【作者】 陈雅娉； 卢懿； 陈建明； 何伟； 胡富强； 吴伟；

【Author】 Yaping Chen1, Yi Lu1, Jianming Chen2, Wei He1, Fuqiang Hu3, WeiWu1 (1. School of Pharmacy, Fudan University, Shanghai 201203; 2. School of Pharmacy, Second Military Medical University, Shanghai 200433; 3.School of Pharmacy, Zhejiang University, Hangzhou 310058)

【机构】 复旦大学药学院； 第二军医大学药学院； 浙江大学药学院；

【摘要】 目的制备载难溶性药物非诺贝特传递体,考察其提高非诺贝特的口服生物利用度。方法以大豆磷脂和脱氧胆酸钠为材料,采用改良的薄膜分散法制备非诺贝特传递体口服给药系统。考察了传递体的粒径、包封率及其影响因素,作为优化处方和工艺的依据。考察了传递体的脂质膜流动性及其微观结构。以微粉化胶囊和脂质体作为对照,考察了传递体中非诺贝特的体外释放和体内生物利用度。结果传递体粒径的影响因素主要有脱氧胆酸钠/大豆磷脂、非诺贝特/大豆磷脂、均质参数和pH。包封率影响因素主要有脱氧胆酸钠/大豆磷脂和pH。传递体微观结构为近球形形态,且非诺贝特对传递体的膜结构没有明显影响。非诺贝特传递体的膜流动性主要受脱氧胆酸钠/大豆磷脂比的影响,脱氧胆酸钠/大豆磷脂比越大,传递体的膜流动性越大,变形性越好。非诺贝特传递体的体外释放性质考察结果表明,非诺贝特从传递体中释放速率与从脂质体中释放速率相近,2h的释放百分率仅为20%,而相同时间内非诺贝特从微粉化胶囊中溶出大于90%。非诺贝特口服后体内生物利用度结果表明,非诺贝特传递体和脂质体的生物利用度分别是微粉化胶囊的5.17和3.28倍,结论传递体使非诺贝特在犬体内生物利用度明显提高,且脱氧胆酸钠起到了一定的作用。更多还原

【Abstract】 OBJECTIVE The main purpose of this study was to evaluate oral bioavailability of the poorly water-soluble drug fenofibrate when transfersomes were used as oral drug delivery systems. METHODS Transfersomes were prepared by a dry-film dispersing method coupled with sonication and homogenization with soybean phosphotidylcholine (SPC) and sodium deoxycholate (SDC) as carrier materials. Several properties of the transfersomes, including particle size, entrapment efficiency and membrane fluidity, were extensively characterized. RESULTS In vitro release experiments indicated that no more than 20% of total fenofibrate was released from SPC/cholesterol (CL) and SPC/SDC liposomes at 2 h, in contrast with near complete release for micronized fenofibrate capsules. Strikingly, in vivo measurements of pharmacokinetics and bioavailability demonstrated higher rates of fenofibrate absorption from both SPC/SDC and SPC/CL liposomes than micronized fenofibrate. The bioavailability of SPC/SDC and SPC/CL liposomes was 5.13-and 3.28-fold higher, respectively, than that of the micronized fenofibrate. The disparity between oral bioavailability and in vitro release for liposomes strongly suggests alternative absorption mechanisms rather than enhanced release. Importantly, SPC/SDC liposomes exhibited a 1.57-fold increase in bioavailability relative to SPC/CL liposomes. CONCLUSION Transfersomes may be used to enhance oral bioavailability of poorly water-soluble drugs.更多还原