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Publisher: Elsevier   (Total: 3044 journals)

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Showing 1 - 200 of 3044 Journals sorted alphabetically
AASRI Procedia     Open Access   (Followers: 15)
Academic Pediatrics     Hybrid Journal   (Followers: 22, SJR: 1.402, h-index: 51)
Academic Radiology     Hybrid Journal   (Followers: 21, SJR: 1.008, h-index: 75)
Accident Analysis & Prevention     Partially Free   (Followers: 84, 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: 28, 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: 341, SJR: 0.726, h-index: 43)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 3)
Acta Biomaterialia     Hybrid Journal   (Followers: 25, SJR: 2.02, h-index: 104)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 1)
Acta de Investigación Psicológica     Open Access   (Followers: 2)
Acta Ecologica Sinica     Open Access   (Followers: 8, SJR: 0.172, h-index: 29)
Acta Haematologica Polonica     Free   (SJR: 0.123, h-index: 8)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.604, h-index: 38)
Acta Materialia     Hybrid Journal   (Followers: 215, SJR: 3.683, h-index: 202)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.615, h-index: 21)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.442, h-index: 21)
Acta Oecologica     Hybrid Journal   (Followers: 10, SJR: 0.915, h-index: 53)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription   (Followers: 1)
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 3, SJR: 0.311, h-index: 16)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 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)
Acute Pain     Full-text available via subscription   (Followers: 13)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.967, h-index: 57)
Addictive Behaviors     Hybrid Journal   (Followers: 15, SJR: 1.514, h-index: 92)
Addictive Behaviors Reports     Open Access   (Followers: 5)
Additive Manufacturing     Hybrid Journal   (Followers: 7, SJR: 1.039, h-index: 5)
Additives for Polymers     Full-text available via subscription   (Followers: 21)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 135, SJR: 5.2, h-index: 222)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.265, h-index: 53)
Advanced Powder Technology     Hybrid Journal   (Followers: 17, SJR: 0.739, h-index: 33)
Advances in Accounting     Hybrid Journal   (Followers: 9, SJR: 0.299, h-index: 15)
Advances in Agronomy     Full-text available via subscription   (Followers: 15, SJR: 2.071, h-index: 82)
Advances in Anesthesia     Full-text available via subscription   (Followers: 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: 22, SJR: 1.286, h-index: 49)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 16, SJR: 3.31, h-index: 42)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.277, h-index: 43)
Advances in Botanical Research     Full-text available via subscription   (Followers: 3, SJR: 0.619, h-index: 48)
Advances in Cancer Research     Full-text available via subscription   (Followers: 25, SJR: 2.215, h-index: 78)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9, SJR: 0.9, h-index: 30)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 2.139, h-index: 42)
Advances in 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: 25, 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 Dermatology     Full-text available via subscription   (Followers: 12)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 11)
Advances in Digestive Medicine     Open Access   (Followers: 5)
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 Food and Nutrition Research     Full-text available via subscription   (Followers: 48, 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: 11)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 2.325, h-index: 20)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 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 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: 6)
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: 15, 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: 61)
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: 349, SJR: 0.606, h-index: 65)
Advances in Structural Biology     Full-text available via subscription   (Followers: 8)
Advances in Surgery     Full-text available via subscription   (Followers: 7, SJR: 0.823, h-index: 27)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 30, SJR: 1.321, h-index: 56)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 16)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 1.878, h-index: 68)
Advances in Water Resources     Hybrid Journal   (Followers: 43, SJR: 2.408, h-index: 94)
Aeolian Research     Hybrid Journal   (Followers: 5, SJR: 0.973, h-index: 22)
Aerospace Science and Technology     Hybrid Journal   (Followers: 318, 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: 407, 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: 39, SJR: 1.546, h-index: 79)
Agriculture and Agricultural Science Procedia     Open Access  
Agriculture and Natural Resources     Open Access   (Followers: 1)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 54, SJR: 1.879, h-index: 120)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.434, h-index: 14)
Air Medical J.     Hybrid Journal   (Followers: 5, SJR: 0.234, h-index: 18)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.285, h-index: 3)
Alcohol     Hybrid Journal   (Followers: 9, SJR: 0.922, h-index: 66)
Alcoholism and Drug Addiction     Open Access   (Followers: 8)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.436, h-index: 12)
Alexandria J. of Medicine     Open Access  
Algal Research     Partially Free   (Followers: 8, SJR: 2.05, h-index: 20)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.46, h-index: 29)
Allergology Intl.     Open Access   (Followers: 4, SJR: 0.776, h-index: 35)
Alpha Omegan     Full-text available via subscription   (SJR: 0.121, h-index: 9)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 8, SJR: 0.158, h-index: 9)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 47, 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: 45, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 39, 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: 33, 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: 192, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 56, SJR: 2.803, h-index: 148)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 4)
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: 24, SJR: 0.59, h-index: 45)
American J. of Pathology     Hybrid Journal   (Followers: 26, SJR: 2.653, h-index: 228)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 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: 9)
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: 37, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 167, 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   (Followers: 1)
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: 157, 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   (Followers: 1, 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)

