Formulation of lipid nanocarrier based drug delivery system of colchicine and its evaluation for antigout potential

Abstract

newline ABSTRACT newlineBackground: Colchicine is a plant alkaloid used in the treatment of gout. The drug is newlinevery potent but having high risk / benefit ratio which limits its therapeutic utilization. newlineObjectives: The aim of the present research work was to develop and optimize Solid newlineLipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs) based newlineTransdermal Patches of Colchicine and to evaluate their potential as transdermal newlinedelivery system for safe and effective management of gout. newlineMethodology: The Col-SLNs and Col-NLCs were formulated and optimized with newlinerespect to percentage of lipid and surfactant to get optimum particle size and newlineentrapment efficiency. The nanoparticles were characterized for their size, shape, zeta newlinepotential and entrapment efficiency. The transdermal potential of Col-SLNs and Col- newlineNLCs was evaluated by ex-vivo drug permeation using wistar rat skin and newlinefluorescence microscopy. The optimized stable formulations were fabricated into newlinetransdermal patches and in-vivo pharmacokinetic and pharmacodynamic study newline(subcutaneous air pouch model) was carried out. newlineResults: newlineThe Particle size, zeta potential and entrapment efficiency of the optimized newlineformulations of F5 (for SLNs) and F9 (for NLCs) were found to be 107 nm, (-) 17.4 newlinemV and 37.25% of SLNs and 90.4, -25.7mV and 46.17% for NLCs respectively. newlineFormulation F5 showed highest transdermal flux 8.76 µg/cm newline11.28µg/cm newline newline2 newline2 newline/hrs and F9 showed newline/hrs respectively. Fluorescence study confirms that Rh B SLNs and Rh B newlineNLCs have more penetration potential through the skin. AUC newline0and#8594;and#8734; newlineof Col-SLNs TP and newlineCol-NLCs TP patch was improved by 2.84 and 2.18 times more than colchicine newlinetransdermal patch. The in vivo pharmacodynamic antigout activity in rats has revealed newlinethe significant improvement in disease condition which is indicated by reduction in newline newlineexudates volume (66.5± 2.4 for Col-SLNs TP, 80.93 ± 3.86 for Col-NLCs TP Vs 3.12 newline± 1.5 for Colchicine TP) and Leukocyte count (48.86 ± 0.81 for Col-SLNs TP, 65.24 newline± 0.9 for Col-NLCs TP Vs