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Publisher: Elsevier   (Total: 3175 journals)

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Showing 1 - 200 of 3175 Journals sorted alphabetically
A Practical Logic of Cognitive Systems     Full-text available via subscription   (Followers: 9)
AASRI Procedia     Open Access   (Followers: 14)
Academic Pediatrics     Hybrid Journal   (Followers: 28, SJR: 1.402, h-index: 51)
Academic Radiology     Hybrid Journal   (Followers: 22, SJR: 1.008, h-index: 75)
Accident Analysis & Prevention     Partially Free   (Followers: 90, SJR: 1.109, h-index: 94)
Accounting Forum     Hybrid Journal   (Followers: 25, SJR: 0.612, h-index: 27)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 33, SJR: 2.515, h-index: 90)
Achievements in the Life Sciences     Open Access   (Followers: 5)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 6, SJR: 0.338, h-index: 19)
Acta Astronautica     Hybrid Journal   (Followers: 376, SJR: 0.726, h-index: 43)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 27, SJR: 2.02, h-index: 104)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 2)
Acta de Investigación Psicológica     Open Access   (Followers: 3)
Acta Ecologica Sinica     Open Access   (Followers: 8, SJR: 0.172, h-index: 29)
Acta Haematologica Polonica     Free   (Followers: 1, SJR: 0.123, h-index: 8)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.604, h-index: 38)
Acta Materialia     Hybrid Journal   (Followers: 236, 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  
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 2, SJR: 0.311, h-index: 16)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 1)
Acta Poética     Open Access   (Followers: 4)
Acta Psychologica     Hybrid Journal   (Followers: 25, 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: 3)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 2)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 3, SJR: 0.383, h-index: 19)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 1)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 6, SJR: 0.141, h-index: 3)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3, SJR: 0.112, h-index: 2)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 6)
Acute Pain     Full-text available via subscription   (Followers: 14)
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: 7)
Additive Manufacturing     Hybrid Journal   (Followers: 9, SJR: 1.039, h-index: 5)
Additives for Polymers     Full-text available via subscription   (Followers: 22)
Advanced Cement Based Materials     Full-text available via subscription   (Followers: 3)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 132, SJR: 5.2, h-index: 222)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.265, h-index: 53)
Advanced Powder Technology     Hybrid Journal   (Followers: 16, SJR: 0.739, h-index: 33)
Advances in Accounting     Hybrid Journal   (Followers: 8, SJR: 0.299, h-index: 15)
Advances in Agronomy     Full-text available via subscription   (Followers: 12, SJR: 2.071, h-index: 82)
Advances in Anesthesia     Full-text available via subscription   (Followers: 27, SJR: 0.169, h-index: 4)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 10, 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: 14, 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: 2, SJR: 0.619, h-index: 48)
Advances in Cancer Research     Full-text available via subscription   (Followers: 28, SJR: 2.215, h-index: 78)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 7, SJR: 0.9, h-index: 30)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 2.139, h-index: 42)
Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 3)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 12)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 27, SJR: 0.183, h-index: 23)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.665, h-index: 29)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 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: 19, SJR: 2.314, h-index: 130)
Advances in Computers     Full-text available via subscription   (Followers: 14, SJR: 0.223, h-index: 22)
Advances in Dermatology     Full-text available via subscription   (Followers: 14)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 10)
Advances in Digestive Medicine     Open Access   (Followers: 8)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 21)
Advances in Ecological Research     Full-text available via subscription   (Followers: 42, SJR: 3.25, h-index: 43)
Advances in Engineering Software     Hybrid Journal   (Followers: 27, SJR: 0.486, h-index: 10)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 6)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 42, SJR: 5.465, h-index: 64)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 1)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 7)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 53, 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: 7)
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: 9, SJR: 0.497, h-index: 31)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 23)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 2, SJR: 0.396, h-index: 27)
Advances in Immunology     Full-text available via subscription   (Followers: 36, SJR: 4.152, h-index: 85)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 1.132, h-index: 42)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 2, SJR: 1.274, h-index: 27)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 3)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.764, h-index: 15)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 9)
Advances in Marine Biology     Full-text available via subscription   (Followers: 14, 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: 21)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 8)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.324, h-index: 8)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 3)
Advances in Oncobiology     Full-text available via subscription   (Followers: 1)
Advances in Organ Biology     Full-text available via subscription   (Followers: 1)
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: 6, SJR: 0.148, h-index: 11)
Advances in Parasitology     Full-text available via subscription   (Followers: 5, 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: 10)
Advances in Pharmacology     Full-text available via subscription   (Followers: 15, SJR: 1.718, h-index: 58)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.384, h-index: 26)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.248, h-index: 11)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 7)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 5)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 17)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 18, SJR: 1.5, h-index: 62)
Advances in Psychology     Full-text available via subscription   (Followers: 59)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6, SJR: 0.478, h-index: 32)
Advances in Radiation Oncology     Open Access  
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 3, SJR: 0.1, h-index: 2)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 5)
Advances in Space Research     Full-text available via subscription   (Followers: 375, SJR: 0.606, h-index: 65)
Advances in Structural Biology     Full-text available via subscription   (Followers: 5)
Advances in Surgery     Full-text available via subscription   (Followers: 9, SJR: 0.823, h-index: 27)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 29, SJR: 1.321, h-index: 56)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 17)
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: 46, SJR: 2.408, h-index: 94)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 0.973, h-index: 22)
Aerospace Science and Technology     Hybrid Journal   (Followers: 333, 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: 6, SJR: 0.344, h-index: 6)
Ageing Research Reviews     Hybrid Journal   (Followers: 9, SJR: 3.289, h-index: 78)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 429, 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: 31, SJR: 1.275, h-index: 74)
Agricultural Water Management     Hybrid Journal   (Followers: 43, SJR: 1.546, h-index: 79)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 1)
Agriculture and Natural Resources     Open Access   (Followers: 2)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 56, SJR: 1.879, h-index: 120)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.434, h-index: 14)
Air Medical J.     Hybrid Journal   (Followers: 5, SJR: 0.234, h-index: 18)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.285, h-index: 3)
Alcohol     Hybrid Journal   (Followers: 11, SJR: 0.922, h-index: 66)
Alcoholism and Drug Addiction     Open Access   (Followers: 9)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.436, h-index: 12)
Alexandria J. of Medicine     Open Access   (Followers: 1)
Algal Research     Partially Free   (Followers: 9, SJR: 2.05, h-index: 20)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.46, h-index: 29)
Allergology Intl.     Open Access   (Followers: 5, SJR: 0.776, h-index: 35)
Alpha Omegan     Full-text available via subscription   (SJR: 0.121, h-index: 9)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 9, SJR: 0.158, h-index: 9)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 48, SJR: 4.289, h-index: 64)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 4)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 6)
American Heart J.     Hybrid Journal   (Followers: 50, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 50, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 42, SJR: 0.574, h-index: 65)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 10, SJR: 1.091, h-index: 45)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.653, h-index: 93)
American J. of Human Genetics     Hybrid Journal   (Followers: 31, SJR: 8.769, h-index: 256)
American J. of Infection Control     Hybrid Journal   (Followers: 26, SJR: 1.259, h-index: 81)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 32, SJR: 2.313, h-index: 172)
American J. of Medicine     Hybrid Journal   (Followers: 42, 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: 189, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 62, SJR: 2.803, h-index: 148)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 6)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.249, h-index: 88)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, h-index: 45)
American J. of Pathology     Hybrid Journal   (Followers: 27, SJR: 2.653, h-index: 228)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 27, SJR: 2.764, h-index: 154)
American J. of Surgery     Hybrid Journal   (Followers: 37, 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: 6)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.066, h-index: 51)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 61, SJR: 0.124, h-index: 9)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 14)
Anales de Cirugia Vascular     Full-text available via subscription  
Anales de Pediatría     Full-text available via subscription   (Followers: 2, SJR: 0.209, h-index: 27)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription   (SJR: 0.104, h-index: 3)
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 4, SJR: 2.577, h-index: 7)
Analytica Chimica Acta     Hybrid Journal   (Followers: 39, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 164, SJR: 0.725, h-index: 154)
Analytical Chemistry Research     Open Access   (Followers: 10, 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   (Followers: 1)

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Journal Cover Advanced Drug Delivery Reviews
  [SJR: 5.2]   [H-I: 222]   [132 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0169-409X
   Published by Elsevier Homepage  [3175 journals]
  • Technological strategies to overcome the mucus barrier in mucosal drug
           delivery
    • Authors: José das Neves; Bruno Sarmento
      Pages: 1 - 2
      Abstract: Publication date: 15 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 124
      Author(s): José das Neves, Bruno Sarmento


      PubDate: 2018-02-15T09:46:58Z
      DOI: 10.1016/j.addr.2018.01.014
      Issue No: Vol. 124 (2018)
       
