A novel nanoparticulate system based on a new cisplatin-hyaluronate complex and N-trimethyl chitosan

Nanoparticles with a positive surface charge were prepared through the electrostatic interaction of a new cisplatin-hyaluronate complex with N-trimethyl chitosan (substitution degree of 85%). With regard to the complex, which has been evaluated for its stability and anticancer activity, a critical comparison with other cisplatin-hyaluronate complexes recently [1] and less recently [2] described in literature suggests that a new entity has been obtained. This is likely due to the combination of the chosen hyaluronate molecular weight with the experimental conditions used for the complexation process. Mean particle diameter was about 195 nm. Drug loading of nanoparticles, which had a zeta potential of about 27 mV, was equal to 6 % w/w. After 24 h, while the cisplatin-hyaluronate complex released 60% w/w drug in phosphate buffered saline at pH 7.4, only 40% w/w of total cisplatin was released from nanoparticles. The results of the investigation of their pharmacological activity appear to be significant, as highlighted by in vitro and in vivo experiments. In particular, the preliminary in vivo experiment, carried out on a murine tumour model, indicated that the antitumor activity of cisplatin was maintained and associated with a markedly reduced overall toxicity. It is likely that even better results might be obtained by using different administration schedules and by working with other tumour models.