Voltammetric/UV-Vis study of temozolomide inclusion complexes with cyclodextrin derivatives.

Temozolomide (TMZ) - a chemotherapeutic agent possessing cytotoxic activity is used in single or combined therapies of human glioma. Difficulties in these applications, connected with low solubility and stability of temozolomide lead us to study the inclusion complexes between TMZ, and three cyclodextrins: β-cyclodextrin (βCD), monodeoxy-6-monoamino-β-cyclodextrin hydrochloride (βCDamine), and β-cyclodextrin containing galactosamine and triazole ring in the side group (βCDgal). The voltammetric and spectroscopy studies showed the improvement of the drug solubility and formation of stable complexes. Higuchi and Connors method was used to determine the solubilities of the drug in the presence of the selected cyclodextrins. Phase solubility diagrams showed increase of TMZ solubility and 1:1 stoichiometry of the complexes formed. The stability constant of TMZ- βCDgal complex was pH - dependent, larger at pH 7.4 (corresponding to the pH of the body fluids), than at pH 5.5, characteristic for the cancer cells environment. βCDgal ligand was an effective complexing agent for TMZ due to additional strong proton-acceptor π-π interactions between the triazole ring of the cyclodextrin and the ring of TMZ. The increased solubility and sustainability of TMZ complexes with βCDgal allow to propose this cyclodextrin as a promising TMZ carrier for further studies in the biological cell environment.