  • Impact of aging, Alzheimer's disease and Parkinson's disease on the
           blood-brain barrier transport of therapeutics
    • Authors: Yijun Pan; Joseph A. Nicolazzo
      Abstract: Publication date: Available online 14 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Yijun Pan, Joseph A. Nicolazzo
      Older people are at greater risk of medicine-induced toxicities resulting from either increased drug sensitivity or age-related pharmacokinetic changes. The scenario is further complicated with the two most prevalent age-related neurodegenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD). With aging, AD and PD, there is growing evidence of altered structure and function of the blood-brain barrier (BBB), including modifications to tight junctions and efflux transporters, such as P-glycoprotein. The subsequent impact on CNS drug exposure and risk of neurotoxicity from systemically-acting medicines is less well characterized. The purpose of this review, therefore, is to provide an overview of the multiple changes that occur to the BBB as a result of aging, AD and PD, and the impact that such changes have on CNS exposure of drugs, based on studies conducted in aged rodents or rodent models of disease, and in elderly people with and without AD or PD.
      Graphical abstract image

      PubDate: 2018-04-15T09:22:44Z
      DOI: 10.1016/j.addr.2018.04.009
       
  • Dosage form modification and oral drug delivery in older people
    • Authors: Esther T.L. Lau; Kathryn J. Steadman; Julie A.Y. Cichero; Lisa M. Nissen
      Abstract: Publication date: Available online 13 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Esther T.L. Lau, Kathryn J. Steadman, Julie A.Y. Cichero, Lisa M. Nissen
      Many people cannot swallow whole tablets and capsules. The cause ranges from difficulties overriding the natural instinct to chew solids/foodstuff before swallowing, to a complex disorder of swallowing function affecting the ability to manage all food and fluid intake. Older people can experience swallowing difficulties because of co-morbidities, age-related physiological changes, and polypharmacy. To make medicines easier to swallow, many people will modify the medication dosage form e.g. split or crush tablets, and open capsules. Some of the challenges associated with administering medicines to older people, and issues with dosage form modification will be reviewed. Novel dosage forms in development are promising and may help overcome some of the issues. However, until these are more readily available, effective interdisciplinary teams, and improving patient health literacy will help reduce the risk of medication misadventures in older people.
      Graphical abstract image

      PubDate: 2018-04-15T09:22:44Z
      DOI: 10.1016/j.addr.2018.04.012
       
  • Scarless wound healing: From development to senescence
    • Authors: Harris Pratsinis; Eleni Mavrogonatou; Dimitris Kletsas
      Abstract: Publication date: Available online 12 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Harris Pratsinis, Eleni Mavrogonatou, Dimitris Kletsas
      An essential element of tissue homeostasis is the response to injuries, cutaneous wound healing being the most studied example. In the adults, wound healing aims at quickly restoring the barrier function of the skin, leading however to scar, a dysfunctional fibrotic tissue. On the other hand, in fetuses a scarless tissue regeneration takes place. During ageing, the wound healing capacity declines; however, in the absence of comorbidities a higher quality in tissue repair is observed. Senescent cells have been found to accumulate in chronic unhealed wounds, but more recent reports indicate that their transient presence may be beneficial for tissue repair. In this review data on skin wound healing and scarring are presented, covering the whole spectrum from early embryonic development to adulthood, and furthermore until ageing of the organism.
      Graphical abstract image

      PubDate: 2018-04-15T09:22:44Z
      DOI: 10.1016/j.addr.2018.04.011
       
  • Delivering drugs to the lungs: The history of repurposing in the treatment
           of respiratory diseases
    • Authors: Stephen P. Newman
      Abstract: Publication date: Available online 11 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Stephen P. Newman
      The repurposing of drug delivery by the pulmonary route has been applied to treatment and prophylaxis of an increasingly wide range of respiratory diseases. Repurposing has been most successful for the delivery of inhaled bronchodilators and corticosteroids in patients with asthma and chronic obstructive pulmonary disease (COPD). Repurposing utilizes the advantages that the pulmonary route offers in terms of more targeted delivery to the site of action, the use of smaller doses, and a lower incidence of side-effects. Success has been more variable for other drugs and treatment indications. Pulmonary delivery is now well established for delivery of inhaled antibiotics in cystic fibrosis (CF), and in the treatment of pulmonary arterial hypertension (PAH). Other inhaled treatments such as those for idiopathic pulmonary fibrosis (IPF), lung transplant rejection or tuberculosis may also become routine. Repurposing has progressed in parallel with the development of new drugs, inhaler devices and formulations.
      Graphical abstract image

      PubDate: 2018-04-15T09:22:44Z
      DOI: 10.1016/j.addr.2018.04.010
       
  • Aptamers as targeting ligands and therapeutic molecules for overcoming
           drug resistance in cancers
    • Authors: Gang Zhou; Olivier Latchoumanin; Lionel Hebbard; Wei Duan; Christopher Liddle; Jacob George; Liang Qiao
      Abstract: Publication date: Available online 6 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Gang Zhou, Olivier Latchoumanin, Lionel Hebbard, Wei Duan, Christopher Liddle, Jacob George, Liang Qiao
      Traditional anticancer therapies are often unable to completely eradicate the tumor bulk due to multi-drug resistance (MDR) of cancers. A number of mechanisms such as micro-environmental stress and overexpression of drug efflux pumps are involved in the MDR process. Hence, therapeutic strategies for overcoming MDR are urgently needed to improve cancer treatment efficacy. Aptamers are short single-stranded oligonucleotides or peptides exhibiting unique three-dimensional structures and possess several unique advantages over conventional antibodies such as low immunogenicity and stronger tissue-penetration capacity. Aptamers targeting cancer-associated receptors have been explored to selectively deliver a therapeutic cargo (anticancer drugs, siRNAs, miRNAs and drug-carriers) to the intratumoral compartment where they can exert better tumor-killing effects. In this review, we summarize current knowledge of the multiple regulatory mechanisms of MDR, with a particular emphasis on aptamer-mediated novel therapeutic agents and strategies that seek to reversing MDR. The challenges associated with aptamer-based agents and approaches are also discussed.
      Graphical abstract image

      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.04.005
       
  • Nucleic acids delivering nucleic acids
    • Authors: Silvia Catuogno; Carla Lucia Esposito; Gerolama Condorelli; Vittorio de Franciscis
      Abstract: Publication date: Available online 6 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Silvia Catuogno, Carla Lucia Esposito, Gerolama Condorelli, Vittorio de Franciscis
      Nucleic acid therapeutics, including siRNAs, miRNAs/antimiRs, gRNAs and ASO, represent innovative and highly promising molecules for the safe treatment of a wide range of pathologies. The efficiency of systemic treatments is impeded by 1) the need to overcome physical and functional barriers in the organism, and 2) to accumulate in the intracellular active site at therapeutic concentrations. Although oligonucleotides either as modified naked molecules or complexed with delivery carriers have revealed to be effectively delivered to the affected target cells, this is restricted to topic treatments or to a few highly vascularized tissues. Therefore, the development of effective strategies for therapeutic nucleic acid selective delivery to target tissues is of primary importance in order to reduce the occurrence of undesired effects on non-target healthy tissues and to permit their translation to clinic. Due to their high affinity for specific ligands, high tissue penetration and chemical flexibility, short single-stranded nucleic acid aptamers are emerging as very attractive carriers for various therapeutic oligonucleotides. Yet, different aptamer-based bioconjugates, able to provide accumulation into target tissues, as well as efficient processing of therapeutic oligonucleotides, have been developed. In this respect, nucleic acid aptamer-mediated delivery strategies represent a powerful approach able to increase the therapeutic efficacy also highly reducing the overall toxicity. In this review, we will summarize recent progress in the field and discuss achieved objectives and optimization of aptamers as delivery carriers of short oligonucleotides.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.04.006
       
  • Repurposing excipients as active inhalation agents: The mannitol story
    • Authors: Sandra D. Anderson; Evangelia Daviskas; John D. Brannan; Hak Kim Chan
      Abstract: Publication date: Available online 5 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Sandra D. Anderson, Evangelia Daviskas, John D. Brannan, Hak Kim Chan
      The story of how we came to use inhaled mannitol to diagnose asthma and to treat cystic fibrosis began when we were looking for a surrogate for exercise as a stimulus to identify asthma. We had proposed that exercise-induced asthma was caused by an increase in osmolarity of the periciliary fluid. We found hypertonic saline to be a surrogate for exercise but an ultrasonic nebuliser was required. We produced a dry powder of sodium chloride but it proved unstable. We developed a spray dried preparation of mannitol and found that bronchial responsiveness to inhaling mannitol identified people with currently active asthma. We reasoned that mannitol had potential to replace the ‘osmotic’ benefits of exercise and could be used as a treatment to enhance mucociliary clearance in patients with cystic fibrosis. These discoveries were the start of a journey to develop several registered products that are in clinical use globally today.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.04.003
       
