In Vitro Susceptibilities of Wild and Drug Resistant Leishmania donovani Amastigote Stages to Andrographolide Nanoparticle: Role of Vitamin E Derivative TPGS for Nanoparticle Efficacy

• DOI: 10.1371/journal.pone.0081492
• Publication Date: 2013-12-10T21:22:34Z
• Authors: Subhasish Mondal; Partha Roy; Suvadra Das; Asim Halder; Arup Mukherjee; Tanmoy Bera
• Keywords: Andrographolide; Miltefosine; Amastigote; Meglumine antimoniate

Visceral leishmaniasis (VL) is a chronic protozoan infection in humans associated with significant global morbidity and mortality. There an urgent need to develop drugs strategy that will improve therapeutic response for effective clinical treatment of drug resistant VL. To address this need, andrographolide (AG) nanoparticles were designed P-gp efflux inhibitor vitamin E TPGS (D-α-tocopheryl polyethyleneglycol 1000 succinate) sensitivity against Leishmania strains. AG loaded PLGA (50∶50) (AGnps) stabilized by prepared delivery into macrophage cells infested sensitive amastigotes parasites. Physico-chemical characterization AGnps photon correlation spectroscopy exhibited average particle size 179.6 nm, polydispersity index 0.245 zeta potential -37.6 mV. Atomic force microscopy transmission electron visualization revealed spherical smooth surfaces. displayed sustained release up 288 hours as well minimal aggregation loss even after three months study period. Antileishmanial activity from selectivity wild-type strain was found be AGnp about one-tenth the dosage free one-third without TPGS. Similar observations also case vitro generated field isolated strains Leishmania. Cytotoxicity significantly less than standard antileishmanial chemotherapeutics like amphotericin B, paromomycin or sodium stibogluconate. Macrophage uptake almost complete within one hour evident fluorescent studies. Thus, based on these observations, it can concluded low-selectivity improved nanomedicines