甘草-淫羊藿活性成分配伍抗肝癌复方纳米胶束制备与评价

Preparation and Evaluation of Compound Anti-hepatocellular Carcinoma Nanomicelles Formulated with Licorice-Epimedium Active Ingredients

基于晚期肝细胞癌(HCC)高侵袭性和对常规化疗的固有耐药性,设计开发了共递送中药活性成分淫羊藿次苷Ⅱ(ICAⅡ)和甘草次酸(GA)的抗肝癌复方纳米胶束。通过单因素及正交实验设计进行处方和工艺优化,在mPEG-PCL-Phe(Boc)为载体材料、ICAⅡ与GA质量比4∶1、药辅质量比1∶9、水浴温度45℃、水化体积4 mL的最佳工艺条件下制备出复方胶束。该复方聚合物胶束具有典型的核-壳结构,粒径为(22.30±0.19)nm,PDI为0.29±0.01,Zeta电位为(-0.94±0.67)mV,胶体稳定性和生物相容性良好。在模拟正常生理条件(pH 7.4)下,可进行长达10 d的缓慢释放,符合一级动力学。与单药胶束相比,复方胶束能显著提高对人肝癌细胞的体外增殖抑制活性。显示甘草-淫羊藿活性成分复方配伍递送系统的抗肝癌潜力。

Based on the high invasiveness of advanced hepatocellular carcinoma(HCC)and its inherent resistance to conventional chemotherapy,an anti-hepatocellular carcinoma compound nanomicelle was designed and developed to co-deliver the active components of traditional Chinese medicine,icarisideⅡ(ICAⅡ)and glycyrrhetinic acid(GA).Formulation and process optimization were conducted through single-factor and orthogonal experimental designs,resulting in the preparation of complex micelles with mPEG-PCL-Phe(Boc)as the carrier material,an ICAⅡ-to-GA mass ratio of 4∶1,drug-accompanying mass ratio of 1∶9,and hydration volume of 4 mL at a water bath temperature of 45℃.The prepared micelles exhibited a typical core-shell structure,with a particle size of(22.30±0.19)nm,PDI of 0.29±0.01,and Zeta potential of(-0.94±0.67)mV,indicating good colloidal stability and biocompatibility.Under simulated physiological conditions(pH 7.4),they can release drugs slowly for up to 10 days,following first-order kinetics.Compared with single drug loaded micelles,the compound micelles significantly enhanced the in vitro proliferation inhibition activity against human liver cancer cells,demonstrating the anti-hepatocarcinoma potential of the licorice-epimedium active ingredient compound compatibility delivery system.