping hematological malignancies at bay as these cancers develop resistance to each round of therapy with time. As a result, there is a continual need for the development of new drugs to combat resistant disease in order to prolong patient life, if not to produce a cure. This review aims to summarize advances in targeting lymphoma, leukemia, and myeloma in both cutting-edge and well established platforms. Current standard of treatment will be reviewed for these malignancies and emphasis will be made on new therapy development in the areas of antibody engineering, epigenetic small molecule inhibiting drugs, vaccine development, and chimeric antigen receptor cell engineering. In addition, platforms for the delivery of these and other drugs will be reviewed including antibody-drug conjugates, micro- and nanoparticles, and multimodal hydrogels. Lastly, we propose that tissue engineered constructs for hematological malignancies are the missing link in targeted drug discovery alongside mouse and patient-derived xenograft models.
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      PubDate: 2017-06-19T13:29:10Z
      DOI: 10.1016/j.addr.2017.06.010
       
  • Bioengineering strategies for inducing tolerance in autoimmune diabetes
    • Authors: Steinunn Baekkeskov; Jeffrey A. Hubbell; Edward A. Phelps
      Abstract: Publication date: Available online 15 June 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Steinunn Baekkeskov, Jeffrey A. Hubbell, Edward A. Phelps
      Type 1 diabetes is an autoimmune disease marked by the destruction of insulin-producing beta cells in the pancreatic islets. Strategies to delay onset or prevent the autoimmune recognition of beta cell antigens or T cell-mediated killing of beta cells have mainly focused on systemic immunomodulation and antigen-specific immunotherapy. To bridge the fields of type 1 diabetes immunology and biomaterials engineering, this article will review recent trends in the etiology of type 1 diabetes immunopathology and will focus on the contributions of emerging bioengineered strategies in the fight against beta cell autoimmunity in type 1 diabetes.
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      PubDate: 2017-06-19T13:29:10Z
      DOI: 10.1016/j.addr.2017.06.007
       
  • Precision Monitoring of Immunotherapies in Solid Organ and Hematopoietic
           Stem Cell Transplantation
    • Authors: Rose Diloreto; Kiran Khush; Iwijn De Vlaminck
      Abstract: Publication date: Available online 15 June 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Rose Diloreto, Kiran Khush, Iwijn De Vlaminck
      Pharmacological immunotherapies are a key component of post-transplant therapy in solid-organ and hematopoietic stem cell transplantation. In current clinical practice, immunotherapies largely follow a one-size fits all approach, leaving a large portion of transplant recipients either over- or under-immunosuppressed, and consequently at risk of infections or immune-mediated complications. Our goal here is to review recent and rapid advances in precision and genomic medicine approaches to monitoring of post-transplant immunotherapies. We will discuss recent advances in precision measurements of pharmacological immunosuppression, measurements of the plasma and gut microbiome, strategies to monitor for allograft injury and post-transplant malignancies via circulating cell-free DNA, and comprehensive measurements of the B and T cell immune cell repertoire.
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      PubDate: 2017-06-19T13:29:10Z
      DOI: 10.1016/j.addr.2017.06.009
       
  • Covalent nanodelivery systems for selective imaging and treatment of brain
           tumors
    • Authors: Julia Y. Ljubimova; Tao Sun; Leila Mashouf; Alexander V. Ljubimov; Liron L. Israel; Vladimir A. Ljubimov; Vida Falahatian; Eggehard Holler
      Abstract: Publication date: Available online 10 June 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Julia Y. Ljubimova, Tao Sun, Leila Mashouf, Alexander V. Ljubimov, Liron L. Israel, Vladimir A. Ljubimov, Vida Falahatian, Eggehard Holler
      Nanomedicine is a rapidly evolving form of therapy that holds a great promise in superior drug delivery efficiency and therapeutic efficacy than conventional cancer treatment. In this review, we attempt to cover the benefits and the limitations of current nanomedicines with special attention to covalent nanoconjugates for imaging and drug delivery in brain. The improvement in brain tumor treatment remains dismal despite decades of efforts in drug development and patient care. One of the major obstacles in brain cancer treatment is the poor drug delivery efficiency owing to the unique blood-brain-barrier (BBB) in the CNS. Although various anti-cancer agents are available to treat tumors outside of the CNS, the majority fails to cross the BBB. In this regard, nanomedicines have increasingly drawn attention due to their multi-functionality and versatility. Nano-drugs can penetrate BBB and other biological barriers, and selectively accumulate in tumor cells, while concurrently decreasing systemic toxicity.
      Graphical abstract image

