Journal Article

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

Roy, Partha, Halder, Asim, Das, Suvadra, Bera, Tanmoy, Mondal, Subhasish, Mukherjee, Arup

2013

Overview

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

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Amastigotes / Amphotericin B / Animals / Atomic force microscopy / Biochemistry / Biological Transport - drug effects / Capsules / Chemotherapy / Chronic infection / Cytotoxicity / Diterpenes - chemistry / Diterpenes - metabolism / Diterpenes - pharmacology / Dosage / Drug delivery systems / Drug Interactions / Drug resistance / Drug Resistance - drug effects / Drug Stability / Drugs / Effectiveness / Efflux / Electron microscopy / Enzymes / Female / Fluorescence / Glycoproteins / Health aspects / Kinetics / Lactic Acid - chemistry / Leishmania / Leishmania donovani / Leishmania donovani - drug effects / Leishmania donovani - growth & development / Leishmaniasis / Load resistance / Localization / Macrophages / Male / Mice / Mice, Inbred BALB C / Microscopy / Morbidity / Nanoparticles / Nanoparticles - chemistry / Parasites / Parasitic diseases / Paromomycin / Particle Size / Pharmaceutical sciences / Photon correlation spectroscopy / Polydispersity / Polyethylene glycol / Polyethylene Glycols - pharmacology / Polyglycolic Acid - chemistry / Polylactide-co-glycolide / Polyvinyl alcohol / Proteins / Protozoa / Selectivity / Sodium / Sodium stibogluconate / Spectroscopy / Tocopherol / Toxicity / Transmission electron microscopy / Tropical diseases / Vector-borne diseases / Visceral leishmaniasis / Vitamin E / Vitamin E - analogs & derivatives / Vitamin E - pharmacology / Zeta potential