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口服两性霉素 B 聚合物纳米粒在体内抗真菌活性方面可与静脉注射用两性霉素 B 脂质体或两性霉素 B 脂复合物相当或更优。

Peroral amphotericin B polymer nanoparticles lead to comparable or superior in vivo antifungal activity to that of intravenous Ambisome® or Fungizone™.

机构信息

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.

出版信息

PLoS One. 2011;6(10):e25744. doi: 10.1371/journal.pone.0025744. Epub 2011 Oct 6.

DOI:10.1371/journal.pone.0025744
PMID:21998690
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3188565/
Abstract

BACKGROUND

Despite advances in the treatment, the morbidity and mortality rate associated with invasive aspergillosis remains unacceptably high (70-90%) in immunocompromised patients. Amphotericin B (AMB), a polyene antibiotic with broad spectrum antifungal activity appears to be a choice of treatment but is available only as an intravenous formulation; development of an oral formulation would be beneficial as well as economical.

METHODOLOGY

Poly(lactide-co-glycolode) (PLGA) nanoparticles encapsulating AMB (AMB-NPs) were developed for oral administration. The AMB-NPs were 113 ± 20 nm in size with ~70% entrapment efficiency at 30% AMB w/w of polymer. The in vivo therapeutic efficacy of oral AMB-NPs was evaluated in neutropenic murine models of disseminated and invasive pulmonary aspergillosis. AMB-NPs exhibited comparable or superior efficacy to that of Ambisome® or Fungizone™ administered parenterally indicating potential of NPs as carrier for oral delivery.

CONCLUSIONS

The present investigation describes an efficient way of producing AMB-NPs with higher AMB pay-load and entrapment efficiency employing DMSO as solvent and ethanol as non-solvent. The developed oral formulation was highly efficacious in murine models of disseminated aspergillosis as well as an invasive pulmonary aspergillosis, which is refractory to treatment with IP Fungizone™ and responds only modestly to AmBisome®.

摘要

背景

尽管在治疗方面取得了进展，但侵袭性曲霉菌病在免疫功能低下患者中的发病率和死亡率仍然高得令人无法接受（70-90%）。两性霉素 B（AMB）是一种具有广谱抗真菌活性的多烯抗生素，似乎是一种治疗选择，但只能作为静脉制剂使用；开发口服制剂不仅具有经济性，而且具有良好的效果。

方法

开发了用于口服给药的聚（乳酸-共-乙醇酸）（PLGA）纳米粒包封 AMB（AMB-NPs）。AMB-NPs 的粒径为 113±20nm，在 30%AMB w/w 的聚合物时，包封效率约为 70%。在中性粒细胞减少症的播散性和侵袭性肺曲霉病的小鼠模型中评估了口服 AMB-NPs 的体内治疗效果。AMB-NPs 与静脉注射的 Ambisome®或 Fungizone™相比具有相当或更好的疗效，表明 NPs 作为口服给药载体的潜力。

结论

本研究描述了一种利用 DMSO 作为溶剂和乙醇作为非溶剂生产具有更高 AMB 载药量和包封效率的 AMB-NPs 的有效方法。开发的口服制剂在播散性曲霉病和侵袭性肺曲霉病的小鼠模型中具有高度疗效，对 IP Fungizone™治疗有抗性，对 AmBisome®的反应也只是适度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d440/3188565/03a770ee2f31/pone.0025744.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d440/3188565/f6b555d0344b/pone.0025744.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d440/3188565/3eee349b14cd/pone.0025744.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d440/3188565/75ea137f29f0/pone.0025744.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d440/3188565/1fed80d858d5/pone.0025744.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d440/3188565/baae1ba6bd36/pone.0025744.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d440/3188565/03a770ee2f31/pone.0025744.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d440/3188565/f6b555d0344b/pone.0025744.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d440/3188565/3eee349b14cd/pone.0025744.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d440/3188565/75ea137f29f0/pone.0025744.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d440/3188565/1fed80d858d5/pone.0025744.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d440/3188565/baae1ba6bd36/pone.0025744.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d440/3188565/03a770ee2f31/pone.0025744.g006.jpg

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