      PubDate: 2017-06-14T13:24:14Z
      DOI: 10.1016/j.addr.2017.06.002
       
  • Pathophysiology of liver fibrosis and the methodological barriers to the
           development of anti-fibrogenic agents
    • Authors: Katrin Böttcher; Massimo Pinzani
      Abstract: Publication date: Available online 6 June 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Katrin Böttcher, Massimo Pinzani
      Liver fibrosis and cirrhosis resulting from long-standing liver damage represents a major health care burden worldwide. To date, there is no anti-fibrogenic agent available, making liver transplantation the only curative treatment for decompensated cirrhotic liver disease. Liver fibrosis can result from different underlying chronic liver disease, such as chronic viral infection, excessive alcohol consumption, fatty liver disease or autoimmune liver diseases. It is becoming increasingly recognised that as a result from different pathogenic mechanisms liver fibrosis must be considered as many different diseases for which individual treatment strategies need to be developed. Moreover, the pathogenic changes of both liver architecture and vascularisation in cirrhotic livers, as well as the lack of “true-to-life” in vitro models have impeded the development of an effective anti-fibrogenic drug. Thus, in order to identify an efficient anti-fibrogenic compound, novel in-vitro models mimicking the interplay between pro-fibrogenic cell populations, immune cells and, importantly, the extracellular matrix need to be developed.
      Graphical abstract image

      PubDate: 2017-06-14T13:24:14Z
      DOI: 10.1016/j.addr.2017.05.016
       
  • Therapeutic pro-fibrogenic signaling pathways in fibroblasts
    • Authors: Stefania Cannito; Erica Novo; Maurizio Parola
      Abstract: Publication date: Available online 1 June 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Stefania Cannito, Erica Novo, Maurizio Parola
      Myofibroblasts (MFs) play a critical role in the progression of chronic inflammatory and fibroproliferative diseases in different tissues/organs, whatever the etiology. Fibrosis is preceded and sustained by persistent injury and inflammatory response in a profibrogenic scenario involving mutual interactions, operated by several mediators and pathways, of MFs and related precursor cells with innate immunity cells and virtually any cell type in a defined tissue. These interactions, mediators and related signaling pathways are critical in initiating and perpetuating the differentiation of precursors cells into MFs that in different tissues share peculiar traits and phenotypic responses, including the ability to proliferate, produce ECM components, migrate and contribute to the modulation of inflammatory response and tissue angiogenesis. Literature studies related to liver, lung and kidney fibrosis have outlined a number of MF-related core regulatory fibrogenic signaling pathways conserved across these different organs and potentially targetable in order to develop effective antifibrotic therapeutic strategies.
      Graphical abstract image

      PubDate: 2017-06-04T16:16:55Z
      DOI: 10.1016/j.addr.2017.05.017
       
  • Engineering in vitro models of hepatofibrogenesis
    • Authors: Giuseppe Mazza; Walid Al-Akkad; Krista Rombouts
      Abstract: Publication date: Available online 31 May 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Giuseppe Mazza, Walid Al-Akkad, Krista Rombouts
      Chronic liver disease is a major cause of morbidity and mortality worldwide marked by chronic inflammation and fibrosis/scarring, resulting in end-stage liver disease and its complications. Hepatic stellate cells (HSCs) are a dominant contributor to liver fibrosis by producing excessive extracellular matrix (ECM), irrespective of the underlying disease aetiologies, and for many decades research has focused on the development of a number of anti-fibrotic strategies targeting this cell. Despite major improvements in two-dimensional systems (2D) by using a variety of cell culture models of different complexity, an efficient anti-fibrogenic therapy has yet to be developed. The development of well-defined three-dimensional (3D) in vitro models, which mimic ECM structures as found in vivo, have demonstrated the importance of cell-matrix bio-mechanics, the complex interactions between HSCs and hepatocytes and other non-parenchymal cells, and this to improve and promote liver cell-specific functions. Henceforth, refinement of these 3D in vitro models, which reproduce the liver microenvironment, will lead to new objectives and to a possible new era in the search for antifibrogenic compounds.
      Graphical abstract image