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Journal Cover Advanced Drug Delivery Reviews
  [SJR: 5.2]   [H-I: 222]   [135 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0169-409X
   Published by Elsevier Homepage  [3044 journals]
  • Recent advance in the pharmacogenomics of human Solute Carrier
           Transporters (SLCs) in drug disposition
    • Authors: Fanfan Zhou; Ling Zhu; Ke Wang; Michael Murray
      Pages: 21 - 36
      Abstract: Publication date: 1 July 2017
      Source:Advanced Drug Delivery Reviews, Volume 116
      Author(s): Fanfan Zhou, Ling Zhu, Ke Wang, Michael Murray
      Drug pharmacokinetics is influenced by the function of metabolising enzymes and influx/efflux transporters. Genetic variability of these genes is known to impact on clinical therapies. Solute Carrier Transporters (SLCs) are the primary influx transporters responsible for the cellular uptake of drug molecules, which consequently, impact on drug efficacy and toxicity. The Organic Anion Transporting Polypeptides (OATPs), Organic Anion Transporters (OATs) and Organic Cation Transporters (OCTs/OCTNs) are the most important SLCs involved in drug disposition. The information regarding the influence of SLC polymorphisms on drug pharmacokinetics is limited and remains a hot topic of pharmaceutical research. This review summarises the recent advance in the pharmacogenomics of SLCs with an emphasis on human OATPs, OATs and OCTs/OCTNs. Our current appreciation of the degree of variability in these transporters may contribute to better understanding the inter-patient variation of therapies and thus, guide the optimisation of clinical treatments.

      PubDate: 2017-09-06T17:10:31Z
      DOI: 10.1016/j.addr.2016.06.004
      Issue No: Vol. 116 (2017)
       
  • The effects of dietary and herbal phytochemicals on drug transporters
    • Authors: Yan Li; Jezrael Revalde; James W. Paxton
      Pages: 45 - 62
      Abstract: Publication date: 1 July 2017
      Source:Advanced Drug Delivery Reviews, Volume 116
      Author(s): Yan Li, Jezrael Revalde, James W. Paxton
      Membrane transporter proteins (the ABC transporters and SLC transporters) play pivotal roles in drug absorption and disposition, and thus determine their efficacy and safety. Accumulating evidence suggests that the expression and activity of these transporters may be modulated by various phytochemicals (PCs) found in diets rich in plants and herbs. PC absorption and disposition are also subject to the function of membrane transporter and drug metabolizing enzymes. PC–drug interactions may involve multiple major drug transporters (and metabolizing enzymes) in the body, leading to alterations in the pharmacokinetics of substrate drugs, and thus their efficacy and toxicity. This review summarizes the reported in vitro and in vivo interactions between common dietary PCs and the major drug transporters. The oral absorption, distribution into pharmacological sanctuaries and excretion of substrate drugs and PCs are considered, along with their possible interactions with the ABC and SLC transporters which influence these processes.
      Graphical abstract image

      PubDate: 2017-09-06T17:10:31Z
      DOI: 10.1016/j.addr.2016.09.004
      Issue No: Vol. 116 (2017)
       
  • Placental control of drug delivery
    • Authors: Sanaalarab Al-Enazy; Shariq Ali; Norah Albekairi; Marwa El-Tawil; Erik Rytting
      Pages: 63 - 72
      Abstract: Publication date: 1 July 2017
      Source:Advanced Drug Delivery Reviews, Volume 116
      Author(s): Sanaalarab Al-Enazy, Shariq Ali, Norah Albekairi, Marwa El-Tawil, Erik Rytting
      The placenta serves as the interface between the maternal and fetal circulations and regulates the transfer of oxygen, nutrients, and waste products. When exogenous substances are present in the maternal bloodstream—whether from environmental contact, occupational exposure, medication, or drug abuse—the extent to which this exposure affects the fetus is determined by transport and biotransformation processes in the placental barrier. Advances in drug delivery strategies are expected to improve the treatment of maternal and fetal diseases encountered during pregnancy.
      Graphical abstract image

      PubDate: 2017-09-06T17:10:31Z
      DOI: 10.1016/j.addr.2016.08.002
      Issue No: Vol. 116 (2017)
       
  • Xenobiotic transporters and kidney injury
    • Authors: Blessy George; Dahea You; Melanie S. Joy; Lauren M. Aleksunes
      Pages: 73 - 91
      Abstract: Publication date: 1 July 2017
      Source:Advanced Drug Delivery Reviews, Volume 116
      Author(s): Blessy George, Dahea You, Melanie S. Joy, Lauren M. Aleksunes
      Renal proximal tubules are targets for toxicity due in part to the expression of transporters that mediate the secretion and reabsorption of xenobiotics. Alterations in transporter expression and/or function can enhance the accumulation of toxicants and sensitize the kidneys to injury. This can be observed when xenobiotic uptake by carrier proteins is increased or efflux of toxicants and their metabolites is reduced. Nephrotoxic chemicals include environmental contaminants (halogenated hydrocarbon solvents, the herbicide paraquat, the fungal toxin ochratoxin, and heavy metals) as well as pharmaceuticals (certain beta-lactam antibiotics, antiviral drugs, and chemotherapeutic drugs). This review explores the mechanisms by which transporters mediate the entry and exit of toxicants from renal tubule cells and influence the degree of kidney injury. Delineating how transport proteins regulate the renal accumulation of toxicants is critical for understanding the likelihood of nephrotoxicity resulting from competition for excretion or genetic polymorphisms that affect transporter function.
      Graphical abstract image

      PubDate: 2017-09-06T17:10:31Z
      DOI: 10.1016/j.addr.2017.01.005
      Issue No: Vol. 116 (2017)
       
  • Preface: Nanoformulations for combination or cascade anticancer therapy
    • Authors: Qiang Zhang; Leaf Huang
      Pages: 1 - 2
      Abstract: Publication date: 1 June 2017
      Source:Advanced Drug Delivery Reviews, Volume 115
      Author(s): Qiang Zhang, Leaf Huang


