积雪草酸脂质纳米粒的微观结构及其对肠吸收动力学的影响  

Microstructure of asiatic acid lipid nanoparticles and its effect on intestinal absorption kinetics

作　　者：张雅雯[1] 尹丽娜[1] 梁泽华[2] 冯霞[1,2] 吴斌丽[1,2] 王俏[1] 朱亮[1,2] 王胜浩[1] 

机构地区：[1]浙江省医学科学院,杭州310013 [2]浙江中医药大学药学院,杭州310053

出　　处：《中国新药杂志》2014年第19期2284-2290,2297,共8页Chinese Journal of New Drugs

基　　金：浙江省科技厅项目(2011F10048);浙江省新世纪151人才工程(第二层次);浙江省卫生高层次创新人才培养工程(2008);浙江省医学重点学科群资助项目(XKQ-010-001)

摘　　要：目的:制备和表征积雪草酸(asiatic acid,AA)的脂质纳米粒AA-SLN和AA-NLC,考察微观结构及其对大鼠在体肠吸收动力学的影响。方法:以单硬脂酸甘油酯及油酸为脂质载体,采用溶剂扩散法制备AA-SLN和AA-NLC,从包封率、载药量、粒径、形态、晶型等方面进行表征,并运用大鼠在体单向灌流模型,考察AA及其纳米粒间的肠吸收差异。结果:制备的AA-SLN和AA-NLC粒径分别为(208±24)和(310±11)nm,包封率分别为(67.6±5.5)%和(77.9±4.8)%。纳米给药后,药物吸收剂量分数(f_a)和肠腔有效吸收系数(P_(eff))较原料明显提高(P<0.05);随着给药剂量的增加,f_a,P_(eff)和吸收速率常数(K_a)均有所下降;由于NLC与SLN微观结构存在差异,吸收百分率及参数均有差异。结论:纳米粒子对AA在大鼠小肠的吸收有促进作用,微观结构的差异影响小肠吸收。Objective： To prepare and characterize asiatic acid （AA） lipid nanoparticles （AA-SLN and AA-NLC） , and further investigate the difference in microstructures and the effect on intestinal absorption characteristics in rats. Methods： AA-SLN and AA-NLC were prepared by a solvent diffusion method. Monostearin and oleic acid were chosen as lipid carriers. The nanoparticles were characterized by entrapment efficiency, drug loading, particle size, morphology and polymorphs. In situ single pass perfusion mode was used to investigate the intestinal absorption differences between AA, AA-SLN and AA-NLC in rats. Results： The mean diameters of AA-SLN and AA-NLC were （208 ± 24） and （310 ±11 ） nm, respectively. The entrapment efficiencies of AA-SLN and AA-NLC were （67.6 ±5.5 ） % and （77.9 ±4.8） % , respectively. The rat small intestinal absorption of both AA-SLN and AA-NLC was better than that of AA solution, and the fraction absorbed （fo） and effective permeability （Peis） were improved significantly （P 〈 0.05）. Besides, fa, Peff and the absorption rate constant （K） were decreased with the increase of dosage. The difference in absorption percentage and parameters of SLN and NLC might be caused by microstructures. Conclusion： Both AA-SLN and AA-NLC can improve the absorption of AA in rat small intestine. Different microstructures may cause the difference in absorption.

关 键 词：积雪草酸 固体脂质纳米粒 纳米结构脂质载体 微观结构 肠吸收动力学 

分 类 号：R94[医药卫生—药剂学]