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Publisher: Elsevier   (Total: 3118 journals)

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Showing 1 - 200 of 3118 Journals sorted alphabetically
A Practical Logic of Cognitive Systems     Full-text available via subscription   (Followers: 7)
AASRI Procedia     Open Access   (Followers: 15)
Academic Pediatrics     Hybrid Journal   (Followers: 25, SJR: 1.402, h-index: 51)
Academic Radiology     Hybrid Journal   (Followers: 22, SJR: 1.008, h-index: 75)
Accident Analysis & Prevention     Partially Free   (Followers: 89, SJR: 1.109, h-index: 94)
Accounting Forum     Hybrid Journal   (Followers: 25, SJR: 0.612, h-index: 27)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 30, SJR: 2.515, h-index: 90)
Achievements in the Life Sciences     Open Access   (Followers: 4)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 5, SJR: 0.338, h-index: 19)
Acta Astronautica     Hybrid Journal   (Followers: 371, SJR: 0.726, h-index: 43)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 3)
Acta Biomaterialia     Hybrid Journal   (Followers: 27, SJR: 2.02, h-index: 104)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 1)
Acta de Investigación Psicológica     Open Access   (Followers: 2)
Acta Ecologica Sinica     Open Access   (Followers: 8, SJR: 0.172, h-index: 29)
Acta Haematologica Polonica     Free   (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: 235, SJR: 3.683, h-index: 202)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.615, h-index: 21)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.442, h-index: 21)
Acta Oecologica     Hybrid Journal   (Followers: 10, SJR: 0.915, h-index: 53)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription   (Followers: 1)
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 3, SJR: 0.311, h-index: 16)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 2)
Acta Poética     Open Access   (Followers: 4)
Acta Psychologica     Hybrid Journal   (Followers: 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: 4)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 3)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 4, SJR: 0.383, h-index: 19)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 2)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 5, SJR: 0.141, h-index: 3)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 4, SJR: 0.112, h-index: 2)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 5)
Acute Pain     Full-text available via subscription   (Followers: 13)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.967, h-index: 57)
Addictive Behaviors     Hybrid Journal   (Followers: 15, SJR: 1.514, h-index: 92)
Addictive Behaviors Reports     Open Access   (Followers: 6)
Additive Manufacturing     Hybrid Journal   (Followers: 7, SJR: 1.039, h-index: 5)
Additives for Polymers     Full-text available via subscription   (Followers: 22)
Advanced Cement Based Materials     Full-text available via subscription   (Followers: 3)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 136, SJR: 5.2, h-index: 222)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.265, h-index: 53)
Advanced Powder Technology     Hybrid Journal   (Followers: 17, SJR: 0.739, h-index: 33)
Advances in Accounting     Hybrid Journal   (Followers: 9, SJR: 0.299, h-index: 15)
Advances in Agronomy     Full-text available via subscription   (Followers: 15, SJR: 2.071, h-index: 82)
Advances in Anesthesia     Full-text available via subscription   (Followers: 27, SJR: 0.169, h-index: 4)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 3)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 6, SJR: 1.054, h-index: 35)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 11, SJR: 0.801, h-index: 26)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 22, SJR: 1.286, h-index: 49)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 16, SJR: 3.31, h-index: 42)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.277, h-index: 43)
Advances in Botanical Research     Full-text available via subscription   (Followers: 3, SJR: 0.619, h-index: 48)
Advances in Cancer Research     Full-text available via subscription   (Followers: 26, SJR: 2.215, h-index: 78)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9, SJR: 0.9, h-index: 30)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 2.139, h-index: 42)
Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 4)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 13)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 26, SJR: 0.183, h-index: 23)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.665, h-index: 29)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 9, SJR: 1.268, h-index: 45)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 29, SJR: 0.938, h-index: 33)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 18, SJR: 2.314, h-index: 130)
Advances in Computers     Full-text available via subscription   (Followers: 16, SJR: 0.223, h-index: 22)
Advances in Dermatology     Full-text available via subscription   (Followers: 12)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 12)
Advances in Digestive Medicine     Open Access   (Followers: 7)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 6)
Advances in Drug Research     Full-text available via subscription   (Followers: 22)
Advances in Ecological Research     Full-text available via subscription   (Followers: 46, SJR: 3.25, h-index: 43)
Advances in Engineering Software     Hybrid Journal   (Followers: 26, SJR: 0.486, h-index: 10)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 8)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 44, SJR: 5.465, h-index: 64)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 3)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 8)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 52, SJR: 0.674, h-index: 38)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 16)
Advances in Genetics     Full-text available via subscription   (Followers: 15, SJR: 2.558, h-index: 54)
Advances in Genome Biology     Full-text available via subscription   (Followers: 11)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 2.325, h-index: 20)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 22, SJR: 0.906, h-index: 24)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 9, SJR: 0.497, h-index: 31)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 26)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 2, SJR: 0.396, h-index: 27)
Advances in Immunology     Full-text available via subscription   (Followers: 36, SJR: 4.152, h-index: 85)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 9, SJR: 1.132, h-index: 42)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 3, SJR: 1.274, h-index: 27)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 4)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.764, h-index: 15)
Advances in Lipobiology     Full-text available via subscription   (Followers: 2)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 9)
Advances in Marine Biology     Full-text available via subscription   (Followers: 16, SJR: 1.645, h-index: 45)
Advances in Mathematics     Full-text available via subscription   (Followers: 10, SJR: 3.261, h-index: 65)
Advances in Medical Sciences     Hybrid Journal   (Followers: 6, SJR: 0.489, h-index: 25)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 5, SJR: 1.44, h-index: 51)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 23)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 10)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 9, SJR: 0.324, h-index: 8)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 4)
Advances in Oncobiology     Full-text available via subscription   (Followers: 3)
Advances in Organ Biology     Full-text available via subscription   (Followers: 2)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 15, SJR: 2.885, h-index: 45)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 7, SJR: 0.148, h-index: 11)
Advances in Parasitology     Full-text available via subscription   (Followers: 7, SJR: 2.37, h-index: 73)
Advances in Pediatrics     Full-text available via subscription   (Followers: 24, SJR: 0.4, h-index: 28)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 13)
Advances in Pharmacology     Full-text available via subscription   (Followers: 15, SJR: 1.718, h-index: 58)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.384, h-index: 26)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.248, h-index: 11)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 8)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 4)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 18)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20, SJR: 1.5, h-index: 62)
Advances in Psychology     Full-text available via subscription   (Followers: 62)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 5, SJR: 0.478, h-index: 32)
Advances in Radiation Oncology     Open Access  
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 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: 366, SJR: 0.606, h-index: 65)
Advances in Structural Biology     Full-text available via subscription   (Followers: 8)
Advances in Surgery     Full-text available via subscription   (Followers: 8, SJR: 0.823, h-index: 27)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 31, SJR: 1.321, h-index: 56)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 16)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 6, SJR: 1.878, h-index: 68)
Advances in Water Resources     Hybrid Journal   (Followers: 45, SJR: 2.408, h-index: 94)
Aeolian Research     Hybrid Journal   (Followers: 5, SJR: 0.973, h-index: 22)
Aerospace Science and Technology     Hybrid Journal   (Followers: 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: 5, 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: 445, 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: 41, SJR: 1.546, h-index: 79)
Agriculture and Agricultural Science Procedia     Open Access  
Agriculture and Natural Resources     Open Access   (Followers: 3)
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: 8)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.436, h-index: 12)
Alexandria J. of Medicine     Open Access   (Followers: 1)
Algal Research     Partially Free   (Followers: 9, SJR: 2.05, h-index: 20)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.46, h-index: 29)
Allergology Intl.     Open Access   (Followers: 4, SJR: 0.776, h-index: 35)
Alpha Omegan     Full-text available via subscription   (SJR: 0.121, h-index: 9)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 9, SJR: 0.158, h-index: 9)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 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: 5)
American Heart J.     Hybrid Journal   (Followers: 49, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 48, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 41, SJR: 0.574, h-index: 65)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 9, SJR: 1.091, h-index: 45)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.653, h-index: 93)
American J. of Human Genetics     Hybrid Journal   (Followers: 32, SJR: 8.769, h-index: 256)
American J. of Infection Control     Hybrid Journal   (Followers: 26, SJR: 1.259, h-index: 81)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 31, SJR: 2.313, h-index: 172)
American J. of Medicine     Hybrid Journal   (Followers: 46, SJR: 2.023, h-index: 189)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 201, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 60, 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: 24, 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: 26, SJR: 2.764, h-index: 154)
American J. of Surgery     Hybrid Journal   (Followers: 35, SJR: 1.286, h-index: 125)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.653, h-index: 70)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 6)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.066, h-index: 51)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 59, SJR: 0.124, h-index: 9)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 13)
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: 36, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 164, SJR: 0.725, h-index: 154)
Analytical Chemistry Research     Open Access   (Followers: 8, SJR: 0.18, h-index: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 12)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 1)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 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  