      PubDate: 2017-09-06T17:10:31Z
      DOI: 10.1016/j.addr.2017.08.007
      Issue No: Vol. 115 (2017)
       
  • Recent advances of controlled drug delivery using microfluidic platforms
    • Authors: Sharma T. Sanjay; Wan Zhou; Maowei Dou; Hamed Tavakoli; Lei Ma; Feng Xu; XiuJun Li
      Abstract: Publication date: Available online 15 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Sharma T. Sanjay, Wan Zhou, Maowei Dou, Hamed Tavakoli, Lei Ma, Feng Xu, XiuJun Li
      Conventional systematically-administered drugs distribute evenly throughout the body, get degraded and excreted rapidly while crossing many biological barriers, leaving minimum amounts of the drugs at pathological sites. Controlled drug delivery aims to deliver drugs to the target sites at desired rates and time, thus enhancing the drug efficacy, pharmacokinetics, and bioavailability while maintaining minimal side effects. Due to a number of unique advantages of the recent microfluidic lab-on-a-chip technology, microfluidic lab-on-a-chip has provided unprecedented opportunities for controlled drug delivery. Drugs can be efficiently delivered to the target sites at desired rates in a well-controlled manner by microfluidic platforms via integration, implantation, localization, automation, and precise control of various microdevice parameters. These features accordingly make reproducible, on-demand, and tunable drug delivery become feasible. On-demand self-tuning dynamic drug delivery systems have shown great potential for personalized drug delivery. This review presents an overview of recent advances in controlled drug delivery using microfluidic platforms. The review first briefly introduces microfabrication techniques of microfluidic platforms, followed by detailed descriptions of numerous microfluidic drug delivery systems that have significantly advanced the field of controlled drug delivery. Those microfluidic systems can be separated into four major categories, namely drug carrier-free micro-reservoir-based drug delivery systems, highly integrated carrier-free microfluidic lab-on-a-chip systems, drug carrier-integrated microfluidic systems, and microneedles. Microneedles can be further categorized into five different types, i.e. solid, porous, hollow, coated, and biodegradable microneedles, for controlled transdermal drug delivery. At the end, we discuss current limitations and future prospects of microfluidic platforms for controlled drug delivery.
      Graphical abstract image

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

      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.003
       
  • Transflammation: Innate Immune Signaling in Nuclear Reprogramming
    • Authors: Shu Meng; Palas Chanda; Rajarajan A. Thandavarayan; John P. Cooke
      Abstract: Publication date: Available online 13 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Shu Meng, Palas Chanda, Rajarajan A. Thandavarayan, John P. Cooke
      Induction of pluripotency in somatic cells by retroviral overexpression of four transcription factors has revolutionized the field of stem cell biology and regenerative medicine. The efficient induction of pluripotency requires the activation of innate immune signaling in a process termed “transflammation” [1]. Specifically, the stimulation of pattern recognition receptors (PRRs) causes global alterations in the expression and activity of epigenetic modifiers to favor an open chromatin configuration. Activation of toll-like receptors (TLR) or RIG-1-like receptors (RLR) [2] trigger signaling cascades that result in NFκB or IRF-3 mediated changes in epigenetic plasticity that facilitate reprogramming. Another form of nuclear reprogramming is so-called direct reprogramming or transdifferentiation of one somatic cell to another lineage. We have shown that transdifferentiation of human fibroblasts to endothelial cells also involves transflammation [3]. Recently, we also identified reactive oxygen species (ROS) [4] and reactive nitrogen species (RNS) [5] as mediators of innate immune signaling in nuclear reprogramming. Innate immune signaling plays a key role in nuclear reprogramming by regulating DNA accessibility (Figure 1). Here, we review recent progress of innate immunity signaling in nuclear reprogramming and epigenetic plasticity.
      Graphical abstract image

      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.010
       
  • Genome stability of programmed stem cell products
    • Authors: Ulrich Martin
      Abstract: Publication date: Available online 13 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Ulrich Martin
      Inherited and acquired genomic abnormalities are known to cause genetic diseases and contribute to cancer formation. Recent studies demonstrated a substantial mutational load in mouse and human embryonic and induced pluripotent stem cells (ESCs and iPSCs). Single nucleotide variants, copy number variations, and larger chromosomal abnormalities may influence the differentiation capacity of pluripotent stem cells and the functionality of their derivatives in disease modelling and drug screening, and are considered a serious risk for cellular therapies based on ESC or iPSC derivatives. This review discusses the types and origins of different genetic abnormalities in pluripotent stem cells, methods for their detection, and the mechanisms of development and enrichment during reprogramming and culture expansion.
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      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.004
       
  • Enzymes as Key Features in Therapeutic Cell Mimicry
    • Authors: Fabian Itel; Philipp S. Schattling; Yan Zhang; Brigitte Städler
      Abstract: Publication date: Available online 12 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Fabian Itel, Philipp S. Schattling, Yan Zhang, Brigitte Städler
      Cell mimicry is a nature inspired concept that aims to substitute for missing or lost (sub)cellular function. This review focuses on the latest advancements in the use of enzymes in cell mimicry for encapsulated catalysis and artificial motility in synthetic bottom-up assemblies with emphasis on the biological response in cell culture or more rarely in animal models. Entities across the length scale from nano-sized enzyme mimics, sub-micron sized artificial organelles and self-propelled particles (swimmers) to micron-sized artificial cells are discussed. Although the field remains in its infancy, the primary aim of this review is to illustrate the advent of nature-mimicking artificial molecules and assemblies on their way to become a complementary alternative to their role models for diverse biomedical purposes.
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      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.006
       
