洛莫司汀-碘海醇复方热敏脂质体的制备与体外释药性考察  

Preparation of compound lomustine-iohexol thermosensitive liposomes and the in vitro release characteristics

作　　者：杨硕晔[1] 王杏林[2] 杨志强[2] 

机构地区：[1]河南工业大学生物工程学院,郑州450001 [2]天津药物研究院,天津300193

出　　处：《中国新药杂志》2014年第3期338-343,共6页Chinese Journal of New Drugs

基　　金：国家973科技计划(2006CB933303)

摘　　要：目的:制备洛莫司汀-碘海醇复方热敏脂质体,并进行质量评价与体外释药性考察。方法:以逆向蒸发法制备洛莫司汀-碘海醇复方热敏脂质体,建立2种药物的体外释放含量测定方法,采用透析法考察热敏脂质体中洛莫司汀与碘海醇的体外释放行为。结果:复方热敏脂质体的粒径约为266.4 nm,Zeta电位约为-21.8 mV,相变温度为41℃,建立的HPLC分析方法快速有效,专属性强,回收率高,可用于热敏脂质体中2种药物的体外含量测定,碘海醇在41℃时的体外释放最优拟合为一级动力学模型,方程为ln(100-Q)=-1.066t-0.049 8(r=0.999 3),8 h累积释放达93.75%;洛莫司汀在41℃时的体外释放最优拟合为Weibull模型,方程为lg[-ln(100-Q)]=1.106 9lgt-0.097 6(r=0.992 3),4 h累积释放达95.03%。结论:采用该处方与工艺可成功制备洛莫司汀-碘海醇复方热敏型脂质体,其包封的2种药物均具有良好的温度控制释放特性。Objective： To prepare compound lomustine-iohexol thermosensetive liposomes, and evaluate the properties and in vitro release behaviors of two drugs enveloped. Methods： Compound lomustine-iohexol ther- mosensetive liposomes were prepared by reverse evaporation method, HPLC assays were developed for determination of lomustine and iohexol in vitro, and their release property was studied by dialysis method. Results： The mean di- ameter of thermosensitive liposomes was 266.4 nm, Zeta potential was -21.8 mV, and phase-transition tempera- ture was 41 ℃. The HPLC assays developed were specific, rapid and reliable, which could be used to determine lomustine and iohexol in vitro accurately. In vitro release tests showed that lomustine and iohexol were released more entirely at 41 ℃. The release profile of iohexol from liposomes at 41 ℃ fitted to first-order kinetics model with the equation of In （100-Q） = -1.066t-0.049 8 （r =0.9993）, whereas the release profile of lomustine from the liposomes at 41 ℃ fitted to Weibull model with the equation of lg[ - In （ 100 - Q） ] = 1. 106 91gt -0. 097 6 （r = 0. 992 3）. Conclusion： The formulation and preparation method can successfully prepare compound lomustine-io- hexol thermosensitive liposomes with good thermal sensitive release behaviors of both drugs.

关 键 词：洛莫司汀 碘海醇 热敏脂质体 相变温度 体外释放 

分 类 号：R943.41[医药卫生—药剂学] R979.11[医药卫生—药学]