Self-nanoemulsifying drug delivery system (SNEDDS) for oral delivery of arteether: pharmacokinetics, toxicity and antimalarial activity in mice

Abstract

Objective: The aim of the study was to develop oral arteether (AE) nano formulations and to investigate its effects in rats; for complete and effective treatment of Plasmodium yoelii nigeriensis infected mice at reduced dose by increasing relative bioavailability. Method: Nano-formulations of arteether have been developed. The relative bioavailability (RB%) was assessed by calculating individual AUC0‒t, AUC0-∞ and Cmax values. Haematological, biochemical parameters were estimated in rats and sections of brain and peripheral organs were analyzed for histopathological changes. The formulations were tested for antimalarial efficacy and safety in Plasmodium yoelii nigeriensis infected swiss mice. Result: The AUC in case of lipid formulations (AUC0-t 4.98±0.79 h. µg/ml) and AUC0-∞ (5.02±0.80 h. µg/ml) were significantly higher (p <0.05) than AE in ground nut oil (GNO) and AE aqueous suspension. The Cmax was also significantly higher for all the formulations. The RB% has been found to be significantly high (257%) in formulations with respect to AE in GNO. No considerable changes have been monitored in the serum biochemical parameters in rats. These formulations have been found to be highly effective against Plasmodium yoelii nigeriensis infected swiss mice even at the lower dose of 12.5 mg/kg x5 days. Conclusion: Overall the developed formulations are safe and provide a non-toxic platform for further clinical studies and can be used in artemisinin-based combination therapies (ACTs).