title: Enhanced antimalarial activity of lumefantrine nanopowder prepared by wet-milling DYNO MILL technique.
abstract: Lumefantrine (LMF) is an antimalarial drug that exhibits poor oral bioavailability, owing to its poor aqueous solubility. To improve its antimalarial activity, nanopowder formulation using DYNO MILL was prepared. Combination of HPMC E3 (4%, w/v) and Tween 80 (2.5%, w/v) as dispersing agents, favored the production of smaller LMF particles with mean size of 0.251 μm. LMF nanopowder showed enhanced dissolution rate attributed to nanonization of LMF. The IC(50) value of nano-sized LMF was found to be 0.1 ng/mL, which was 175-times lower than the IC(50) value of unmilled LMF powder (17.5 ng/mL) and 42-times lower than the IC(50) value of chloroquine (4.2 ng/mL). The in vivo antimalarial activity demonstrated an enhanced antimalarial potential of LMF nanopowder against P. Yoelii nigeriensis compared to unmilled drug. Wet-milling using DYNO MILL offers a highly effective approach to produce stable drug nanopowders. Furthermore, LMF nanopowder makes the Coartem therapy more effective.
authors.affiliation: School of Pharmacy and Medical Sciences, Singhania University, Rajasthan, India.
authors.forename: Sachin
authors.initials: S
authors.lastname: Gahoi
authors.forename: Gaurav K
authors.initials: GK
authors.lastname: Jain
authors.forename: Renu
authors.initials: R
authors.lastname: Tripathi
authors.forename: Swaroop K
authors.initials: SK
authors.lastname: Pandey
authors.forename: Mohammed
authors.initials: M
authors.lastname: Anwar
authors.forename: Musarrat H
authors.initials: MH
authors.lastname: Warsi
authors.forename: Mayank
authors.initials: M
authors.lastname: Singhal
authors.forename: Roop K
authors.initials: RK
authors.lastname: Khar
authors.forename: Farhan J
authors.initials: FJ
authors.lastname: Ahmad
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004983:Ethanolamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005449:Fluorenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D021261:Parasitic Sensitivity Tests; D010316:Particle Size; D010963:Plasmodium falciparum / Q000187:drug effects*; D013499:Surface Properties; D017155:Wettability
chemical_list: D000962:Antimalarials; D004983:Ethanolamines; D005449:Fluorenes; D000078102:Lumefantrine