      PubDate: 2017-06-04T16:16:55Z
      DOI: 10.1016/j.addr.2017.05.018
       
  • Molecular properties associated with transporter-mediated drug disposition
    • Authors: Manthena V. Varma; Yurong Lai; Ayman El-Kattan
      Abstract: Publication date: Available online 26 May 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Manthena V. Varma, Yurong Lai, Ayman El-Kattan
      Membrane transporters play a key role in the absorption, distribution, clearance and elimination of drugs. Understanding the drug properties and structure activity relationships (SAR) for affinity to membrane transporters is critical to optimize clearance and pharmacokinetics during drug design. To facilitate the early identification of clearance mechanism, a framework named the extended clearance classification system (ECCS) was recently introduced. Using in vitro and physicochemical properties that are readily available in early drug discovery, ECCS has been successfully applied to identify major clearance mechanism and to implicate the role of membrane transporters in determining pharmacokinetics. While the crystal structures for most of the drug transporters are currently not available, ligand-based modeling approaches that use information obtained from the structure and molecular properties of the ligands have been applied to associate the drug-related properties and transporter-mediated disposition. The approach allows prospective prediction of transporter both substrate and/or inhibitor affinity and build quantitative structure-activity relationship (QSAR) to enable early optimization of pharmacokinetics, tissue distribution and drug-drug interaction risk. Drug design applications can be further improved through uncovering transporter protein crystal structure and generation of quality data to refine and develop viable predictive models.
      Graphical abstract image

      PubDate: 2017-05-30T08:17:39Z
      DOI: 10.1016/j.addr.2017.05.014
       
  • Delivering safer immunotherapies for cancer
    • Authors: Lauren Milling; Yuan Zhang; Darrell J. Irvine
      Abstract: Publication date: Available online 22 May 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Lauren Milling, Yuan Zhang, Darrell J. Irvine
      Cancer immunotherapy is now a powerful clinical reality, with a steady progression of new drug approvals and a massive pipeline of additional treatments in clinical and preclinical development. However, modulation of the immune system can be a double-edged sword: Drugs that activate immune effectors are prone to serious non-specific systemic inflammation and autoimmune side effects. Drug delivery technologies have an important role to play in harnessing the power of immune therapeutics while avoiding on-target/off-tumor toxicities. Here we review mechanisms of toxicity for clinically-relevant immunotherapeutics, and discuss approaches based in drug delivery technology to enhance the safety and potency of these treatments. These include strategies to merge drug delivery with adoptive cellular therapies, targeting immunotherapies to tumors or select immune cells, and localizing therapeutics intratumorally. Rational design employing lessons learned from the drug delivery and nanomedicine fields has the potential to facilitate immunotherapy reaching its full potential.
      Graphical abstract image

      PubDate: 2017-05-25T15:19:01Z
      DOI: 10.1016/j.addr.2017.05.011
       
  • Bio-synthetic materials for immunomodulation of islet transplants
    • Authors: Greg A. Foster; Andrés J. García
      Abstract: Publication date: Available online 19 May 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Greg A. Foster, Andrés J. García
      Clinical islet transplantation is an effective therapy in restoring physiological glycemic control in type 1 diabetics. However, allogeneic islets derived from cadaveric sources elicit immune responses that result in acute and chronic islet destruction. To prevent immune destruction of islets, transplant recipients require lifelong delivery of immunosuppressive drugs, which are associated with debilitating side effects. Biomaterial-based strategies to eliminate the need for immunosuppressive drugs are an emerging therapy for improving islet transplantation. In this context, two main approaches have been used: 1) encapsulation of islets to prevent infiltration and contact of immune cells, and 2) local release of immunomodulatory molecules from biomaterial systems that suppress local immunity. Synthetic biomaterials provide excellent control over material properties, molecule presentation, and therapeutic release, and thus, are an emerging platform for immunomodulation to facilitate islet transplantation. This review highlights various synthetic biomaterial-based strategies for preventing immune rejection of islet allografts.
      Graphical abstract image

