Chitosan and Chitosan derivative nanoparticles bearing cisplatin complexed with polycarboxylate polymer

Cisplatin, a widely used antineoplastic drug, presents various adverse effects. Cisplatin complexes with polycarboxylate polymers have been proved biologically active, less toxic than Cisplatin and effective in suppressing ovarian tumour growth in vivo. Nanoparticles bearing such complexes could further improve their pharmacological action. Our current work deals with the preparation of nanoparticles via electrostatic interaction between some of the above complexes, which are anionic macromolecules, and chitosan or chitosan derivatives chosen as cationic polyelectrolytes. The polycarboxylate polymers used to address this aim were sodium alginate (ALGI), Poly-L-glutamic acid sodium salt (PLGLU) and sodium hyaluronate (HA), while the chitosan derivatives were N-trimethyl chitosan (TMC) and N-trimethyl glycol chitosan (TMGC). In chronological order, the first nanoparticle formulation was prepared using chitosan or TMC with a DDP-ALGI complex. This formulation yielded significant results in terms of particle properties and antitumor activity in vitro. The results of this work were published recently [1]. The investigation was then continued by preparing nanoparticles through the interaction of TMC or TMGC with a DDP-PLGLU complex. Interesting results were obtained with TMC/DDP-PLGLU nanoparticles, which showed cytotoxicity lower than that of TMC/DDP-ALGI nanoparticles. Those made of TMGC and DDP-PLGLU had a low stability at physiological pH (7.4), so this system was not subjected to further investigation. Finally, we studied the nanoparticles made of TMC and a DDP-HA complex. This formulation showed interesting features allowing the transformation of the negatively charged macromolecular DDP-HA complex into a different system with new properties, such as small size, a positive zeta potential and a good drug loading. In vitro pharmacological experiments indicated that both the complex, obtained under particular experimental conditions, and the nanoparticles yielded promising results for further in vivo studies of their antitumor activity.