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Advanced Drug Delivery Reviews

C L Nemeth, A S Fine, A Fatemi
The focus of regenerative therapies is to replace or enrich diseased or injured cells and tissue in an attempt to replenish the local environment and function, while slowing or halting further degeneration. Targeting neurological diseases specifically is difficult, due to the complex nature of the central nervous system, including the difficulty of bypassing the brain's natural defense systems. While cell-based regenerative therapies show promise in select tissues, preclinical and clinical studies have been largely unable to transfer these successes to the brain...
May 14, 2019: Advanced Drug Delivery Reviews
Klearchos K Papas, Hector De Leon, Thomas M Suszynski, Robert C Johnson
Human allogeneic islet transplantation (ITx) is emerging as a promising treatment option for qualified patients with T1D. However, widespread clinical application of allogeneic ITx is hindered by two critical barriers: the need for systemic immunosuppression and the limited supply of human islet tissue. Biocompatible, retrievable immunoisolation devices containing glucose-responsive insulin-secreting tissue may address both critical barriers by enabling the more effective and efficient use of allogeneic islets without immunosuppression in the near-term, and ultimately the use of a cell source with a virtually unlimited supply, such as human stem cell derived β-cells or xenogeneic (porcine) islets with minimal or no immunosuppression...
May 8, 2019: Advanced Drug Delivery Reviews
Parichehr Hassanzadeh, Fatemeh Atyabi, Rassoul Dinarvand
Over the last decade, increasing interest has been attracted towards the application of artificial intelligence (AI) technology for analyzing and interpreting the biological or genetic information, accelerated drug discovery, and identification of the selective small-molecule modulators or rare molecules and prediction of their behavior. Application of the automated workflows and databases for rapid analysis of the huge amounts of data and artificial neural networks (ANNs) for development of the novel hypotheses and treatment strategies, prediction of disease progression, and evaluation of the pharmacological profiles of drug candidates may significantly improve treatment outcomes...
May 6, 2019: Advanced Drug Delivery Reviews
Christina Leichner, Max Jelkmann, Andreas Bernkop-Schnürch
Thiolated polymers designated "thiomers" are obtained by covalent attachment of thiol functionalities on the polymeric backbone of polymers. In 1998 these polymers were first described as mucoadhesive and in situ gelling compounds forming disulfide bonds with cysteine-rich substructures of mucus glycoproteins and crosslinking through inter- and intrachain disulfide bond formation. In the following, it was shown that thiomers are able to form disulfides with keratins and membrane-associated proteins exhibiting also cysteine-rich substructures...
April 24, 2019: Advanced Drug Delivery Reviews
Nathan D Donahue, Handan Acar, Stefan Wilhelm
Nanoparticle-based therapeutics and diagnostics are commonly referred to as nanomedicine and may significantly impact the future of healthcare. However, the clinical translation of these technologies is challenging. One of these challenges is the efficient delivery of nanoparticles to specific cell populations and subcellular targets in the body to elicit desired biological and therapeutic responses. It is critical for researchers to understand the fundamental concepts of how nanoparticles interact with biological systems to predict and control in vivo nanoparticle transport for improved clinical benefit...
April 22, 2019: Advanced Drug Delivery Reviews
Perrin H Beatty, John D Lewis
Nanoparticle platforms are particularly attractive for theranostic applications due to their capacity for multifunctionality and multivalency. Some of the most promising nano-scale scaffold systems have been co-opted from nature including plant viruses such as cowpea mosaic virus (CPMV). The use of plant viruses like CPMV as viral nanoparticles is advantageous for many reasons; they are non-infectious and nontoxic to humans and safe for use in intravital imaging and drug delivery. The CPMV capsid icosahedral shape allows for enhanced multifunctional group display and the ability to carry specific cargoes...
April 17, 2019: Advanced Drug Delivery Reviews
F Rahbarizadeh, D Ahmadvand, S M Moghimi
Redirecting the recognition specificity of T lymphocytes to designated tumour cell surface antigens by transferring chimeric antigen receptor (CAR) genes is becoming an effective strategy to combat cancer. Today, CAR T-cell therapy has proven successful in the treatment of haematological malignancies and the first CD19 CAR T-cell products has already entered the market. This success is expanding CAR design for broader malignancies including solid tumours. Nevertheless, CARs such as those built on antigen-specific single chain antibody variable fragment (scFv) may induce some adverse effects...