      PubDate: 2017-05-21T07:36:28Z
      DOI: 10.1016/j.addr.2017.05.012
       
  • Combinatorial Drug Delivery Approaches for Immunomodulation
    • Authors: Joshua M. Stewart; Benjamin G. Keselowsky
      Abstract: Publication date: Available online 19 May 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Joshua M. Stewart, Benjamin G. Keselowsky
      Immunotherapy has been widely explored for applications to both augment or suppress intrinsic host immunity. Clinical achievements have seen a number of immunotherapeutic drugs displace established strategies like chemotherapy in treating immune-associated diseases. However, single drug approaches modulating an individual arm of the immune system are often incompletely effective. Imperfect mechanistic understanding and heterogeneity within disease pathology have seen monotherapies inadequately equipped to mediate complete disease remission. Recent success in applications of combinatorial immunotherapy has suggested that targeting multiple biological pathways simultaneously may be critical in treating complex immune pathologies. Drug delivery approaches through engineered biomaterials offer the potential to augment desired immune responses while mitigating toxic side-effects by localizing immunotherapy. This review discusses recent advances in immunotherapy and highlights newly explored combinatorial drug delivery approaches. Furthermore, prospective future directions for immunomodulatory drug delivery to exploit are provided.
      Graphical abstract image

      PubDate: 2017-05-21T07:36:28Z
      DOI: 10.1016/j.addr.2017.05.013
       
  • Macrophage-based therapeutic strategies in regenerative medicine
    • Authors: Kara L. Spiller; Timothy J. Koh
      Abstract: Publication date: Available online 16 May 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Kara L. Spiller, Timothy J. Koh
      Mounting evidence suggests that therapeutic cell and drug delivery strategies designed to actively harness the regenerative potential of the inflammatory response have great potential in regenerative medicine. In particular, macrophages have emerged as a primary target because of their critical roles in regulating multiple phases of tissue repair through their unique ability to rapidly shift phenotypes. Herein, we review macrophage-based therapies, focusing on the translational potential for cell delivery of ex vivo-activated macrophages and delivery of molecules and biomaterials to modulate accumulation and phenotype of endogenous macrophages. We also review current obstacles to progress in translating basic findings to therapeutic applications, including the need for improved understanding of context-dependent macrophage functions and the myriad factors that regulate macrophage phenotype; potential species-specific differences (e.g. humans versus mice); quality control issues; and the lack of standardized procedures and nomenclature for characterizing macrophages. Looking forward, the inherent plasticity of macrophages represents a daunting challenge for harnessing these cells in regenerative medicine therapies but also great opportunity for improving patient outcomes in a variety of pathological conditions.
      Graphical abstract image

      PubDate: 2017-05-21T07:36:28Z
      DOI: 10.1016/j.addr.2017.05.010
       
  • Hepatic stellate cells as key target in liver fibrosis
    • Authors: Takaaki Higashi; Scott L. Friedman; Yujin Hoshida
      Abstract: Publication date: Available online 12 May 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Takaaki Higashi, Scott L. Friedman, Yujin Hoshida
      Progressive liver fibrosis, induced by chronic viral and metabolic disorders, leads to more than one million deaths annually via development of cirrhosis, although no antifibrotic therapy has been approved to date. Transdifferentiation (or “activation”) of hepatic stellate cells is the major cellular source of matrix protein-secreting myofibroblasts, the major driver of liver fibrogenesis. Paracrine signals from injured epithelial cells, fibrotic tissue microenvironment, immune and systemic metabolic dysregulation, enteric dysbiosis, and hepatitis viral products can directly or indirectly induce stellate cell activation. Dysregulated intracellular signaling, epigenetic changes, and cellular stress response represent candidate targets to deactivate stellate cells by inducing reversion to inactivated state, cellular senescence, apoptosis, and/or clearance by immune cells. Cell type- and target-specific pharmacological intervention to therapeutically induce the deactivation will enable more effective and less toxic precision antifibrotic therapies.
      Graphical abstract image

