Topical hydrogel matrix loaded with Simvastatin microparticles for enhanced wound healing activity

Abstract

A prolonged release drug delivery system was developed by loading Simvastatin-chitosan microparticles into poly vinyl alcohol (PVA) hydrogels for enhanced wound healing efficiency. The microparticles prepared by ionic gelation method with varying composition of chitosan and surfactants (Tween 80/Pluronic F-127) were optimized for entrapment efficiency, morphology and drug-polymer interactions. Microparticles prepared with 0.3% between 80 and 0.5:5 chitosan: drug ratio showed maximum entrapment efficiency of 82% with spherical morphology and mild interaction between drug and chitosan. 5% PVA solutions loaded with pure drug and drug loaded microparticles at three different doses (2.5mg, 5mg and 10mg equivalent of drug) were chemically cross linked using gluteraldehyde and HCl. The formulated hydrogels were optimized for swelling, in vitro release behavior and in vivo wound healing effect. Hydrogels containing 2.5mg equivalent dose of Simvastatin microparticles exhibited maximum cumulative percentage drug release of 92% (n=3) at the end of 7days. The in vitro drug release data was supported by the higher swelling index of the low dose hydrogels. The in vivo wound healing study was performed using Wistar rats (n=30, 5 groups with 6 animals in each group) for the formulated hydrogels (at 3 doses) and compared with the untreated animals and the positive control group treated with conventional topical Simvastatin ointment (1%). The wound healing effect was comparable to the in vitro results, wherein the animals treated with low dose hydrogels (replaced every 7days) exhibited considerable reduction in the wound area compared to medium and high dose hydrogels. Statistically significant difference (P<0.05) was observed in the wound area of the animals treated with low dose hydrogels compared to 1% ointment and untreated animals, as estimated by two-way ANOVA. The histopathology images of the different groups of animals also displayed the comparative changes in the wound healing process. Hence, the incorporation of Simvastatin-chitosan microparticles in PVA hydrogels has demonstrated significant wound healing efficiency at optimum dose.