基于甲氧基聚乙二醇-胆固醇的新型胶束载体研究

Novel Micellar Delivery System Based on Methoxy Poly(ethylene glycol)-Cholesterol

目的合成新型载体材料甲氧基聚乙二醇-胆固醇,并对其胶束成型工艺和毒性进行系统研究,为其作为药物载体提供参考。方法丁二酰化胆固醇与聚乙二醇单甲醚通过酯键偶联,合成甲氧基聚乙二醇-胆固醇;通过共溶剂蒸发法、乳化溶剂蒸发法和薄膜分散法将甲氧基聚乙二醇-胆固醇制备成胶束;并采用MCF-7、MDA-MB-231、4T1、SKOV-3和AD293细胞对胶束的毒性进行系统评价。结果两步反应即可制得甲氧基聚乙二醇-胆固醇,产率高达70.3%。3种方法均可成功制得甲氧基聚乙二醇-胆固醇胶束,粒径为20～150 nm。甲氧基聚乙二醇-胆固醇材料本身与其胶束浓度低于20μmol·L-1没有显著毒性;制备成胶束后对SKOV-3及MCF-7的IC50值明显降低。结论甲氧基聚乙二醇-胆固醇合成工艺简单、成本低廉、易于放大生产,胶束成型工艺简单,毒性较低,可用于包载溶解特性不同的药物,是一种有广泛应用前景的胶束载体。

ObjectiveTo synthesize methoxy poly（ethylene glycol）-cholesterol（mPEG-Chol）, prepare mPEG-Chol micelles and investigate the in vitro cytotoxicity. Methods mPEG-Chol was achieved by conjugating cholesterol succinic ester（Chol-suc） with mPEG. mPEG-Chol micelles were constructed through different Methods including co-evaporation method, emulsion evaporation method and film dispersion method. The cytotoxicity of micelles was assessed systemically on different cell lines including MCF-7, MDA-MB-231, 4T1, SKOV-3 and AD293. Results mPEG-Chol was synthesized successfully with the yield of 70.3% and could form micelles via three different Methods. The size of mPEG-Chol micelles ranged from 20 to 150 nm. mPEG-Chol had no cell growth inhibition activity when set at the concentration of 20 μmol·L-1. The micelles showed different cytotoxicity compared with the mPEG-Chol molecular form. The IC50 values of micelles to SKOV-3 and MCF-7 were significantly lower than molecules. Conclusion The synthesis process of mPEG-Chol is simple, cost-effective and easy to scale up massively. Micelles with low toxicity could be fabricated easily. Therefore, mPEG-Chol would be one of potential biomaterials to encapsulate various drugs with different solubility.