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Journal Cover Advanced Drug Delivery Reviews
  [SJR: 5.2]   [H-I: 222]   [136 followers]  Follow
    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0169-409X
   Published by Elsevier Homepage  [3118 journals]
  • Multifunctional hybrid graphene oxide for circulating tumor cell isolation
           and analysis
    • Authors: Avijit PramaniK; Stacy Jones; Ye Gao; Carrie Sweet; Aruna Vangara; Salma Begum; Paresh Chandra Ray
      Abstract: Publication date: Available online 10 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Avijit PramaniK, Stacy Jones, Ye Gao, Carrie Sweet, Aruna Vangara, Salma Begum, Paresh Chandra Ray
      Even in 21st century, >90% cancer-associated deaths are caused by metastatic disease. Circulating tumor cells (CTCs), which circulate in the blood stream after release from primary tumors, extravasate and form fatal metastases in different organs. Several clinical trials indicate that CTCs can be used as a liquid biopsy of tumors for early diagnosis of cancers. Since CTCs are extremely rare and exhibit heterogeneous biology due to epithelial-mesenchymal transition (EMT), oncologists continue to face enormous challenges in using CTCs as a true “liquid biopsy” for cancer patients. Recent advancements in nanoscience allow us to design nano-architectures with the capability of targeted CTCs isolation and identification. In the current review, we discuss contribution from different groups on the development of graphene oxide based nanoarchitecture for effective isolation and accurate identification of CTCs from whole blood. In the last few years, using zero-dimensional (0D), two dimensional (2D) and three dimensional (3D) multifunctional hybrid graphene oxide (GO), different types of nanoarchitectures have been designed. These nanoarchitectures represent a highly powerful platform for CTC diagnosis. We discuss the major design criteria that have been used to develop hybrid GO nanoarchitectures for selective capture and accurate identification of heterogeneous CTCs from whole blood. At the end, we conclude with the promises, major challenges, and prospect to clinically translate the identification of CTCs using GO based nanotechnology.
      Graphical abstract image

      PubDate: 2018-01-10T12:54:40Z
      DOI: 10.1016/j.addr.2018.01.004
       
  • Size-based separation methods of circulating tumor cells
    • Authors: Si-Jie Hao; Yuan Wan; Yi-Qiu Xia; Xin Zou; Si-Yang Zheng
      Abstract: Publication date: Available online 8 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Si-Jie Hao, Yuan Wan, Yi-Qiu Xia, Xin Zou, Si-Yang Zheng
      Circulating tumor cells (CTCs) originate from the primary tumor mass and enter into the peripheral bloodstream. Compared to other “liquid biopsy” portfolios such as exosome, circulating tumor DNA/RNA (ctDNA/RNA), CTCs have incomparable advantages in analyses of transcriptomics, proteomics, and signal colocalization. Hence, CTCs hold the key to understanding the biology of metastasis and play a vital role in cancer diagnosis, treatment monitoring, and prognosis. Size-based enrichment featureS prominently in CTC isolation. It is a label-free, simple and fast method. Enriched CTCs remain unmodified and viable for a wide range of subsequent analyses. In this review, we comprehensively summarize the differences of size and deformability between CTCs and blood cells, which would facilitate the development of technologies of size-based CTC isolation. Then we review representative size-/deformability-based technologies available for CTC isolation and highlight the recent achievements in molecular analysis of isolated CTCs. To wrap up, we discuss the substantial challenges facing the field, and elaborate on prospects.
      Graphical abstract image

      PubDate: 2018-01-10T12:54:40Z
      DOI: 10.1016/j.addr.2018.01.002
       
  • Molecular analysis of circulating tumors cells: Biomarkers beyond
           enumeration
    • Authors: William L. Hwang; Haley M. Pleskow; David T. Miyamoto
      Abstract: Publication date: Available online 8 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): William L. Hwang, Haley M. Pleskow, David T. Miyamoto
      Advances in our molecular understanding of cancer biology have paved the way to an expanding compendium of molecularly-targeted therapies, accompanied by the urgent need for biomarkers that enable the precise selection of the most appropriate therapies for individual cancer patients. Circulating biomarkers such as circulating tumor cells (CTCs) are poised to fill this need, since they are “liquid biopsies” that can be performed non-invasively and serially, and may capture the spectrum of spatial and temporal tumor heterogeneity better than conventional tissue biopsies. Increasing evidence suggests that moving beyond the enumeration of CTCs towards more sophisticated molecular analyses can provide actionable data that may predict and potentially improve clinical outcomes. In this review, we discuss the potential of molecular CTC analyses to serve as prognostic and predictive biomarkers to guide cancer therapy and early cancer detection. As technologies to capture and analyze CTCs continue to increase in sophistication, we anticipate that the potential clinical applications of CTCs will grow exponentially in the coming years.
      Graphical abstract image

      PubDate: 2018-01-10T12:54:40Z
      DOI: 10.1016/j.addr.2018.01.003
       
  • Co association of mucus modulating agents and nanoparticles for mucosal
           drug delivery
    • Authors: Catherine Taylor Nordgård; Kurt I. Draget
      Abstract: Publication date: Available online 4 January 2018
      Source:Advanced Drug Delivery Reviews
      Author(s): Catherine Taylor Nordgård, Kurt I. Draget
      Nanoparticulate drug delivery systems (nDDS) offer a variety of options when it comes to routes of administration. One possible path is crossing mucosal barriers, such as in the airways and in the GI tract, for systemic distribution or local treatment. The main challenge with this administration route is that the size and surface properties of the nanoparticles, as opposed to small molecular drugs, very often results in mucosal capture, immobilization and removal, which in turn results in a very low bioavailability. Strategies to overcome this challenge do exist, like surface ‘stealth’ modification with PEG. Here we review an alternative or supplemental strategy, co-association of mucus modulating agents with the nDDS to improve bioavailability, where the nDDS may be surface modified or unmodified. This contribution presents some examples on how possible co-association systems may be achieved, using currently marketed mucolytic drugs, alternative formulations or novel agents.
      Graphical abstract image

      PubDate: 2018-01-10T12:54:40Z
      DOI: 10.1016/j.addr.2018.01.001
       
  • Blood derivatives awaken in regenerative medicine strategies to modulate
           wound healing
    • Authors: Bárbara B. Mendes; Manuel Gómez-Florit; Pedro S. Babo; Rui L. Reis; Rui M.A. Domingues; Manuela E. Gomes
      Abstract: Publication date: Available online 28 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Bárbara B. Mendes, Manuel Gómez-Florit, Pedro S. Babo, Rui L. Reis, Rui M.A. Domingues, Manuela E. Gomes
      Blood components play key roles in the modulation of the wound healing process and, together with the provisional fibrin matrix ability to selectively bind bioactive molecules and control its spatial-temporal presentation, define the complex microenvironment that characterize this biological process. As a biomimetic approach, the use of blood derivatives in regenerative strategies has awaken as a source of multiple therapeutic biomolecules. Nevertheless, and despite their clinical relevance, blood derivatives have been showing inconsistent therapeutic results due to several factors, including proper control over their delivery mechanisms. Herein, we highlight recent trends on the use biomaterials to protect, sequester and deliver these pools of biomolecules in tissue engineering and regenerative medicine approaches. Particular emphasis is given to strategies that enable to control their spatiotemporal delivery and improve the selectivity of presentation profiles of the biomolecules derived from blood derivatives rich in platelets. Finally, we discussed possible directions for biomaterials design to potentiate the aimed regenerative effects of blood derivatives and achieve efficient therapies.
      Graphical abstract image

      PubDate: 2018-01-02T19:46:06Z
      DOI: 10.1016/j.addr.2017.12.018
       
  • Targeting renal fibrosis: Mechanisms and drug delivery systems
    • Authors: Madalina V. Nastase; Jinyang Zeng-Brouwers; Malgorzata Wygrecka; Liliana Schaefer
      Abstract: Publication date: Available online 27 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Madalina V. Nastase, Jinyang Zeng-Brouwers, Malgorzata Wygrecka, Liliana Schaefer
      Renal fibrosis is the common outcome of many chronic kidney diseases (CKD) independent of the underlying etiology. Despite a host of promising experimental data, currently available strategies only ameliorate or delay the progression of CKD but do not reverse fibrosis. One of the major impediments of translating novel antifibrotic strategies from bench to bedside is due to the intricacies of the drug delivery process. In this review, we briefly describe mechanisms of renal fibrosis and methods of drug transfer into the kidney. Various tools used in gene therapy to administer nucleic acids in vivo are discussed. Furthermore, we review the modes of action of protein- or peptide-based drugs with target-specific antibodies and cytokines incorporated in hydrogels. Additionally, we assess an intriguing new method to deliver drugs specifically to tubular epithelial cells via conjugation with ligands binding to the megalin receptor. Finally, plant-derived compounds with antifibrotic properties are also summarized.
      Graphical abstract image

