Abstract
Purpose The present work describes the systematic development of ganoderic acid (GA)-loaded solid lipid nanoparticles (SLNs) for the treatment of hepatocellular carcinoma (HCC). Methods 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. Results 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. IC(50)values of GA-SLNs and GA solution after 72 h exposure were found to be 25.1 mu g/mL and 36.2 mu g/mL, respectively. Moreover, particle size and amount of GA entrapped in SLNs exhibited nonsignificant difference over a 12-week storage period at 25 degrees 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. Conclusions Overall, GA-SLNs showed better chemoprotective effect over GA solution, thus construed superior efficacy of the developed nanoformulation for the treatment of HCC.