Neurodegenerative disorders including Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, and stroke are rapidly increasing as population ages. The field of nanomedicine is rapidly expanding and promises revolutionary advances to the diagnosis and treatment of devastating human diseases. This paper provides an overview of novel nanomaterials that have potential to improve diagnosis and therapy of neurodegenerative disorders. Examples include liposomes, nanoparticles, polymeric micelles, block ionomer complexes, nanogels, and dendrimers that have been tested clinically or in experimental models for delivery of drugs, genes, and imaging agents. More recently discovered nanotubes and nanofibers are evaluated as promising scaffolds for neuroregeneration. Novel experimental neuroprotective strategies also include nanomaterials, such as fullerenes, which have antioxidant properties to eliminate reactive oxygen species in the brain to mitigate oxidative stress. Novel technologies to enable these materials to cross the blood brain barrier will allow efficient systemic delivery of therapeutic and diagnostic agents to the brain. Furthermore, by combining such nanomaterials with cell-based delivery strategies, the outcomes of neurodegenerative disorders can be greatly improved.
As an emerging research direction, nanomedicine has been increasingly utilized to treat inflammatory diseases. In this head-to-head comparison study, four established nanomedicine formulations of dexamethasone, including liposomes (L-Dex), core-crosslinked micelles (M-Dex), slow releasing polymeric prodrugs (P-Dex-slow) and fast releasing polymeric prodrugs (P-Dex-fast), were evaluated in an adjuvant-induced arthritis rat model with an equivalent dose treatment design. It was found that after a single i.v. injection, the formulations with the slower drug release kinetics (i.e. M-Dex and P-Dex-slow) maintained longer duration of therapeutic activity than those with relatively faster drug release kinetics, resulting in better joint protection. This finding will be instructional in the future development and optimization of nanomedicines for the clinical management of rheumatoid arthritis. The outcome of this study also illustrates the value of such head-to-head comparison studies in translational nanomedicine research.
To achieve highly effective glucocorticoid targeting for rheumatoid arthritis therapy, novel, polymerizable and hydrolytically cleavable dexamethasone (DEX) derivatives were covalently entrapped in core-crosslinked polymeric micelles. By varying the oxidation degree of the thioether in the drug linker, the release rate of DEX could be tightly controlled. Upon administration of the most rapidly releasing DEX-micelles, highly efficient disease treatment was achieved in two different animal models of inflammatory arthritis.
Polymerisierbare und hydrolytisch spaltbare Derivate von Dexamethason (DEX, roter Punkt) wurden kovalent in kernverknüpften Polymer‐Micellen bestehend aus einem temperaturempfindlichen Blockcopolymer (gelber und grauer Baustein) eingeschlossen. Die Freisetzungsrate konnte über den Oxidationsgrad des Thioethers im Linker des Wirkstoffderivats gesteuert werden. Mit den DEX‐Micellen wurde entzündliche rheumatische Arthritis in zwei Tiermodellen effizient behandelt.
PURPOSE
To investigate the efficacy and safety of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-dexamethasone conjugate (P-Dex) in the collagen-induced arthritis (CIA) mouse model.
METHODS
HPMA copolymer labeled with a near infrared fluorescence (NIRF) dye was administered to mice with CIA to validate its passive targeting to inflamed joints and utility as a drug carrier system. The CIA mice were treated with P-Dex, dexamethasone (Dex) or saline and the therapeutic efficacy and skeletal toxicity evaluated using clinical scoring and micro-computed tomography (µ-CT).
RESULTS
The NIRF signal of the HPMA copolymer localized to arthritic joints consistent with its passive targeting to sites of inflammation. While the CIA mice responded more rapidly to P-Dex compared to Dex, the final clinical score and endpoint µ-CT analyses of localized bone erosions indicated that both single dose P-Dex and dose equivalent daily Dex led to comparable clinical efficacy after 30 days. µ-CT analysis of the proximal tibial metaphyses showed that P-Dex treatment was associated with significantly higher BMD and BV/TV compared to Dex and the saline control, consistent with reduced glucocorticoid (GC) skeletal toxicity.
CONCLUSION
These results validate the therapeutic efficacy of P-Dex in the CIA mouse model. P-Dex treatment averted the adverse effects of GC’s on systemic bone loss, supporting its utility in clinical development for the management of rheumatoid arthritis.
Rheumatoid Arthritis (RA) is a chronic autoimmune disease and considered to be one of the major public health problems worldwide. In the past decade numerous drug delivery systems have been developed to improve the treatment outcome of RA. A stable endogenous protein, albumin has been employed as a non-immunogenic delivery carrier and extensively researched in various disease therapies. To provide the prospective for future research, this review summarizes the application of albumin as drug or imaging agent carriers for RA and proposes potential future directions. There are three major types of albumin-based carrier systems for RA, including albumin drug conjugates, albumin particles and genetic infusion albumin. Their imaging or therapeutic effects have been proved in clinic or preclinical studies.Citation: Ren K, Dusad A, Dong R, Quan L (2013) Albumin as a Delivery Carrier for Rheumatoid Arthritis.
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