Comparative pharamacokinetics and in-vivo efficacy of an intravenous formulation of halofantrine in long-circulating nanocapsules in Plasmodium berghei-infected mice

摘要

surface-modified nanocapsules (NC) bearing methoxy-PEG chains grafted to a biodegradable polymer (PLA) are able to overcome or delay the massive uptake by the MPS~(1). They offer the potential for targeting the antimalarial drug halofantrine to parasitized red blood cells (RBC) due to their abiltiy to circulate longer in the blood~(2). Halofantrine (Hf) often exhibits low bioavailability, since its oral absorption can be limited by its poor solubility~(3). The development of a parenteral formualtion of Hf free base using long circulating NC is one strategy to obtain sustained drug levels in the blood, reduce doses and achieve a rapid therapeutic effect in treatment of cerebral malaria. In this work, the pharmacokinetic profile of Hf-loaded NC was investigated in P. berghei-infected mice and compared with the only previously described intravenous formulation of the solubilized drug, which provokes irritation at the site of injection~(4). Furthermore, we have evaluated their efficacy in vivo in the same infected mouse model.