羧甲基壳聚糖包衣尼莫地平纳米脂质体的制备及其在小鼠体内的组织分布

Studies on the preparation of carboxymethyl chitosan-coated nimodipine nanoliposomes and their tissue distribution in mice

目的:制备羧甲基壳聚糖(CMC)包衣尼莫地平(NMD)纳米脂质体,并考察其在小鼠体内的组织分布。方法:采用薄膜分散法制备NMD脂质体,用CMC包衣后经高压均质机乳匀,得到CMC包衣NMD纳米脂质体。测定其包封率,Zeta电位,粒径大小及分布。对小鼠尾静脉注射普通NMD脂质体,CMC包衣脂质体(未乳匀),纳米脂质体(未包衣),CMC包衣纳米脂质体,于预定时间测定血浆及心,肝,脾,肺,肾,脑组织中的血药浓度,计算相关靶向参数。结果:包衣纳米脂质体的包封率为(71.2±4.8)%,Zeta电位为(-11.4±1.6)mV,平均粒径为(95.4±7.2)nm(n=3),与市售NMD注射液相比,脑组织中的TI,RTE分别为310.7%,58.25%。结论:本实验制备的CMC包衣NMD纳米脂质体包封率高,粒径达纳米级,并具有较好的脑靶向性。

OBJECTIVE To prepare carboxymethyl chitosan （CMC）-coated nimodipine（NMD） nanoliposomes and study their tissue distribution in mice. METHODS NMD liposomes were prepared by the film dispersion method. CMC were used to coat the liposomes followed by extruded through high pressure homogenizer to get CMC-coated NMD nanoliposomes. The encapsulation efficiency, zeta potential , average size and size distribution were determined. Marketed NMD injection, common NMD liposomes, non-extruded CMC-eoated NMD liposomes, non-coated NMD nanoliposomes and CMC-coated NMD nanoliposomes was injected in mice through tail vein, respectively. At predetermined times, NMD concentration was detected in mice tissues ,including plasma ,heart, liver, spleen, lung, kidney and brain. RESULTS The encapsulation efficiency of the nanoliposomes was （71.2 ± 4. 8）% , while the zeta potencial and average size was （ - 11.4 ± 1.6） mV and （95.4 ± 7. 2） nm, respectively （n = 3） . Compared with the marketed NMD injection, TI and RTE for brain of CMC-coated NMD nanoliposomes was 310. 7% and 58. 25%, respectively. CONCLUSION The CMC-coated NMD nanoliposomes had promising encapsulation efficiency , nanometeric sizes and targeting tendency for brain in vivo.