十六酸拉米夫定酯固体脂质纳米粒的肝靶向研究

Characteristics of liver targeting Lamivudyl palmitate Solid Lipid Nanoparticles

目的 制备十六酸拉米夫定酯固体脂质纳米粒 (LAP -SLN)和半乳糖苷修饰的十六酸拉米夫定酯固体脂质纳米粒(LAP -GSLN) ,探讨并比较二者的肝靶向作用。方法 采用薄膜超声分散法制备LAP -SLN和LAP -GSLN ;透射电镜研究其形态、粒径及粒径分布 ;RP -HPLC测定载药量、包封率。小鼠尾静脉给药后 ,RP -HPLC测定拉米夫定 (Lamivudine ,LA)在血清及肝、肾、肺、脾中的浓度。结果 LAP -SLN和LAP -SLN的粒径分布分别为 2 80 .8± 98.2nm和 2 5 7.4± 92 .3nm ,载药量分别为 9.6 3%和 9.11% ,包封率分别为 97.6 9%和 95 .82 %。LA -sol,LAP -SLN和LAP -GSLN的靶向效率分别为 0 .89,1.2 6和 4 .6 6。结论 LAP -SLN和LAP -GSLN在体内具有良好的肝靶向性 ,对提高药物疗效 ,减少用量 ,降低毒副作用有一定意义。LAP -GSLN的靶向作用强于LAP -SLN。

Aim To prepare lamivudyl palmitate solid lipid nanoparticles(LAP-SLN) and the nanoparticles modified by a galactoside (LAP-GSLN) as well as to investigate and compare their liver targeting effect.Methods Galactoside (Galβ 1-(CH 2CH 2O) 3-C 12H 25) was synthesized. LAP-SLN and LAP-GSLN were prepared by thin layer ultrasonic technique.Transmission electron microscopy was employed to study the shape, mean size and particle distribution of LAP-SLN and LAP-GSLN.Drug loading and entrapment efficiency were also studied.The concentration of LA in serum and various organs were determined by RP-HPLC after iv administration of SLN.Results The diameter distribution of LAP-SLN and LAP-GSLN was 280.8±98.16nm and 257.4±92.3nm respectively; drug loading was 9.36 % and 9.11% respectively,and entrapment efficiency was 97.69% and 95.82% respectively.Targeting efficiency for LAP-GSLN,LAP-SLN and LA solution was 0.89,1.26 and 4.66 respectively.Conclusion Both LAP-SLN and LAP-GSLN showed a good liver-targeting efficiency in vivo,which may reduce the side effects of LA,decrease dose and improve its efficacy.LAP-GSLN has a stronger targeting effect than LAP-SLN.