  • Transforming nanomedicine manufacturing toward Quality by Design and
           microfluidics
    • Authors: Stefano Colombo; Moritz Beck-Broichsitter; Johan Peter Bøtker; Martin Malmsten; Jukka Rantanen; Adam Bohr
      Abstract: Publication date: Available online 5 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Stefano Colombo, Moritz Beck-Broichsitter, Johan Peter Bøtker, Martin Malmsten, Jukka Rantanen, Adam Bohr
      Nanopharmaceuticals aim at translating the unique features of nano-scale materials into therapeutic products and consequently their development relies critically on the progression in manufacturing technology to allow scalable processes complying with process economy and quality assurance. The relatively high failure rate in translational nanopharmaceutical research and development, with respect to new products on the market, is at least partly due to immature bottom-up manufacturing development and resulting sub-optimal control of quality attributes in nanopharmaceuticals. Recently, quality-oriented manufacturing of pharmaceuticals has undergone an unprecedented change toward process and product development interaction. In this context, Quality by Design (QbD) aims to integrate product and process development resulting in an increased number of product applications to regulatory agencies and stronger proprietary defense strategies of process-based products. Although QbD can be applied to essentially any production approach, microfluidic production offers particular opportunities for QbD-based manufacturing of nanopharmaceuticals. Microfluidics provides unique design flexibility, process control and parameter predictability, and also offers ample opportunities for modular production setups, allowing process feedback for continuously operating production and process control. The present review aims at outlining emerging opportunities in the synergistic implementation of QbD strategies and microfluidic production in contemporary development and manufacturing of nanopharmaceuticals. In doing so, aspects of design and development, but also technology management, are reviewed, as is the strategic role of these tools for aligning nanopharmaceutical innovation, development, and advanced industrialization in the broader pharmaceutical field.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.04.004
       
  • The apparent competitive action of ECM proteases and cross-linking enzymes
           during fibrosis: applications to drug discovery
    • Authors: Nikolaos A. Afratis; Mordehay Klepfish; Nikos K. Karamanos; Irit Sagi
      Abstract: Publication date: Available online 5 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Nikolaos A. Afratis, Mordehay Klepfish, Nikos K. Karamanos, Irit Sagi
      Progressive loss of organ function in most organs is associated with fibrosis, a tissue state associated with abnormal matrix buildup. If highly progressive, the fibrotic process eventually leads to organ failure and death. Fibrosis is a basic connective tissue lesion defined by the increase in the amount of fibrillar extracellular matrix (ECM) components in a tissue or organ. In addition, intrinsic changes in important structural cells can induce the fibrotic response by regulating the differentiation, recruitment, proliferation and activation of extracellular matrix-producing myofibroblasts. ECM enzymes belonging to the family of matrix metalloproteinases (MMPs) and lysyl oxidases (LOXs) play a crucial role in ECM remodeling and regeneration. MMPs have a catalytic role in degradation of ECM, whereas LOX/LOXLs mediate ECM, especially collagen, cross-linking and stiffening. Importantly, enzymes from both families are elevated during the fibrotic response to tissue injury and its resolution. Yet, the apparent molecular competition or antagonistic activities of these enzyme families during the various stages of fibrosis is often overlooked. In this review, we discuss the diverse roles of MMPs and LOX/LOXL2 in chronic organ fibrosis. Finally, we review contemporary therapeutic strategies for fibrosis treatment, based on neutralization of MMP and LOX activity, as well as the development of novel drug delivery approaches.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.03.004
       
  • Microfluidics in nanoparticle drug delivery; From synthesis to
           pre-clinical screening
    • Authors: Jungho Ahn; Jihoon Ko; Somin Lee; James Yu; YongTae Kim; Noo Li Jeon
      Abstract: Publication date: Available online 5 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Jungho Ahn, Jihoon Ko, Somin Lee, James Yu, YongTae Kim, Noo Li Jeon
      Microfluidic technologies employ nano and microscale fabrication techniques to develop highly controllable and reproducible fluidic microenvironments. Utilizing microfluidics, lead compounds can be produced with the controlled physicochemical properties, characterized in a high-throughput fashion, and evaluated in in vitro biomimetic models of human organs; organ-on-a-chip. As a step forward from conventional in vitro culture methods, microfluidics shows promise in effective preclinical testing of nanoparticle-based drug delivery. This review presents a curated selection of state-of-the-art microfluidic platforms focusing on the fabrication, characterization, and assessment of nanoparticles for drug delivery applications. We also discuss the current challenges and future prospects of nanoparticle drug delivery development using microfluidics.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.04.001
       
  • Instructive microenvironments in skin wound healing: Biomaterials as
           signal releasing platforms
    • Authors: Oscar Castaño; Soledad Pérez-Amodio; Claudia Navarro; Miguel Ángel Mateos-Timoneda; Elisabeth Engel
      Abstract: Publication date: Available online 5 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Oscar Castaño, Soledad Pérez-Amodio, Claudia Navarro, Miguel Ángel Mateos-Timoneda, Elisabeth Engel
      Skin wound healing aims to repair and restore tissue through a multistage process that involves different cells and signalling molecules that regulate the cellular response and the dynamic remodelling of the extracellular matrix. Nowadays, several therapies that combine biomolecule signals (growth factors and cytokines) and cells are being proposed. However, a lack of reliable evidence of their efficacy, together with associated issues such as high costs, a lack of standardization, no scalable processes, and storage and regulatory issues, are hampering their application. In situ tissue regeneration appears to be a feasible strategy that uses the body's own capacity for regeneration by mobilizing host endogenous stem cells or tissue-specific progenitor cells to the wound site to promote repair and regeneration. The aim is to engineer instructive systems to regulate the spatio-temporal delivery of proper signalling based on the biological mechanisms of the different events that occur in the host microenvironment. This review describes the current state of the different signal cues used in wound healing and skin regeneration, and their combination with biomaterial supports to create instructive microenvironments for wound healing.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.03.012
       
  • Drug delivery systems and materials for wound healing applications
    • Authors: Saghi Saghazadeh; Chiara Rinoldi; Maik Schot; Sara Saheb Kashaf; Fatemeh Sharifi; Elmira Jalilian; Kristo Nuutila; Giorgio Giatsidis; Pooria Mostafalu; Hossein Derakhshandeh; Kan Yue; Wojciech Swieszkowski; Adnan Memic; Ali Tamayol; Ali Khademhosseini
      Abstract: Publication date: Available online 5 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Saghi Saghazadeh, Chiara Rinoldi, Maik Schot, Sara Saheb Kashaf, Fatemeh Sharifi, Elmira Jalilian, Kristo Nuutila, Giorgio Giatsidis, Pooria Mostafalu, Hossein Derakhshandeh, Kan Yue, Wojciech Swieszkowski, Adnan Memic, Ali Tamayol, Ali Khademhosseini
      Chronic, non-healing wounds place a significant burden on patients and healthcare systems, resulting in impaired mobility, limb amputation, or even death. Chronic wounds result from a disruption in the highly orchestrated cascade of events involved in wound closure. Significant advances in our understanding of the pathophysiology of chronic wounds have resulted in the development of drugs designed to target different aspects of the impaired processes. However, the hostility of the wound environment rich in degradative enzymes and its elevated pH, combined with differences in the time scales of different physiological processes involved in tissue regeneration require the use of effective drug delivery systems. In this review, we will first discuss the pathophysiology of chronic wounds and then the materials used for engineering drug delivery systems. Different passive and active drug delivery systems used in wound care will be reviewed. In addition, the architecture of the delivery platform and its ability to modulate drug delivery are discussed. Emerging technologies and the opportunities for engineering more effective wound care devices are also highlighted.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.04.008
       
  • Clinical indications for, and the future of, circulating tumor cells
    • Authors: Dominic H. Moon; Daniel P. Lindsay; Seungpyo Hong; Andrew Z. Wang
      Abstract: Publication date: Available online 5 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Dominic H. Moon, Daniel P. Lindsay, Seungpyo Hong, Andrew Z. Wang
      Circulating tumor cells (CTCs) are cells that have detached from the primary tumor and entered circulation with potential to initiate a site of metastasis. Currently, CTC detection using CellSearch is cleared by the Food and Drug Administration for monitoring metastatic breast, prostate, and colorectal cancers as a prognostic biomarker for progression-free and overall survival. Accumulating evidence suggests CTCs have similar prognostic value in other metastatic and non-metastatic settings. Current research efforts are focused on extending the utility of CTCs beyond a prognostic biomarker to help guide clinical decision-making. These include using CTCs as a screening tool for diagnosis, liquid biopsy for molecular profiling, predictive biomarker to specific therapies, and monitoring tool to assess response and guide changes to treatment. CTCs have unique advantages vs circulating tumor DNA in this endeavor. Indications for CTCs in daily practice will expand as isolation techniques improve and clinical studies validating their utility continue to grow.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.04.002
       