      PubDate: 2018-01-02T19:46:06Z
      DOI: 10.1016/j.addr.2017.12.019
       
  • Ophthalmic gels: Past, present and future
    • Authors: Ali A. Al-Kinani; Ghada Zidan; Naba Elsaid; Ali Seyfoddin; Adam W.G. Alani; Raid G. Alany
      Abstract: Publication date: Available online 27 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Ali A. Al-Kinani, Ghada Zidan, Naba Elsaid, Ali Seyfoddin, Adam W.G. Alani, Raid G. Alany
      Aqueous gels formulated using hydrophilic polymers (hydrogels) along with those based on stimuli responsive polymers (in situ gelling or gel forming systems) continue to attract increasing interest for various eye health-related applications. They allow the incorporation of a variety of ophthalmic pharmaceuticals to achieve therapeutic levels of drugs and bioactives at target ocular sites. The integration of sophisticated drug delivery technologies such as nanotechnology-based ones with intelligent and environment responsive systems can extend current treatment duration to provide more clinically relevant time courses (weeks and months instead of hours and days) which will inevitably reduce dose frequency, increase patient compliance and improve clinical outcomes. Novel applications and design of contact lenses and intracanalicular delivery devices along with the move towards integrating gels into various drug delivery devices like intraocular pumps, injections and implants has the potential to reduce comorbidities caused by glaucoma, corneal keratopathy, cataract, diabetic retinopathies and age-related macular degeneration. This review describes ophthalmic gelling systems with emphasis on mechanism of gel formation and application in ophthalmology. It provides a critical appraisal of the techniques and methods used in the characterization of ophthalmic preformed gels and in situ gelling systems along with a thorough insight into the safety and biocompatibility of these systems. Newly developed ophthalmic gels, hydrogels, preformed gels and in situ gelling systems including the latest in the area of stimuli responsive gels, molecularly imprinted gels, nanogels, 3D printed hydrogels; 3D printed devices comprising ophthalmic gels are covered. Finally, new applications of gels in the production of artificial corneas, corneal wound healing and hydrogel contact lenses are described.
      Graphical abstract image

      PubDate: 2018-01-02T19:46:06Z
      DOI: 10.1016/j.addr.2017.12.017
       
  • Advances and new technologies in the treatment of burn injury
    • Authors: Yiwei Wang; Peter K.M. Maitz
      Pages: 1 - 2
      Abstract: Publication date: 1 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 123
      Author(s): Yiwei Wang, Peter K.M. Maitz


      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.11.011
      Issue No: Vol. 123 (2017)
       
  • Burn injury: Challenges and advances in burn wound healing, infection,
           pain and scarring
    • Authors: Yiwei Wang; Joanneke Beekman; Jonathan Hew; Stuart Jackson; Andrea C. Issler-Fisher; Roxanne Parungao; Sepher S. Lajevardi; Zhe Li; Peter K.M. Maitz
      Pages: 3 - 17
      Abstract: Publication date: 1 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 123
      Author(s): Yiwei Wang, Joanneke Beekman, Jonathan Hew, Stuart Jackson, Andrea C. Issler-Fisher, Roxanne Parungao, Sepher S. Lajevardi, Zhe Li, Peter K.M. Maitz
      Severe burn injuries are the most traumatic and physically debilitating injuries affecting nearly every organ system and leading to significant morbidity and mortality. Early burn wound excision and skin grafting are common clinical practices that have significantly improved the outcomes for severe burn injured patients by reducing mortality rate and days of hospital stay. However, slow wound healing, infection, pain, and hypertrophic scarring continue to remain a major challenge in burn research and management. In the present article, we review and discuss issues in the current treatment of burn injuries; the advances and novel strategies developed in the past decade that have improved burn management; and also, pioneer ideas and studies in burn research which aims to enhance burn wound care with a focus on burn wound infection, pain management, treatments for scarring and skin tissue engineering.
      Graphical abstract image

      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.09.018
      Issue No: Vol. 123 (2017)
       
  • Advances in keratinocyte delivery in burn wound care
    • Authors: Britt ter Horst; Gurpreet Chouhan; Naiem S. Moiemen; Liam M. Grover
      Pages: 18 - 32
      Abstract: Publication date: 1 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 123
      Author(s): Britt ter Horst, Gurpreet Chouhan, Naiem S. Moiemen, Liam M. Grover
      This review gives an updated overview on keratinocyte transplantation in burn wounds concentrating on application methods and future therapeutic cell delivery options with a special interest in hydrogels and spray devices for cell delivery. To achieve faster re-epithelialisation of burn wounds, the original autologous keratinocyte culture and transplantation technique was introduced over 3 decades ago. Application types of keratinocytes transplantation have improved from cell sheets to single-cell solutions delivered with a spray system. However, further enhancement of cell culture, cell viability and function in vivo, cell carrier and cell delivery systems remain themes of interest. Hydrogels such as chitosan, alginate, fibrin and collagen are frequently used in burn wound care and have advantageous characteristics as cell carriers. Future approaches of keratinocyte transplantation involve spray devices, but optimisation of application technique and carrier type is necessary.
      Graphical abstract image

      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.06.012
      Issue No: Vol. 123 (2017)
       
  • Nanomedicine and advanced technologies for burns: Preventing infection and
           facilitating wound healing
    • Authors: Mirza Ali Mofazzal Jahromi; Parham Sahandi Zangabad; Seyed Masoud Moosavi Basri; Keyvan Sahandi Zangabad; Ameneh Ghamarypour; Amir R. Aref; Mahdi Karimi; Michael R. Hamblin
      Pages: 33 - 64
      Abstract: Publication date: 1 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 123
      Author(s): Mirza Ali Mofazzal Jahromi, Parham Sahandi Zangabad, Seyed Masoud Moosavi Basri, Keyvan Sahandi Zangabad, Ameneh Ghamarypour, Amir R. Aref, Mahdi Karimi, Michael R. Hamblin
      According to the latest report from the World Health Organization, an estimated 265,000 deaths still occur every year as a direct result of burn injuries. A widespread range of these deaths induced by burn wound happens in low- and middle-income countries, where survivors face a lifetime of morbidity. Most of the deaths occur due to infections when a high percentage of the external regions of the body area is affected. Microbial nutrient availability, skin barrier disruption, and vascular supply destruction in burn injuries as well as systemic immunosuppression are important parameters that cause burns to be susceptible to infections. Topical antimicrobials and dressings are generally employed to inhibit burn infections followed by a burn wound therapy, because systemic antibiotics have problems in reaching the infected site, coupled with increasing microbial drug resistance. Nanotechnology has provided a range of molecular designed nanostructures (NS) that can be used in both therapeutic and diagnostic applications in burns. These NSs can be divided into organic and non-organic (such as polymeric nanoparticles (NPs) and silver NPs, respectively), and many have been designed to display multifunctional activity. The present review covers the physiology of skin, burn classification, burn wound pathogenesis, animal models of burn wound infection, and various topical therapeutic approaches designed to combat infection and stimulate healing. These include biological based approaches (e.g. immune-based antimicrobial molecules, therapeutic microorganisms, antimicrobial agents, etc.), antimicrobial photo- and ultrasound-therapy, as well as nanotechnology-based wound healing approaches as a revolutionizing area. Thus, we focus on organic and non-organic NSs designed to deliver growth factors to burned skin, and scaffolds, dressings, etc. for exogenous stem cells to aid skin regeneration. Eventually, recent breakthroughs and technologies with substantial potentials in tissue regeneration and skin wound therapy (that are as the basis of burn wound therapies) are briefly taken into consideration including 3D-printing, cell-imprinted substrates, nano-architectured surfaces, and novel gene-editing tools such as CRISPR-Cas.
      Graphical abstract image

      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.08.001
      Issue No: Vol. 123 (2017)
       
  • The effects of major burn related pathophysiological changes on the
           pharmacokinetics and pharmacodynamics of drug use: An appraisal utilizing
           antibiotics
    • Authors: Andrew A. Udy; Jason A. Roberts; Jeffrey Lipman; Stijn Blot
      Pages: 65 - 74
      Abstract: Publication date: 1 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 123
      Author(s): Andrew A. Udy, Jason A. Roberts, Jeffrey Lipman, Stijn Blot
      Patients suffering major burn injury represent a unique population of critically ill patients. Widespread skin and tissue damage causes release of systemic inflammatory mediators that promote endothelial leak, extravascular fluid shifts, and cardiovascular derangement. This phase is characterized by relative intra-vascular hypovolaemia and poor peripheral perfusion. Large volume intravenous fluid resuscitation is generally required. The patients' clinical course is then typically complicated by ongoing inflammation, protein catabolism, and marked haemodynamic perturbation. At all times, drug distribution, metabolism, and elimination are grossly distorted. For hydrophilic agents, changes in volume of distribution and clearance are marked, resulting in potentially sub-optimal drug exposure. In the case of antibiotics, this may then promote treatment failure, or the development of bacterial drug resistance. As such, empirical dose selection and pharmaceutical development must consider these features, with the application of strategies that attempt to counter the unique pharmacokinetic changes encountered in this setting.
      Graphical abstract image

