Arthemeter-loaded lipid nanoparticles produced by modified thin-film hydration: Pharmacokinetics, toxicological and in vivo anti-malarial activity

• Published in: European journal of pharmaceutical sciences Vol. 40; no. 5; pp. 448 - 455
• Main Authors: Aditya, N.P., Patankar, S., Madhusudhan, B., Murthy, R.S.R., Souto, E.B.
• Format: Journal Article
• Language: English
• Published: Kindlington Elsevier B.V 11-08-2010; Elsevier
• Subjects: Animals; Antimalarials - chemistry; Antimalarials - pharmacokinetics; Antimalarials - therapeutic use; Antimalarials - toxicity; Artemether; Artemisinins - chemistry; Artemisinins - pharmacokinetics; Artemisinins - therapeutic use; Artemisinins - toxicity; Biological and medical sciences; Drug Carriers - chemistry; Drug Compounding; General pharmacology; Hepatotoxicity; Lipid nanoparticles; Lipids; Malaria; Malaria - drug therapy; Malaria - parasitology; Medical sciences; Mice; Nanoparticles; Nephrotoxicity; Parasitemia; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Plasmodium berghei; Plasmodium berghei - drug effects; Technology, Pharmaceutical; Plasmodium berghei; Malaria; Artemether; Parasitemia; Hepatotoxicity; Nephrotoxicity; Lipid nanoparticles; Antimalarial; Protozoal disease; Nanoparticle; Toxicity; Liver; Lipids; Kidney; Thin film; Microparticle; Protozoa; Apicomplexa; Urinary system disease; Pharmaceutical technology; Hydration; Parasitosis; Infection; In vivo; Parasiticide; Pharmacokinetics
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2010.05.007

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 120
nm (PI
<
0.250), −38
mV 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.