  • Controlled release technology for anti-angiogenesis treatment of posterior
           eye diseases: Current status and challenges
    • Authors: Chi Ming Laurence Lau; Yu Yu; Ghodsiehsadat Jahamir; Ying Chau
      Abstract: Publication date: Available online 4 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Chi Ming Laurence Lau, Yu Yu, Ghodsiehsadat Jahamir, Ying Chau
      Antiangiogenic therapeutics, such as corticosteroids, VEGF targeting antibodies and aptamers have been demonstrated effective in controlling retinal and choroidal neovascularization related vision loss. However, to manage the chronic conditions, it requires long term and frequent intravitreal injections of these drugs, resulting in poor patient compliance and suboptimal treatment. In addition, emerging drugs such as tyrosine kinase inhibitors and siRNAs received much expectations, but the late stage clinical trials encountered various obstacles. Controlled release technology could improve the existing treatment regimen by extending therapeutic duration, reducing risks and burdens caused by frequent injections, and enabling new drugs to overcome the hurdles of translation. Here, we give qualitative and quantitative discussions about the principle mechanisms of polymeric reservoir, polymeric matrix and hydrogel systems. We also reveal the design rationales of the existing drug delivery and release systems in preclinical and clinical stages. Lastly, the animal models of ocular angiogenesis diseases are critically reviewed, which could help to facilitate the translation of controlled release technologies from bench to bedside.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.03.013
       
  • Aptamer chemistry
    • Authors: Pascal Röthlisberger; Marcel Hollenstein
      Abstract: Publication date: Available online 4 April 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Pascal Röthlisberger, Marcel Hollenstein
      Aptamers are single-stranded DNA or RNA molecules capable of tightly binding to specific targets. These functional nucleic acids are obtained by an in vitro Darwinian evolution method coined SELEX (Systematic Evolution of Ligands by EXponential enrichment). Compared to their proteinaceous counterparts, aptamers offer a number of advantages including a low immunogenicity, a relative ease of large-scale synthesis at affordable costs with little or no batch-to-batch variation, physical stability, and facile chemical modification. These alluring properties have propelled aptamers into the forefront of numerous practical applications such as the development of therapeutic and diagnostic agents as well as the construction of biosensing platforms. However, commercial success of aptamers still proceeds at a weak pace. The main factors responsible for this delay are the susceptibility of aptamers to degradation by nucleases, their rapid renal filtration, suboptimal thermal stability, and the lack of functional group diversity. Here, we describe the different chemical methods available to mitigate these shortcomings. Particularly, we describe the chemical post-SELEX processing of aptamers to include functional groups as well as the inclusion of modified nucleoside triphosphates into the SELEX protocol. These methods will be illustrated with successful examples of chemically modified aptamers used as drug delivery systems, in therapeutic applications, and as biosensing devices.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.04.007
       
  • Insulin Delivery Systems Combined with Microneedle Technology
    • Authors: Xuan Jin; Dan Dan Zhu; Bo Zhi Chen; Mohammad Ashfaq; Xin Dong Guo
      Abstract: Publication date: Available online 29 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Xuan Jin, Dan Dan Zhu, Bo Zhi Chen, Mohammad Ashfaq, Xin Dong Guo
      Diabetes, a metabolic disorder of glucose, is a serious chronic disease and an important public health problem. Insulin is one of the hormones for modulating blood glucose level and the products of which is indispensable for most diabetes patients. Introducing microneedles (MNs) to insulin delivery is promising to pave the way for modulating glucose level noninvasively of diabetes patients, as which born to be painless, easy to handle and no need of any power supply. In this work, we review the process of insulin delivery systems (IDSs) based on MN technology in terms of two categories: drug free MNs and drug loaded MNs. Drug free MNs include solid MNs (“poke and patch”), hollow MNs (“poke and flow”) and reservoir-based swelling MNs (“poke and swell R-type”), and drug loaded MNs include coated MNs (“coat and poke”), dissolving MNs (“poke and release”) and insulin incorporated swelling MNs (“poke and swell I-type”). Majority researches of MN-based IDSs have been conducted by using hollow MNs or dissolving MNs, and almost all clinical trials for MN-based IDSs have employed hollow MNs. “Poke and patch” approach dramatically increase skin permeability compared to traditional transdermal patch, but MNs fabricated from silicon or metal may leave sharp waste in the skin and cause a safety issue. “Poke and flow” approach, similar to transitional subcutaneous (SC) injection, is capable of producing faster insulin absorption and action than SC injection but may associate with blockage, leakage and low flow rate. Coated MNs are able of retaining the activity of drug, which loaded in a solid phase, for a long time, however have been relatively less studied for insulin application as the low drug dosing. “Poke and release” approach leaves no biohazardous sharp medical waste and is capable of rapid drug release. “Poke and swell R-type” can be seen as a combination of “poke and flow” and “poke and patch” approach, while “poke and swell I-type” is an approach between “coat and poke” and “poke and release” approach. Insulin MNs are promising for painless diabetes therapeutics, and additional efforts for addressing fundamental issues including the drug loading, the PK/PD profile, the storage and the safety of insulin MNs will accelerate the clinical transformation.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.03.011
       
  • Transdermal immunomodulation: Principles, advances and perspectives
    • Authors: Zongmin Zhao; Anvay Ukidve; Anshuman Dasgupta; Samir Mitragotri
      Abstract: Publication date: Available online 29 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Zongmin Zhao, Anvay Ukidve, Anshuman Dasgupta, Samir Mitragotri
      Immunomodulation, manipulation of the immune responses towards an antigen, is a promising strategy to treat cancer, infectious diseases, allergies, and autoimmune diseases, among others. Unique features of the skin including the presence of tissue-resident immune cells, ease of access and connectivity to other organs makes it a unique target organ for immunomodulation. In this review, we summarize advances in transdermal delivery of agents for modulating the immune responses for vaccination as well as tolerization. The biological foundation of skin-based immunomodulation and challenges in its implementation are described. Technological approaches aimed at enhancing the delivery of immunomodulatory therapeutics into skin are also discussed in this review. Progress made in the treatment of several specific diseases including cancer, infections and allergy are discussed. Finally, this review discusses some practical considerations and offers some recommendations for future studies in the field of transdermal immunomodulation.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.03.010
       
  • Drug delivery to the lens for the management of cataracts
    • Authors: Thilini R. Thrimawithana; Ilva D. Rupenthal; Simon S. Räsch; Julie C. Lim; James D. Morton; Craig R. Bunt
      Abstract: Publication date: Available online 28 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Thilini R. Thrimawithana, Ilva D. Rupenthal, Simon S. Räsch, Julie C. Lim, James D. Morton, Craig R. Bunt
      Cataracts are one of the most prevalent diseases of the lens, affecting its transparency and are the leading cause of reversible blindness in the world. The clarity of the lens is essential for its normal physiological function of refracting light onto the retina. Currently there is no pharmaceutical treatment for prevention or cure of cataracts and surgery to replace the affected lens remains the gold standard in the management of cataracts. Pharmacological treatment for prevention of cataracts is hindered by many physiological barriers that must be overcome by a therapeutic agent to reach the avascular lens. Various therapeutic agents and formulation strategies are currently being investigated to prevent cataract formation as access to surgery is limited. This review provides a summary of recent research in the field of drug delivery to the lens for the management of cataracts including models used to study cataract treatments and discusses the future perspectives in the field.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.03.009
       
  • Delivery systems of current biologicals for the treatment of chronic
           cutaneous wounds and severe burns
    • Authors: Meilang Xue; Ruilong Zhao; Haiyan Lin; Christopher Jackson
      Abstract: Publication date: Available online 19 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Meilang Xue, Ruilong Zhao, Haiyan Lin, Christopher Jackson
      While wound therapy remains a clinical challenge in current medical practice, much effort has focused on developing biological therapeutic approaches. This paper presents a comprehensive review of delivery systems for current biologicals for the treatment of chronic wounds and severe burns. The biologicals discussed here include proteins such as growth factors and gene modifying molecules, which may be delivered to wounds free, encapsulated, or released from living systems (cells, skin grafts or skin equivalents) or biomaterials. Advances in biomaterial science and technologies have enabled the synthesis of delivery systems such as scaffolds, hydrogels and nanoparticles, designed to not only allow spatially and temporally controlled release of biologicals, but to also emulate the natural extracellular matrix microenvironment. These technologies represent an attractive field for regenerative wound therapy, by offering more personalised and effective treatments.
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.03.002
       
  • Advances in microfluidics for lipid nanoparticles and extracellular
           vesicles and applications in drug delivery systems
    • Authors: Masatoshi Maeki; Niko Kimura; Yusuke Sato; Hideyoshi Harashima; Manabu Tokeshi
      Abstract: Publication date: Available online 19 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Masatoshi Maeki, Niko Kimura, Yusuke Sato, Hideyoshi Harashima, Manabu Tokeshi
      Lipid-based nanobiomaterials as liposomes and lipid nanoparticles (LNPs) are the most widely used nanocarriers for drug delivery systems (DDSs). Extracellular vesicles (EVs) and exosomes are also expected to be applied as DDS nanocarriers. The performance of nanomedicines relies on their components such as lipids, targeting ligands, encapsulated DNA, encapsulated RNA, and drugs. Recently, the importance of the nanocarrier sizes smaller than 100 nm is attracting attention as a means to improve the nanomedicine performance. Microfluidics and lab-on-a chip technologies make it possible to produce size-controlled LNPs by a simple continuous flow process and to separate EVs from blood samples by using a surface marker, ligand or electric charge, or by making a mass or particle size discrimination. Here, we overview recent advances in microfluidic devices and techniques for liposomes, LNPs and EVs and their applications for DDSs.
      Graphical abstract image

