Development of Amphotericin B Loaded PLGA Nanoparticles for Effective Treatment of Visceral Leishmaniasis

摘要

Aim of present investigation was to develop novel nanoparticulate carrier of Amphotericin B (AmB) for effective treatment of visceral leishmaniasis. PLGA nanoparticles (PN Ps) were prepared with emulsion solvent evaporation method. Prepared nanoparticles were characterized for size, polydispersity index (PI), shape, morphology, surface charge, and drug release. In vitro antileishmanial potential of AmB loaded PNPs was assessed on GFP transfected parasite (promastigote model, Dd8 strain) and infected macrophages (amastigotes macrophages model) cell line (J774.A1 murine macropbage-like cell line) using FACS and geimsa staining method, respectively and results were compared with marketed liposomal formulation (AmBisome?). The developed PNPs were found to be of nanometric size (168 nm), having low polydispersity index (0.15) and good entrapment efficiency (53.0%). Transmission electron microscopy (TEM) showed that the PNPs were spherical in shape. The zeta potential of AmB loaded PNPs, surface was found to be -46.7 mV. PNPs showed biphasic release characterized by an initial burst followed by controlled release. In vitro antileishmanial activity against promastigote model showed about 85% inhibition and with insignificant difference amontgst plain drug, AmBisome~R and PNPs. The activity of AmB (1μM) as plain drug, AmBisome~R and PNPs against L. donovani in intraamstigote macropage model showed percent inhibition 71.77%, 83.03%, 84.06%, respectively. Accordingly, PNPs showed potential antileishmanial activity and is equivalent to marketed AmBisome?. Results suggest that developed novel nanoparticulate carrier could provide controlled, safe, effective and economical delivery of AmB for effective treatment of visceral leishmaniasis as an alternative to lipid based formulations.