Dual drug encapsulation in a novel nano-vesicular carrier for the treatment of cutaneous melanoma: characterization and in vitro/in vivo evaluation

Abstract

The objective of this research was to develop and evaluate a dual drug-loaded dermal targeted vesicle for the treatment of cutaneous melanoma. In this debut study, dacarbazine (DAC) and tretinoin (all-trans retinoic acid, TRA) were used as active agents, together or separately. Transethosomes (TES) and liposomes (LS, control) were developed as the carriers and optimized by both in vitro and in vivo studies. The results showed that the permeability of the active agents from TES was superior to that of LS. In the in vivo studies, TES contributed a higher DAC concentration in plasma (DAC–TES: 102 ng ml⁻¹, DAC/TRA–TES: 100 ng ml⁻¹, DAC/TRA–LS: 30 ng ml⁻¹) and vesicles were found to be safe by histopathology images. Furthermore, drug distributions were validated by confocal laser scanning microscopy (CLSM) and the mechanism of enhanced skin permeation was determined by Fourier transform infrared spectroscopy (FTIR). The vesicular formulations were tested on B16–F10 cells and DAC/TRA–TES showed an improvement in the cytotoxic effect with respect to other formulations. The superior internalisation of TES was also detected by the extent and time-dependence of the vesicular–cell interactions. All of the detailed evidence indicated that dual drug-loaded TES could provide promising tuning for transdermal delivery systems for the treatment of cutaneous melanoma and shows immense potential for the development of dual drug systems’ synergistic effects in the near future.