      PubDate: 2017-05-16T03:31:47Z
      DOI: 10.1016/j.addr.2017.05.007
       
  • Modulating Angiogenesis with Integrin-Targeted Nanomedicines
    • Authors: Aroa Duro-Castano; Elena Gallon; Caitlin Decker; María J. Vicent
      Abstract: Publication date: Available online 12 May 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Aroa Duro-Castano, Elena Gallon, Caitlin Decker, María J. Vicent
      Targeting angiogenesis-related pathologies, which include tumorigenesis and metastatic processes, has become an attractive strategy for the development of efficient guided nanomedicines. In this respect, integrins are cell-adhesion molecules involved in angiogenesis signaling pathways and are overexpressed in many angiogenic processes. Therefore, they represent specific biomarkers not only to monitor disease progression but also to rationally design targeted nanomedicines. Arginine-glycine-aspartic (RGD) containing peptides that bind to specific integrins have been widely utilized to provide ligand-mediated targeting capabilities to small molecules, peptides, proteins, and antibodies, as well as to drug/imaging agent-containing nanomedicines, with the final aim of maximizing their therapeutic index. Within this review, we aim to cover recent and relevant examples of different integrin-assisted nanosystems including polymeric nanoconstructs, liposomes, and inorganic nanoparticles applied in drug/gene therapy as well as imaging and theranostics. We will also critically address the overall benefits of integrin-targeting.
      Graphical abstract image

      PubDate: 2017-05-16T03:31:47Z
      DOI: 10.1016/j.addr.2017.05.008
       
  • Applying nanomedicine in maladaptive inflammation and angiogenesis
    • Authors: Amr Alaarg; Carlos Pérez-Medina; Josbert M. Metselaar; Matthias Nahrendorf; Zahi A. Fayad; Gert Storm; Willem J.M. Mulder
      Abstract: Publication date: Available online 12 May 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Amr Alaarg, Carlos Pérez-Medina, Josbert M. Metselaar, Matthias Nahrendorf, Zahi A. Fayad, Gert Storm, Willem J.M. Mulder
      Inflammation and angiogenesis drive the development and progression of multiple devastating diseases such as atherosclerosis, cancer, rheumatoid arthritis, and inflammatory bowel disease. Though these diseases have very different phenotypic consequences, they possess several common pathophysiological features in which monocyte recruitment, macrophage polarization, and enhanced vascular permeability play critical roles. Thus, developing rational targeting strategies tailored to the different stages of the journey of monocytes, from bone marrow to local lesions, and their extravasation from the vasculature in diseased tissues will advance nanomedicine. The integration of in vivo imaging uniquely allows studying nanoparticle kinetics, accumulation, clearance, and biological activity, at levels ranging from subcellular to an entire organism, and will shed light on the fate of intravenously administered nanomedicines. We anticipate that convergence of nanomedicines, biomedical engineering, and life sciences will help to advance clinically relevant therapeutics and diagnostic agents for patients with chronic inflammatory diseases.
      Graphical abstract image

      PubDate: 2017-05-16T03:31:47Z
      DOI: 10.1016/j.addr.2017.05.009
       
  • Peptide-modified nanomedicines for targeting cells at the tumor
           microenvironment
    • Authors: Ayelet David
      Abstract: Publication date: Available online 12 May 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Ayelet David
      Since their initial discovery more than 30 years ago, tumor-homing peptides have become an increasingly useful tool for targeted delivery of therapeutic and diagnostic agents into tumors. Today, it is well accepted that cells at tumor microenvironment (TME) contributes in many ways to cancer development and progression. Tumor-homing peptide are highly suitable ligands to actively target cells at the TME owing to their small size, low immunogenicity, stability, easy manufacturing and low cost. When conjugated to nanosized medicines (nanomedicines) these ligands can interact specifically with surface receptors expressed on cells in the heterogeneous TME, improve cellular uptake of nanomedicines by target cells, and potentially impair tumor growth and progression. Moreover, peptide-modified nanomedicines can accumulate in the target tissue at higher concentrations than would small conjugates, thus increase overall target tissue exposure to the therapeutic agent, enhance therapeutic efficacy and reduce side effects. This review describes the most studied peptide–directed nanomedicines aimed at targeting cells in the TME, discusses major obstacles and principles in the design of ligands for drug targeting and provides an overview of homing peptides in ligand-targeted nanomedicines that are currently in development for cancer therapy and diagnosis.
      Graphical abstract image

