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目的制备具有高包封率和良好稳定性的全缘千里光碱(INT)脂质体,并将其制成凝胶剂。方法以离心-超滤法测定脂质体的包封率。以包封率为主要指标筛选脂质体制备工艺、主要辅料磷脂与处方中磷脂-胆固醇比例;通过均匀设计法优选制备脂质体的工艺条件;考察药脂比包封率;通过pH梯度主动载药法提高脂质体的包封率;确定脂质体及其凝胶剂的处方工艺,并进行质量与稳定性评价。结果制备INT脂质体的最适方法为薄膜分散法,最适的磷脂为注射级大豆磷脂,处方中磷脂-胆固醇的最佳比例为4∶1;药脂比为1∶10时,薄膜分散法制备INT脂质体的最佳工艺参数为:成膜温度46.3℃,水化液用pH4.0柠檬酸缓冲液(CBS4.0),体积为15.0mL,包封率可达57.45%;药脂比由1∶20增加1∶2,包封率均在60%左右;pH梯度主动载药可显著提高脂质体的药物包封率,主动载药中较合适的水化液为CBS4.0。优选的脂质体包封率为75.21%,平均粒径为284nm,Zeta电位为2.23mV,稳定性实验证明,该脂质体及其凝胶剂稳定性良好。结论薄膜分散法结合pH梯度载药可以制备稳定且高包封率的INT脂质体凝胶剂。
Objective To prepare lipopolysaccharide (INT) liposomes with high encapsulation efficiency and good stability, and to make them into gels. Methods The entrapment efficiency of liposomes was determined by centrifugation and ultrafiltration. The entrapment efficiency was used as the main index to screen the preparation process of liposomes, the ratio of phospholipid to cholesterol in the prescription and the ratio of phospholipid to cholesterol in the prescription. The optimal preparation conditions of the liposomes were determined by uniform design method. Drug-loading method to improve the encapsulation efficiency of liposomes; liposomes and gel formulations to determine the prescription process, and quality and stability evaluation. Results The optimal method for preparation of INT liposomes was thin-film dispersion method. The optimal phospholipid was injection-grade soya lecithin. The optimum ratio of phospholipid-cholesterol in prescription was 4:1. When the lipid-lipid ratio was 1:10, The optimal preparation parameters of INT liposomes were as follows: the film formation temperature was 46.3 ℃, the pH was 4.0 for citric acid buffer solution (CBS4.0), the volume was 15.0mL, the entrapment efficiency was 57.45%. The lipid ratio increased from 1:20 to 1:2, and the entrapment efficiency was about 60%. Active loading with pH gradient significantly increased the drug encapsulation efficiency of liposomes. CBS4 was the most suitable hydration solution for active drug loading. 0. The optimal liposome entrapment efficiency was 75.21%, the average particle size was 284 nm, and the zeta potential was 2.23 mV. The stability experiments showed that the liposomes and their gels had good stability. Conclusion The method of film dispersion combined with pH gradient drug delivery can prepare INT liposome gel with high stability and encapsulation efficiency.