Development and in vitro/in vivo evaluation of HPMC/chitosan gel containing simvastatin loaded self-assembled nanomicelles as a potent wound healing agent

Abstract

The aim of this study was to develop hydroxypropyl methyl cellulose (HPMC)/chitosan gel containing polymeric micelles loaded with simvastatin (Sim) and evaluates its wound healing properties in rats. An irregular full factorial design was employed to evaluate the effects of various formulation variables including polymer/drug ratio, hydration temperature, hydration time, and organic solvent type on the physicochemical characteristics of pluronic F127-cholesterol nanomicelles prepared using the film hydration method. Among single studied factors, solvent type had the most impact on the amount of drug loading and zeta potential. Particle size and release efficiency was more affected by hydration temperature. The optimized formulation suggested by desirability of 93.5 was prepared using 1 mg of Sim, 10 mg of copolymer, dichloromethane as the organic solvent, hydration time of 45 min and hydration temperature of 25 degrees C. The release of the drug from nanomicelles was found to be biphasic and showed a rapid release in the first stage followed by a sustained release for 96 h. The gel-contained nanomicelles exhibited pseudo-plastic flow and more sustained drug release profile compared to nanomicelles. In excision wound model on normal rats, the wound closure of the group treated by Sim loaded micelles-gel was superior to other groups. Taken together, Sim loaded micelles-gel may represent a novel topical formulation for wound healing.