  • Antibody Directed Enzyme Prodrug Therapy (ADEPT): Trials and Tribulations
    • Authors: Surinder K. Sharma; Kenneth D. Bagshawe
      Abstract: Publication date: Available online 12 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Surinder K. Sharma, Kenneth D. Bagshawe
      Antibody directed enzyme prodrug therapy has the potential to be an effective therapy for most common solid cancers. Clinical studies with CPG2 system have shown the feasibility of this approach. The key limitation has been immunogenicity of the enzyme. Technologies now exist to eliminate this problem. Non-immunogenic enzymes in combination with prodrugs that generate potent cytotoxic drugs can provide a powerful approach to cancer therapy. ADEPT has the potential to be non -toxic to normal tissue and can therefore be combined with other modalities including immunotherapy for greater clinical benefit.

      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.009
       
  • Designer Bacteria as Intratumoural Enzyme Biofactories
    • Authors: Panos Lehouritis; Glenn Hogan; Mark Tangney
      Abstract: Publication date: Available online 12 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Panos Lehouritis, Glenn Hogan, Mark Tangney
      Bacterial-directed enzyme prodrug therapy (BDEPT) is an emerging form of treatment for cancer. It is a biphasic variant of gene therapy in which a bacterium, armed with an enzyme that can convert an inert prodrug into a cytotoxic compound, induces tumour cell death following tumour-specific prodrug activation. BDEPT combines the innate ability of bacteria to selectively proliferate in tumours, with the capacity of prodrugs to undergo contained, compartmentalised conversion into active metabolites in vivo. Although BDEPT has undergone clinical testing, it has received limited clinical exposure, and has yet to achieve regulatory approval. In this article, we review BDEPT from the system designer's perspective, and provide detailed commentary on how the designer should strategize its development de novo. We report on contemporary advancements in this field which aim to enhance BDEPT in terms of safety and efficacy. Finally, we discuss clinical and regulatory barriers facing BDEPT, and propose promising approaches through which these hurdles may best be tackled.
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      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.012
       
  • Overcoming ocular drug delivery barriers through the use of pHysical
           forces
    • Authors: Di Huang; Ying-Shan Chen; Ilva D. Rupenthal
      Abstract: Publication date: Available online 12 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Di Huang, Ying-Shan Chen, Ilva D. Rupenthal
      Overcoming the physiological barriers in the eye remains a key obstacle in the field of ocular drug delivery. While ocular barriers naturally have a protective function, they also limit drug entry into the eye. Various pharmaceutical strategies, such as novel formulations and physical force-based techniques, have been investigated to weaken these barriers and transport therapeutic agents effectively to both the anterior and the posterior segments of the eye. This review summarizes and discusses the recent research progress in the field of ocular drug delivery with a focus on the application of physical methods, including electrical fields, sonophoresis, and microneedles, which can enhance penetration efficiency by transiently disrupting the ocular barriers in a minimally or non-invasive manner.
      Graphical abstract image

      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.008
       
  • Two-step polymer- and liposome- enzyme prodrug therapies for cancer: PDEPT
           and PELT concepts and future perspectives
    • Authors: Anna Scomparin; Helena F. Florindo; Galia Tiram; Elaine L. Ferguson; Ronit Satchi-Fainaro
      Abstract: Publication date: Available online 12 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Anna Scomparin, Helena F. Florindo, Galia Tiram, Elaine L. Ferguson, Ronit Satchi-Fainaro
      Polymer-directed enzyme prodrug therapy (PDEPT) and polymer enzyme liposome therapy (PELT) are two-step therapies developed to provide anticancer drugs site-selective intratumoral accumulation and release. Nanomedicines, such as polymer-drug conjugates and liposomal drugs, accumulate in the tumor site due to extravasation-dependent mechanism (enhanced permeability and retention – EPR – effect), and further need to cross the cellular membrane and release their payload in the intracellular compartment. The subsequent administration of a polymer-enzyme conjugate able to accumulate in the tumor tissue and to trigger the extracellular release of the active drug showed promising preclinical results. The development of polymer-enzyme, polymer-drug conjugates and liposomal drugs had undergone a vast advancement over the past decades. Several examples of enzyme mimics for in vivo therapy can be found in the literature. Moreover, polymer therapeutics often present an enzyme-sensitive mechanism of drug release. These nanomedicines can thus be optimal substrates for PDEPT and this review aims to provide new insights and stimuli towards the future perspectives of this promising combination.
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      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.011
       
  • (Re-)programming of subtype specific cardiomyocytes
    • Authors: Frauke Hausburg; Julia Jeannine Jung; Matti Hoch; Markus Wolfien; Arash Yavari; Christian Rimmbach; Robert David
      Abstract: Publication date: Available online 12 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Frauke Hausburg, Julia Jeannine Jung, Matti Hoch, Markus Wolfien, Arash Yavari, Christian Rimmbach, Robert David
      Adult cardiomyocytes (CMs) possess a highly restricted intrinsic regenerative potential — a major barrier to the effective treatment of a range of chronic degenerative cardiac disorders characterized by cellular loss and/or irreversible dysfunction and which underlies the majority of deaths in developed countries. Both stem cell programming and direct cell reprogramming hold promise as novel, potentially curative approaches to address this therapeutic challenge. The advent of induced pluripotent stem cells (iPSCs) has introduced a second pluripotent stem cell source besides embryonic stem cells (ESCs), enabling even autologous cardiomyocyte production. In addition, the recent achievement of directly reprogramming somatic cells into cardiomyocytes is likely to become of great importance. In either case, different clinical scenarios will require the generation of highly pure, specific cardiac cellular-subtypes. In this review, we discuss these themes as related to the cardiovascular stem cell and programming field, including a focus on the emergent topic of pacemaker cell generation for the development of biological pacemakers and in vitro drug testing.
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      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.005
       
