两性霉素B长循环纳米粒的研究

 目的探讨两性霉素B(AmB)/聚乙二醇-聚谷氨酸苄(PEG-PBLG)纳米粒的体内分布,及其是否具有长循环特性。方法透析法制备AmB/PEG-PBLG纳米粒,测定其粒径,表面形态,临界聚集浓度,载药量和体内分布。结果PEG-PBLG纳米粒呈球形且分散性良好,临界聚集浓度远低于低分子表面活性剂,不同相对分子质量材料制备的载药纳米粒平均粒径分别为83.3,106.6和294.6nm,载药量为26.31%～32.46%。AmB/PEG-PBLG纳米粒在肾组织中的浓度远低于AmB注射液。粒径为83.3nmAmB/PEG-PBLG纳米粒药-时曲线下面积为AmB的2倍,半衰期为AmB的2.6倍,而粒径为294.6nm的载药纳米粒药-时曲线下面积小于AmB。结论AmB/PEG-PBLG纳米粒能减少AmB在肾脏中分布,且粒径小于100nm的纳米粒能有效延长在体内循环的时间。

Study on long-circulation nanoparticles loaded with amphotericin B

OBJECTIVE To investigate the biodistribution and long-circulation properties of the amphotericin B (AmB) loaded poly (ethylene glycol)-poly(γ-benzyle-L-glutamate) (PEG-PBLG) nanoparticles.METHODS AmB-loaded PEG-PBLG nanoparticles were prepared by dialysis method. The particle size, morphology, critical aggregation concentration, drug loading content and biodistribution were measured. RESULTS The nanoparticles were spherical and discrete. The critical aggregation concentration of the nanoparticles was much lower than that of low molecular weight of surfactants. Drug loading content was in the range of 26.31%～32.46 %. Particle size was 83.3,106.6 and 294.6 nm respectively when the nanoparticles were prepared with different molecular weight of PEG-PBLC. Compared to the AmB formulation with sodium deoxycholate, the AmB-loaded nanoparticles had lower level in kidney. The AUC and halflife of AmB/nanoparticles with 83.3 nm in diameter were 2 fold larger and 2.6 fold longer than those of AmB/sodium deoxycholate formulation. However, the AUC of AmB/ nanoparticles with 294.6 nm was the smaller one.CONCLUSION AmB-loaded nanoparticles reduce biodistribution in kidney and the nanoparticles with smaller size (87.3 nm) can prolong the circulation time in mice.