Preparation and In Vitro/Vivo Evaluation of Nano-Liposomal Form of Febrifugine Hydrochloride.

Febrifugine hydrochloride (FFH) has strong pharmacological antimalarial effect. However, compared with oral administration, the efficacy of intravenous administration is significantly reduced. In this study, we prepared conventional liposomes and PEGylated liposomes to improve the efficacy of its intravenous injection. Both liposome formulations were prepared using a modified ethanol injection method. Their mean particle sizes were 126.23 and 114.93 nm, mean zeta potentials were -6.25 and -26.33 mV, and entrapment efficiencies (EE) were 89.43 and 96.42%, respectively. The in vitro release profile indicated that the release of FFH from PEGylated liposomes and conventional liposomes was slower than free FFH, with sustained-release effect of PEGylated liposomes being more significant. PEGylated liposomes demonstrated excellent antimalarial activities in vitro superior to free FFH and conventional FFH-loaded liposomes. In addition, the PEGylated liposomes resulted in enhanced antimalarial effect in P. berghei infected mice in vivo with delayed recrudescence and prolonged survival time, compared with free FFH and conventional FFH-loaded liposomes administration. Based on these exciting experimental results, PEGylated liposomes could be a potential drug delivery system for FFH, with enhanced pharmacodynamics of intravenous injection.