治疗肺纤维化的吡非尼酮pH敏感脂质体的制备和体外释放  

Preparation and in vitro Release of Pirfenidone-loaded pH-sensitive Liposomes for Treating Pulmonary Fibrosis

作　　者：韩美珊 朱效素 吕晓燕 刘沙 孙考祥[1] HAN Mei-shan;ZHU Xiao-su;LV Xiao-yan;LIU Sha;SUN Kao-xiang(School of Pharmacy,Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University),Ministry of Education,Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong,Yantai University,Yantai 264005,China)

机构地区：[1]烟台大学药学院,新型制剂与生物技术药物研究山东省高校协同创新中心、分子药理和药物评价教育部重点实验室,山东烟台264005

出　　处：《烟台大学学报（自然科学与工程版）》2021年第3期302-307,共6页Journal of Yantai University(Natural Science and Engineering Edition)

摘　　要：为了延长吡非尼酮口服给药半衰期,减少药物用量从而降低不良反应,同时响应肺纤维化的酸性微环境,设计将吡非尼酮包载在pH敏感脂质体中,考察脂质体的制备方法,根据包封率及粒径确定最佳工艺,并对制备的脂质体进行表征。采用硫酸铵梯度法制备的脂质体包封率为(88.25±1.85)%,平均粒径为109.0±3.4 nm。脂质体在pH为7.4的PBS中释放缓慢,24 h内可释放50%左右,而在pH为5.5的PBS中释放迅速,24 h内可释放80%左右。体外释放实验表明pH敏感脂质体能够响应于酸性微环境释放药物,以减少药物的不良反应,提高生物利用度和半衰期,为吡非尼酮的扩大应用奠定基础。To increase the half-life and bioavailability of pirfenidone and reduce adverse reactions,pirfenidone is encapsulated in pH-sensitive liposomes to give a targeted nano-delivery system tailored to the acidic microenvironment of pulmonary fibrosis.The preparation method for the pirfenidone-loaded pH-sensitive liposomes is developed using the encapsulation efficiency and particle size as indicators.In addition,the morphology,particle size,encapsulation efficiency,and in vitro release of the liposomes are evaluated using the optimized process.The encapsulation efficiency of the pH-sensitive liposomes using the ammonium sulfate gradient method is(88.25±1.85)% and the particle size is 109.0±3.4 nm.The liposomes exhibit rapid release in PBS at pH 5.5,and the drug release amount reaches 80% in 24 h.In contrast,in PBS at pH 7.4,only 50% of the drug is released within 24 h.The in vitro release experiment indicates that the pH-sensitive liposomes exhibit microenvironment targeting that may reduce adverse reactions and increase bioavailability,providing a foundation for expanding the application of pirfenidone.

关 键 词：吡非尼酮 肺纤维化 pH敏感脂质体 硫酸铵梯度法 

分 类 号：R944[医药卫生—药剂学]