Development and Evaluation of Simvastatin Loaded Transfersomal Hydrogel for the Management of Atherosclerosis

Abstract

Simvastatin is mainly used for management of atherosclerosis, possess problems when administered orally like poor solubility (BCS class II) and low bioavailability (<5%). The current study aimed to design and developed simvastatin loaded transfersomes based transdermal hydrogel for the targeted delivery. The formulation was evaluated in Poloxamer-407 induced hyperlipidemia rat model for the management of atherosclerosis. Thin film hydration method was used for the preparation of simvastatin loaded transfersomes which was loaded into the carbopol 934 hydrogel. Simvastatin loaded transfersomes were evaluated through using particle size analysis, zeta potential, PDI, DSC, FTIR, XRD, in vitro drug release, ex vivo, skin irritation studies and in vivo studies. The transfersomes revealed uniform particle size of 128.7 nm, PDI 0.273 and zeta potential of -20.4 mV and EE of 83.1%. In vitro drug release showed sustained release of simvastatin. Ex vivo permeation studies showed maximum permeation through skin at pH 7.4. In vivo studies revealed remarkable decrease in elevated serum lipids compared to that of untreated and free simvastatin treated rat model. The poloxamer injection considerably elevated the levels of cholesterol in all groups during the first 24 hours. Similar was the case with vLDL, the level of HDL decreases sharply within first 24 hours after the poloxamer 407 injection. The normal group didn’t show any significant change in the levels of cholesterol, TG, HDL, and vLDL which proves the hyperlipidemic action of poloxamer 407. The transdermal administration of free simvastatin and simvastatin loaded transfersomal hydrogel decreased the level of hyperlipidemia that also decreased the atherogenic index in 72 hours study. Comparing the atherogenic index between the diseased control group, free simvastatin hydrogel treated group and simvastatin loaded transfersomal hydrogel treated-group, it is shown in results above that the atherogenic index was lowered in simvastatin loaded transfersomal hydrogel treated group of Poloxamer 407 induced hyperlipidemia. Increased cholesterol level and triglyceride level with decreased high density lipoproteins in serum may give rise to atherosclerotic plaque. Simvastatin loaded transfersomal hydrogel reduced the TG and TC levels significantly. LDL levels were significantly decreased by simvastatin loaded transfersomal hydrogel therefore results imply that simvastatin loaded transfersomal hydrogel provides advantage by decreasing lipid profile. So, simvastatin loaded transfersomes based transdermal hydrogel showed great potential for management of atherosclerosis.