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. 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.

Conclusions

Overall, GA-SLNs showed better chemoprotective effect over GA solution, thus construed superior efficacy of the developed nanoformulation for the treatment of HCC.

中文翻译：

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灵芝酸固体脂质纳米颗粒对肝细胞癌治疗和管理的意义

目的

本工作描述了负载灵芝酸（GA）的固体脂质纳米颗粒（SLN）的系统开发，用于治疗肝细胞癌（HCC）。

方法

采用全因子设计优化通过热均质法制备的GA负载SLN，其中Capmul MCMC10和大豆卵磷脂用作固体脂质和表面活性剂，而泊洛沙姆188用作稳定剂。对GA-SLN进行了详细的体外和体内表征研究。

结果

优化的GA-SLNs的粒径为73 nm，包封率为66％，负载量为11.53％。通过微透析袋法进行的体外药物释放研究表明，在8小时内观察到70％以上的药物释放。通过MTT法对HepG2细胞系进行GA-SLNs的体外细胞毒性研究表明，GA-SLNs比GA溶液和空白SLNs具有相对更高的细胞毒性。暴露72 h后，GA-SLNs和GA溶液的IC ₅₀值分别为25.1μg/ mL和36.2μg/ mL。此外，在25°C / 75％RH下，在12周的存储时间内，SLN中所夹带的GA的粒径和数量没有显着差异。GA-SLNs在雄性Wistar大鼠体内的体内抗癌活性显示出明显的降低（P <0.001）肝结节的大小和氧化应激水平的变化呈剂量依赖性。

结论

总体而言，GA-SLN比GA溶液显示出更好的化学保护作用，因此可以解释开发的纳米制剂在治疗HCC中的优越功效。