      PubDate: 2017-05-16T03:31:47Z
      DOI: 10.1016/j.addr.2017.05.006
       
  • Lysosomal Enzyme Replacement Therapies: Historical Development, Clinical
           Outcomes, and Future Perspectives
    • Authors: Melani Solomon; Silvia Muro
      Abstract: Publication date: Available online 11 May 2017
      Source:Advanced Drug Delivery Reviews
      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: 2017-05-16T03:31:47Z
      DOI: 10.1016/j.addr.2017.05.004
       
  • Designer outer membrane vesicles as immunomodulatory systems –
           reprogramming bacteria for vaccine delivery
    • Authors: Yehou M.D. Gnopo; Hannah C. Watkins; Taylor C. Stevenson; Matthew P. DeLisa; David Putnam
      Abstract: Publication date: Available online 10 May 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Yehou M.D. Gnopo, Hannah C. Watkins, Taylor C. Stevenson, Matthew P. DeLisa, David Putnam
      Vaccines often require adjuvants to be effective. Traditional adjuvants, like alum, activate the immune response but in an uncontrolled way. Newer adjuvants help to direct the immune response in a more coordinated fashion. Here, we review the opportunity to use the outer membrane vesicles (OMVs) of bacteria as a way to modulate the immune response toward making more effective vaccines. This review outlines the different types of OMVs that have been investigated for vaccine delivery and how they are produced. Because OMVs are derived from bacteria, they have compositions that may not be compatible with parenteral delivery in humans; therefore, we also review the strategies brought to bear to detoxify OMVs while maintaining an adjuvant profile. OMV-based vaccines can be derived from the pathogens themselves, or can be used as surrogate constructs to mimic a pathogen through the heterologous expression of specific antigens in a desired host source strain, and approaches to doing so are reviewed. Additionally, the emerging area of engineered pathogen-specific carbohydrate sequences, or glycosylated OMVs is reviewed and contrasted with protein antigen delivery. Existing OMV-based vaccines as well as their routes of administration round out the text. Overall, this is an exciting time in the OMV field as it matures and leads to more effective and targeted ways to induce desired pathogen-specific immune responses.
      Graphical abstract image

      PubDate: 2017-05-11T01:51:32Z
      DOI: 10.1016/j.addr.2017.05.003
       
  • Surface Engineering for Lymphocyte Programming
    • Authors: Elana Ben-Akiva; Randall A. Meyer; David R. Wilson; Jordan J. Green
      Abstract: Publication date: Available online 10 May 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Elana Ben-Akiva, Randall A. Meyer, David R. Wilson, Jordan J. Green
      The once nascent field of immunoengineering has recently blossomed to include approaches to deliver and present biomolecules to program diverse populations of lymphocytes to fight disease. Building upon improved understanding of the molecular and physical mechanics of lymphocyte activation, varied strategies for engineering surfaces to activate and deactivate T-Cells, B-Cells and natural killer cells are in preclinical and clinical development. Surfaces have been engineered at the molecular level in terms of the presence of specific biological factors, their arrangement on a surface, and their diffusivity to elicit specific lymphocyte fates. In addition, the physical and mechanical characteristics of the surface including shape, anisotropy, and rigidity of particles for lymphocyte activation have been fine-tuned. Utilizing these strategies, acellular systems have been engineered for the expansion of T-Cells and natural killer cells to clinically relevant levels for cancer therapies as well as engineered to program B-Cells to better combat infectious diseases.
      Graphical abstract image

      PubDate: 2017-05-11T01:51:32Z
      DOI: 10.1016/j.addr.2017.05.005
       
  • Screening for new pharmaceutical solid forms using mechanochemistry: A
           practical guide
    • Authors: Dritan Hasa; William Jones
      Abstract: Publication date: Available online 3 May 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Dritan Hasa, William Jones
      Within the pharmaceutical industry, and elsewhere, the screening for new solid forms is a mandatory exercise for both existing and new chemical entities. This contribution focuses on mechanochemistry as a versatile approach for discovering new and alternative solid forms. Whilst a series of recently published extensive reviews exist which focus on mechanistic aspects and potential areas of development of mechanochemistry, in this review we focus on particular practical aspects of mechanochemistry in order to allow full optimisation of the approach in searches for new solid forms including polymorphs, salts and cocrystals as well as their solvated/hydrated analogues. As a consequence of the apparent experimental simplicity of the method (compared to more traditional protocols e.g. solvent-based methods), the high efficiency and range of conditions available in a mechanochemical screen, mechanochemistry should not be considered simply as an alternative method when other screening methods are not successful, but rather as a key strategy in any fully effective solid form screen providing reduced effort and time as well as the potential of requiring reduced amounts of material.
      Graphical abstract image

