Ordóñez-Gutiérrez Lara, Espada-Fernández Raquel, Dea-Ayuela María Auxiliadora, Torrado Juan José, Bolás-Fernandez Francisco, Alunda José María
Department of Animal Health, Faculty of Veterinary Medicine, Avda. Puerta de Hierro s/n, Complutense University, Madrid 28040, Spain.
Int J Antimicrob Agents. 2007 Oct;30(4):325-9. doi: 10.1016/j.ijantimicag.2007.05.013. Epub 2007 Jul 13.
The in vitro antileishmanial activities of various new amphotericin B (AMB) formulations were investigated, including microspheres of hydrophilic albumin with three AMB aggregation forms (monomeric, dimeric and multiaggregate) and the polymers of polylactic-co-glycolic acid, Resomer RG502 and RG503 with the multiaggregate AMB form. This in vitro study was performed on the extracellular promastigote form and the intracellular amastigote form of a canine strain of Leishmania infantum (UCM 20) using the infected J774 murine macrophage-like cell line. Albumin-encapsulated forms did not show any toxicity for murine cells and had lower median effective concentration (EC50) values (ca. 0.003 microg/mL) for L. infantum amastigotes than free formulations (0.03 microg/mL). In addition, the aggregation state of AMB had a notable effect on the antileishmanial activity of the drug. Results obtained in vitro point towards interest in monomeric AMB encapsulated in microspheres in the chemotherapeutic control of leishmaniasis.
研究了各种新型两性霉素B（AMB）制剂的体外抗利什曼原虫活性，包括具有三种AMB聚集形式（单体、二聚体和多聚体）的亲水性白蛋白微球，以及具有多聚体AMB形式的聚乳酸-乙醇酸共聚物Resomer RG502和RG503。这项体外研究使用感染的J774鼠巨噬细胞样细胞系，对婴儿利什曼原虫（UCM 20）犬株的细胞外前鞭毛体形式和细胞内无鞭毛体形式进行。白蛋白包封形式对鼠细胞未显示任何毒性，对婴儿利什曼原虫无鞭毛体的半数有效浓度（EC50）值（约0.003微克/毫升）低于游离制剂（0.03微克/毫升）。此外，AMB的聚集状态对该药物的抗利什曼原虫活性有显著影响。体外获得的结果表明，微球包封的单体AMB在利什曼病的化疗控制中具有应用价值。
