Anticancer activity of topical ointments with histone deacetylase inhibitor, trichostatin A

Background. Trichostatin A (TSA), being a strong specific histone deacetylase (HDAC) inhibitor, may lead to the inhibition of growth, differentiation and/or apoptosis of cells in a number of tumors. Semisolid drug formulations for topical release of anticancer agents may be an alternative strategy or a supplement of the systemic therapy. Objectives. To prepare semisolid formulations with TSA to be used directly on the skin and to assess the anticancer effect in vivo on a mouse model with L1 neoplastic tumors. Material and methods. Twenty-fourformulations were prepared in the form of semisolid systems containing TSA as the active ingredient. Then, an in vitro study was performed concerning the release of the active substance from the prepared formulations. Four formulations were selected for in vivo studies: oil-in-water cream, hydrogel, w/o emulsion ointment on the absorptive hydrophobic medium, and o/w emulsion gel. The tumor size and mouse body weight were measured during the experiment. The tumors and healthy skin of the mice were assessed regarding the skin barrier function with the Corneometer and Tewameter probes. Results. The semisolid formulation with TSA applied on the skin reduced the growth of neoplastic tumors as compared with the control group. This is especially pronounced in the case of w/o emulsion ointment and o/w emulsion gel. The Corneometer shows that neoplastic tumor growth and formulations on the skin have no effect on the skin condition in comparison with the mouse skin without tumor. The measurement performed with the Tewameter has revealed impaired skin barrier function of neoplastic tumors. Conclusions. Semisolid formulations with TSA fit well in the mainstream of research into topical medicines applied directly on neoplastic tumors, which may support and supplement current oncological treatment.