      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.03.008
       
  • In situ forming injectable hydrogels for drug delivery and wound repair
    • Authors: Robert Dimatteo; Nicole J. Darling; Tatiana Segura
      Abstract: Publication date: Available online 19 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Robert Dimatteo, Nicole J. Darling, Tatiana Segura
      Hydrogels have been utilized in regenerative applications for many decades because of their biocompatibility and similarity in structure to the native extracellular matrix. Initially, these materials were formed outside of the patient and implanted using invasive surgical techniques. However, advances in synthetic chemistry and materials science have now provided researchers with a library of techniques whereby hydrogel formation can occur in situ upon delivery through standard needles. This provides an avenue to minimally invasively deliver therapeutic payloads, fill complex tissue defects, and induce the regeneration of damaged portions of the body. In this review, we highlight these injectable therapeutic hydrogel biomaterials in the context of drug delivery and tissue regeneration for skin wound repair.
      Graphical abstract image

      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.03.007
       
  • Nanopharmaceuticals for wound healing – Lost in translation'
    • Authors: Mukul Ashtikar; Matthias G. Wacker
      Abstract: Publication date: Available online 19 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Mukul Ashtikar, Matthias G. Wacker
      Today, many of the newly developed pharmaceuticals and medical devices take advantage of nanotechnology and with a rising incidence of chronic diseases such as diabetes and cardiovascular disease, the number of patients afflicted globally with non-healing wounds is growing. This has created a requirement for improved therapies and wound care. However, converting the strategies applied in early research into new products is still challenging. Many of them fail to comply with the market requirements. This review discusses the legal and scientific challenges in the design of nanomedicines for wound healing. Are they lost in translation or is there a new generation of therapeutics in the pipeline?
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      PubDate: 2018-04-10T18:23:06Z
      DOI: 10.1016/j.addr.2018.03.005
       
  • NanoVelcro rare-cell assays for detection and characterization of
           circulating tumor cells
    • Authors: Yu Jen Jan; Jie-Fu Chen; Yazhen Zhu; Yi-Tsung Lu; Szu Hao Chen; Howard Chung; Matthew Smalley; Yen-Wen Huang; Jiantong Dong; Hsiao-Hua Yu; James S. Tomlinson; Shuang Hou; Vatche G. Agopian; Edwin M. Posadas; Hsian-Rong Tseng
      Abstract: Publication date: Available online 15 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Yu Jen Jan, Jie-Fu Chen, Yazhen Zhu, Yi-Tsung Lu, Szu Hao Chen, Howard Chung, Matthew Smalley, Yen-Wen Huang, Jiantong Dong, Hsiao-Hua Yu, James S. Tomlinson, Shuang Hou, Vatche G. Agopian, Edwin M. Posadas, Hsian-Rong Tseng
      Circulating tumor cells (CTCs) are cancer cells shredded from either a primary tumor or a metastatic site and circulate in the blood as the potential cellular origin of metastasis. By detecting and analyzing CTCs, we will be able to noninvasively monitor disease progression in individual cancer patients and obtain insightful information for assessing disease status, thus realizing the concept of “tumor liquid biopsy”. However, it is technically challenging to identify CTCs in patient blood samples because of the extremely low abundance of CTCs among a large number of hematologic cells. In order to address this challenge, our research team at UCLA pioneered a unique concept of “NanoVelcro” cell-affinity substrates, in which CTC capture agent-coated nanostructured substrates were utilized to immobilize CTCs with remarkable efficiency. Four generations of NanoVelcro CTC assays have been developed over the past decade for a variety of clinical utilities. The 1st-gen NanoVelcro chips, composed of a silicon nanowire substrate (SiNS) and an overlaid microfluidic chaotic mixer, were created for CTC enumeration. The 2nd-gen NanoVelcro chips (i.e., NanoVelcro-LMD), based on polymer nanosubstrates, were developed for single-CTC isolation in conjunction with the use of the laser microdissection (LMD) technique. By grafting thermoresponsive polymer brushes onto SiNS, the 3rd-gen Thermoresponsive NanoVelcro chips have demonstrated the capture and release of CTCs at 37 and 4 °C respectively, thereby allowing for rapid CTC purification while maintaining cell viability and molecular integrity. Fabricated with boronic acid-grafted conducting polymer-based nanomaterial on chip surface, the 4th-gen NanoVelcro Chips (Sweet chip) were able to purify CTCs with well-preserved RNA transcripts, which could be used for downstream analysis of several cancer specific RNA biomarkers. In this review article, we will summarize the development of the four generations of NanoVelcro CTC Assays, and the clinical applications of each generation of devices.
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      PubDate: 2018-03-17T17:52:01Z
      DOI: 10.1016/j.addr.2018.03.006
       
  • Bioactive scaffolds based on elastin-like materials for wound healing
    • Authors: J. Carlos Rodríguez-Cabello; I. González de Torre; A. Ibañez-Fonzeca; M. Alonso
      Abstract: Publication date: Available online 15 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): J. Carlos Rodríguez-Cabello, I. González de Torre, A. Ibañez-Fonzeca, M. Alonso
      Wound healing is a complex process that, in healthy tissues, starts immediately after the injury. Even though it is a natural well-orchestrated process, large trauma wounds, or injuries caused by acids or other chemicals, usually produce a non-elastic deformed tissue that not only have biological reduced properties but a clear aesthetic effect. One of the main drawbacks of the scaffolds used for wound dressing is the lack of elasticity, driving to non-elastic and contracted tissues. In the last decades, elastin based materials have gained in importance as biomaterials for tissue engineering applications due to their good cyto- and bio-compatibility, their ease handling and design, production and modification. Synthetic elastin or elastin like-peptides (ELPs) are the two main families of biomaterials that try to mimic the outstanding properties of natural elastin, elasticity among others; although there are no in vivo studies that clearly support that these two families of elastin based materials improve the elasticity of the artificial scaffolds and of the regenerated skin. Within the next pages a review of the different forms (coacervates, fibres, hydrogels and biofunctionalized surfaces) in which these two families of biomaterials can be processed to be applied in the wound healing field have been done. Here, we explore the mechanical and biological properties of these scaffolds as well as the different in vivo approaches in which these scaffolds have been used.
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      PubDate: 2018-03-17T17:52:01Z
      DOI: 10.1016/j.addr.2018.03.003
       
  • The suprachoroidal space as a route of administration to the posterior
           segment of the eye
    • Authors: Bryce Chiang; Jaehwan Jung; Mark Prausnitz
      Abstract: Publication date: Available online 12 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Bryce Chiang, Jaehwan Jung, Mark Prausnitz
      The suprachoroidal space (SCS) is a potential space between the sclera and choroid that traverses the circumference of the posterior segment of the eye. The SCS is an attractive site for drug delivery because it targets the choroid, retinal pigment epithelium and retina with high bioavailability, while maintaining low levels elsewhere in the eye. Indeed, phase III clinical trials are investigating the safety and efficacy of SCS drug delivery. Here, we review the anatomy and physiology of the SCS; methods to access the SCS; kinetics of SCS drug delivery; strategies to target within the SCS; current and potential clinical indications; and the safety and efficacy of this approach in preclinical animal studies and clinical trials.
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      PubDate: 2018-03-17T17:52:01Z
      DOI: 10.1016/j.addr.2018.03.001
       
  • Corrigendum to ‘Tumor-targeting peptides from combinatorial libraries’
           [Adv Drug Deliv Rev.110–111 (2017) 13–37]
    • Authors: Ruiwu Liu; Xiaocen Li; Wenwu Xiao; Kit S. Lam
      Abstract: Publication date: Available online 9 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Ruiwu Liu, Xiaocen Li, Wenwu Xiao, Kit S. Lam


      PubDate: 2018-03-17T17:52:01Z
      DOI: 10.1016/j.addr.2018.02.005
       
  • Drug delivery and Epimorphic salamander-type mouse regeneration: A full
           parts and labor plan
    • Authors: Ellen Heber-Katz; Phillip Messersmith
      Abstract: Publication date: Available online 7 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Ellen Heber-Katz, Phillip Messersmith
      The capacity to regenerate entire body parts, tissues, and organs had generally been thought to be lost in evolution with very few exceptions (eg. the liver) surviving in mammals. The discovery of the MRL mouse and the elucidation of the underlying molecular pathway centering around hypoxia inducible factor, HIF-1α, has allowed a drug and materials approach to regeneration in mice and hopefully humans. The HIF-1α pathway is ancient and permitted the transition from unicellular to multicellular organisms. Furthermore, HIF-1α and its regulation by PHDs, important oxygen sensors in the cell, provides a perfect drug target. We review the historical background of regeneration biology, the discovery of the MRL mouse, and its underlying biology, and novel approaches to drugs, targets, and delivery systems.
      Graphical abstract image

