Amphoteric polyamidoamines as innovative tools to selectively direct antimalarial drug towards plasmodium-infected red blood cells

Malaria is one of the main medical concerns worldwide because of the number of people affected, the severity of the disease, and the complexity of the life cycle of its causative agent, the protist
Plasmodium sp
. The clinical, social and economic burden of malaria has led for the last 100 years to several waves of serious efforts to reach its control and eventual eradication, without success to this day. The arsenal of strategies deployed has included fighting the mosquito vector with insecticides, distributing mosquito nets, desiccating swampy areas, using an ever growing number of drugs against the parasite, and developing vaccination approaches, none of them being capable yet of claiming victory. The emergence of drug resistance severely limits the arsenal of available drugs against pathogens, a situation which is favored when parasites are exposed to low levels of antimalarial drugs, for instance where a full course of treatment is not completed, or where long-acting drugs are administered, which are eliminated slowly from the body. With the advent of nanoscience, renewed hopes have appeared of finally obtaining the
magic bullet
against malaria. Novel delivery formulations are likely to optimize the therapeutic efficacy of antimalarials. In particular, targeted nanovectors, such as liposomes, solid-lipid nanoparticles, nano-/microemulsions and polymer-based nanocarriers have been receiving special attention in order to minimize the side effects of drug therapy and achieve the intake of doses sufficiently low to be innocuous for the patient but locally high enough to be lethal for the malaria parasite. The aim of this project is to develop a few biocompatible prototype
Trojan horse
nanovectors that were found particularly promising in preliminary evaluations, having proved capable of specifically targeting and intracellularly colocalizing with
P. falciparum
in parasitized red blood cells (pRBCs), eventually delivering their antimalarial cargo inside them, and ultimately eliminating detectable parasitemia both in
P. falciparum
cultures and in malaria-infected mice. In addition, some of them appeared endowed with antimalarial activity
per se
.