[Long circulating nanocapsules: interest in the treatment of severe malaria with halofantrine]

The aim of the work was to develop a new submicronic delivery system that can be used with poorly water soluble drugs for which sustained circulating concentrations are necessary. This system consists of oily core surrounded by a shell made of a copolymer of poly (D,L-lactid) and poly (ethylene glycol). Covalent coupling between the hydrophylic poly (ethylene glycol) and poly (D,L lactid) and high molecular weight of the poly (ethylene glycol) chains yield long circulating particles after intra-venous administration in mice. Halofantrine, a very effective drug administrated for the treatment of severe malaria caused by Plasmodium, for which no injectable preparation exists. Results showed that percentage of loading, yield of encapsulation and physical stability were more favourable with surface modified nanocapsules. Release of halofantrine was clearly related to partition between oil and external medium. Serum proteins in the medium, increased halofantrine release from nanocapsules and poly (ethylene glycol) grafted nanocapsules reduced this phenomenum. The pharmacokinetics of the free drug was modified to maintain it in blood circulation. It is important to note that high plasma concentrations of halofantrine were correlated with higher activity against parasites in mice infected with Plasmodium berghei.