Enhanced antifungal effects of amphotericin B-TPGS-b-(PCL-ran-PGA) nanoparticles in vitro and in vivo.
Enhanced antifungal effects of amphotericin B-TPGS-b-(PCL-ran-PGA) nanoparticles in vitro and in vivo.
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DOI：
10.2147/ijn.s71623
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发表时间：
2014
影响因子：
8
通讯作者：
Liu F
中科院分区：
文献类型：
--
作者：
Tang X;Zhu H;Sun L;Hou W;Cai S;Zhang R;Liu F
两性霉素B(AMB)是一种具有广谱抗真菌活性的多烯类抗生素，但其临床毒性和较差的溶解性限制了AMB在临床上的广泛应用。近年来，新型载药纳米粒子--两嵌段共聚物D-succinate-b-poly(ε-caprolactone-ran-glycolide)-生育酚聚乙二醇1000α(PLGA-TPGS)因其毒性低、药效增强而受到特别关注。本研究旨在制备载AMB的PLGA-TPGS纳米粒(AMB-NPs)，并评价其体内外抗真菌作用。采用改进的纳米沉淀法制备了AMB-NPs，并对其进行了物理性质、体外释药、稳定性、包封率和毒性等方面的研究。最后，考察了AMB-NPs的体内外抗真菌活性。AMB-NPs为稳定球形，平均粒径约为110 nm，包封率接近85%，呈现典型的两相释放规律。AMB-NPs对白色念珠菌的实际最低抑菌浓度明显低于游离AMB，且AMB-NPs对血细胞毒性较小。体内实验表明，与游离的AMB相比，AMB-NPs具有更好的抗真菌效果和更长的抗真菌时间。AMB-PLGA-TPGS纳米粒系统通过提高AMB的抗真菌活性和降低其毒性，显著提高了AMB的生物利用度，有望成为抗真菌治疗的良好药物载体。
Amphotericin B (AMB) is a polyene antibiotic with broad spectrum antifungal activity, but its clinical toxicities and poor solubility limit the wide application of AMB in clinical practice. Recently, new drug-loaded nanoparticles (NPs) – diblock copolymer D-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) (PLGA-TPGS) – have received special attention for their reduced toxicity, and increased effectiveness of drug has also been reported. This study aimed to develop AMB-loaded PLGA-TPGS nanoparticles (AMB-NPs) and evaluate their antifungal effects in vitro and in vivo. AMB-NPs were prepared with a modified nanoprecipitation method and then characterized in terms of physical characteristics, in vitro drug release, stability, drug-encapsulation efficiency, and toxicity. Finally, the antifungal activity of AMB-NPs was investigated in vitro and in vivo. AMB-NPs were stable and spherical, with an average size of around 110 nm; the entrapment efficacy was closed to 85%, and their release exhibited a typically biphasic pattern. The actual minimum inhibitory concentration of AMB-NPs against Candida albicans was significantly lower than that of free AMB, and AMB-NPs were less toxic on blood cells. In vivo experiments indicated that AMB-NPs achieved significantly better and prolonged antifungal effects when compared with free AMB. The AMB-PLGA-TPGS NP system significantly improves the AMB bioavailability by improving its antifungal activities and reducing its toxicity, and thus, these NPs may become a good drug carrier for antifungal treatment.