Title : Development of arteether nanoemulsion for improved oral bioavailability and antimalarial efficacy against Plasmodium yoelii nigeriensis
Abstract:
Background: Arteether (ART) is a potent antimalarial drug, but its clinical utility is limited due to low aqueous solubility and poor oral bioavailability. This study aimed to develop an ART-loaded nanoemulsion (ART-NE) to improve systemic exposure and antimalarial efficacy against Plasmodium yoelii nigeriensis in a murine model.
Methods: ART-NE was prepared via high-pressure homogenization, optimizing the ratio of oil, surfactant, and co-surfactant. The formulation was characterized for droplet size, zeta potential, drug-loading efficiency, and in vitro release. Pharmacokinetics were assessed in rats after oral administration. For efficacy, infected Swiss mice were treated with ART-NE (12.5 mg/kg, once daily × 5 days) and compared with ART in conventional oil and intramuscular ART.
Results: The optimized nanoemulsion exhibited a mean droplet size of 148 ± 8 nm, zeta potential of –25.1 ± 2.9 mV, and a loading efficiency of ~90%.
In vitro release studies showed a sustained release of ~58% of ART over 12 hours.
Pharmacokinetic data in rats revealed a 3.1-fold increase in oral bioavailability for ART-NE versus ART in oil (AUC?–? ≈ 2,070 h·ng/mL, C??? ≈ 1,440 ng/mL).
In the mouse malaria model, ART-NE achieved a ~78% cure rate, compared to ~28% for the conventional oral formulation, and the efficacy was nearly comparable to 100% survival with intramuscular ART.
Conclusion: The developed ART-nanoemulsion significantly enhances the oral bioavailability and therapeutic efficacy of arteether in malaria. This non-injectable formulation could provide a patient-friendly alternative to parenteral ART, with the potential to improve treatment outcomes.
Keywords: Arteether, Nanoemulsion, Bioavailability, Malaria, Plasmodium Yoelii Nigeriensis.
