Artesunate-loaded bilosomes with enhanced oral bioavailability: in silico and in vitro study against Leishmania donovani promastigotes and in vivo pharmacokinetic assessment in rats

Abstract

The deadly parasite disease known as visceral leishmaniasis (VL) is caused by the protozoa of Leishmania donovani. Artesunate (ART) has been reported to act against VL. However, its medical use is limited owing to the fact that it belongs to BCS class II. Thus, the aim of the present work was to prepare ART-loaded bilosomes (ART-BIL) to mitigate the drawbacks associated with ART. Box–Behnken design was used to optimize ART-BIL prepared by the ethanol injection method. ART-BIL were characterized for vesicle size, entrapment efficiency, FTIR, DSC, TEM, in vitro drug release, in silico molecular docking, in vitro antileishmanial activity against Leishmania donovani, and in vivo pharmacokinetic assessment. The optimized spherical ART-BIL was found to have a vesicle size of 186.7 ± 15.0 nm and an entrapment efficiency of 95.36 ± 2.5%. Spherical, non-aggregated vesicles demonstrated a biphasic drug release profile with a remarkable increase in the dissolution rate of artesunate compared to an artesunate dispersion. In silico molecular docking studies revealed the antileishmanial potential of artesunate and chenodeoxycholic acid by binding them to glyceraldehyde 3-phosphate dehydrogenase (G3PDH). Further, in vitro antileishmanial studies showed a significant enhancement in the antileishmanial potential of artesunate while in vivo pharmacokinetic studies demonstrated 1.39 and 1.47 fold increases in the C_max and AUC of ART when formulated into bilosomes. ART-loaded bilosomes could be a promising drug delivery system for the treatment of visceral leishmaniasis.