      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.09.019
      Issue No: Vol. 123 (2017)
       
  • Scar management in burn injuries using drug delivery and molecular
           signaling: Current treatments and future directions
    • Authors: Saeid Amini-Nik; Yusef Yousuf; Marc G. Jeschke
      Pages: 135 - 154
      Abstract: Publication date: 1 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 123
      Author(s): Saeid Amini-Nik, Yusef Yousuf, Marc G. Jeschke
      In recent decades, there have been tremendous improvements in burn care that have allowed patients to survive severe burn injuries that were once fatal. However, a major limitation of burn care currently is the development of hypertrophic scars in approximately 70% of patients. This significantly decreases the quality of life for patients due to the physical and psychosocial symptoms associated with scarring. Current approaches to manage scarring include surgical techniques and non-surgical methods such as laser therapy, steroid injections, and compression therapy. These treatments are limited in their effectiveness and regularly fail to manage symptoms. As a result, the development of novel treatments that aim to improve outcomes and quality of life is imperative. Drug delivery that targets the molecular cascades of wound healing to attenuate or prevent hypertrophic scarring is a promising approach that has therapeutic potential. In this review, we discuss current treatments for scar management after burn injury, and how drug delivery targeting molecular signaling can lead to new therapeutic strategies.
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      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.07.017
      Issue No: Vol. 123 (2017)
       
  • ADDR Editor’s Collection 2017
    • Authors: Hamidreza Ghandehari
      First page: 1
      Abstract: Publication date: 1 December 2017
      Source:Advanced Drug Delivery Reviews, Volume 122
      Author(s): Hamidreza Ghandehari


      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.11.009
      Issue No: Vol. 122 (2017)
       
  • The battle of “nano” paclitaxel
    • Authors: Alexandros Marios Sofias; Michael Dunne; Gert Storm; Christine Allen
      Pages: 20 - 30
      Abstract: Publication date: 1 December 2017
      Source:Advanced Drug Delivery Reviews, Volume 122
      Author(s): Alexandros Marios Sofias, Michael Dunne, Gert Storm, Christine Allen
      Paclitaxel (PTX) is one of the three most widely used chemotherapeutic agents, together with doxorubicin and cisplatin, and is first or second line treatment for several types of cancers. In 2000, Taxol, the conventional formulation of PTX, became the best-selling cancer drug of all time with annual sales of 1.6 billion. In 2005, the introduction of the albumin-based formulation of PTX, known as Abraxane, ended Taxol's monopoly of the PTX market. Abraxane's ability to push the Taxol innovator and generic formulations aside attracted fierce competition amongst competitors worldwide to develop their own unique, new and improved formulation of PTX. At this time there are at least 18 companies focused on pre-clinical and/or clinical development of nano-formulations of PTX. These pharmaceutical companies are investing substantial capital to capture a share of the lucrative global PTX market. It is hoped that any formulation that dominates the market will result in tangible benefits to patients in terms of both survival and quality of life. Given all of this activity, here we address the question: Who is going to win the battle of “nano” paclitaxel?
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      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.02.003
      Issue No: Vol. 122 (2017)
       
  • Nanoparticles for drug delivery to the anterior segment of the eye
    • Authors: Dileep R. Janagam; Linfeng Wu; Tao L. Lowe
      Pages: 31 - 64
      Abstract: Publication date: 1 December 2017
      Source:Advanced Drug Delivery Reviews, Volume 122
      Author(s): Dileep R. Janagam, Linfeng Wu, Tao L. Lowe
      Commercially available ocular drug delivery systems are effective but less efficacious to manage diseases/disorders of the anterior segment of the eye. Recent advances in nanotechnology and molecular biology offer a great opportunity for efficacious ocular drug delivery for the treatments of anterior segment diseases/disorders. Nanoparticles have been designed for preparing eye drops or injectable solutions to surmount ocular obstacles faced after administration. Better drug pharmacokinetics, pharmacodynamics, non-specific toxicity, immunogenicity, and biorecognition can be achieved to improve drug efficacy when drugs are loaded in the nanoparticles. Despite the fact that a number of review articles have been published at various points in the past regarding nanoparticles for drug delivery, there is not a review yet focusing on the development of nanoparticles for ocular drug delivery to the anterior segment of the eye. This review fills in the gap and summarizes the development of nanoparticles as drug carriers for improving the penetration and bioavailability of drugs to the anterior segment of the eye.
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      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.04.001
      Issue No: Vol. 122 (2017)
       
  • Molecular links among non-biodegradable nanoparticles, reactive oxygen
           species, and autophagy
    • Authors: Uche C. Anozie; Paul Dalhaimer
      Pages: 65 - 73
      Abstract: Publication date: 1 December 2017
      Source:Advanced Drug Delivery Reviews, Volume 122
      Author(s): Uche C. Anozie, Paul Dalhaimer
      For nanoparticles to be successful in combating diseases in the clinic in the 21st century and beyond, they must localize to target areas of the body and avoid damaging non-target, healthy tissues. Both soft and stiff, bio-degradable and non-biodegradable nanoparticles are anticipated to be used to this end. It has been shown that stiff, non-biodegradable nanoparticles cause reactive oxygen species (ROS) generation and autophagy in a variety of cell lines in vitro. Both responses can lead to significant remodeling of the cytosol and even apoptosis. Thus these are crucial cellular functions to understand. Improved assays have uncovered crucial roles of the Akt/mTOR signaling pathway in both ROS generation and autophagy initiation after cells have internalized stiff, non-biodegradable nanoparticles over varying geometries in culture. Of particular – yet unresolved – interest is how these nanoparticles cause the activation of these pathways. This article reviews the most recent advances in nanoparticle generation of ROS and autophagy initiation with a focus on stiff, non-biodegradable technologies. We provide experimental guidelines to the reader for fleshing out the effects of their nanoparticles on the above pathways with the goal of tuning nanoparticle design.
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      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.01.001
      Issue No: Vol. 122 (2017)
       
  • Macrophage-based therapeutic strategies in regenerative medicine
    • Authors: Kara L. Spiller; Timothy J. Koh
      Pages: 74 - 83
      Abstract: Publication date: 1 December 2017
      Source:Advanced Drug Delivery Reviews, Volume 122
      Author(s): Kara L. Spiller, Timothy J. Koh
      Mounting evidence suggests that therapeutic cell and drug delivery strategies designed to actively harness the regenerative potential of the inflammatory response have great potential in regenerative medicine. In particular, macrophages have emerged as a primary target because of their critical roles in regulating multiple phases of tissue repair through their unique ability to rapidly shift phenotypes. Herein, we review macrophage-based therapies, focusing on the translational potential for cell delivery of ex vivo-activated macrophages and delivery of molecules and biomaterials to modulate accumulation and phenotype of endogenous macrophages. We also review current obstacles to progress in translating basic findings to therapeutic applications, including the need for improved understanding of context-dependent macrophage functions and the myriad factors that regulate macrophage phenotype; potential species-specific differences (e.g. humans versus mice); quality control issues; and the lack of standardized procedures and nomenclature for characterizing macrophages. Looking forward, the inherent plasticity of macrophages represents a daunting challenge for harnessing these cells in regenerative medicine therapies but also great opportunity for improving patient outcomes in a variety of pathological conditions.
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      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.05.010
      Issue No: Vol. 122 (2017)
       
  • Mimicking oxygen delivery and waste removal functions of blood
    • Authors: Huaifa Zhang; Jake E. Barralet
      Pages: 84 - 104
      Abstract: Publication date: 1 December 2017
      Source:Advanced Drug Delivery Reviews, Volume 122
      Author(s): Huaifa Zhang, Jake E. Barralet
      In addition to immunological and wound healing cell and platelet delivery, ion stasis and nutrient supply, blood delivers oxygen to cells and tissues and removes metabolic wastes. For decades researchers have been trying to develop approaches that mimic these two immediately vital functions of blood. Oxygen is crucial for the long-term survival of tissues and cells in vertebrates. Hypoxia (oxygen deficiency) and even at times anoxia (absence of oxygen) can occur during organ preservation, organ and cell transplantation, wound healing, in tumors and engineering of tissues. Different approaches have been developed to deliver oxygen to tissues and cells, including hyperbaric oxygen therapy (HBOT), normobaric hyperoxia therapy (NBOT), using biochemical reactions and electrolysis, employing liquids with high oxygen solubility, administering hemoglobin, myoglobin and red blood cells (RBCs), introducing oxygen-generating agents, using oxygen-carrying microparticles, persufflation, and peritoneal oxygenation. Metabolic waste accumulation is another issue in biological systems when blood flow is insufficient. Metabolic wastes change the microenvironment of cells and tissues, influence the metabolic activities of cells, and ultimately cause cell death. This review examines advances in blood mimicking systems in the field of biomedical engineering in terms of oxygen delivery and metabolic waste removal.
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      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.02.001
      Issue No: Vol. 122 (2017)
       
