Physicochemical Characteristics of Pentamidine-Loaded Polymethacrylate Nanoparticles: Implication in the Intracellular Drug Release in Leishmania Major Infected Mice

摘要: This work describes the preparation, physicochemical properties, tolerance and intracellular trafficking of pentamidine loaded nanoparticles. Pentamidine was bound to polymer by ionic interaction. interaction involved carboxylic acid functions methacrylic (10% polymer) amine groups drug. fixation release were pH dependent. An acidic led a decrease or release. At 5, which is value lysosomes parasitophorous vacuoles, reached up 50%. this value, ionized therefore can not traverse biological membranes. Unloaded nanoparticles pentamidine-loaded tested in vitro on U937 cells no cytotoxicity observed. In vivo, Leishmania infected mice, significant weight loss found. Ultrastructural studies showed different steps drug inside Leismania-infected Kupffer cells. The nanoparticle uptake macrophagic location phagocytosis vacuoles fused with primary form secondary lysosomes. Ultimate fusion containing also Nanoparticles identified close amastigotes but internalization parasite