Arteether nanoemulsion for enhanced efficacy against Plasmodium yoelii nigeriensis malaria: An approach by enhanced bioavailability

Abstract

The present work is focused on the preparation of nanoemulsions (NEs) loaded with arteether (ART) for its enhanced efficacy against malaria parasites. ART-NEs have been prepared using high pressure homogenization (HPH) technique with the aim of improving its solubility and thus its bioavailability. ART-NEs were optimized in terms of pressure and number of cycles. Globule size and size distributions were chosen as quality parameters. The maximum drug loading was achieved up to 93±7.4% with globule size 156±10.2nm and zeta potential of -23.3±3.4mV. The developed ART-NEs were found to be stable in terms of globule size and size distribution at different pH. The in-vitro release profile of the ART-NEs showed 62% drug release within 12 h. The percentage cell viability of blank NEs were within acceptable limits. A sensitive assay method for the determination of ART in rat plasma by liquid chromatography–mass spectrometry (LC-MS) was employed after oral administration of ART-NEs. The pharmacokinetic study showed significantly enhanced bioavailability of ART in ART-NE-V. The area under curve (AUC) of ART-NE-V was AUC0-t 1988.411±119.66h.ng/ml which was significantly higher (p <0.05) than ART in ground nut oil (GNO) AUC0-t 671.852±187.05 h.ng/ml. The Cmax of ART-NE-V (1506±161.22ng/ml) was also significantly higher (p<0.05) than ART in GNO (175.2±16.54ng/ml) and ART given intramuscularly (IM) (278.05±38.59 ng/ml). The ART-NE-V was having significantly high antimalarial efficacy and survival rate of mice giving 80% cure rate at 12.5mg/kg for 5 days in comparison to 30% cure rate of ART in GNO at the same daily dose and it was also comparable to the 100% cure rate at 12.5mg/kg for 5 days for ART given intramuscularly. In conclusion ART-NE can be a promising oral delivery system for ART.