  • Stem cell therapy clinical research: A regulatory conundrum for academia
    • Authors: Anjali Nagpal; Chris Juttner; Monica Anne Hamilton-Bruce; Paul Rolan; Simon A. Koblar
      Pages: 105 - 114
      Abstract: Publication date: 1 December 2017
      Source:Advanced Drug Delivery Reviews, Volume 122
      Author(s): Anjali Nagpal, Chris Juttner, Monica Anne Hamilton-Bruce, Paul Rolan, Simon A. Koblar
      The encouraging pace of discovery and development in the field of regenerative medicine holds tremendous potential for bringing therapies to the clinic that may offer meaningful benefit to patients, particularly in diseases with no or suboptimal therapeutic options. Academic researchers will continue to play a critical role in developing concepts and therapies, thus determining whether regenerative medicine will be able to live up to this potential that clearly excites clinicians, researchers and patients alike. This review summarises recent developments in regulatory frameworks across different countries that aim to ensure adequate oversight of the development of regenerative medicine products, which are unique in structural and functional complexity when compared to traditional chemical drugs and fully characterised biological drugs. It discusses the implications of these developments for researchers aiming to make the challenging transition from laboratory to clinical development of these therapies and considers possible pragmatic solutions that could accelerate this process that is essential to maintain research credibility and ensure patient safety.
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      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2016.10.001
      Issue No: Vol. 122 (2017)
       
  • Microfluidics for producing poly (lactic-co-glycolic acid)-based
           pharmaceutical nanoparticles
    • Authors: Xuanyu Li; Xingyu Jiang
      Abstract: Publication date: Available online 24 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Xuanyu Li, Xingyu Jiang
      Microfluidic chips allow the rapid production of a library of nanoparticles (NPs) with distinct properties by changing the precursors and the flow rates, significantly decreasing the time for screening optimal formulation as carriers for drug delivery compared to conventional methods. The batch-to-batch reproducibility which is essential for clinical translation is achieved by precisely controlling the precursors and the flow rate, regardless of operators. Poly (lactic-co-glycolic acid) (PLGA) is the most widely used Food and Drug Administration (FDA)-approved biodegradable polymers. Researchers often combine PLGA with lipids or amphiphilic molecules to assemble into a core/shell structure to exploit the potential of PLGA-based NPs as powerful carriers for cancer-related drug delivery. In this review, we discuss the advantages associated with microfluidic chips for producing PLGA-based functional nanocomplexes for drug delivery. These laboratory-based methods can readily scale up to provide sufficient amount of PLGA-based NPs in microfluidic chips for clinical studies and industrial-scale production.
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      PubDate: 2017-12-26T19:45:56Z
      DOI: 10.1016/j.addr.2017.12.015
       
  • Rescue plan for Achilles: Therapeutics steering the fate and functions of
           stem cells in tendon wound healing
    • Authors: Magdalena Schneider; Peter Angele; Tero A.H. Järvinen; Denitsa Docheva
      Abstract: Publication date: Available online 24 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Magdalena Schneider, Peter Angele, Tero A.H. Järvinen, Denitsa Docheva
      Due to the increasing age of our society and a rise in engagement of young people in extreme and/or competitive sports, both tendinopathies and tendon ruptures present a clinical and financial challenge. Tendon has limited natural healing capacity and often responds poorly to treatments, hence it requires prolonged rehabilitation in most cases. Till today, none of the therapeutic options has provided successful long-term solutions, meaning that repaired tendons do not recover their complete strength and functionality. Our understanding of tendon biology and healing increases only slowly and the development of new treatment options is insufficient. In this review, following discussion on tendon structure, healing and the clinical relevance of tendon injury, we aim to elucidate the role of stem cells in tendon healing and discuss new possibilities to enhance stem cell treatment of injured tendon. To date, studies mainly apply stem cells, often in combination with scaffolds or growth factors, to surgically created tendon defects. Deeper understanding of how stem cells and vasculature in the healing tendon react to growth factors, common drugs used to treat injured tendons and promising cellular boosters could help to develop new and more efficient ways to manage tendon injuries.
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      PubDate: 2017-12-26T19:45:56Z
      DOI: 10.1016/j.addr.2017.12.016
       
  • Editorial board members
    • Abstract: Publication date: 1 January 2018
      Source:Advanced Drug Delivery Reviews, Volume 123


      PubDate: 2017-12-23T19:45:52Z
       
  • miRNA delivery for skin wound healing
    • Authors: Zhao Meng; Dezhong Zhou; Yongsheng Gao; Ming Zeng; Wenxin Wang
      Abstract: Publication date: Available online 19 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Zhao Meng, Dezhong Zhou, Yongsheng Gao, Ming Zeng, Wenxin Wang
      The wound healing has remained a worldwide challenge as one of significant public health problems. Pathological scars and chronic wounds caused by injury, aging or diabetes lead to impaired tissue repair and regeneration. Due to the unique biological wound environment, the wound healing is a highly complicated process, efficient and targeted treatments are still lacking. Hence, research-driven to discover more efficient therapeutics is a highly urgent demand. Recently, the research results have revealed that microRNA (miRNA) is a promising tool in therapeutic and diagnostic fields because miRNA is an essential regulator in cellular physiology and pathology. Therefore, new technologies for wound healing based on miRNA have been developed and miRNA delivery has become a significant research topic in the field of gene delivery.
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      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.12.011
       
  • Current and future technological advances in transdermal gene delivery
    • Authors: Xianfeng Chen
      Abstract: Publication date: Available online 19 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Xianfeng Chen
      Transdermal gene delivery holds significant advantages as it is able to minimize the problems of systemic administration such as enzymatic degradation, systemic toxicity, and poor delivery to target tissues. This technology has the potential to transform the treatment and prevention of a range of diseases. However, the skin poses a great barrier for gene delivery because of the “bricks-and-mortar” structure of the stratum corneum and the tight junctions between keratinocytes in the epidermis. This review systematically summarizes the typical physical and chemical approaches to overcome these barriers and facilitate gene delivery via skin for applications in vaccination, wound healing, skin cancers and skin diseases. Next, the advantages and disadvantages of different approaches are discussed and the insights for future development are provided.
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      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.12.014
       
  • Engineered cell and tissue models of pulmonary fibrosis
    • Authors: Aswin Sundarakrishnan; Ying Chen; Lauren D. Black; Bree B. Aldridge; David L. Kaplan
      Abstract: Publication date: Available online 18 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Aswin Sundarakrishnan, Ying Chen, Lauren D. Black, Bree B. Aldridge, David L. Kaplan
      Pulmonary fibrosis includes several lung disorders characterized by scar formation and Idiopathic Pulmonary Fibrosis (IPF) is a particularly severe form of pulmonary fibrosis of unknown etiology with a mean life expectancy of 3 years’ post diagnosis. Treatments for IPF are limited to two FDA approved treatments, pirfenidone and nintedanib. Most lead candidate drugs that are identified in pre-clinical animal studies fail in human clinical trials. Thus, there is a need for advanced humanized in vitro models of the lung to improve candidate treatments prior to moving to human clinical trials. The development of 3D tissue models has created systems capable of emulating human lung structure, function, and cell and matrix interactions. The specific models accomplish these features and preliminary studies conducted using some of these systems have shown potential for in vitro anti-fibrotic drug testing. Further characterization and improvements will enable these tissue models to extend their utility for in vitro drug testing, to help identify signaling pathways and mechanisms for new drug targets, and potentially reduce animal models as standard pre-clinical models of study. In the current review, we contrast different in vitro models based on increasing dimensionality (2D, 2.5D and 3D), with added focus on contemporary 3D pulmonary models of fibrosis.
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      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.12.013
       