  • Stem cell-based peripheral vascular regeneration
    • Authors: Yasuyuki Fujita; Atsuhiko Kawamoto
      Abstract: Publication date: Available online 11 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Yasuyuki Fujita, Atsuhiko Kawamoto
      Chronic critical limb ischemia (CLI) represents an end-stage manifestation of peripheral arterial disease (PAD). CLI patients are at very high risk of amputation and cardiovascular complications, leading to severe morbidity and mortality. Because many patients with CLI are ineligible for conventional revascularization procedures, it is urgently needed to explore alternative strategies to improve blood supply in the ischemic tissue. Although researchers initially focused on gene/protein therapy using proangiogenic growth factors/cytokines, recent discovery of somatic stem/progenitor cells including bone marrow (BM)-derived endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) has drastically developed the field of therapeutic angiogenesis for CLI. Overall, early phase clinical trials demonstrated that stem/progenitor cell therapies may be safe, feasible and potentially effective. However, only few late-phase clinical trials have been conducted. This review provides an overview of the preclinical and clinical reports to demonstrate the usefulness and the current limitations of the cell-based therapies.
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      PubDate: 2017-09-17T06:24:19Z
      DOI: 10.1016/j.addr.2017.09.001
       
  • Targeting and Isolation of Cancer Cells Using Micro/Nanomotors
    • Authors: Weiwei Gao; Berta Esteban-Fernández de Ávila; Liangfang Zhang; Joseph Wang
      Abstract: Publication date: Available online 9 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Weiwei Gao, Berta Esteban-Fernández de Ávila, Liangfang Zhang, Joseph Wang
      Micro/nanomotors distinguish themselves with in situ energy conversion capability for autonomous movement, a feature that confers remarkable potential to improve cancer treatment. In this review article, three areas are highlighted where micro/nanomotors have established themselves with unique contributions, including propelled navigation to promote cancer cell targeting, powered cell membrane penetration to enhance intracellular delivery, and steered isolation of circulating cancer cells for detection. Progress made in these areas has offered promising inspiration and opportunities aimed for enhancing the efficiency and precision of drug targeting to cancer cells, improving the capability of delivering anticancer drug into cytoplasm for bioactivity, and enabling more rapid and sensitive cancer cell detection. Herein, we review each area with highlights of the current and forthcoming micro/nanomotor techniques in advancing cancer diagnosis and treatment.
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      PubDate: 2017-09-11T03:30:42Z
      DOI: 10.1016/j.addr.2017.09.002
       
  • PEGylation for enhancing nanoparticle diffusion in mucus
    • Authors: Justin T. Huckaby; Samuel K. Lai
      Abstract: Publication date: Available online 4 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Justin T. Huckaby, Samuel K. Lai
      The viscoelastic mucus secretions coating exposed organs such as the lung airways and the female reproductive tract can trap and quickly eliminate not only foreign pathogens and ultrafine particles but also particle-based drug delivery systems, thus limiting sustained and targeted drug delivery at mucosal surfaces. To improve particle distribution across the mucosa and enhance delivery to the underlying epithelium, many investigators have sought to develop nanoparticles capable of readily traversing mucus. The first synthetic nanoparticles shown capable of rapidly penetrating physiological mucus secretions utilized a dense coating of polyethylene glycol (PEG) covalently grafted onto the surface of preformed polymeric nanoparticles. In the decade since, PEG has become the gold standard in engineering mucus-penetrating drug carriers for sustained and targeted drug delivery to the lungs, gastrointestinal tract, eyes, and female reproductive tract. This review summarizes the history of the development of various PEG-based mucus-penetrating particles, and highlights the key physicochemical properties of PEG coatings and PEGylation strategies to achieve muco-inert PEG coatings on nanoparticle drug carriers for improved drug and gene delivery at mucosal surfaces.
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      PubDate: 2017-09-06T17:10:31Z
      DOI: 10.1016/j.addr.2017.08.010
       
  • Device-assisted transdermal drug delivery
    • Authors: Hyunjae Lee; Changyeong Song; Seungmin Baik; Dokyoon Kim; Taeghwan Hyeon; Dae-Hyeong Kim
      Abstract: Publication date: Available online 1 September 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Hyunjae Lee, Changyeong Song, Seungmin Baik, Dokyoon Kim, Taeghwan Hyeon, Dae-Hyeong Kim
      Transdermal drug delivery is a prospective drug delivery strategy to complement the limitations of conventional drug delivery systems including oral and injectable methods. This delivery route allows both convenient and painless drug delivery and a sustained release profile with reduced side effects. However, physiological barriers in the skin undermine the delivery efficiency of conventional patches, limiting drug candidates to small-molecules and lipophilic drugs. Recently, transdermal drug delivery technology has advanced from unsophisticated methods simply relying on natural diffusion to drug releasing systems that dynamically respond to external stimuli. Furthermore, physical barriers in the skin have been overcome using microneedles, and controlled delivery by wearable biosensors has been enabled ultimately. In this review, we classify the evolution of advanced drug delivery strategies based on generations and provide a comprehensive overview. Finally, the recent progress in advanced diagnosis and therapy through customized drug delivery systems based on real-time analysis of physiological cues is highlighted.
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      PubDate: 2017-09-06T17:10:31Z
      DOI: 10.1016/j.addr.2017.08.009
       
