title: Arthemeter-loaded lipid nanoparticles produced by modified thin-film hydration: Pharmacokinetics, toxicological and in vivo anti-malarial activity.
abstract: Artemether-loaded lipid nanoparticles (ARM-LNP) composed of 5% (w/v) lipid mass were produced by a modified thin-film hydration method using glyceryl trimyristate (solid lipid) and soybean oil (as liquid lipid in a concentration ranging from 0 to 45% (w/v) with respect to the total lipid mass). The particles were loaded with 10% of the anti-malarial ARM and surface-tailored with a combination of non-ionic, cationic or anionic surfactants. ARM-LNP were further characterized for their mean particle size, zeta potential and encapsulation efficiency, reporting optimized values below 120nm (PI<0.250), -38mV and 97% (w/w), respectively. ARM-LNP composed of 45% soybean oil depicted a spherical-like shape by transmission electron microscopy and a biphasic release profile in phosphate buffer. Haemolytic activity was within the acceptable range (7%) revealing low toxicity risk of LNP for parenteral delivery of ARM. Biocompatibility was confirmed by hepato- and nephrotoxicity analyses. Histopathological analysis showed no significant histological changes in liver and kidney tissues in adult Swiss Albino mice treated with the selected formulations. In vivo anti-malarial activity of ARM was enhanced when formulated as LNP, in comparison to a conventional plain drug solution and to a marketed formulation which are currently in use to treat malaria patients.
authors.affiliation: Department of Biochemistry, P.G Center, Kuvempu University, Karnataka, India.
authors.forename: N P
authors.initials: NP
authors.lastname: Aditya
authors.forename: S
authors.initials: S
authors.lastname: Patankar
authors.forename: B
authors.initials: B
authors.lastname: Madhusudhan
authors.forename: R S R
authors.initials: RS
authors.lastname: Murthy
authors.forename: E B
authors.initials: EB
authors.lastname: Souto
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use* / Q000633:toxicity; D000077549:Artemether; D037621:Artemisinins / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use* / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding; D008055:Lipids; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D053758:Nanoparticles; D010316:Particle Size; D010962:Plasmodium berghei / Q000187:drug effects; D013678:Technology, Pharmaceutical
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004337:Drug Carriers; D008055:Lipids; D000077549:Artemether