betadex and Psoriasis

Topics: Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Cell Line; Curcumin; Drug Carriers; Drug Liberation; Epichlorohydrin; Humans; Psoriasis; Solubility

Combination of curcumin with anti-inflammatory drug like caffeine shows augmented antipsoriatic action compared to curcumin alone and reduce the time taken for treatment of Psoriasis.. The objective of the present study was to develop nanosponge (NS) based topical gel of curcumin (CUR) and caffeine (CFN) combination that acts as a potential system for the treatment of psoriasis.. NS composed of dimethyl carbonate (DMC) as crosslinker and beta-cyclodextrin (β-CD) as polymer were prepared by hot melt method and incorporated in topical gels. Factorial design (3. The physical and chemical characteristics exhibited by the prepared NS and gels (F1-F9) were found to be optimal. The optimization resulted in achieving formulation N10 with 69.72% in vitro drug release and 12,329.78cp viscosity. Histopathology studies revealed that prepared nanogel has promising anti-psoriatic activity. The results concluded that CUR and CFN combination has reduced the time required for showing anti-psoriatic activity to 10 days when compared to CUR alone that took around 20 days. Moreover, the nanogel has depicted sustained drug release till 12 h.. From the experimental findings it has been concluded that CUR and CFN combination significantly augmented the anti-psoriatic efficacy with respect to individual components and also reduced the time required for onset of effect. Thus, the proposed nanogel would be an imperative drug delivery system for more effective anti-psoriatic therapy. Graphical abstract.

Topics: Administration, Topical; Animals; beta-Cyclodextrins; Caffeine; Curcumin; Delayed-Action Preparations; Disease Models, Animal; Drug Combinations; Drug Compounding; Female; Formates; Imiquimod; Male; Mice; Nanostructures; Particle Size; Psoriasis

Psoriasis is a chronic inflammatory skin disease characterized by altered proliferation and differentiation of keratinocytes as well as infiltration of immune cells. Increased expression of Th17 cells and cytokines secreted by them provides evidence for its central role in the pathogenesis of psoriasis. IL-17A, signature cytokine of Th17 cells was found to be highly differentially expressed in psoriatic lesional skin. However, cellular and molecular mechanism by which IL-17A exerts its function on keratinocyte is incompletely understood. To understand IL-17A mediated signal transduction pathways, gene expression profiling was done and differentially expressed genes were analysed by IPA software. Here, we demonstrate that during IL-17A signaling total cholesterol levels were elevated, which in turn resulted in the suppression of genes of cholesterol and fatty acid biosynthesis. We found that accumulation of cholesterol was essential for IL-17A signaling as reduced total cholesterol levels by methyl β cyclodextrin (MBCD), significantly decreased IL-17A induced secretion of CCL20, IL-8 and S100A7 from the keratinocytes. To our knowledge this study for the first time unveils that high level of intracellular cholesterol plays a crucial role in IL-17A signaling in keratinocytes and may explain the strong association between psoriasis and dyslipidemia.

Topics: Adolescent; Adult; Aged; beta-Cyclodextrins; Cell Differentiation; Cell Proliferation; Chemokine CCL20; Child; Cholesterol; Dyslipidemias; Fatty Acids; Female; Gene Expression Profiling; Gene Expression Regulation; Humans; Interleukin-17; Interleukin-8; Keratinocytes; Male; Middle Aged; Psoriasis; S100 Calcium Binding Protein A7; S100 Proteins; Signal Transduction