宝藿苷Ⅰ混合胶束的制备、表征及其体外活性研究
Preparation of BaohuosideⅠ-loaded Mixed Micelles and Its Anti-tumor Activity
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摘要: 目的 制备宝藿苷Ⅰ混合胶束，并评价其体外活性。方法 采用薄膜水化法制备包载宝藿苷Ⅰ的聚乙二醇-15-羟基硬脂酸酯/泊洛沙姆188混合胶束(BSPM)，通过正交设计法优化BSPM的制备处方和工艺；对该混合胶束的粒径和形态进行表征，并评价其体外释放行为；通过细胞毒性和细胞摄取实验考察宝藿苷Ⅰ混合胶束的体外抗肿瘤活性。结果 所制备的BSPM呈球形，形态规则，粒径均一，平均粒径约为33.59 nm，包封率大于80%，BSPM释药缓慢，24 h药物体外释放率为82.56%。BSPM对人乳腺癌MDA-MB-231细胞的细胞毒性和细胞摄取率显著高于宝藿苷Ⅰ原料药。结论 BSPM粒径小，包封率高，可增加宝藿苷Ⅰ的细胞摄取，增强细胞毒性作用，是一种有效的且具有应用前景的抗肿瘤药物制剂。Abstract: OBJECTIVE Preparation of baohuosideⅠ-loaded mixed micelles and its anti-tumor activity. METHODS BaohuosideⅠ-loaded Solutol HS 15/Poloxamer 188 mixed micelles (BSPM) was prepared by thin-film hydration method and the preparation process of BSPM was optimized by orthogonal design. The formulation of BSPM was evaluated and the in vitro release behavior of BSPM was determined. Cell toxicity and uptake assays were employed to evaluate the anti-tumor activities. The targeting effect of BSPM was studied by fluorescence labeling. RESULTS The BSPM prepared showed spherical and regular shape， with an average particle size of 33.59 nm and its entrapment efficiency more than 80%. The 24 h-accumulated release ratio in vitro of BSPM was up to 82.56%. Cytotoxicity of BSPM on human breast cancer cell line MDA-MB-231 was significantly stronger than that of free baohuosideⅠ and the uptake rate was improved. CONCLUSION The BSPM which shows small particle size and high entrapment efficiency can enhance cell toxicity and uptake. It is an effective and promising formulation for anti-tumor drug.
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