title: Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis.
abstract: Visceral leishmaniasis (VL) is a fatal, vector-borne disease caused by the intracellular protozoa of the genusLeishmania. 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 ofLeishmania donovaniamastigotes and the number of infected macrophages ex vivo with an IC50of 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.
authors.affiliation: Parasite Immunology Laboratory, Department of Biotechnology, Jamia Hamdard, Hamdard University, New Delhi, India.
authors.forename: Muzamil Y
authors.initials: MY
authors.lastname: Want
authors.affiliation: Parasite Immunology Laboratory, Department of Biotechnology, Jamia Hamdard, Hamdard University, New Delhi, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Islammudin
authors.affiliation: Parasite Immunology Laboratory, Department of Biotechnology, Jamia Hamdard, Hamdard University, New Delhi, India.
authors.forename: Garima
authors.initials: G
authors.lastname: Chouhan
authors.affiliation: Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Taibah University, Medina, Saudi Arabia.
authors.forename: Hani A
authors.initials: HA
authors.lastname: Ozbak
authors.affiliation: Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Taibah University, Medina, Saudi Arabia.
authors.forename: Hassan A
authors.initials: HA
authors.lastname: Hemeg
authors.affiliation: Department of Chemistry, University of Kalyani, Kalyani, India.
authors.forename: Asoke P
authors.initials: AP
authors.lastname: Chattopadhyay
authors.affiliation: Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Taibah University, Medina, Saudi Arabia.
authors.forename: Farhat
authors.initials: F
authors.lastname: Afrin
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D000917:Antibody Formation / Q000187:drug effects; D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use; D037621:Artemisinins / Q000494:pharmacology / Q000627:therapeutic use*; D065546:Drug Liberation; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D007893:Leishmania donovani / Q000187:drug effects; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000276:immunology; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D009569:Nitric Oxide / Q000378:metabolism; D010316:Particle Size; D015203:Reproducibility of Results; D013154:Spleen / Q000187:drug effects; D055672:Static Electricity
chemical_list: D000890:Anti-Infective Agents; D000981:Antiprotozoal Agents; D037621:Artemisinins; D008081:Liposomes; D009569:Nitric Oxide; C031327:artemisinin
keywords: Box–Behnken; Leishmania; artemisinin; drug delivery; nanoliposomes; visceral leishmaniasis