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目的:运用改良的硫酸铵梯度法制备叶酸受体靶向伊马替尼pH敏感脂质体(FSLI),并评价其质量。方法:采用改良的硫酸铵梯度法制备FSLI,以包封率为指标进行制备工艺的优化;采用琼脂糖凝胶CL-4B柱分离脂质体和游离药,HPLC法测定FSLI的包封率;运用Zeta PALS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FSLI在不同pH环境中的药物释放情况,并考察FSLI在不同pH、37℃水浴中的粒径随时间的变化情况。结果:制得的FSLI为圆形或类圆形的大单室脂质体,平均粒径为(155.2±1.92)nm,Zeta电位为-(29.36±3.21)mV,平均包封率为(90.7±1.70)%。FSLI在pH 7.4的中性环境中药物释放缓慢24 h累积释放度为2.76%而在pH 5.5的酸性环境中药物释放显著加快24 h累计释放度均达到93.2%表现出非常强的pH敏感性能。FSLI在pH 7.4的中性环境中不具有融合性能而在pH 5.5的酸性环境中粒径迅速增大脂质体发生融合。结论:采用改良硫酸铵梯度法制备的FSLI,能获得较高的包封率,并具有良好的pH敏感性能。
OBJECTIVE: To prepare folic acid receptor targeted imatinib pH-sensitive liposomes (FSLI) using a modified ammonium sulfate gradient method and to evaluate its quality. Methods: FSLI was prepared by a modified ammonium sulfate gradient method. The encapsulation efficiency was used as an index to optimize the preparation process. The liposomes and free drugs were separated by CL-4B column and the encapsulation efficiency of FSLI was determined by HPLC. Zeta PALS particle size analyzer was used to determine the average size and Zeta potential of liposomes. The morphology of liposomes was observed by transmission electron microscopy. The release of FSLI in different pH environments was investigated by dynamic dialysis. pH, 37 ° C water bath particle size changes over time. Results: The obtained FSLIs were round or round-shaped macromolecular liposomes with an average particle size of (155.2 ± 1.92) nm and a Zeta potential of - (29.36 ± 3.21) mV with an average entrapment efficiency of (90.7 ± 1.70)%. The release of FSLI was slow at 24 h in a neutral pH 7.4 environment and reached a cumulative release of 2.76% at 24 h. However, the release of FSLI was significantly faster at pH 5.5 at 93.2% with 24 h cumulative release showing very strong pH-sensitive properties. FSLI does not have a fusogenic property in a neutral pH of pH 7.4 and the liposome rapidly increases in size in an acidic pH 5.5 environment. Conclusion: FSLI prepared by modified ammonium sulfate gradient method can obtain higher entrapment efficiency and has good pH sensitivity.