叶酸修饰的pH响应型阿霉素脂质体的制备及理化性质评价

发布时间：2018-10-24 18:43

【摘要】：目的:制备叶酸修饰的pH响应型阿霉素脂质体(FRLD),并对其理化性质进行评价。方法:采用硫酸铵梯度法制备FRLD,以包封率为指标运用正交设计法进行制备工艺的优化;用CL-4B琼脂糖凝胶柱分离-高效液相色谱法测定FRLD的包封率;运用粒径电位分析仪测定脂质体的平均粒径及Zeta电位,透射电镜观察脂质体的形态;运用动态透析法考察FRLD在不同pH环境中的药物释放情况,并考察FRLD在不同pH环境(pH 7.4和5.5)37℃水浴中的粒径随时间的变化情况。结果:制得的FRLD为圆形或类圆形的大单室脂质体,平均粒径(153.8±2.62)nm,Zeta电位为(-24.62±2.28)mV,平均包封率为89.45%。FRLD在pH 7.4的中性环境中,药物释放缓慢,24 h累积释放5.5%,而在pH 5.5的酸性环境中,药物释放显著加快,24 h累计释放率均达到90.8%,表现出非常强的pH敏感性能。FRLD在pH 7.4的中性环境中粒径保持稳定,而在pH 5.5的酸性环境中,粒径随孵育时间显著增加,脂质体发生融合。结论:采用硫酸铵梯度法制备的FRLD,能获得较高的包封率,并具有良好的pH响应性能。
[Abstract]:Aim: to prepare folic acid modified pH responsive doxorubicin liposome (FRLD), and evaluate its physical and chemical properties. Methods: the preparation of FRLD, by ammonium sulfate gradient method was optimized by orthogonal design, and the encapsulation efficiency of FRLD was determined by CL-4B agarose gel column separation and HPLC. The average particle size and Zeta potential of liposomes were measured by particle size potential analyzer, the morphology of liposomes was observed by transmission electron microscope, and the drug release of FRLD in different pH environments was investigated by dynamic dialysis method. The variation of FRLD particle size with time in different pH environments (pH 7.4 and 5.5) at 37 鈩，

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