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负载两性霉素B的聚乳酸-羟基乙酸共聚物纳米颗粒的活性及体内追踪

Activity and in vivo tracking of Amphotericin B loaded PLGA nanoparticles.

作者信息

Souza A C O, Nascimento A L, de Vasconcelos N M, Jerônimo M S, Siqueira I M, R-Santos L, Cintra D O S, Fuscaldi L L, Pires Júnior O R, Titze-de-Almeida R, Borin M F, Báo S N, Martins O P, Cardoso V N, Fernandes S O, Mortari M R, Tedesco A C, Amaral A C, Felipe M S S, Bocca A L

机构信息

Biology Institute, University of Brasília, DF, Brazil.

Faculty of Agronomy and Veterinary Medicine, University of Brasília, DF, Brazil.

出版信息

Eur J Med Chem. 2015 May 5;95:267-76. doi: 10.1016/j.ejmech.2015.03.022. Epub 2015 Mar 14.

Abstract

The development of biocompatible polymeric nanoparticles has become an important strategy for optimizing the therapeutic efficacy of many classical drugs, as it may expand their activities, reduce their toxicity, increase their bioactivity and improve biodistribution. In this study, nanoparticles of Amphotericin B entrapped within poly (lactic-co-glycolic) acid and incorporated with dimercaptosuccinic acid (NANO-D-AMB) as a target molecule were evaluated for their physic-chemical characteristics, pharmacokinetics, biocompatibility and antifungal activity. We found high plasma concentrations of Amphotericin B upon treatment with NANO-D-AMB and a high uptake of nanoparticles in the lungs, liver and spleen. NANO-D-AMB exhibited antifungal efficacy against Paracoccidioides brasiliensis and induced much lower cytotoxicity levels compared to D-AMB formulation in vivo and in vitro. Together, these results confirm that NANO-D-AMB improves Amphotericin B delivery and suggest this delivery system as a potential alternative to the use of Amphotericin B sodium deoxycholate.

摘要

生物相容性聚合物纳米颗粒的研发已成为优化许多传统药物治疗效果的重要策略,因为它可以扩大药物活性、降低毒性、提高生物活性并改善生物分布。在本研究中,评估了包裹在聚(乳酸-乙醇酸)共聚物中并结合二巯基琥珀酸(NANO-D-AMB)作为靶向分子的两性霉素B纳米颗粒的理化特性、药代动力学、生物相容性和抗真菌活性。我们发现用NANO-D-AMB治疗后,两性霉素B在血浆中的浓度很高,且纳米颗粒在肺、肝和脾中的摄取量也很高。与D-AMB制剂相比,NANO-D-AMB在体内和体外均表现出对巴西副球孢子菌的抗真菌功效,且诱导的细胞毒性水平低得多。总之,这些结果证实NANO-D-AMB改善了两性霉素B的递送,并表明该递送系统是使用两性霉素B脱氧胆酸钠的潜在替代方案。

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