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The anticoccidial drug monensin, a carboxylic ionophore, has been shown to have antimalarial properties. Here, we developed a liposome-based drug delivery of monensin and evaluated its antimalarial activity in lipid formulations of soya phosphatidylcholine (SPC) cholesterol (Chol) containing either stearylamine (SA) or phosphatidic acid (PA) and different densities of distearoyl phosphatidylethanolamine-methoxy-polyethylene glycol 2000 (DSPE-mPEG-2000). These formulations were found to be more effective than a comparable dose of free monensin in<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium falciparum<\/jats:named-content>(3D7) cultures and established mice models of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium berghei<\/jats:named-content>strains NK65 and ANKA. Parasite killing was determined by a radiolabeled [<jats:sup>3<\/jats:sup>H]hypoxanthine incorporation assay (<jats:italic>in vitro<\/jats:italic>) and microscopic counting of Giemsa-stained infected erythrocytes (<jats:italic>in vivo<\/jats:italic>). The enhancement of antimalarial activity was dependent on the liposomal lipid composition and preferential uptake by infected red blood cells (RBCs). The antiplasmodial activity of monensin in SA liposome (50% inhibitory concentration [IC<jats:sub>50<\/jats:sub>], 0.74 nM) and SPC:Chol-liposome with 5 mol% DSPE-mPEG 2000 (IC<jats:sub>50<\/jats:sub>, 0.39 nM) was superior to that of free monensin (IC<jats:sub>50<\/jats:sub>, 3.17 nM), without causing hemolysis of erythrocytes. Liposomes exhibited a spherical shape, with sizes ranging from 90 to 120 nm, as measured by dynamic light scattering and high-resolution electron microscopy. Monensin in long-circulating liposomes of stearylamine with 5 mol% DSPE-mPEG 2000 in combination with free artemisinin resulted in enhanced killing of parasites, prevented parasite recrudescence, and improved survival. This is the first report to demonstrate that monensin in PEGylated stearylamine (SA) liposome has therapeutic potential against malaria infections.<\/jats:p>","DOI":"10.1128\/aac.01796-15","type":"journal-article","created":{"date-parts":[[2015,12,15]],"date-time":"2015-12-15T04:43:50Z","timestamp":1450154630000},"page":"1304-1318","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":58,"title":["Stearylamine Liposomal Delivery of Monensin in Combination with Free Artemisinin Eliminates Blood Stages of Plasmodium falciparum in Culture and P. berghei Infection in Murine Malaria"],"prefix":"10.1128","volume":"60","author":[{"given":"Vinoth","family":"Rajendran","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Delhi South Campus, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shilpa","family":"Rohra","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Delhi South Campus, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohsin","family":"Raza","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Delhi South Campus, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gulam Mustafa","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Delhi South Campus, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suparna","family":"Dutt","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prahlad C.","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Delhi South Campus, New Delhi, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1128\/AAC.01304-09","article-title":"Decreased in vitro susceptibility of Plasmodium falciparum isolates to artesunate, mefloquine, chloroquine, and quinine in Cambodia from to 2007","volume":"54","author":"Lim P","year":"2001","unstructured":"Lim P, Wongsrichanalai C, Chim P, Khim N, Kim S, Chy S, Sem R, Nhem S, Yi P, Duong S, Bouth DM, Genton B, Beck HP, Gobert JG, Rogers WO, Coppee JY, Fandeur T, Mercereau-Puijalon O, Ringwald P, Le Bras J, Ariey F. 2001. 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