Pharmacokinetics and in vivo chemosuppressive activity studies on cryptolepine hydrochloride and cryptolepine hydrochloride-loaded gelatine nanoformulation designed for parenteral administration for the treatment of malaria

Abstract

The main objective of this investigation was to establish the pharmacokinetics profile and in vivo chemosuppressive activities of cryptolepine hydrochloride-loaded gelatine nanoparticles (CHN) designed for parenteral administration for the treatment of malaria in comparison to the drug free in solution (CHS). Single-dose pharmacokinetics was investigated in Wistar rats by administering CHN or CHS (equivalent to 10. mg/kg of drug) by IV bolus injection via the lateral tail vein. The drug concentration in plasma was monitored over a 24-h period following administration. Chemosuppressive activity was investigated in Wistar rats challenged with P berghei parasites. Animals were given a daily dose of either CHN or CHS, equivalent to 2.5-100. mg/kg by intraperitoneal injection. The level of parasitaemia was determined by light microscopy by examining Giemsa-stained thin blood smears prepared from the tail end on day four of infection. It was found that CHN attained a higher (4.5-folds) area under the curve (AUC (0-24)) compared to CHS. CHS however produced a higher volume of distribution (4-folds). Distribution and elimination rates were higher with CHS which resulted in a lower (11.7. h) elimination half-life compared to that of CHN (21.85. h). The superior pharmacokinetic profile of CHN translated into superior chemosuppressive activity at all dose levels relative to CHS. As a conclusion, loading cryptolepine hydrochloride into gelatine nanoparticles improved both pharmacokinetics and in vivo antiplasmodial activity of the compound with the highest chemosuppression (97.89. ±. 3.10) produced by 100. mg/kg of CHN. © 2013 Elsevier B.V.