Nanoformulations of a Triazene Analogue with Specific Affinity to Human Melanoma

Abstract Malignant melanoma remains an aggressive malignancy conferring a very poor prognosis and standard treatments have not demonstrated an overall survival benefits. The alkylating agents triazenes have been used for treatment of malignant melanoma. However, their lack of specificity toward tumor cells requires the urgent development of novel therapeutic strategies. Therefore, the main objectives of the present work were the use of a triazene prodrug, previously synthesized and adequately formulated in liposomes. This triazene prodrug has demonstrated in previous work to be a good substrate for tyrosinase, an enzyme that is overexpressed in melanoma cells. After optimization of liposome preparation conditions and selection of most appropriated lipid compositions, it was possible to achieve high incorporation efficiencies. The association of this prodrug in liposomes, primarily relies in the possibility of solving solubility problems, increasing internalization in melanoma cell lines, protecting the molecule from premature degradation and enhancing its therapeutic index. Prodrug in free and liposomal forms demonstrated a high stability in the presence of human plasma, at 37°C. The in vitro tests, performed in human melanoma cell lines, demonstrated that the incorporation of TPD in liposomes was able to potentiate the cytotoxic effect of this triazene prodrug. The IC 50 for the prodrug in free form was superior to 125 µM, whereas in the liposomal form this value ranged from 13 to 22 µM being dependent on the lipid composition. The obtained results represent an excellent approach to fight malignant melanoma