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[摘要]
目的 确定槐定碱热敏脂质体最佳处方及制备工艺。方法 比较pH梯度法、逆向蒸发法、pH梯度结合逆向法3种制备方法对槐定碱热敏脂质体包封率的影响;单因素考察药脂比、载药温度、载药时间对脂质体包封率的影响,并以热敏脂质体分别于37、43 ℃累积释药率为评价指标,采用Design-expert 8.05软件进行中心复合设计,建立各指标与因素之间的数学关系,通过效应面法优化处方工艺条件,通过验证性实验进行预测分析。结果 3种制备方法中pH梯度结合逆向法制备的槐定碱热敏脂质体包封率较高;载药温度为35 ℃、载药时间为1 h,药脂比小于1∶10时,脂质体的包封率达到75%以上;中心优化设计考察得最佳处方工艺条件:脂药比为17.80,DPPC/MSPC为9.50制得的脂质体在37 ℃时释药达到4.30%,43 ℃释药79.03%,包封率为(81.33±1.24)%,载药量为(3.95±0.76)%,平均粒径为136 nm。结论 以pH梯度结合逆向法制备槐定碱热敏脂质体包封率较高,热敏释药性质良好。
[Key word]
[Abstract]
Objective To optimize the formulation and preparation parameters of sophoridine thermosentitive liposomes. Methods The effects of three kinds of preparation methods, such as pH-gradients method, reverse evaporation technique, and pH-gradient method coupled with reverse evaporation technique on encapsulation efficiency (EE) were compared. The influences of sophoridine- DPPC ratio, temperature, and time on the entrapment efficiencies were investigated by single design. The cumulative release percents of sophoridine thermosensitive liposomes at 37 ℃ and 43 ℃ respectively were used as the influence factors, Design-expert 8.05 software was used to establish the mathematical relationship of parameters and factors, and response surface method was used to optimize formulation and process. The experimental results of the thermosensitive liposomes prepared under the optimal conditions were compared with the predicted value. Results The EE with pH-gradient method coupled with reverse evaporation technique was higher than those with other two methods. When the water bath temperature was 35 ℃, the time was 1 h, and the ratio of sophoridine- DPPC was less than 1∶10, the EE of thermosensitive liposomes was above 75%. The optimal conditions were as follows: the ratio of sophoridine-DPPC was 17.80 and the ratio of DPPC-MSPC was 9.50. In such conditions, the cumulative release percents of sophoridine thermosensitive liposomes at 37 ℃ and 43 ℃ were 4.30% and 79.03%, respectively, the EE was (81.33 ± 1.24)%, the drug loading was (3.95 ± 0.76)%, and the average particle size was 136 nm. Conclusion The sophoridine thermosensitive liposomes with high EE and good thermal drug release properties could be prepared by pH-gradient method coupled with reverse evaporation technique.
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[基金项目]
基金项目:江西省卫生厅项目(2011A138);江西省教育厅项目(GJJ12534)