  • Electroactive biomaterials: Vehicles for controlled delivery of
           therapeutic agents for drug delivery and tissue regeneration
    • Authors: Biranche Tandon; Adrián Magaz; Richard Balint; Jonny J. Blaker; Sarah H. Cartmell
      Abstract: Publication date: Available online 17 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Biranche Tandon, Adrián Magaz, Richard Balint, Jonny J. Blaker, Sarah H. Cartmell
      Electrical stimulation for delivery of biochemical agents such as genes, proteins and RNA molecules amongst others, holds great potential for controlled therapeutic delivery and in promoting tissue regeneration. Electroactive biomaterials have the capability of delivering these agents in a localized, controlled, responsive and efficient manner. These systems have also been combined for the delivery of both physical and biochemical cues and can be programmed to achieve enhanced effects on healing by establishing control over the microenvironment. This review focuses on current state-of-the-art research in electroactive-based materials towards the delivery of drugs and other therapeutic signalling agents for wound care treatment. Future directions and current challenges for developing effective electroactive approach based therapies for wound care are discussed.
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      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.12.012
       
  • Functional therapies for cutaneous wound repair in epidermolysis bullosa
    • Authors: Patricia Peking; Ulrich Koller; Eva M. Murauer
      Abstract: Publication date: Available online 15 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Patricia Peking, Ulrich Koller, Eva M. Murauer
      Chronic wounding as a result of recurrent skin blistering in the painful genetic skin disease epidermolysis bullosa, may lead to life-threatening infections, increased risk of tumor formation, and other serious medical complications. Therefore, epidermolysis bullosa patients have an urgent need for optimal wound care and tissue regeneration. Therapeutic strategies using gene-, protein-, and cell-therapies are being developed to improve clinical symptoms, and some of them have already been investigated in early clinical trials. The most favorable options of functional therapies include gene replacement, gene editing, RNA targeting, and harnessing natural gene therapy. This review describes the current progress of the different approaches targeting autologous skin cells, and will discuss the benefits and challenges of their application.
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      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.12.003
       
  • Nanomaterials and molecular transporters to overcome the bacterial
           envelope barrier: Towards advanced delivery of antibiotics
    • Authors: Rita S. Santos; Céu Figueiredo; Nuno F. Azevedo; Kevin Braeckmans; Stefaan C. De Smedt
      Abstract: Publication date: Available online 14 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Rita S. Santos, Céu Figueiredo, Nuno F. Azevedo, Kevin Braeckmans, Stefaan C. De Smedt
      With the dramatic consequences of bacterial resistance to antibiotics, nanomaterials and molecular transporters have started to be investigated as alternative antibacterials or anti-infective carrier systems to improve the internalization of bactericidal drugs. However, the capability of nanomaterials/molecular transporters to overcome the bacterial cell envelope is poorly understood. It is critical to consider the sophisticated architecture of bacterial envelopes and reflect how nanomaterials/molecular transporters can interact with these envelopes, being the major aim of this review. The first part of this manuscript overviews the permeability of bacterial envelopes and how it limits the internalization of common antibiotic and novel oligonucleotide drugs. Subsequently we critically discuss the mechanisms that allow nanomaterials/molecular transporters to overcome the bacterial envelopes, focusing on the most promising ones to this end – siderophores, cyclodextrins, metal nanoparticles, antimicrobial/cell-penetrating peptides and fusogenic liposomes. This review may stimulate drug delivery and microbiology scientists in designing effective nanomaterials/molecular transporters against bacterial infections.
      Graphical abstract image

      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.12.010
       
  • Expression, activity and pharmacokinetic impact of ocular transporters
    • Authors: Kati-Sisko Vellonen; Laura Pelkonen; Eliisa Mannermaa; Marika Ruponen; Arto Urtti; Heidi Kidron
      Abstract: Publication date: Available online 14 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Kati-Sisko Vellonen, Laura Pelkonen, Eliisa Mannermaa, Marika Ruponen, Arto Urtti, Heidi Kidron
      The eye is protected by several tissues that limit the permeability and entry of potentially harmful substances, but also hamper the delivery of drugs in the treatment of ocular diseases. Active transport across the ocular barriers may affect drug distribution, but the impact of drug transporters on ocular drug delivery is not well known. We have collected and critically reviewed the literature for ocular expression and activity of known drug transporters. The review concentrates on drug transporters that have been functionally characterized in ocular tissues or primary cells and on transporters for which there is available expression data at the protein level. Species differences are highlighted, since these may explain observed inconsistencies in the influence of specific transporters on drug disposition. There is variable evidence about the pharmacokinetic role of transporters in ocular tissues. The strongest evidence for the role of active transport is available for the blood-retinal barrier. We explored the role of active transport in the cornea and blood retinal barrier with pharmacokinetic simulations. The simulations show that the active transport is important only in the case of specific parameter combinations.
      Graphical abstract image

      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.12.009
       
  • Nanoplasmonic sensors for detecting circulating cancer biomarkers
    • Authors: Abdul Rahim Ferhan; Joshua A. Jackman; Jae Hyeon Park; Nam-Joon Cho; Dong-Hwan Kim
      Abstract: Publication date: Available online 14 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Abdul Rahim Ferhan, Joshua A. Jackman, Jae Hyeon Park, Nam-Joon Cho, Dong-Hwan Kim
      The detection of cancer biomarkers represents an important aspect of cancer diagnosis and prognosis. Recently, the concept of liquid biopsy has been introduced whereby diagnosis and prognosis are performed by means of analyzing biological fluids obtained from patients to detect and quantify circulating cancer biomarkers. Unlike conventional biopsy whereby primary tumor cells are analyzed, liquid biopsy enables the detection of a wide variety of circulating cancer biomarkers, including microRNA (miRNA), circulating tumor DNA (ctDNA), proteins, exosomes and circulating tumor cells (CTCs). Among the various techniques that have been developed to detect circulating cancer biomarkers, nanoplasmonic sensors represent a promising measurement approach due to high sensitivity and specificity as well as ease of instrumentation and operation. In this review, we discuss the relevance and applicability of three different categories of nanoplasmonic sensing techniques, namely surface plasmon resonance (SPR), localized surface plasmon resonance (LSPR) and surface-enhanced Raman scattering (SERS), for the detection of different classes of circulating cancer biomarkers.

      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.12.004
       
  • Implications of melanin binding in ocular drug delivery
    • Authors: Anna-Kaisa Rimpelä; Mika Reinisalo; Laura Hellinen; Evgeni Grazhdankin; Heidi Kidron; Arto Urtti; Eva M. del Amo
      Abstract: Publication date: Available online 13 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Anna-Kaisa Rimpelä, Mika Reinisalo, Laura Hellinen, Evgeni Grazhdankin, Heidi Kidron, Arto Urtti, Eva M. del Amo
      Pigmented ocular tissues contain melanin within the intracellular melanosomes. Drugs bind to melanin at varying extent that ranges from no binding to extensive binding. Binding may lead to drug accumulation to the pigmented tissues and prolonged drug retention in the melanin containing cells. Therefore, melanin binding is an important feature that affects ocular drug delivery and biodistribution, but this topic has not been reviewed since 1998. In this review, we present current knowledge on ocular melanin, melanosomes and binding of drugs to pigmented cells and tissues. In vitro, in vivo and in silico methods in the field were critically evaluated, because the literature in this field can be confusing if the reader does not properly understand the methodological aspects. Literature analysis includes a comprehensive Table of literature data on melanin binding of drugs. Furthermore, we aimed to give some insights beyond the current literature by making a chemical structure based classification model for melanin binding of drugs and kinetic simulations that revealed significant interplay between melanin binding and drug permeability across the melanosomal and plasma membranes. Overall, more mechanistic and systematic research is needed before the impact of melanin binding on ocular drug delivery can be properly understood and predicted.
      Graphical abstract image

      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.12.008
       
  • Efficacy and safety concerns over the use of mucus modulating agents for
           drug delivery using nanoscale systems
    • Authors: Peter I. Chater; Matthew D. Wilcox; Jeffrey P. Pearson
      Abstract: Publication date: Available online 13 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Peter I. Chater, Matthew D. Wilcox, Jeffrey P. Pearson
      Drug delivery to the mucus covered mucosae is fraught with difficulties and many different approaches have been developed to permeate the mucus barrier. Generally by modifying the delivery system to avoid interaction with the mucus. These modifications are reviewed here in terms of efficacy and safety. These are particular problems for oral delivery the pharmaceutical industry's favoured route for drug administration. For effective delivery through the gastrointestinal tract a drug must pass through three barriers in sufficient amounts to yield a biological effect. These barriers are the digestive barrier in the lumen, the mucus barrier, and the epithelial barrier. Other approaches involve mucolytic agents added with or prior to the delivery system or agents regulating mucus production and are reviewed here. In terms of safety, a key property of a mucus modulating delivery system is that it must not damage the protective function of the mucus layer.
      Graphical abstract image

