两性霉素B聚氰基丙烯酸正丁酯纳米粒的制备及小鼠体内分布研究

Preparation of amphotericin B-polybutylcyanoacrylate-loaded nanoparticles and its distribution in mice

目的:制备携载两性霉素的聚氰基丙烯酸正丁酯纳米粒(AmB-PBCA-NP),研究其对血脑屏障的透过能力。方法:孵化法制备AmB-PBCA-NP,以聚山梨酯-80进行表面修饰,建立高效液相色谱分析法,流动相选择乙腈-水(40:60)及4%乙酸,405 nm处检测。小鼠分3组,每组28只,分别注射AmB粉针剂、脂质体(AmB-L)及纳米制剂(AmB-PBCA-NP),通过检测小鼠脑组织等脏器中的药物浓度,评价其主动脑靶向作用。结果:AmB-PBCA-NP平均粒径94.38 nm,平均包封率为82%,载药量56.1%。给药后AmB粉针剂组小鼠脑内未能检测出药物,AmB-L组于3 h后测得微量浓度,而AmB-PBCA-NP组小鼠30 min即测得可观浓度,3 h后达133 ng/g。结论:聚山梨酯-80修饰的AmB-PBCA-NP具有主动脑靶向作用。

Objective： To prepare amphotericin B-polybutylcyanoacrylate-loaded nanoparticle （AmB-PBCA-NP） and to assess their ability to pass the blood-brain barrier. Methods.- AmB-PBCA-NP was prepared by incubation, with the surface modified by polysorbate 80. High-performance liquid chromatography （HPLC） method was established using acetonitrile and water （40 ： 60, 4% of acetic acid） as mobile phase; detection was done at 405 nm. Mice were divided into 3 groups： AmB- injected, AmB-lipid-injected, and AmB-PBCA-NP-injected group. Brain-targeting ability of AmB-PBCA-NP was then evaluated by determination of AmB concentrations in mice brain and other specimens. Results： The mean diameter of the prepared AmB- PBCA-NP was 94.38 nm; the mean entrapment efficiency of the particles was 82% ; and the drug loading rate was 56.10%. It was found that AmB alone failed to pass the blood-brain barrier; only very low level of AmB was detected in AmB-lipid group 3 h after injection; moderate concentration of Amb was detected 30 min after injection of AmB-PBCA-NP and the concentration peaked at 133 ng/g 3 h after injection. Conclusion： AmB-PBCA-NP modified by polysorbate 80 can pass the blood-brain barrier .