STUDY OF ACTION OF LOADED AND UNLOADED DRUG CARRIERS AGAINST LEISHMANIA IN AN INVITRO MODEL

Antileishmanial chemotherapy is hampered by the location of parasites within lysosomal vacuoles of the macrophages which restricts the bioav ailability of many potential antileishmanial compounds. In this study, the effectiveness of pentamidine targeted to the infected cells by a linkage to a colloidal drug carrier, methacrylate polymere nanoparticl es was explored. In the same way, polyisoalkylcyanoacrylate nanosphere s which have, in vitro, trypanolytic properties were also tested. The study was performed in an in vitro model using Leishmania major amasti gote stages within the U 937 human monohistiocytic cell line. The anti leishmanial activities of unloaded or pentamidine-loaded nanoparticles were compared to those of the free drugs. The 50 % effective concentr ation of targeted pentamidine was 0.10 mug/ml, while it was up to 2.7 mug/ml with the free drug after a 24-hour incubation time. The pentami dine-bound nanoparticles proved to be 25 times more active than the fr ee drug. Unloaded polyisoalkylcyanoacrylate nanoparticles destroyed in tracellular amastigote stages (50 % EC = 15 mug/ml) but at a level clo se to the cytotoxic concentration.