      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.12.006
       
  • Fibrin-based delivery strategies for acute and chronic wound healing
    • Authors: P. Heher; S. Mühleder; R. Mittermayr; H. Redl; P. Slezak
      Abstract: Publication date: Available online 13 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): P. Heher, S. Mühleder, R. Mittermayr, H. Redl, P. Slezak
      Fibrin, a natural hydrogel, is the end product of the physiological blood coagulation cascade and naturally involved in wound healing. Beyond its role in hemostasis, it acts as a local reservoir for growth factors and as a provisional matrix for invading cells that drive the regenerative process. Its unique intrinsic features do not only promote wound healing directly via modulation of cell behavior but it can also be fine-tuned to evolve into a delivery system for sustained release of therapeutic biomolecules, cells and gene vectors. To further augment tissue regeneration potential, current strategies exploit and modify the chemical and physical characteristics of fibrin to employ combined incorporation of several factors and their timed release. In this work we show advanced therapeutic approaches employing fibrin matrices in wound healing and cover the many possibilities fibrin offers to the field of regenerative medicine.
      Graphical abstract image

      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.12.007
       
  • Integration of biomimicry and nanotechnology for significantly improved
           detection of circulating tumor cells (CTCs)
    • Authors: Ja Hye Myung; Sin-jung Park; Andrew Z. Wang; Seungpyo Hong
      Abstract: Publication date: Available online 13 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Ja Hye Myung, Sin-jung Park, Andrew Z. Wang, Seungpyo Hong
      Circulating tumor cells (CTCs) have received a great deal of scientific and clinical attention as a biomarker for diagnosis and prognosis of many types of cancer. Given their potential significance in clinics, a variety of detection methods, utilizing the recent advances in nanotechnology and microfluidics, have been introduced in an effort of achieving clinically significant detection of CTCs. However, effective detection and isolation of CTCs still remain a tremendous challenge due to their extreme rarity and phenotypic heterogeneity. Among many approaches that are currently under development, this review paper focuses on a unique, promising approach that takes advantages of naturally occurring processes achievable through application of nanotechnology to realize significant improvement in sensitivity and specificity of CTC capture. We provide an overview of successful outcome of this biomimetic CTC capture system in detection of tumor cells from in vitro, in vivo, and clinical pilot studies. We also emphasize the clinical impact of CTCs as biomarkers in cancer diagnosis and predictive prognosis, which provides a cost-effective, minimally invasive method that potentially replaces or supplements existing methods such as imaging technologies and solid tissue biopsy. In addition, their potential prognostic values as treatment guidelines and that ultimately help to realize personalized therapy are discussed.
      Graphical abstract image

      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.12.005
       
  • Technological strategies to estimate and control diffusive passage times
           through the mucus barrier in mucosal drug delivery
    • Authors: Jay M. Newby; Ian Seim; Martin Lysy; Yun Ling; Justin Huckaby; Samuel K. Lai; M. Gregory Forest
      Abstract: Publication date: Available online 12 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Jay M. Newby, Ian Seim, Martin Lysy, Yun Ling, Justin Huckaby, Samuel K. Lai, M. Gregory Forest
      In mucosal drug delivery, two design goals are desirable: 1) insure drug passage through the mucosal barrier to the epithelium prior to drug removal from the respective organ via mucus clearance; and 2) design carrier particles to achieve a prescribed arrival time and drug uptake schedule at the epithelium. Both goals are achievable if one can control “one-sided” diffusive passage times of drug carrier particles: from deposition at the mucus interface, through the mucosal barrier, to the epithelium. The passage time distribution must be, with high confidence, shorter than the timescales of mucus clearance to maximize drug uptake. For 100nm and smaller drug-loaded nanoparticulates, as well as pure drug powders or drug solutions, diffusion is normal (i.e., Brownian) and rapid, easily passing through the mucosal barrier prior to clearance. Major challenges in quantitative control over mucosal drug delivery lie with larger drug-loaded nanoparticulates that are comparable to or larger than the pores within the mucus gel network, for which diffusion is not simple Brownian motion and typically much less rapid; in these scenarios, a timescale competition ensues between particle passage through the mucus barrier and mucus clearance from the organ. In the lung, as a primary example, coordinated cilia and air drag continuously transport mucus toward the trachea, where mucus and trapped cargo are swallowed into the digestive tract. Mucus clearance times in lung airways range from minutes to hours or significantly longer depending on deposition in the upper, middle, lower airways and on lung health, giving a wide time window for drug-loaded particle design to achieve controlled delivery to the epithelium. We review the physical and chemical factors (of both particles and mucus) that dictate particle diffusion in mucus, and the technological strategies (theoretical and experimental) required to achieve the design goals. First we describe an idealized scenario — a homogeneous viscous fluid of uniform depth with a particle undergoing passive normal diffusion — where the theory of Brownian motion affords the ability to rigorously specify particle size distributions to meet a prescribed, one-sided, diffusive passage time distribution. Furthermore, we describe how the theory of Brownian motion provides the scaling of one-sided diffusive passage times with respect to mucus viscosity and layer depth, and under reasonable caveats, one can also prescribe passage time scaling due to heterogeneity in viscosity and layer depth. Small-molecule drugs and muco-inert, drug-loaded carrier particles 100nm and smaller fall into this class of rigorously controllable passage times for drug delivery. Second we describe the prevalent scenarios in which drug-loaded carrier particles in mucus violate simple Brownian motion, instead exhibiting anomalous sub-diffusion, for which all theoretical control over diffusive passage times is lost, and experiments are prohibitive if not impossible to measure one-sided passage times. We then discuss strategies to overcome these roadblocks, requiring new particle-tracking experiments and emerging advances in theory and computation of anomalous, sub-diffusive processes that are necessary to predict and control one-sided particle passage times from deposition at the mucosal interface to epithelial uptake. We highlight progress to date, remaining hurdles, and prospects for achieving the two design goals for 200nm and larger, drug-loaded, non-dissolving, nanoparticulates.
      Graphical abstract image

      PubDate: 2017-12-23T19:45:52Z
      DOI: 10.1016/j.addr.2017.12.002
       
  • Drug delivery and tissue engineering to promote wound healing in the
           Immunocompromised host: Current challenges and future directions
    • Authors: Alexander M. Tatara; Dimitrios P. Kontoyiannis; Antonios G. Mikos
      Abstract: Publication date: Available online 6 December 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Alexander M. Tatara, Dimitrios P. Kontoyiannis, Antonios G. Mikos
      As regenerative medicine matures as a field, more promising technologies are being translated from the benchtop to the clinic. However, many of these strategies are designed with otherwise healthy hosts in mind and validated in animal models without other co-morbidities. In reality, many of the patient populations benefiting from drug delivery and tissue engineering-based devices to enhance wound healing also have significant underlying immunodeficiency. Specifically, patients suffering from diabetes, malignancy, human immunodeficiency virus, post organ transplantation, and other compromised states have significant pleotropic immune defects that affect wound healing. In this work, we review the role of different immune cells in the regenerative process, highlight the effect of several common immunocompromised states on wound healing, and discuss different drug delivery strategies for overcoming immunodeficiencies.
      Graphical abstract image

      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.12.001
       
  • The state-of-play and future of antibody therapeutics
    • Authors: Zehra Elgundi; Mouhamad Reslan Esteban Cruz Vicki Sifniotis Veysel Kayser
      Abstract: Publication date: 1 December 2017
      Source:Advanced Drug Delivery Reviews, Volume 122
      Author(s): Zehra Elgundi, Mouhamad Reslan, Esteban Cruz, Vicki Sifniotis, Veysel Kayser
      It has been over four decades since the development of monoclonal antibodies (mAbs) using a hybridoma cell line was first reported. Since then more than thirty therapeutic antibodies have been marketed, mostly as oncology, autoimmune and inflammatory therapeutics. While antibodies are very efficient, their cost-effectiveness has always been discussed owing to their high costs, accumulating to more than one billion dollars from preclinical development through to market approval. Because of this, therapeutic antibodies are inaccessible to some patients in both developed and developing countries. The growing interest in biosimilar antibodies as affordable versions of therapeutic antibodies may provide alternative treatment options as well potentially decreasing costs. As certain markets begin to capitalize on this opportunity, regulatory authorities continue to refine the requirements for demonstrating quality, efficacy and safety of biosimilar compared to originator products. In addition to biosimilars, innovations in antibody engineering are providing the opportunity to design biobetter antibodies with improved properties to maximize efficacy. Enhancing effector function, antibody drug conjugates (ADC) or targeting multiple disease pathways via multi-specific antibodies are being explored. The manufacturing process of antibodies is also moving forward with advancements relating to host cell production and purification processes. Studies into the physical and chemical degradation pathways of antibodies are contributing to the design of more stable proteins guided by computational tools. Moreover, the delivery and pharmacokinetics of antibody-based therapeutics are improving as optimized formulations are pursued through the implementation of recent innovations in the field.
      Graphical abstract image

