Scleroderma: An insight into causes, pathogenesis and treatment strategies.

Scleroderma is an autoimmune disorder, characterized by morphological changes in skin followed by visceral organs. The pathogenesis of scleroderma involves immune imbalance and generation of auto antibodies. The major causes of scleroderma include multitude of factors such as immune imbalance, oxidative stress, genetics and environment factors. A constant effort has been made to treat scleroderma through different approaches and necessitates life time administration of drugs for maintenance of a good quality life. It has been reported more in women compared to men. Traditional treatment strategies are restricted by limited therapeutic capability due to associated side effects. Advancement in development of novel drug delivery approaches has opened a newer avenue for efficient therapy. Current review is an effort to reflect scleroderma in provisions of its pathogenesis, causative factors, and therapeutic approaches, with concern to mode of action, pharmacokinetics, marketed products, and side effects of drugs.

In vitro and In vivo characterization of quercetin loaded multiphase hydrogel for wound healing application.

The present work aim to prepare and evaluate multiphase hydrogel system incorporated with quercetin loaded liposomes (QLH), for wound healing. The quercetin loaded liposomal hydrogel were prepared by taking 15% carbopol and varying gelatin ratio. The clear and transparent hydrogel was obtained by taking ratio of gelatin to carbapol (6/4) compared to other ratios. The best prepared hydrogel were characterized for surface morphology, water vapor transmission rate (WVTR), swelling ratio, hemocompatibility, stability, in-vitro release and in-vivo studies. The evaluated results of (QLH) for surface morphology, WVTR, swelling ratio, hemocompatibility and in-vitro release were found to be significant compared to other prepared formulations. Consequently, on basis of optimized hydrogel was selected to study wound healing activity in albino rats. The results demonstrated accelerated wound-healing with significant decrease in wound closure time compared to conventional dosage form. The results of in-vitro and in-vivo promises reliable mode of treatment for connective tissue disorder as wound healing.

Folate-Conjugated Superoxide Dismutase Adsorbed Over Antioxidant Mimicking Nanomatrix Frameworks for Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease occurring in larger population, characterized by synovial inflammation followed by destruction of joint. Major concerned factor for cause of RA has been related to oxidative stress due to environmental toxicity and immune imbalance. Reactive oxygen species generated from macrophages communes series of oxidation at cellular and genetic level and leads to generation of inflammatory cytokines for provoking inflammation in RA. Superoxide dismutase and catalase are supposed to be potential antioxidant enzymes to scavange free radicals. However, many clinical studies report reduced potency of enzyme due to lack of its targeting efficacy. Therefore, the aim of the work involves development of nanomatrix mimicking as catalase over which folate-linked superoxide dismutase was adsorbed for a macrophage targeting. The developed formulation was optimized, characterized for morphological studies, enzyme loading efficiency, protein activity, and in vitro drug release. Quantification of interleukin 6 was performed by indirect enzyme linked immunosborent assay over macrophage cell lines to determine in vitro treatment efficacy. It is concluded that the prepared system can act as enzyme reservoir to deliver acid labile enzymes in controlled form to efficiently treat RA.

Role of enzymatic free radical scavengers in management of oxidative stress in autoimmune disorders.

Autoimmune disorders are distinct with over production and accumulation of free radicals due to its undisclosed genesis. The cause of numerous disorders as cancer, arthritis, psoriasis, diabetes, alzheimer's, cardiovascular disease, Parkinson's, respiratory distress syndrome, colitis, crohn's, pulmonary fibrosis, obesity and ageing have been associated with immune dysfunction and oxidative stress. In an oxidative stress, reactive oxygen species generally provoke the series of oxidation at cellular level. The buildup of free radicals in turn triggers various inflammatory cells causing release of various inflammatory interleukins, cytokines, chemokines, and tumor necrosis factors which mediate signal transduction and transcription pathways as nuclear factor- kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), hypoxia-inducible factor-1 (HIF-1α) and nuclear factor-erythroid 2-related factor (Nrf2). The imbalance could only be combat by supplementing natural defensive antioxidant enzymes such as superoxide dismutase and catalase. The efficiency of these enzymes is enhanced by use of colloidal carriers which include cellular carriers, vesicular and particulate systems like erythrocytes, leukocytes, platelets, liposomes, transferosomes, solid lipid nanoparticles, microspheres, emulsions. Thus this review provides a platform for understanding importance of antioxidant enzymes and its therapeutic applications in treatment of various autoimmune disorders.

Novel catalase loaded nanocores for the treatment of inflammatory bowel diseases.

Inflammatory bowel disease (IBD) is an inflammatory disorder of the digestive tract reported to be primarily caused by oxidative stress. In this study, alginate encapsulated nanoceramic carriers were designed to deliver acid labile antioxidant enzyme catalase orally. Complete system was characterized for size, loading efficiency, in vitro antioxidant assay and in vitro release. The prepared nanoceramic system was found to be spherical with diameter of 925 ± 6.81 nm. The in vitro release data followed the Higuchi model in acidic buffer whereas in alkaline pH sustained and almost first order release of enzyme was observed up to 6 h.