  • Preface: Molecular Mechanisms, Novel Modes of Regulation, and Therapeutic
           Strategies
    • Authors: Guofeng
      Abstract: Publication date: 1 July 2017
      Source:Advanced Drug Delivery Reviews, Volume 116
      Author(s): Guofeng You


      PubDate: 2017-09-06T17:10:31Z
       
  • Biochemical studies on the structure–function relationship of major drug
           
    • Authors: Mei Hong
      Abstract: Publication date: 1 July 2017
      Source:Advanced Drug Delivery Reviews, Volume 116
      Author(s): Mei Hong
      Human drug transporters often play key roles in determining drug accumulation within cells. Their activities are often directly related to therapeutic efficacy, drug toxicity as well as drug–drug interactions. However, the progress for interpretation of their crystal structures is relatively slow. Hence, conventional biochemical studies together with computer modeling became useful manners to reveal essential structures of these membrane proteins. Over the years, quite a few structure–function relationship information had been obtained for members of the two major transporter families: the ATP-binding cassette family and the solute carrier family. Critical structural features of drug transporters include transmembrane domains, post-translational modification sites and domains for cell surface assembly and protein–protein interactions. Alterations at these important sites may affect protein stability, trafficking to the plasma membrane and/or ability of transporters to interact with substrates.
      Graphical abstract image

      PubDate: 2017-09-06T17:10:31Z
       
  • Loops and layers of post-translational modifications of drug transporters
    • Authors: Guofeng
      Abstract: Publication date: 1 July 2017
      Source:Advanced Drug Delivery Reviews, Volume 116
      Author(s): Da Xu, Guofeng You
      Drug transporters encoded by solute carrier (SLC) family are distributed in multiple organs including kidney, liver, placenta, brain, and intestine, where they mediate the absorption, distribution, and excretion of a diverse array of environmental toxins and clinically important drugs. Alterations in the expression and function of these transporters play important roles in intra- and inter-individual variability of the therapeutic efficacy and the toxicity of many drugs. Consequently, the activity of these transporters must be highly regulated to carry out their normal functions. While it is clear that the regulation of these transporters tightly depends on genetic mechanisms, many studies have demonstrated that these transporters are the target of various post-translational modifications. This review article summarizes the recent advances in identifying the posttranslational modifications underlying the regulation of the drug transporters of SLC family. Such mechanisms are pivotal not only in physiological conditions, but also in diseases.
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      PubDate: 2017-09-06T17:10:31Z
       
  • Experimental cocrystal screening and solution based scale-up
           cocrystallization methods
    • Authors: Maria Malamatari; Steven A. Ross; Dennis Douroumis; Sitaram P. Velaga
      Abstract: Publication date: Available online 12 August 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Maria Malamatari, Steven A. Ross, Dennis Douroumis, Sitaram P. Velaga
      Cocrystals are crystalline single phase materials composed of two or more different molecular and/or ionic compounds generally in a stoichiometric ratio which are neither solvates nor simple salts. If one of the components is an active pharmaceutical ingredient (API), the term pharmaceutical cocrystal is often used. There is a growing interest among drug development scientists in exploring cocrystals, as means to address physicochemical, biopharmaceutical and mechanical properties and expand solid form diversity of the API. Conventionally, coformers are selected based on crystal engineering principles, and the equimolar mixtures of API and coformers are subjected to solution-based crystallization that are commonly employed in polymorph and salt screening. However, the availability of new knowledge on cocrystal phase behaviour in solid state and solutions has spurred the development and implementation of more rational experimental cocrystal screening as well as scale-up methods. This review aims to provide overview of commonly employed solid form screening techniques in drug development with an emphasis on cocrystal screening methodologies. The latest developments in understanding and the use of cocrystal phase diagrams in both screening and solution based scale-up methods are also presented. Final section is devoted to reviewing the state of the art research covering solution based scale-up cocrystallization process for different cocrystals besides more recent continuous crystallization methods.
      Graphical abstract image

      PubDate: 2017-08-20T16:12:20Z
      DOI: 10.1016/j.addr.2017.08.006
       
  • Nano-sized and other improved reporters for Magnetic Resonance Imaging of
           angiogenesis
    • Authors: Simonetta Geninatti Crich; Enzo Terreno; Silvio Aime
      Abstract: Publication date: Available online 9 August 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Simonetta Geninatti Crich, Enzo Terreno, Silvio Aime
      Magnetic Resonance Imaging (MRI) enables to provide anatomical, functional and molecular information of pathological angiogenesis when used with properly tailored imaging probes. Functional studies have been the domain of Dynamic Contrast Enhancement (DCE) -MRI protocols from which it is possible to extract quantitative estimations on key parameters such as the volumes of vascular and extracellular compartments and the rates of the bidirectional exchange of the imaging reporters across the endothelial barrier. Whereas paramagnetic Gd-complexes able to reversibly bind to serum albumin act better than the clinically used small-sized, hydrophilic species, new findings suggest that an accurate assessment of the vascular volume is possible by analyzing images acquired upon the i.v. administration of Gd-labelled Red Blood Cells (RBCs). As far as it concerns molecular MRI, among the many available biomarkers, αvβ3 integrins are the most investigated ones. The low expression of these targets makes mandatory the use of nano-sized systems endowed with the proper signal enhancing capabilities. A number of targeted nano-particles have been investigated including micelles, liposomes, iron oxides and perfluorocarbon containing systems. Finally, a growing attention is devoted to the design and testing of “theranostic” agents based on the exploitation of MRI to monitor drug delivery processes and therapeutic outcome.
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      PubDate: 2017-08-10T14:52:05Z
      DOI: 10.1016/j.addr.2017.08.004
       
