The New Permeability Pathways: Targets and Selective Routes for the Development of New Antimalarial Agents

The malaria parasite, Plasmodium falciparum, spends part of its complex life cycle within the red blood cells of a human host. During this time, the parasite alters the permeability of the red blood cell's plasma membrane to allow the uptake of nutrients, the removal of "waste" and volume and ion regulation of the infected cell. The increased permeability is due to the induction of new permeability pathways (NPP), which are obvious chemotherapeutic antimalarial targets and/or selective routes for drugs, which target the internal parasite. This review covers our present understanding of the NPP, the methods used to screen for putative inhibitors of the NPP, the current repertoire of NPP inhibitors and the problems that need to be addressed to realise the potential of the NPP as antimalarial targets. In addition, the review will cover the use of the NPP as specific drug delivery routes.