      PubDate: 2017-05-06T07:28:46Z
      DOI: 10.1016/j.addr.2017.05.001
       
  • Substrate Mediated Enzyme Prodrug Therapy
    • Authors: Betina Fejerskov; Morten T. Jarlstad Olesen; Alexander N. Zelikin
      Abstract: Publication date: Available online 27 April 2017
      Source:Advanced Drug Delivery Reviews
      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: 2017-04-30T15:33:56Z
      DOI: 10.1016/j.addr.2017.04.013
       
  • Progress in tumor-associated macrophage (TAM)-targeted therapeutics
    • Authors: Chayanon Ngambenjawong; Heather H. Gustafson; Suzie H. Pun
      Abstract: Publication date: Available online 25 April 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Chayanon Ngambenjawong, Heather H. Gustafson, Suzie H. Pun
      As an essential innate immune population for maintaining body homeostasis and warding off foreign pathogens, macrophages display high plasticity and perform diverse supportive functions specialized to different tissue compartments. Consequently, aberrance in macrophage functions contributes substantially to progression of several diseases including cancer, fibrosis, and diabetes. In the context of cancer, tumor-associated macrophages (TAMs) in tumor microenvironment (TME) typically promote cancer cell proliferation, immunosuppression, and angiogenesis in support of tumor growth and metastasis. Oftentimes, the abundance of TAMs in tumor is correlated with poor disease prognosis. Hence, significant attention has been drawn towards development of cancer immunotherapies targeting these TAMs; either depleting them from tumor, blocking their pro-tumoral functions, or restoring their immunostimulatory/tumoricidal properties. This review aims to introduce readers to various aspects in development and evaluation of TAM-targeted therapeutics in pre-clinical and clinical stages.
      Graphical abstract image

      PubDate: 2017-04-30T15:33:56Z
      DOI: 10.1016/j.addr.2017.04.010
       
  • Harnessing macrophage plasticity for tissue regeneration
    • Authors: Tim D. Smith; Raji R. Nagalla; Esther Y. Chen; Wendy F. Liu
      Abstract: Publication date: Available online 25 April 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Tim D. Smith, Raji R. Nagalla, Esther Y. Chen, Wendy F. Liu
      Macrophages are versatile and plastic effector cells of the immune system, and contribute to diverse immune functions including pathogen or apoptotic cell removal, inflammatory activation and resolution, and tissue healing. Macrophages function as signaling regulators and amplifiers and influencing their activity is a powerful approach for controlling inflammation or inducing a wound-healing response in regenerative medicine. This review discusses biomaterials-based approaches for altering macrophage activity, approaches for targeting drugs to macrophages, and approaches for delivering macrophages themselves as a therapeutic intervention.
      Graphical abstract image

      PubDate: 2017-04-30T15:33:56Z
      DOI: 10.1016/j.addr.2017.04.012
       
  • Biomaterials Strategies for Generating Therapeutic Immune Responses
    • Authors: Sean H. Kelly; Lucas S. Shores; Nicole L. Votaw; Joel H. Collier
      Abstract: Publication date: Available online 25 April 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Sean H. Kelly, Lucas S. Shores, Nicole L. Votaw, Joel H. Collier
      Biomaterials employed to raise therapeutic immune responses have become a complex and active field. Historically, vaccines have been developed primarily to fight infectious diseases, but recent years have seen the development of immunologically active biomaterials towards an expanding list of non-infectious diseases and conditions including inflammation, autoimmunity, wounds, cancer, and others. This review structures its discussion of these approaches around a progression from single-target strategies to those that engage increasingly complex and multifactorial immune responses. First the targeting of specific individual cytokines is discussed, both in terms of delivering the cytokines or blocking agents, and in terms of active immunotherapies that raise neutralizing immune responses against such single cytokine targets. Next, non-biological complex drugs such as randomized polyamino acid copolymers are discussed in terms of their ability to raise multiple different therapeutic immune responses, particularly in the context of autoimmunity. Last, biologically derived matrices and materials are discussed in terms of their ability to raise complex immune responses in the context of tissue repair. Collectively, these examples reflect the tremendous diversity of existing approaches and the breadth of opportunities that remain for generating therapeutic immune responses using biomaterials.
      Graphical abstract image