April 17, 2019: Advanced Drug Delivery Reviews
Alan Chramiec, Gordana Vunjak-Novakovic
Tissue engineering is becoming increasingly successful in providing in vitro models of human tissues that can be used for ex vivo recapitulation of functional tissues as well as predictive testing of drug efficacy and safety. From simple tissue models to microphysiological platforms comprising multiple tissue types connected by vascular perfusion, these "tissues on a chip" are emerging as a fast track application for tissue engineering, with great potential for modeling diseases and supporting the development of new drugs and therapeutic targets...
April 16, 2019: Advanced Drug Delivery Reviews
Daniel Getts, Robert Hoffmeister, Alfonso Quintás-Cardama
Chimeric antigen receptor (CAR) T cells have been remarkably successful in patients with hematological malignancies expressing the CD19 surface antigen, but such level of success is far from being replicated in solid tumors. Engineered T cell receptor (TCR) T cells targeting cancer antigens were first developed over two decades ago and represent an alternative adoptive T cell approach that has produced provocative clinical data in solid cancers. However, several factors may hinder this technology from realizing its full potential, including the need for HLA matching, HLA downregulation by cancer cells, the suppressive tumor microenvironment, and tissue liabilities resulting from targeting antigens shared with normal tissues...
April 11, 2019: Advanced Drug Delivery Reviews
Muthanna Abdulkarim, Peeyush Kumar Sharma, Mark Gumbleton
Mucus is a dynamic barrier which covers and protects the underlying mucosal epithelial membrane against bacteria and foreign particles. This protection mechanism extends to include therapeutic macromolecules and nanoparticles (NPs) through trapping of these particles. Mucus is not only a physical barrier that limiting particles movements based on their sizes but it selectively binds with particles through both hydrophilic and lipophilic interactions. Therefore, nano-carriers for mucosal delivery should be designed to eliminate entrapment by the mucus barrier...
April 8, 2019: Advanced Drug Delivery Reviews
Jiah Shin Chin, Leigh Madden, Sing Yian Chew, David L Becker
Acute wound healing is an orderly process of four overlapping events: haemostasis, inflammation, proliferation and remodelling. A drug delivery system with a temporal control of release could promote each of these events sequentially. However, acute wound healing normally proceeds very well in healthy individuals and there is little need to promote it. In the elderly and diabetics however, healing is often slow and wounds can become chronic and we need to promote their healing. Targeting the events of acute wound healing would not be appropriate for a chronic wound, which have stalled in the proinflammatory phase...
April 5, 2019: Advanced Drug Delivery Reviews
Sawsan Amara, Claire Bourlieu, Lydie Humbert, Dominique Rainteau, Frédéric Carrière
The lipids and some surfactants present in oral lipid-based drug delivery systems are potential substrates for the various lipases involved in gastrointestinal (GI) lipolysis. The levels of these enzymes, together with pH and biliairy secretion, are important parameters that condition the fate of lipid-based formulations (LBF) and the dispersion, solubilization and absorption of lipophilic drugs in the GI tract. Since in vitro methods of digestion are now combined with dissolution assays for a better assessment of LBF performance, it is essential to have a basic knowledge on lipase, pH and bile acid (BA) levels in vivo to develop relevant in vitro models...
March 26, 2019: Advanced Drug Delivery Reviews
William Ong, Coline Pinese, Sing Yian Chew
Neural tissue regeneration following traumatic injuries is often subpar. As a result, the field of neural tissue engineering has evolved to find therapeutic interventions and has seen promising outcomes. However, robust nerve and myelin regeneration remain elusive. One possible reason may be the fact that tissue regeneration often follows a complex sequence of events in a temporally-controlled manner. Although several other fields of tissue engineering have begun to recognise the importance of delivering two or more biomolecules sequentially for more complete tissue regeneration, such serial delivery of biomolecules in neural tissue engineering remains limited...
