Nanopartículas como vehículos para la administración oral de antimaláricos

Abstract

The aim of this work was to study the ability of bioadhesive cyclodextrin-poly(anhydride) nanoparticles as carriers for the oral delivery of two antimalarial drugs: atovaquone (ATO) and GW844520X (520X). In order to increase the loading capacity of these drugs by poly(anhydride) nanoparticles, the following oligosaccharides were assayed: 2-hydroxypropyl-£]-cyclodextrin (HPCD), randomly methylated ¿Ò-cyclodextrin, 2,6-di-O-methyl-¿Ò-cyclodextrin (DCMD), randomly methylated-¿Ò-cyclodextrin (RMCD) and sulfobuthyl ether-¿Ò-cyclodextrin (SBECD). Nanoparticles were obtained by desolvation after the incubation between the poly(anhydride) and the drug-cyclodextrin complexes, and showed adequate physicochemical properties in terms of size, drug loading and yield. For the pharmacokinetic studies, formulations were administered orally in male Wistar rats. Nanoparticle formulations induced higher and more prolonged plasmatic levels of the drugs than control suspensions in methylcellulose, increasing significantly the relative oral bioavailability of both compounds. The encapsulation of atovaquone in cyclodextrins-poly(anhydride) nanoparticles seems to be an interesting strategy to improve the oral bioavailability of this antiprotozoan drug.