依托泊苷长循环热敏前体脂质体的制备工艺研究

Preparedtion Technology of Etoposide Long-Circulating Thermo-Sensitive Proliposomes

目的:对依托泊苷(Etoposide,VP-16)长循环热敏前体脂质体的制备工艺进行研究,并对该制备工艺进行方法学及制剂质量考察。方法:应用薄膜分散法制成VP-16长循环热敏脂质体,进一步借助冷冻干燥技术进行依托泊苷长循环热敏前体脂质体的制备;采用zeta电势测定仪及HPLC等技术进行方法学考察,主要包括脂质体的包封率、粒径、载药量、电位、释放度、稳定性。结果:VP-16长循环热敏前体脂质体水合形成长循环热敏脂质体,粒径为(105.2±3.4)nm,Zeta电位为(-11.9±1.7)m V,包封率可达96.8%;该脂质体在相变温度42℃下药物释放达到96%以上。结论:VP-16长循环热敏前体脂质体的制备工艺稳定,脂质体载药量大,包封率高;药物含量及包封率的测定方法简单、快速而准确,因而,该研究可为VP-16开发成静脉注射用新制剂提供数据支持。

Objective： Study on the preparation technology of Etoposide（VP-16） long-circulating thermo-sensitive proliposomes and investigate its methodology. Methods： Film dispersion method was used to prepare VP-16 long-circulating thermo-sensitive liposomes which were further prepared as VP-16 long-circulating proliposomes by vacuum freeze-drying technique. The shape and size distribution of proliposomes were detected by transmission electron Zetasizer, and the content of VP-16 was determined by HPLC.The encapsulation efficiency（EE） and the release rate of liposome were computed as well. Results： The VP-16 long-circulating thermo-sensitive liposomes aquated as the Etoposide long-circulating proliposomes, the appearance of liposomes was whole round, distribution uniform, the mean particle size were（105.2±3.4） nm, and zeta potential were（-11.9±1.7） m V. The liposome 42 ℃ temperature under the drug release above 96%. Conclusion：The preparation technology of Etoposide long-circulating thermo-sensitive proliposomes was stable, drug loading and entrapping capacity of liposomes were well. The methods for determination of Etoposide content and entrapment efficiency were simple, rapid and accurate. These studies can provide bases for further developing VP-16 as thermo-sensitive liposomes intravenous injection.