Biodegradable polymeric nanoformulation based on the antiprotozoal canthin-6-one

Abstract

The efficacy of antiprotozoal agents against intracellular infections is very often limited by an almost negligible access to the cellular level where the pathogens are hidden. As a result, high doses of the chemotherapy agents are needed to be administered, but the great incidence of severe adverse drug effects generally leads to pharmacotherapy failure. To enhance the pharmacological effect of the antiprotozoal and antifungal canthin-6-one, loading into biodegradable poly(octylcyanoacrylate) nanoparticles has been considered. The preparation of canthin-6-one nanoformulation (average size ≈170 nm) has been performed by a single-absorption procedure with high drug loading and little burst release as determined by RP-HPLC. Further characterization of this nanoformulation has been carry out by electrophoretic measurements, analysis of the surface thermodynamics of the nanoparticles, and 1H-NMR analysis. Nanoparticles loaded with canthin-6-one were characterized by a significant hydrophobicity and a great surface electrical charge under physiological conditions. These are two key physicochemical factors determining recognition by the reticuloendothelial system, resulting in a fast intracellular uptake by infected phagocytes. It is expected that this nanoformulation offers potential applications for an efficient canthin-6-one delivery to intracellular infections.