      PubDate: 2018-03-17T17:52:01Z
      DOI: 10.1016/j.addr.2018.02.006
       
  • Tackling muscle fibrosis: From molecular mechanisms to next generation
           engineered models to predict drug delivery
    • Authors: S. Bersini; M. Gilardi; M. Mora; S. Krol; C. Arrigoni; C. Candrian; S. Zanotti; M. Moretti
      Abstract: Publication date: Available online 5 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): S. Bersini, M. Gilardi, M. Mora, S. Krol, C. Arrigoni, C. Candrian, S. Zanotti, M. Moretti
      Muscle fibrosis represents the end stage consequence of different diseases, among which muscular dystrophies, leading to severe impairment of muscle functions. Muscle fibrosis involves the production of several growth factors, cytokines and proteolytic enzymes and is strictly associated to inflammatory processes. Moreover, fibrosis causes profound changes in tissue properties, including increased stiffness and density, lower pH and oxygenation. Up to now, there is no therapeutic approach able to counteract the fibrotic process and treatments directed against muscle pathologies are severely impaired by the harsh conditions of the fibrotic environment. The design of new therapeutics thus need innovative tools mimicking the obstacles posed by the fibrotic environment to their delivery. This review will critically discuss the role of in vivo and 3D in vitro models in this context and the characteristics that an ideal model should possess to help the translation from bench to bedside of new candidate anti-fibrotic agents.
      Graphical abstract image

      PubDate: 2018-03-06T14:45:40Z
      DOI: 10.1016/j.addr.2018.02.009
       
  • Limiting angiogenesis to modulate scar formation
    • Authors: Stefanie Korntner; Christine Lehner; Renate Gehwolf; Andrea Wagner; Moritz Grütz; Nadja Kunkel; Herbert Tempfer; Andreas Traweger
      Abstract: Publication date: Available online 3 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Stefanie Korntner, Christine Lehner, Renate Gehwolf, Andrea Wagner, Moritz Grütz, Nadja Kunkel, Herbert Tempfer, Andreas Traweger
      Angiogenesis, the process of new blood vessel formation from existing blood vessels, is a key aspect of virtually every repair process. During wound healing an extensive, but immature and leaky vascular plexus forms which is subsequently reduced by regression of non-functional vessels. More recent studies indicate that uncontrolled vessel growth or impaired vessel regression as a consequence of an excessive inflammatory response can impair wound healing, resulting in scarring and dysfunction. However, in order to elucidate targetable factors to promote functional tissue regeneration we need to understand the molecular and cellular underpinnings of physiological angiogenesis, ranging from induction to resolution of blood vessels. Especially for avascular tissues (e.g. cornea, tendon, ligament, cartilage, etc.), limiting rather than boosting vessel growth during wound repair potentially is beneficial to restore full tissue function and may result in favourable long-term healing outcomes.
      Graphical abstract image

      PubDate: 2018-03-06T14:45:40Z
      DOI: 10.1016/j.addr.2018.02.010
       
  • Responsive triggering systems for delivery in chronic wound healing
    • Authors: Mangesh Morey; Abhay Pandit
      Abstract: Publication date: Available online 2 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Mangesh Morey, Abhay Pandit
      Non-communicable diseases including cancer, cardiovascular disease, diabetes, and neuropathy are chronic in nature. Treatment of these diseases with traditional delivery systems is limited due to lack of site-specificity, non-spatiotemporal release and insufficient doses. Numerous responsive delivery systems which respond to both physiological and external stimuli have been reported in the literature. However, effective strategies incorporating a multifactorial approach are required to control these complex wounds. This can be achieved by fabricating spatiotemporal release systems, multimodal systems or dual/multi-stimuli responsive delivery systems loaded with one or more bioactive components. Critically, these next generation stimuli responsive delivery systems that are at present not feasible are required to treat chronic wounds. This review provides a critical assessment of recent developments in the field of responsive delivery systems, highlighting their limitations and providing a perspective on how these challenges can be overcome.
      Graphical abstract image

      PubDate: 2018-03-06T14:45:40Z
      DOI: 10.1016/j.addr.2018.02.008
       
  • Lumican as a multivalent effector in wound healing
    • Authors: Konstantina Karamanou; Gwenn Perrot; Francois-Xavier Maquart; Stéphane Brézillon
      Abstract: Publication date: Available online 1 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Konstantina Karamanou, Gwenn Perrot, Francois-Xavier Maquart, Stéphane Brézillon
      Wound healing, a complex physiological process, is responsible for tissue repair after exposure to destructive stimuli, without resulting in complete functional regeneration. Injuries can be stromal or epithelial, and most cases of wound repair have been studied in the skin and cornea. Lumican, a small leucine-rich proteoglycan, is expressed in the extracellular matrices of several tissues, such as the cornea, cartilage, and skin. This molecule has been shown to regulate collagen fibrillogenesis, keratinocyte phenotypes, and corneal transparency modulation. Lumican is also involved in the extravasation of inflammatory cells and angiogenesis, which are both critical in stromal wound healing. Lumican is the only member of the small leucine-rich proteoglycan family expressed by the epithelia during wound healing. This review summarizes the importance of lumican in wound healing and potential methods of lumican drug delivery to target wound repair are discussed. The involvement of lumican in corneal wound healing is described based on in vitro and in vivo models, with critical emphasis on its underlying mechanisms of action. Similarly, the expression and role of lumican in the healing of other tissues are presented, with emphasis on skin wound healing. Overall, lumican promotes normal wound repair and broadens new therapeutic perspectives for impaired wound healing.
      Graphical abstract image

      PubDate: 2018-03-06T14:45:40Z
      DOI: 10.1016/j.addr.2018.02.011
       
  • Wound healing related agents: Ongoing research and perspectives
    • Authors: Konstantina Kaplani; Stamatina Koutsi; Vasileios Armenis; Foteini G. Skondra; Nickolas Karantzelis; Spyridon Champeris Tsaniras; Stavros Taraviras
      Abstract: Publication date: Available online 1 March 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Konstantina Kaplani, Stamatina Koutsi, Vasileios Armenis, Foteini G. Skondra, Nickolas Karantzelis, Spyridon Champeris Tsaniras, Stavros Taraviras
      Wound healing response plays a central part in chronic inflammation, affecting millions of people worldwide. It is a dynamic process that can lead to fibrosis, if tissue damage is irreversible and wound resolution is not attained. It is clear that there is a tight interconnection among wound healing, fibrosis and a variety of chronic disease conditions, demonstrating the heterogeneity of this pathology. Based on our further understanding of the cellular and molecular mechanisms underpinning tissue repair, new therapeutic approaches have recently been developed that target different aspects of the wound healing process and fibrosis. Nevertheless, several issues still need to be taken into consideration when designing modern wound healing drug delivery formulations. In this review, we highlight novel pharmacological agents that hold promise for targeting wound repair and fibrosis. We also focus on drug-delivery systems that may enhance current and future therapies.
      Graphical abstract image

      PubDate: 2018-03-06T14:45:40Z
      DOI: 10.1016/j.addr.2018.02.007
       
  • No title
    • Authors: Furka
      Abstract: Publication date: Available online 13 February 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Árpád Furka


      PubDate: 2018-02-15T09:46:58Z
       
  • Nanomedicines and gene therapy for the delivery of growth factors to
           improve perfusion and oxygenation in wound healing
    • Authors: Céline M. Desmet; Véronique Préat; Bernard Gallez
      Abstract: Publication date: Available online 12 February 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Céline M. Desmet, Véronique Préat, Bernard Gallez
      Oxygen plays a key role in wound healing, and hypoxia is a major cause of wound healing impairment; therefore, treatments to improve hemodynamics and increase wound oxygenation are of particular interest for the treatment of chronic wounds. This article describes the roles of oxygen and angiogenesis in wound healing as well as the tools used to evaluate tissue oxygenation and perfusion and then presents a review of nanomedicines and gene therapies designed to improve perfusion and oxygenation and accelerate wound healing.
      Graphical abstract image

      PubDate: 2018-02-15T09:46:58Z
      DOI: 10.1016/j.addr.2018.02.001
       
  • Combined use of nanocarriers and physical methods for percutaneous
           penetration enhancement
    • Authors: Nina Dragicevic; Howard Maibach
      Abstract: Publication date: Available online 6 February 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Nina Dragicevic, Howard Maibach
      Dermal and transdermal drug delivery (due to its non-invasiveness, avoidance of the first-pass metabolism, controlling the rate of drug input over a prolonged time, etc.) have gained significant acceptance. Several methods are employed to overcome the permeability barrier of the skin, improving drug penetration into/through skin. Among chemical penetration enhancement methods, nanocarriers have been extensively studied. When applied alone, nanocarriers mostly deliver drugs to skin and can be used to treat skin diseases. To achieve effective transdermal drug delivery, nanocarriers should be applied with physical methods, as they act synergistically in enhancing drug penetration. This review describes combined use of frequently used nanocarriers (liposomes, novel elastic vesicles, lipid-based and polymer-based nanoparticles and dendrimers) with the most efficient physical methods (microneedles, iontophoresis, ultrasound and electroporation) and demonstrates superiority of the combined use of nanocarriers and physical methods in drug penetration enhancement compared to their single use.
      Graphical abstract image

