目的 制備α-常春藤皂苷（α-Hed）聚合物膠束（α-Hed-PMs），并評價其對HepG2細胞的抑制效果。方法 以Pluronic F127和TPGS作為載體材料，采用溶劑蒸發(fā)-薄膜水化分散法將α-Hed制備成α-Hed-PMs，通過對粒徑分布、Zeta電位和包封率進行綜合評估確定α-Hed-PMs的處方組成；測定α-Hed-PMs的臨界膠束濃度；在透射電鏡下觀察α-Hed-PMs的微觀形貌；通過差示掃描量熱法（DSC）判斷α-Hed在膠束中的存在狀態(tài)；考察α-Hed-PMs在pH 5.0、6.0、7.4緩沖液中的稀釋穩(wěn)定性及釋藥速率；比較α-Hed原料藥和α-Hed-PMs （4、8、16、32、64 μg·mL^-1）對HepG2細胞的體外抑制作用；制備HepG2細胞荷瘤小鼠，考察股靜脈注射0.9%氯化鈉溶液（對照組）、α-Hed和α-Hed-PMs （給藥劑量均為30 mg·kg^-1）對腫瘤體積的影響。結(jié)果 α-Hed-PMs的最優(yōu)處方組成： Pluronic F127和TPGS質(zhì)量比為6∶ 1，所形成的聚合物膠束臨界膠束濃度為0.031 mg·mL^-1；在透射電鏡下可觀察到α-Hed-PMs呈類球形分布；DSC測定結(jié)果顯示α-Hed在膠束中以非結(jié)晶形式存在；α-Hed-PMs經(jīng)pH 5.0、6.0、7.4緩沖液稀釋后，在24 h內(nèi)均未出現(xiàn)絮凝或沉淀，粒徑也基本未發(fā)生改變； α-Hed原料藥4 h基本釋放完全，α-Hed-PMs在不同pH值緩沖液中均為前期藥物釋放較快，后期藥物釋放平緩，在50 h基本釋放完全；體內(nèi)外實驗結(jié)果顯示α-Hed-PMs對HepG2細胞的抑制作用均優(yōu)于α-Hed原料藥。結(jié)論 以Pluronic F127和TPGS作為載體材料將α-Hed制備成α-Hed-PMs，可達到更好的抗腫瘤效果。

Objective To prepare α-hederin-loaded polymer micelles (α-Hed-PMs) and evaluate its inhibition effect on HepG2 cells. Methods The α -Hed-PMs were prepared by solvent evaporation-thin film hydration dispersion method using Pluronic F127 and TPGS as carrier materials. The formulation composition of α-Hed-PMs was determined by comprehensive evaluation of particle size distribution, Zeta potential and encapsulation efficiency. The critical micelle concentration of polymer micelles was determined. The microstructure of α-Hed-PMs was observed under transmission electron microscope. The presence status of α-Hed in micelles was determined by DSC. The stability and drug release rate of α-Hed-PMs in medium solution with different pH values (5.0, 6.0 and 7.4) were investigated. The inhibition effect of α-Hed and α-Hed-PMs (4, 8, 16, 32, and 64 μg·mL^-1) were compared in vitro and in vivo. HepG2 tumor bearing mice were prepared, and the effects of 0.9% sodium chloride solution (control group), α-Hed and α-Hed-PMs (dose of 30 mg·kg^-1) on tumor volume were investigated. Results The optimal composition of α-Hed-PMs was as follows: the mass ratio of Pluronic F127 to TPGS was 6∶1. The critical micelle concentration was 0.031 mg·mL^-1. The spherical distribution of α-HedPMs could be observed under transmission electron microscope. The results of DSC showed that α-Hed existed in amorphous form in micelles. After dilution with pH 5.0, 6.0, and 7.4 buffer solutions, α-Hed PMs showed no flocculation or precipitation within 24 hours, and their particle size remained largely unchanged. The α -Hed raw material was basically completely released within four hours, the drug release rate of α-Hed-PMs in different pH values was faster in the early stage and gentle in the late stage, with almost complete release after 50 hours. The results of in vivo and in vitro showed that α-Hed-PMs had better inhibitory effect on HepG2 cells than α-hederin. Conclusion In this study, α-Hed was prepared into polymer micelles using Pluronic F127 and TPGS as carrier materials, which could achieve better anti-tumor effect.

R943