      PubDate: 2017-04-30T15:33:56Z
      DOI: 10.1016/j.addr.2017.04.009
       
  • Progress and opportunities for enhancing the delivery and efficacy of
           checkpoint inhibitors for cancer immunotherapy
    • Authors: David M. Francis; Susan N. Thomas
      Abstract: Publication date: Available online 25 April 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): David M. Francis, Susan N. Thomas
      Despite the advent of immune checkpoint blockade for effective treatment of advanced malignancies, only a minority of patients respond to therapy and significant immune-related adverse events remain to be minimized. Innovations in engineered drug delivery systems and controlled release strategies can improve drug accumulation at and retention within target cells and tissues in order to enhance therapeutic efficacy while simultaneously reducing drug exposure in off target tissues to minimize the potential for treatment-associated toxicities. This review will outline basic principles of the immune physiology of checkpoint signaling, the existing knowledge of dose-efficacy relationships in checkpoint inhibition, the influence of administration route on treatment efficacy, as well as the resulting checkpoint inhibitor antibody biodistribution profiles amongst target versus systemic tissues. It will also highlight recent successes in the application of drug delivery principles and technologies towards augmenting checkpoint blockade therapy in cancer. Delivery strategies that have been developed for other therapeutic and immunotherapy applications with as-of-yet underexplored potential in checkpoint inhibition therapy will also be discussed.
      Graphical abstract image

      PubDate: 2017-04-30T15:33:56Z
      DOI: 10.1016/j.addr.2017.04.011
       
  • Near-infrared light-activatable polymeric nanoformulations for combined
           therapy and imaging of cancer
    • Authors: Xiuli Yue; Qiang Zhang; Zhifei Dai
      Abstract: Publication date: Available online 25 April 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Xiuli Yue, Qiang Zhang, Zhifei Dai
      Near infrared (NIR) light allows deep tissue penetration and high spatial resolution due to the reduced scattering of long-wavelength photons. NIR light-activatable polymer nanoparticles are widely exploited for enhanced cancer imaging (diagnosis) and therapy owing to their superior photostability, photothermal conversion efficiency (or high emission rate), and minimal toxicity to cells and tissues. This review surveys the most recent advances in the synthesis of different NIR-absorbing and emissive polymer nanoformulations, and their applications for cancer imaging, photothermal therapy, theranostics and combination therapy by delivering multiple small molecule chemotherapeutics. Photo-responsive drug delivery systems for NIR light-triggered drug release are also discussed with particular emphasis on their molecular designs and formulations as well as photo-reaction mechanisms. Finally, outlook and challenges are presented regarding potential clinical applications of NIR light-activatable nanoformulations.
      Graphical abstract image

      PubDate: 2017-04-30T15:33:56Z
      DOI: 10.1016/j.addr.2017.04.007
       
  • Current state and challenges in developing oral vaccines
    • Authors: Julia E. Vela Ramirez; Lindsey A. Sharpe; Nicholas A. Peppas
      Abstract: Publication date: Available online 22 April 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Julia E. Vela Ramirez, Lindsey A. Sharpe, Nicholas A. Peppas
      While vaccination remains the most cost effective strategy for disease prevention, communicable diseases persist as the second leading cause of death worldwide. There is a need to design safe, novel vaccine delivery methods to protect against unaddressed and emerging diseases. Development of vaccines administered orally is preferable to traditional injection-based formulations for numerous reasons including improved safety and compliance, and easier manufacturing and administration. Additionally, the oral route enables stimulation of humoral and cellular immune responses at both systemic and mucosal sites to establish broader and long-lasting protection. However, oral delivery is challenging, requiring formulations to overcome the harsh gastrointestinal (GI) environment and avoid tolerance induction to achieve effective protection. Here we address the rationale for oral vaccines, including key biological and physicochemical considerations for next-generation oral vaccine design.
      Graphical abstract image

      PubDate: 2017-04-23T07:42:45Z
      DOI: 10.1016/j.addr.2017.04.008
       
 
 
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