      PubDate: 2017-12-07T06:23:10Z
       
  • Pulmonary drug delivery to older people
    • Authors: Martin Wallin; Tatsuaki Tagami; Lan Chen; Mingshi Yang; Hak-Kim Chan
      Abstract: Publication date: Available online 29 November 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Martin Wallin, Tatsuaki Tagami, Lan Chen, Mingshi Yang, Hak-Kim Chan
      Pulmonary diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are common in older people. Treatment principles are well established in this group of patients; however, inadequate training and improper inhaler techniques often results in poor treatment outcomes. Healthcare professionals often do not have the required knowledge about the most common inhaler devices. Age-related conditions like cognitive ability and physical strength would also impact on the inhaler usage. Pharmacokinetics and pharmacodynamics may be affected by physiological changes, like impaired renal and hepatic functions and reduced lung functions. Adjusting and optimizing the inhaler device to the patient preferences, improvement of the drug formulation and inhalers, and using different adherence strategies might improve the treatment outcomes in elderly patients.
      Graphical abstract image

      PubDate: 2017-12-07T06:23:10Z
      DOI: 10.1016/j.addr.2017.11.010
       
  • Bench-to-bedside translation of dendrimers: Reality or utopia' A
           concise analysis
    • Authors: Serge Mignani; João Rodrigues; Helena Tomas; René Roy; Xiangyang Shi; Jean-Pierre Majoral
      Abstract: Publication date: Available online 16 November 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Serge Mignani, João Rodrigues, Helena Tomas, René Roy, Xiangyang Shi, Jean-Pierre Majoral
      Nanomedicine, which is an application of nanotechnologies in healthcare is developed to improve the treatments and lives of patients suffering from a range of disorders and to increase the successes of drug candidates. Within the nanotechnology universe, the remarkable unique and tunable properties of dendrimers have made them promising tools for diverse biomedical applications such as drug delivery, gene therapy and diagnostic. Up-to-date, very few dendrimers has yet gained regulatory approval for systemic administration, why? In this critical review, we briefly focus on the list of desired basic dendrimer requirements for decision-making purpose by the scientists (go/no-go decision), in early development stages, to become clinical candidates, and to move towards Investigational New Drugs (IND) application submission. In addition, the successful translation between research and clinic should be performed by the implementation of a simple roadmap to jump the ‘valley of death’ successfully.
      Graphical abstract image

      PubDate: 2017-11-26T02:18:38Z
      DOI: 10.1016/j.addr.2017.11.007
       
  • Injectable Network Biomaterials via Molecular or Colloidal Self-Assembly
    • Authors: Jugal Kishore Sahoo; Michael A. VandenBerg; Matthew J. Webber
      Abstract: Publication date: Available online 10 November 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Jugal Kishore Sahoo, Michael A. VandenBerg, Matthew J. Webber
      Self-assembly is a powerful tool to create functional materials. A specific application for which self-assembled materials are ideally suited is in creating injectable biomaterials. Contrasting with traditional biomaterials that are implanted through surgical means, injecting biomaterials through the skin offers numerous advantages, expanding the scope and impact for biomaterials in medicine. In particular, self-assembled biomaterials prepared from molecular or colloidal interactions have been frequently explored. The strategies to create these materials are varied, taking advantage of engineered oligopeptides, proteins, and nanoparticles as well as affinity-mediated crosslinking of synthetic precursors. Self-assembled materials typically facilitate injectability through two different mechanisms: i) in situ self-assembly, whereby materials would be administered in a monomeric or oligomeric form and self-assemble in response to some physiologic stimulus, or ii) self-assembled materials that, by virtue of their dynamic, non-covalent interactions, shear-thin and self-heal to facilitate flow within a syringe and subsequent reassembly of material form at the injection site. Indeed, many classes of materials are capable of being injected using a combination of these two mechanisms. Particular utility has been noted for self-assembled biomaterials in the context of tissue engineering, regenerative medicine, drug delivery, and immunoengineering. Given the controlled and multifunctional nature of many self-assembled materials demonstrated to date, we project a future where injectable self-assembled biomaterials afford improved practice in advancing healthcare.
      Graphical abstract image

      PubDate: 2017-11-16T12:01:25Z
      DOI: 10.1016/j.addr.2017.11.005
       
  • MEMS devices for drug delivery
    • Authors: Hyunjoo J. Lee; Nakwon Choi; Eui-Sung Yoon; Il-Joo Cho
      Abstract: Publication date: Available online 5 November 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Hyunjoo J. Lee, Nakwon Choi, Eui-Sung Yoon, Il-Joo Cho
      Novel drug delivery systems based on microtechnology have advanced tremendously, but yet face some technological and societal hurdles to fully achieve their potential. The novel drug delivery systems aim to deliver drugs in a spatiotemporal- and dosage-controlled manner with a goal to address the unmet medical needs from oral delivery and hypodermic injection. The unmet needs include effective delivery of new types of drug candidates that are otherwise insoluble and unstable, targeted delivery to areas protected by barriers (e.g. brain and posterior eye segment), localized delivery of potent drugs, and improved patient compliance. After scrutinizing the design considerations and challenges associated with delivery to areas that cannot be efficiently targeted through standard drug delivery (e.g. brain, posterior eye segment, and gastrointestinal tract), this review provides a summary of recent advances that addressed these challenges and summarizes yet unresolved problems in each target area. The opportunities for innovation in devising the novel drug delivery systems are still high; with integration of advanced microtechnology, advanced fabrication of biomaterials, and biotechnology, the novel drug delivery is poised to be a promising alternative to the oral administration and hypodermic injection for a large spectrum of drug candidates.
      Graphical abstract image

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

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

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

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

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

      PubDate: 2017-11-02T00:40:33Z
      DOI: 10.1016/j.addr.2017.10.012
       
  • Restoration of skin pigmentation after deep partial or full-thickness burn
           injury
    • Authors: Niann-Tzyy Dai; Hsin-I Chang; Yi-Wen Wang; Keng-Yen Fu; Tai-Chun Huang; Nien-Chi Huang; Jhen-Kai Li; Pai-Shan Hsieh; Lien-Guo Dai; Chao-Kuei Hsu; Peter K. Maitz
      Abstract: Publication date: Available online 24 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Niann-Tzyy Dai, Hsin-I Chang, Yi-Wen Wang, Keng-Yen Fu, Tai-Chun Huang, Nien-Chi Huang, Jhen-Kai Li, Pai-Shan Hsieh, Lien-Guo Dai, Chao-Kuei Hsu, Peter K. Maitz
      Significant skin pigmentation changes occur when patients suffer deep burn injuries. These pigmentation disorders may cause not only cosmetic and psychological issues, but more importantly it increases the risk of skin cancer or photoaging. Severe burns significantly effect on the process of repigmentation as the pigmentation is tightly regulated by cell proliferation and differentiation of melanocytes and melanocyte stem cells which are housing in the epidermis and hair follicles of the skin. In the present review, we discuss the possible mechanisms to replenish the melanocytes from the healthy epidermis and hair follicles surrounding burn wounds. The molecular mechanisms of skin repigmentation following healing of burn injuries includes the differentiation of melanoblasts into melanocytes, the distribution and responses of melanocytes and melanocyte stem cells after burn injury, and the regulation of melanin production. We also reviewed advanced therapeutic strategies to treat pigmentation disorders, such as convectional surgery, laser, UV treatment and emerging concepts in skin tissue-engineering.
      Graphical abstract image

      PubDate: 2017-10-26T01:44:14Z
      DOI: 10.1016/j.addr.2017.10.010
       
  • The application of mesenchymal stem cells to treat thermal and radiation
           burns
    • Authors: Kathleen Rodgers; Sachin S. Jadhav
      Abstract: Publication date: Available online 12 October 2017
      Source:Advanced Drug Delivery Reviews
      Author(s): Kathleen Rodgers, Sachin S. Jadhav
      Mesenchymal stem cells (MSCs) have been developed for a number of indications due to their regenerative and anti-inflammatory phenotypes and their utility is enhanced by the fact that allogeneic transplant is feasible with this cell type. Animal studies and early human cases indicate that this has the potential to be an exciting new therapy for treating chronic non-healing wounds such as diabetic ulcers, burns and cutaneous radiation burns. This review will focus on the use of MSCs to treat thermal and radiation burns. Large, severe burns are difficult to treat and pose a major public health burden worldwide. They are characterized by an extensive loss of the outer protective barrier, delayed wound healing, increased oxidative stress and a heightened inflammatory state. The breakdown of the protective barrier results in increased susceptibility to fluid loss and bacterial sepsis. In the case of radiation burns, chronic inflammation can result in subsequent waves of tissue injury leading to skin breakdown and necrosis. The aim of this review is to summarize the current knowledge on MSCs in treating thermal and radiation burns along with the specific scope of characterizing the biologic function of MSCs that help enhance wound healing in these chronic injuries.
      Graphical abstract image

      PubDate: 2017-10-18T00:26:56Z
      DOI: 10.1016/j.addr.2017.10.003
       
 
 
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