Pharmacokinetic Profiling of Prepared Artemisinin-Loaded Poly(lactic co-glycolic acid) Nanoparticles in Mice Infected with Artemisinin-Sensitive and-Resistant Plasmodium berghei K173 Using by HPLC-MS/MS Assay

Abstract

Low solubility and bio-availability of artmisinin (ART) limit the clinical efficacy and unfortunately, the resistance of Plasmodium to ART has been gradually reported in recent years. In order to improve its dissolvebility, we therefore prepared ART-loaded poly(lactic co-glycolic acid) (PLGA) nanoparticles and characterized them. Later, the pharmacokinetic differences between ART original materials and artemisinin-loaded nanoparticles in mice infected with ART-sensitive and-resistant Plasmodium berghei K173 were investigated by orally administrated (40 mg/kg) by using a successfully developed and validated LC-MS/MS detection method. ART-loaded nanoparticles exhibited a smooth and spherical shape with average diameters of 193.80±7.65 nm. In vitro release results showed that ART-loaded nanoparticles displayed a stable sustained release effect. Meanwhile, the pharmacokinetic properties of ART-loaded nanoparticles were significantly improved when compared with the crude materials both in two groups. The AUC(0−t) significantly increased 2.91 and 2.85 folds as well as 4.03, 3.61 folds higher half-life period (t1/2) and 2.76, 3.27 folds higher maximum retention time (MRT), respectively. CL, meanwhile, declined 3.33 and 3.33 folds. These results suggested that ART-loaded nanoparticles enhanced the retention of ART in vivo and contributed to its long-lasting antimalarial effect.