Implications of Solid Lipid Nanoparticles of Ganoderic Acid for the Treatment and Management of Hepatocellular Carcinoma

Abstract

The present work describes the systematic development of ganoderic acid (GA)–loaded solid lipid nanoparticles (SLNs) for the treatment of hepatocellular carcinoma (HCC). A full factorial design was employed for optimization of the GA-loaded SLNs prepared by hot-homogenization method, where Capmul MCMC10 and soy lecithin were used as solid lipid and surfactant, while poloxamer 188 was used as stabilizer. GA-SLNs were subjected to detailed in vitro and in vivo characterization studies. The optimized GA-SLNs exhibited particle size of 73 nm, entrapment efficiency of 66% and loading capacity of 11.53%. In vitro drug release study carried out by microdialysis bag method indicated more than 70% drug release was observed within the 8-h time period. In vitro cytotoxicity study of GA-SLNs performed on HepG2 cell line by MTT assay indicated that GA-SLNs exhibited comparatively higher cytotoxicity than GA solution and Blank SLNs. IC50 values of GA-SLNs and GA solution after 72 h exposure were found to be 25.1 μg/mL and 36.2 μg/mL, respectively. Moreover, particle size and amount of GA entrapped in SLNs exhibited nonsignificant difference over a 12-week storage period at 25 °C/75% RH. In vivo anticancer activity of GA-SLNs in male Wistar rats demonstrated significant reduction (P < 0.001) in the size of hepatic nodules and variation in the levels of oxidative stress in a dose-dependent manner. Overall, GA-SLNs showed better chemoprotective effect over GA solution, thus construed superior efficacy of the developed nanoformulation for the treatment of HCC.