Journal Article

Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis

Y. Want, Muzamil, Islamuddin, Mohammad, P. Chattopadhyay, Asoke, Chouhan, Garima, A. Ozbak, Hani, A. Hemeg, Hassan, Afrin, Farhat

2017

Overview

Visceral leishmaniasis (VL) is a fatal, vector-borne disease caused by the intracellular protozoa of the genus . Most of the therapeutics for VL are toxic, expensive, or ineffective. Sesquiterpenes are a new class of drugs with proven antimicrobial and antiviral activities. Artemisinin is a sesquiterpene lactone with potent antileishmanial activity, but with limited access to infected cells, being a highly lipophilic molecule. Association of artemisinin with liposome is a desirable strategy to circumvent the problem of poor accessibility, thereby improving its efficacy, as demonstrated in a murine model of experimental VL. Nanoliposomal artemisinin (NLA) was prepared by thin-film hydration method and optimized using Box-Behnken design with a mean particle diameter of 83±16 nm, polydispersity index of 0.2±0.03, zeta potential of -27.4±5.7 mV, and drug loading of 33.2%±2.1%. Morphological study of these nanoliposomes by microscopy showed a smooth and spherical surface. The mechanism of release of artemisinin from the liposomes followed the Higuchi model in vitro. NLA was free from concomitant signs of toxicity, both ex vivo in murine macrophages and in vivo in healthy BALB/c mice. NLA significantly denigrated the intracellular infection of amastigotes and the number of infected macrophages ex vivo with an IC of 6.0±1.4 µg/mL and 5.1±0.9 µg/mL, respectively. Following treatment in a murine model of VL, NLA demonstrated superior efficacy compared to artemisinin with a percentage inhibition of 82.4%±3.8% in the liver and 77.6%±5.5% in spleen at the highest dose of 20 mg/kg body weight with modulation of cell-mediated immunity towards protective Th1 type. This study is the first report on the use of a liposomal drug delivery system for artemisinin as a promising alternative intervention against VL.

• Publisher: Dove Medical Press Limited,Dove Press,Dove Medical Press
• Subject: Analysis / Animals / Anti-Infective Agents - pharmacology / Antibody Formation - drug effects / Antiprotozoal Agents - pharmacology / Antiprotozoal Agents - therapeutic use / Artemisinin / Artemisinins - pharmacology / Artemisinins - therapeutic use / Box-Behnken / Caprolactone / Complications and side effects / Dosage and administration / Drug delivery / Drug delivery systems / Drug Liberation / Drug therapy / Female / Health aspects / Immunity, Cellular - drug effects / Leishmania / Leishmania donovani - drug effects / Leishmaniasis, Visceral - drug therapy / Leishmaniasis, Visceral - immunology / Liposomes / Macrophages - drug effects / Macrophages - parasitology / Mice / Mice, Inbred BALB C / Nanoliposomes / Nanoparticles - chemistry / Nitric Oxide - metabolism / Original Research / Particle Size / Physiological aspects / Properties / Reproducibility of Results / Spleen - drug effects / Static Electricity / Visceral leishmaniasis