      PubDate: 2018-02-15T09:46:58Z
      DOI: 10.1016/j.addr.2018.02.003
       
  • Scarring vs. functional healing: Matrix-based strategies to regulate
           tissue repair
    • Authors: Timothy J. Keane; Christine-Maria Horejs; Molly M. Stevens
      Abstract: Publication date: Available online 6 February 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Timothy J. Keane, Christine-Maria Horejs, Molly M. Stevens
      All vertebrates possess mechanisms to restore damaged tissues with outcomes ranging from regeneration to scarring. Unfortunately, the mammalian response to tissue injury most often culminates in scar formation. Accounting for nearly 45% of deaths in the developed world, fibrosis is a process that stands diametrically opposed to functional tissue regeneration. Strategies to improve wound healing outcomes therefore require methods to limit fibrosis. Wound healing is guided by precise spatiotemporal deposition and remodelling of the extracellular matrix (ECM). The ECM, comprising the non-cellular component of tissues, is a signaling depot that is differentially regulated in scarring and regenerative healing. This Review focuses on the importance of the native matrix components during mammalian wound healing alongside a comparison to scar-free healing and then presents an overview of matrix-based strategies that attempt to exploit the role of the ECM to improve wound healing outcomes.
      Graphical abstract image

      PubDate: 2018-02-15T09:46:58Z
      DOI: 10.1016/j.addr.2018.02.002
       
  • Integrins in wound healing, fibrosis and tumor stroma: High potential
           targets for therapeutics and drug delivery
    • Authors: Jonas Schnittert; Ruchi Bansal; Gert Storm; Jai Prakash
      Abstract: Publication date: Available online 4 February 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Jonas Schnittert, Ruchi Bansal, Gert Storm, Jai Prakash
      Wound healing is a complex process, which ultimately leads to fibrosis if not repaired well. Pathologically very similar to fibrosis is the tumor stroma, found in several solid tumors which are regarded as wounds that do not heal. Integrins are heterodimeric surface receptors which control various physiological cellular functions. Additionally, integrins also sense ECM-induced extracellular changes during pathological events, leading to cellular responses, which influence ECM remodeling. The purpose and scope of this review is to introduce integrins as key targets for therapeutics and drug delivery within the scope of wound healing, fibrosis and the tumor stroma. This review provides a general introduction to the biology of integrins including their types, ligands, and meaαns of signaling and interaction with growth factor receptors. Furthermore, we highlight integrins as key targets for therapeutics and drug delivery, based on their biological role, expression pattern within human tissues and at cellular level. Next, therapeutic approaches targeting integrins, with a focus on clinical studies, and targeted drug delivery strategies based on αligands are described.
      Graphical abstract image

      PubDate: 2018-02-05T09:38:17Z
      DOI: 10.1016/j.addr.2018.01.020
       
  • Ocular translational science: A review of development steps and paths
    • Authors: Brenda K. Mann; Darren L. Stirland; Hee-Kyoung Lee; Barbara M. Wirostko
      Abstract: Publication date: Available online 4 February 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Brenda K. Mann, Darren L. Stirland, Hee-Kyoung Lee, Barbara M. Wirostko
      Developing successful drug delivery methods is challenging for any tissue, and the eye is no exception. Translating initial concepts into advanced technologies treating diseases in preclinical models and finally into functional and marketable products for humans can be particularly daunting. While referring to specific ophthalmic companies and products, this review considers key exchanges that lead to successful translation. By building on basic science discoveries in the academic setting, applied science can perform proof-of-concept work with simple, benchtop experiments. Eventually, simple models need to be translated to more robust ones where cells, tissues, and entire organisms are incorporated. Successful translation also includes performing due diligence of the intellectual property, understanding the market needs, undertaking clinical development, meeting regulatory requirements, and eventually scale up manufacturing. Different stages of the translation can occur in different environments, including moving from academia to industry, from one company to another, or between veterinary and human applications. The translation process may also rely on contract organizations to move through the complex landscape. While the path to a commercial, marketable product may not look the same each time, it is important to design a development plan with clear goals and milestones to keep on track.
      Graphical abstract image

      PubDate: 2018-02-05T09:38:17Z
      DOI: 10.1016/j.addr.2018.01.012
       
  • Clinical applications of the CellSearch platform in cancer patients
    • Authors: Sabine Riethdorf; Linda O'Flaherty; Claudia Hille; Klaus Pantel
      Abstract: Publication date: Available online 2 February 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Sabine Riethdorf, Linda O'Flaherty, Claudia Hille, Klaus Pantel
      The CellSearch® system (CS) enables standardized enrichment and enumeration of circulating tumor cells (CTCs) that are repeatedly assessable via non-invasive “liquid biopsy”. While the association of CTCs with poor clinical outcome for cancer patients has clearly been demonstrated in numerous clinical studies, utilizing CTCs for the identification of therapeutic targets, stratification of patients for targeted therapies and uncovering mechanisms of resistance is still under investigation. Here, we comprehensively review the current benefits and drawbacks of clinical CTC analyses for patients with metastatic and non-metastatic tumors. Furthermore, the review focuses on approaches beyond CTC enumeration that aim to uncover therapeutically relevant antigens, genomic aberrations, transcriptional profiles and epigenetic alterations of CTCs at a single cell level. This characterization of CTCs may shed light on the heterogeneity and genomic landscapes of malignant tumors, an understanding of which is highly important for the development of new therapeutic strategies.
      Graphical abstract image

      PubDate: 2018-02-03T09:37:41Z
      DOI: 10.1016/j.addr.2018.01.011
       
  • Fluorescence anisotropy imaging in drug discovery
    • Authors: Claudio Vinegoni; Paolo Fumene Feruglio; Ignacy Gryczynski; Ralph Mazitschek; Ralph Weissleder
      Abstract: Publication date: Available online 2 February 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Claudio Vinegoni, Paolo Fumene Feruglio, Ignacy Gryczynski, Ralph Mazitschek, Ralph Weissleder
      Non-invasive measurement of drug-target engagement can provide critical insights in the molecular pharmacology of small molecule drugs. Fluorescence polarization/fluorescence anisotropy measurements are commonly employed in protein/cell screening assays. However, the expansion of such measurements to the in vivo setting have proven difficult until recently. With the advent of high-resolution fluorescence anisotropy microscopy it is now possible to perform kinetic measurements of intracellular drug distribution and target engagement in commonly used mouse models. In this review we discuss the background, current advances and future perspectives in intravital fluorescence anisotropy measurements to derive pharmacokinetic and pharmacodynamic measurements in single cells and whole organs.
      Graphical abstract image

      PubDate: 2018-02-03T09:37:41Z
      DOI: 10.1016/j.addr.2018.01.019
       
  • Wound healing in the eye: Therapeutic prospects
    • Authors: Mohammed Ziaei; Carol Greene; Colin R. Green
      Abstract: Publication date: Available online 31 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Mohammed Ziaei, Carol Greene, Colin R. Green
      In order to maintain a smooth optical surface the corneal epithelium has to continuously renew itself so as to maintain its function as a barrier to fluctuating external surroundings and various environmental insults. After trauma, the cornea typically re-epithelializes promptly thereby minimizing the risk of infection, opacification or perforation. A persistent epithelial defect (PED) is usually referred to as a non-healing epithelial lesion after approximately two weeks of treatment with standard therapies to no avail. They occur following exposure to toxic agents, mechanical injury, and ocular surface infections and are associated with significant clinical morbidity in patients, resulting in discomfort or visual loss. In the case of deeper corneal injury and corneal pathology the wound healing cascade can also extend to the corneal stroma, the layer below the epithelium. Although significant progress has been made in recent years, pharmaco-therapeutic agents that promote corneal healing remain limited. This article serves as a review of current standard therapies, recently introduced alternative therapies gaining in popularity, and a look into the newest developments into ocular wound healing.
      Graphical abstract image