March 22, 2019: Advanced Drug Delivery Reviews
Tim Meyer, Malte Tiburcy, Wolfram-Hubertus Zimmermann
Facilitated by the introduction of human induced pluripotent stem cells and protocols for their efficient directed differentiation at high quantity and quality, innovative human heart muscle models are being developed for applications in drug screens. Employed models range from the microscopic cardiomyocytes-on-a-chip scale to the cardiac macrotissues-on-a-plate scale. Whilst cardiomyocyte-on-a-chip models can be readily adapted to high-throughput primary screening, they are limited as to the deep phenotyping of contractility, and here in particular contractile force development...
March 19, 2019: Advanced Drug Delivery Reviews
Yuwei Wang, David W Grainger
Given the successful entry of several liposomal drug products into market, and some with decades of clinical efficacy, liposomal drug delivery systems have proven capabilities to overcome certain limitations of traditional drug delivery, especially for toxic and biologic drugs. This experience has helped promote new liposomal approaches to emerging drug classes and current therapeutic challenges. All approved liposomal dosage forms are parenteral formulations, a pathway demonstrating greatest safety and efficacy to date...
March 18, 2019: Advanced Drug Delivery Reviews
Elizabeth Smith, Joshua E Porterfield, Rangaramanujam M Kannan
Nanotechnology has the potential to open many novel diagnostic and treatment avenues for disorders of the central nervous system (CNS). In this review, we discuss recent developments in the applications of nanotechnology in CNS therapies, diagnosis and biology. Novel approaches for the diagnosis and treatment of neuroinflammation, brain dysfunction, psychiatric conditions, brain cancer, and nerve injury provide insights into the potential of nanomedicine. We also highlight nanotechnology-enabled neuroscience techniques such as electrophysiology and intracellular sampling to improve our understanding of the brain and its components...
March 4, 2019: Advanced Drug Delivery Reviews
Vibhuti Agrahari, Pierre-Alain Burnouf, Thierry Burnouf, Vivek Agrahari
Nanocarriers (synthetic/cell-based have attracted enormous interest for various therapeutic indications, including neurodegenerative disorders. A broader understanding of the impact of nanomedicines design is now required to enhance their translational potential. Nanoformulations in vivo journey is significantly affected by their physicochemical properties including the size, shape, hydrophobicity, elasticity, and surface charge/chemistry/morphology, which play a role as an interface with the biological environment...
February 22, 2019: Advanced Drug Delivery Reviews
Carly S Filgueira, Stephen R Igo, Dennis K Wang, Matteo Hirsch, Daryl G Schulz, Brian Bruckner, Alessandro Grattoni
The pericardium, which surrounds the heart, provides a unique enclosed volume and a site for the delivery of agents to the heart and coronary arteries. While strategies for targeting the delivery of therapeutics to the heart are lacking, various technologies and nanodelivery approaches are emerging as promising methods for site specific delivery to increase therapeutic myocardial retention, efficacy, and bioactivity, while decreasing undesired systemic effects. Here, we provide a literature review of various approaches for intrapericardial delivery of agents...
February 21, 2019: Advanced Drug Delivery Reviews
Megerle L Scherholz, Naomi Schlesinger, Ioannis P Androulakis
Glucocorticoids influence a wide array of metabolic, anti-inflammatory, immunosuppressive, and cognitive signaling processes, playing an important role in homeostasis and preservation of normal organ function. Synthesis is regulated by the hypothalamic-pituitary-adrenal (HPA) axis of which cortisol is the primary glucocorticoid in humans. Synthetic glucocorticoids are important pharmacological agents that augment the anti-inflammatory and immunosuppressive properties of endogenous cortisol and are widely used for the treatment of asthma, Crohn's disease, and rheumatoid arthritis, amongst other chronic conditions...
February 21, 2019: Advanced Drug Delivery Reviews
Marie Rouquette, Sinda Lepetre-Mouelhi, Patrick Couvreur
Adenosine is a fascinating compound, crucial in many biochemical processes: this ubiquitous nucleoside serves as an essential building block of RNA, is also a component of ATP and regulates numerous pathophysiological mechanisms via binding to four extracellular receptors. Due to its hydrophilic nature, it belongs to a different world than lipids, and has no affinity for them. Since the 1970's, however, new discoveries have emerged and prompted the scientific community to associate adenosine with the lipid family, especially via liposomal preparations and bioconjugation...
February 21, 2019: Advanced Drug Delivery Reviews
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