  • Current developments and applications of microfluidic technology toward
           clinical translation of nanomedicines
    • Authors: Dongfei Liu; Hongbo Zhang; Flavia Fontana; Jouni T. Hirvonen; Hélder A. Santos
      Abstract: Publication date: Available online 8 August 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Dongfei Liu, Hongbo Zhang, Flavia Fontana, Jouni T. Hirvonen, Hélder A. Santos
      Nanoparticulate drug delivery systems hold great potential for the therapy of many diseases, especially cancer. However, the translation of nanoparticulate drug delivery systems from academic research to the industrial and clinical practice has been slow. This slow translation can be ascribed to the high batch-to-batch variations and insufficient production rate of the conventional methods, and the lack of technologies for rapid screening of nanoparticulate drug delivery systems with high correlation to the in vivo tests. These issues can be addressed by the microfluidic technologies. For example, microfluidics can not only produce nanoparticles in a well-controlled, reproducible, and high-throughput manner, but also create 3D environments with continuous flow to mimic the physiological and/or pathological processes. This review provides an overview of the microfluidic devices developed to prepare nanoparticulate drug delivery systems, including drug nanosuspensions, polymer nanoparticles, polyplexes, structured nanoparticles and theranostic nanoparticles. We also highlight the recent advances of microfluidic systems in fabricating the increasingly realistic models of the in vivo milieu for rapid screening of nanoparticles. Overall, the microfluidic technologies offer a promise approach to accelerate the clinical translation of nanoparticulate drug delivery systems.
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      PubDate: 2017-08-10T14:52:05Z
      DOI: 10.1016/j.addr.2017.08.003
       
  • Nanomedicine and advanced technologies for burns: Preventing infection and
           facilitating wound healing
    • Authors: Mirza Ali Mofazzal Jahromi; Parham Sahandi Zangabad; Seyed Masoud Moosavi Basri; Keyvan Sahandi Zangabad; Ameneh Ghamarypour; Amir R. Aref; Mahdi Karimi; Michael R. Hamblin
      Abstract: Publication date: Available online 4 August 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Mirza Ali Mofazzal Jahromi, Parham Sahandi Zangabad, Seyed Masoud Moosavi Basri, Keyvan Sahandi Zangabad, Ameneh Ghamarypour, Amir R. Aref, Mahdi Karimi, Michael R. Hamblin
      According to the latest report from the World Health Organization, an estimated 265,000 deaths still occur every year as a direct result of burn injuries. A widespread range of these deaths induced by burn wound happens in low- and middle-income countries, where survivors face a lifetime of morbidity. Most of the deaths occur due to infections when a high percentage of the external regions of the body area is affected. Microbial nutrient availability, skin barrier disruption, and vascular supply destruction in burn injuries as well as systemic immunosuppression are important parameters that cause burns to be susceptible to infections. Topical antimicrobials and dressings are generally employed to inhibit burn infections followed by a burn wound therapy, because systemic antibiotics have problems in reaching the infected site, coupled with increasing microbial drug resistance. Nanotechnology has provided a range of molecular designed nanostructures (NS) that can be used in both therapeutic and diagnostic applications in burns. These NSs can be divided into organic and non-organic (such as polymeric nanoparticles (NPs) and silver NPs, respectively), and many have been designed to display multifunctional activity. The present review covers the physiology of skin, burn classification, burn wound pathogenesis, animal models of burn wound infection, and various topical therapeutic approaches designed to combat infection and stimulate healing. These include biological based approaches (e.g. immune-based antimicrobial molecules, therapeutic microorganisms, antimicrobial agents, etc.), antimicrobial photo- and ultrasound-therapy, as well as nanotechnology-based wound healing approaches as a revolutionizing area. Thus, we focus on organic and non-organic NSs designed to deliver growth factors to burned skin, and scaffolds, dressings, etc. for exogenous stem cells to aid skin regeneration. Eventually, recent breakthroughs and technologies with substantial potentials in tissue regeneration and skin wound therapy (that are as the basis of burn wound therapies) are briefly taken into consideration including 3D–printing, cell-imprinted substrates, nano-architectured surfaces, and novel gene-editing tools such as CRISPR-Cas.
      Graphical abstract image

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

      PubDate: 2017-08-10T14:52:05Z
      DOI: 10.1016/j.addr.2017.07.018
       
  • Evaluation of Transporters in Drug Development: Current Status and
           Contemporary Issues
    • Authors: Sue-Chih Lee; Vikram Arya; Xinning Yang; Donna A. Volpe; Lei Zhang
      Abstract: Publication date: Available online 29 July 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Sue-Chih Lee, Vikram Arya, Xinning Yang, Donna A. Volpe, Lei Zhang
      Transporters govern the access of molecules to cells or their exit from cells, thereby controlling the overall distribution of drugs to their intracellular site of action. Clinically relevant drug-drug interactions mediated by transporters are of increasing interest in drug development. Drug transporters, acting alone or in concert with drug metabolizing enzymes, can play an important role in modulating drug absorption, distribution, metabolism and excretion, thus affecting the pharmacokinetics and/or pharmacodynamics of a drug. The drug interaction guidance documents from regulatory agencies include various decision criteria that may be used to predict the need for in vivo assessment of transporter-mediated drug-drug interactions. Regulatory science research continues to assess the prediction performances of various criteria as well as to examine the strength and limitations of each prediction criterion to foster discussions related to harmonized decision criteria that may be used to facilitate global drug development. This review discusses the role of transporters in drug development with a focus on methodologies in assessing transporter-mediated drug-drug interactions, challenges in both in vitro and in vivo assessments of transporters, and emerging transporter research areas including biomarkers, assessment of tissue concentrations, and effect of diseases on transporters.
      Graphical abstract image