      PubDate: 2018-02-03T09:37:41Z
      DOI: 10.1016/j.addr.2018.01.006
       
  • Enhancing patient-level clinical data access to improve trial outcomes,
           promote evidence-based practice and incentivize therapeutic innovation
    • Authors: Alice Fortunato; David W. Grainger; Mohamed Abou-El-Enein
      Abstract: Publication date: Available online 31 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Alice Fortunato, David W. Grainger, Mohamed Abou-El-Enein
      Clinical trials are crucial to determining the human safety and efficacy of new therapeutic interventions and innovations. Extraordinary amounts of human experiential data are generated over the course of any clinical drug or therapeutics trial. However, much of these data is never made publicly accessible, either archived openly in accessible formats or venues, published in peer-reviewed journals, or provided to researchers for analysis and scrutiny. Improved, reliable data sharing is essential to inform clinical outcomes and incentivize therapeutic improvements; this need, and the call and concept to improve clinical trial and human therapeutics data accessibility is not new. From patient benefit and value-based medicine perspectives, patient data sharing informs and guides cost savings by eliminating unfruitful therapies, or duplicative trial efforts, also identifying new drug-patient correlations and facilitating improved research strategies. Several recent public and private shifts in clinical data sharing policies and procedures promise to improve access and data utility for patient therapeutic gain. Nonetheless, pharmaceutical industry must at some level protect their commercial interests and avoid misuse of their clinical data. Jeopardizing pharma industry incentives endangers substantial industrial investments in pharmaceutical research and development required for on-going therapeutics innovation. Thus, consistent policies and procedures for sharing human therapeutic performance data that satisfy both clinical data producers and users must become available. Despite some important and impacting recent data sharing developments, further improvements should be considered within the pharmaceutical sector for essential transparency that benefits all stakeholders.
      Graphical abstract image

      PubDate: 2018-02-03T09:37:41Z
      DOI: 10.1016/j.addr.2018.01.017
       
  • Extracellular vesicles as modulators of wound healing
    • Authors: Joana Cabral; Aideen E. Ryan; Matthew D. Griffin; Thomas Ritter
      Abstract: Publication date: Available online 31 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Joana Cabral, Aideen E. Ryan, Matthew D. Griffin, Thomas Ritter
      Impaired healing of cutaneous wounds and ulcers continues to have a major impact on the quality of life of millions of people. In recent years, the capacity for stem and progenitor cells to promote wound repair has been investigated with evidence that secreted factors are responsible for the observed therapeutic benefits. This review addresses current evidence in support of stem/progenitor cell-derived extracellular vesicles (EVs) as a regenerative therapy for acceleration of wound healing. Encouraging results for local or systemic administration of EVs have been reported in a range of clinically-relevant animal models of cutaneous wounds. Furthermore, a number of plausible mechanisms involving EV-mediated transfer of proteins and RNAs that trigger pro-repair pathways in target cells have been demonstrated experimentally. However, for successful clinical translation in the coming years, further emphasis on standardized experimental protocols, detailed methodological reporting and clear definition of EV-based therapeutic products will be required.
      Graphical abstract image

      PubDate: 2018-02-03T09:37:41Z
      DOI: 10.1016/j.addr.2018.01.018
       
  • Role of MicroRNAs in the pathogenesis and treatment of progressive liver
           injury in NAFLD and liver fibrosis
    • Authors: Qiaozhu Su; Virender Kumar; Neetu Sud; Ram I. Mahato
      Abstract: Publication date: Available online 31 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Qiaozhu Su, Virender Kumar, Neetu Sud, Ram I. Mahato
      Non-alcoholic fatty liver disease (NAFLD) increases the risk of various liver injuries, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis, and ultimately hepatocellular carcinoma (HCC). Ample evidence has suggested that aberrant expression of microRNAs (miRNAs) is functionally involved in the activation of cellular stress, inflammation and fibrogenesis in hepatic cells, including hepatocytes, Kupffer and hepatic stellate cells (HSCs), at different pathological stages of NAFLD and liver fibrosis. Here, we overview recent findings on the potential role of miRNAs in the pathogenesis of NAFLD, including lipotoxicity, oxidative stress, metabolic inflammation and fibrogenesis. We critically assess the literatures on both human subjects and animal models of NAFLD and liver fibrosis with miRNA dysregulation and their mechanisms of actions and liver damage. We further highlight the potential use of miRNA mimics or antimiRNAs as therapeutic approaches for the prevention and treatment of NAFLD and liver fibrosis.
      Graphical abstract image

      PubDate: 2018-02-03T09:37:41Z
      DOI: 10.1016/j.addr.2018.01.009
       
  • Polymeric Microneedles for Transdermal Protein Delivery
    • Authors: Yanqi Ye; Jicheng Yu; Di Wen; Anna R. Kahkoska; Zhen Gu
      Abstract: Publication date: Available online 31 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Yanqi Ye, Jicheng Yu, Di Wen, Anna R. Kahkoska, Zhen Gu
      The intrinsic properties of therapeutic proteins present a major impediment for transdermal delivery, including their relatively large molecule size and susceptibility to degradation. One solution is to utilize microneedles (MNs), which are capable of painlessly traversing the stratum corneum and directly translocating protein drugs into the systematic circulation. MNs can be designed to incorporate appropriate structural materials as well as therapeutics or formulations with tailored physicochemical properties. This platform has been applied to deliver drugs both locally and systemically in applications ranging from vaccination to diabetes and cancer therapy. This review surveys the current design and use of polymeric MNs for transdermal protein delivery. The clinical potential and future translation of MNs are also discussed.
      Graphical abstract image

      PubDate: 2018-02-03T09:37:41Z
      DOI: 10.1016/j.addr.2018.01.015
       
  • Clinical utility of non-EpCAM based circulating tumor cell assays
    • Authors: R. Garland Austin; Tony Jun Huang; Mengxi Wu; Andrew J. Armstrong; Tian Zhang
      Abstract: Publication date: Available online 31 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): R. Garland Austin, Tony Jun Huang, Mengxi Wu, Andrew J. Armstrong, Tian Zhang
      Methods enabling the isolation, detection, and characterization of circulating tumor cells (CTCs) in blood have clear potential to facilitate precision medicine approaches in patients with cancer, not only for prognostic purposes but also for prediction of the benefits of specific therapies in oncology. However, current CTC assays, which capture CTCs based on expression of epithelial cell adhesion molecule (EpCAM), fail to capture cells from de-differentiated tumors and carcinomas undergoing loss of the epithelial phenotype during the invasion/metastatic process. To address this limitation, many groups are developing non-EpCAM based CTC assays that incorporate nanotechnology to improve test sensitivity for rare but important cells that may otherwise go undetected, and therefore may improve upon clinical utility. In this review, we outline emerging non-EpCAM based CTC assays utilizing nanotechnology approaches for CTC capture or characterization, including dendrimers, magnetic nanoparticles, gold nanoparticles, negative selection chip or software-based on-slide methods, and nano-scale substrates. In addition, we address challenges that remain for the clinical translation of these platforms.
      Graphical abstract image

      PubDate: 2018-02-03T09:37:41Z
      DOI: 10.1016/j.addr.2018.01.013
       
  • Improving long-term subcutaneous drug delivery by regulating
           material-bioenvironment interaction
    • Authors: Wei Chen; Bryant C. Yung; Zhiyong Qian; Xiaoyuan Chen
      Abstract: Publication date: Available online 31 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Wei Chen, Bryant C. Yung, Zhiyong Qian, Xiaoyuan Chen
      Subcutaneous long-acting release (LAR) formulations have been extensively developed in the clinic to increase patient compliance and reduce treatment cost. Despite preliminary success for some LAR systems, a major obstacle limiting the therapeutic effect remains on their interaction with surrounding tissues. In this review, we summarize how living bodies respond to injected or implanted materials, and highlight some typical strategies based on smart material design, which may significantly improve long-term subcutaneous drug delivery. Moreover, possible strategies to achieve ultra-long (months, years) subcutaneous drug delivery systems are proposed. Based on these discussions, we believe the well-designed subcutaneous long-acting formulations will hold great promise to improve patient quality of life in the clinic.
      Graphical abstract image

      PubDate: 2018-02-03T09:37:41Z
      DOI: 10.1016/j.addr.2018.01.016
       
  • Delivery of cellular factors to regulate bone healing
    • Authors: Alexander Haumer; Paul Emile Bourgine; Paola Occhetta; Gordian Born; Roberta Tasso; Ivan Martin
      Abstract: Publication date: Available online 31 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Alexander Haumer, Paul Emile Bourgine, Paola Occhetta, Gordian Born, Roberta Tasso, Ivan Martin
      Bone tissue has a strong intrinsic regenerative capacity, thanks to a delicate and complex interplay of cellular and molecular processes, which tightly involve the immune system. Pathological settings of anatomical, biomechanical or inflammatory nature may lead to impaired bone healing. Innovative strategies to enhance bone repair, including the delivery of osteoprogenitor cells or of potent cytokines/morphogens, indicate the potential of ‘orthobiologics’, but are not fully satisfactory. Here, we review different approaches based on the delivery of regenerative cues produced by cells but in cell-free, possibly off-the-shelf configurations. Such strategies exploit the paracrine effect of the secretome of mesenchymal stem/stromal cells, presented in soluble form, shuttled through extracellular vesicles, or embedded within the network of extracellular matrix molecules. In addition to osteoinductive molecules, attention is given to factors targeting the resident immune cells, to reshape inflammatory and immunity processes from scarring to regenerative patterns.
      Graphical abstract image

      PubDate: 2018-02-03T09:37:41Z
      DOI: 10.1016/j.addr.2018.01.010
       
 
 
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