注射用亮菌甲素纳米结构脂质载体系统的制备、体外释药及体内药动学研究

 目的 制备注射用亮菌甲素纳米结构脂质载体系统（AML-NLC），并考察其理化性质、体外释放及体内药动学性质。方法 采用超声破碎法结合冷冻干燥工艺制备注射用亮菌甲素纳米结构脂质载体系统；考察脂质纳米粒形态、粒径分布、载药量及微渗析法测定包封率；以市售亮菌甲素注射液为对照，考察其体外释放特性及大鼠体内药动学行为。结果 注射用亮菌甲素脂质纳米粒的平均粒径为111 nm；包封率为（75.7±1.34）%，载药量为（0.04±0.01）%；在pH 5.6磷酸盐缓冲溶液中24 h 的累积释放百分率在90%以上，药物释放以Weibull分布模型拟合最好；亮菌甲素注射液与脂质纳米粒溶液在大鼠体内的消除半衰期分别为59.7和115.2 min，静注脂质纳米粒后AUC值是亮菌甲素注射液的151.1%。结论 采用超声破碎法-冷冻干燥工艺制备注射用亮菌甲素脂质纳米粒，包封率较高，粒径分布均匀；与注射液相比，脂质纳米粒的体内释药显著慢于注射液，具有缓释效果。

Preparation,In Vitro Release and Pharmacokinetics of Armillarisin A-Loaded Nanostructured Lipid Carriers for Intravenous Injection

OBJECTIVE To prepare armillarisin A-loaded nanostructured lipid carriers(AML-NLC) for intravenous injection and investigate its release characteristics in vitro and its pharmacokinetics in rats.METHODS Armillarisin A-loaded nanostructured lipid carriers for intravenous injection were prepared by emulsification-ultrasonication and lyophilization.The shapes and sizes of the lipid nanoparticles and the drug-loading capability were evaluated.Entrapment efficiency was determined by microdialysis method.The in vitro drug release behavior was investigated by dialysis method.The pharmacokinetics in rats were compared with those of armillarisin A injection.RESULTS The mean particle size,entrapment efficiency and drug-loading capability were 111 nm,(75.7±1.34)% and(0.04±0.01)%,respectively.The in vitro cumulative release rate in pH 5.6 phosphate buffer reached above 90% in 48 h.The in vitro drug release behavior was fitted well by Weibull equation.The elimination half lives of AML injection and AML-NLC after iv injection in rats were 59.7 and 115.2 min,respectively.And the absolute bioavailability of AMLS-NLC was 151.1%.CONCLUSION Armillarisin A lipid nanoparticles are prepared by emulsification-ultrasonication and lyophilization,which show high entrapment rate and even distribution.The lipid nanoparticles show sustained release in vitro compared with ordinary injection.