The aim of this work was to develop a formulation for Z-DEVD-FMK, a peptide which is a caspase inhibitor and has been used in experimental animal studies for a decade. Peptide loaded chitosan nanoparticles were obtained by ionotropic gelation process and Z-DEVD-FMK was quantified by an HPLC method. The influence of the initial peptide concentration on the nanoparticle characteristics and release behavior was evaluated. The CS nanoparticles have a particle diameter (Z-average) ranging from approximately 313-412 nm and a positive zeta potential (20-28 mV). The formulation with the initial peptide concentration of 400 ng/ml provided the highest loading capacity (0.46%) and the highest extent of release (65% at 24 h) suggesting the possibility to achieve a therapeutic dose. According to the data obtained, this chitosan-based nanotechnology opens new and interesting perspectives for anticaspase activity. (c) 2005 Elsevier B.V. All rights reserved.