去氢骆驼蓬碱脂质体制备工艺优化及抗肝癌活性

Optimization of the Preparation Process of Harmine Liposomes and Their Anti-hepatocarcinoma Activity

关键词:  去氢骆驼蓬碱  脂质体  制备工艺  抗肝癌活性

Key words:  harmine  liposome  preparation process  anti-hepatocarcinoma activity

摘要:

目的 制备去氢骆驼蓬碱脂质体并对其制备工艺进行优化，评价脂质体的相关表征及对肝癌细胞的毒性。方法 用薄膜水化法制备去氢骆驼蓬碱脂质体。以包封率作为评价指标，以大豆卵磷脂和药物的质量比、大豆卵磷脂与胆固醇的质量比和超声时间作为评价因素对脂质体包封率的影响。并对脂质体的粒径、Zeta电位、外观和稳定性进行评价。CCK-8法对比去氢骆驼蓬碱和去氢骆驼蓬碱脂质体的抗肝癌细胞增殖活性。结果 最优制备工艺：大豆卵磷脂和药物的质量比为11.4：1，大豆卵磷脂与胆固醇的质量比为4.4：1，超声时间为33 min。在此条件下制备的脂质体的包封率为81.88%，粒径为143.65 nm，Zeta电位为-12.68 mV，低温环境稳定性良好，具有缓释效应。去氢骆驼蓬碱脂质体的抗肝癌细胞增殖活性大于裸药。结论 所制得的去氢骆驼蓬碱脂质体包封率和稳定性均符合标准。将去氢骆驼蓬碱制备成为脂质体能提高其抗肝癌细胞增殖活性。

Abstract:

OBJECTIVE To prepare harmine liposomes and optimize their preparation process, and to evaluate the characteristics of liposomes and their toxicity to liver cancer cells. METHODS The harmine liposomes were prepared by membrane hydration method. Taking the encapsulation rate as the evaluation index, the influence of the mass ratio of soybean lecithin to drug, the mass ratio of soybean lecithin to cholesterol and the ultrasound time as evaluation factors on the encapsulation rate of liposomes was studied. The particle size, Zeta potential, appearance and stability of liposomes were evaluated. The CCK-8 method was used to compare the anti-proliferative activity of harmine and harmine liposomes on liver cancer cells. RESULTS The optimal preparation process was as follows:the mass ratio of soybean lecithin to drug was 11.4:1, the mass ratio of soybean lecithin to cholesterol was 4.4:1, and the ultrasound time was 33 min. The encapsulation efficiency of liposomes prepared under these conditions was about 81.88%, the particle size was 143.65 nm, the Zeta potential was -12.68 mV, which stability was good in low temperature environment with slow release effect. The anti proliferative activity of harmine liposomes on liver cancer cells was greater than that of naked drugs. CONCLUSION The encapsulation rate and stability of the prepared harmine liposomes meet the standard. The preparation of harmine as a liposome can improve the its proliferative activity on liver cancer cells.