      PubDate: 2017-08-01T01:07:23Z
      DOI: 10.1016/j.addr.2017.07.020
       
  • Scar management in burn injuries using drug delivery and molecular
           signaling: Current treatments and future directions
    • Authors: Saeid Amini-Nik; Yusef Yousuf; Marc G. Jeschke
      Abstract: Publication date: Available online 27 July 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Saeid Amini-Nik, Yusef Yousuf, Marc G. Jeschke
      In recent decades, there have been tremendous improvements in burn care that have allowed patients to survive severe burn injuries that were once fatal. However, a major limitation of burn care currently is the development of hypertrophic scars in approximately 70% of patients. This significantly decreases the quality of life for patients due to the physical and psychosocial symptoms associated with scarring. Current approaches to manage scarring include surgical techniques and non-surgical methods such as laser therapy, steroid injections, and compression therapy. These treatments are limited in their effectiveness and regularly fail to manage symptoms. As a result, the development of novel treatments that aim to improve outcomes and quality of life is imperative. Drug delivery that targets the molecular cascades of wound healing to attenuate or prevent hypertrophic scarring is a promising approach that has therapeutic potential. In this review, we discuss current treatments for scar management after burn injury, and how drug delivery targeting molecular signaling can lead to new therapeutic strategies.
      Graphical abstract image

      PubDate: 2017-08-01T01:07:23Z
      DOI: 10.1016/j.addr.2017.07.017
       
  • The role of mucus in cell-based models used to screen mucosal drug
           delivery
    • Authors: Anna Lechanteur; José das Neves; Bruno Sarmento
      Abstract: Publication date: Available online 25 July 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Anna Lechanteur, José das Neves, Bruno Sarmento
      The increasing interest in developing tools to predict drug absorption through mucosal surfaces is fostering the establishment of epithelial cell-based models. Cell-based in vitro techniques for drug permeability assessment are less laborious, cheaper and address the concerns of using laboratory animals. Simultaneously, in vitro barrier models that thoroughly simulate human epithelia or mucosae may provide useful data to speed up the entrance of new drugs and new drug products into the clinics. Nevertheless, standard cell-based in vitro models that intend to reproduce epithelial surfaces often discard the role of mucus in influencing drug permeation/absorption. Biomimetic models of mucosae in which mucus production has been considered may not be able to fully reproduce the amount and architecture of mucus, resulting in biased characterization of permeability/absorption. In these cases, artificial mucus may be used to supplement cell-based models but still proper identification and quantification are required. In this review, considerations regarding the relevance of mucus in the development of cell-based epithelial and mucosal models mimicking the gastro-intestinal tract, the cervico-vaginal tract and the respiratory tract, and the impact of mucus on the permeability mechanisms are addressed. From simple epithelial monolayers to more complexes 3D structures, the impact of the presence of mucus for the extrapolation to the in vivo scenario is critically analyzed. Finally, an overview is provided on several techniques and methods to characterize the mucus layer over cell-based barriers, in order to intimately reproduce human mucosal layer and thereby, improve in vitro/in vivo correlation.
      Graphical abstract image

      PubDate: 2017-08-01T01:07:23Z
      DOI: 10.1016/j.addr.2017.07.019
       
  • Gene Regulation in Adult Neural Stem Cells. Current Challenges and
           Possible Applications
    • Authors: Juan Manuel Encinas; Carlos P. Fitzsimons
      Abstract: Publication date: Available online 25 July 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Juan Manuel Encinas, Carlos P. Fitzsimons
      Adult neural stem and progenitor cells (NSPCs) offer a unique opportunity for neural regeneration and niche modification in physiopathological conditions, harnessing the capability to modify from neuronal circuits to glial scar. Findings exposing the vast plasticity and potential of NSPCs have accumulated over the past years and we currently know that adult NSPCs can naturally give rise not only to neurons but also to astrocytes and reactive astrocytes, and eventually to oligodendrocytes through genetic manipulation. We can consider NSPCs as endogenous flexible tools to fight against neurodegenerative and neurological disorders and aging. In addition, NSPCs can be considered as active agents contributing to chronic brain alterations and as relevant cell populations to be preserved, so that their main function, neurogenesis, is not lost in damage or disease. Altogether we believe that learning to manipulate NSPC is essential to prevent, ameliorate or restore some of the cognitive deficits associated with brain disease and injury, and therefore should be considered as target for future therapeutic strategies. The first step to accomplish this goal is to target them specifically, by unveiling and understanding their unique markers and signaling pathways.
      Graphical abstract image

      PubDate: 2017-08-01T01:07:23Z
      DOI: 10.1016/j.addr.2017.07.016
       
  • 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.
      Graphical abstract image

      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
       
  • 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.
      Graphical abstract image

      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.
      Graphical abstract image

      PubDate: 2017-07-14T13:49:34Z
      DOI: 10.1016/j.addr.2017.07.004
       
  • 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.
      Graphical abstract image

      PubDate: 2017-07-14T13:49:34Z
      DOI: 10.1016/j.addr.2017.07.007
       
  • 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.
      Graphical abstract image

      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
       
  • 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
       
  • 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
       
 
 
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