Chitosan nanoparticles as delivery systems for doxorubicin

The aim of this paper was to evaluate the potential of chitosan nanoparticl es as carriers for the anthracycline drug, doxorubicin (DOX). The challenge was to entrap a cationic, hydrophilic molecule into nanoparticles formed b y ionic gelation of the positively charged polysaccharide chitosan. To achi eve this objective, we attempted to mask the positive charge of DOX by comp lexing it with the polyanion, dextran sulfate. This modification doubled DO X encapsulation efficiency relative to controls and enabled real loadings u p to 4.0 wt.% DOX. Separately, we investigated the possibility of forming a complex between chitosan and DOX prior to the formation of the particles. Despite the low complexation efficiency, no dissociation of the complex was observed upon formation of the nanoparticles. Fluorimetric analysis of the drug released in vitro showed an initial release phase, the intensity of w hich was dependent on the association mode, followed by a very slow release , The evaluation of the activity of DOX-loaded nanoparticles in cell cultur es indicated that those containing dextran sulfate were able to maintain cy tostatic activity relative to free DOX, while DOX complexed to chitosan bef ore nanoparticle formation showed slightly decreased activity. Additionally . confocal studies showed that DOX was not released in the cell culture med ium but entered the cells while remaining associated to the nanoparticles. In conclusion, these preliminary studies showed the feasibility of chitosan nanoparticles to entrap the basic drug DOX and to deliver it into the cell s in its active form, (C) 2001 Elsevier Science B.V. All rights reserved.