Nanovesicular carrier-based formulation for skin cancer targeting: evaluation of cytotoxicity, intracellular uptake, and preclinical anticancer activity

Context: Skin cancer has turned into global epidemic leading to higher incidences among cancer stricken population. Objective: The aim of the present investigation is to evaluate the anticancer potential and intracellular uptake of a novel nanovesicular formulation of 5-FU. Materials and methods: Detailed intracellular uptake study in conjunction with estimation of intracellular reactive oxygen species was done using skin melanoma cell lines (A375) along with cytotoxicity studies. To further obtain the mechanistic insights into inhibition of tumor cell proliferation, cell-cycle arrest studies were conducted. The preclinical anticancer activity was carried out employing in vivo DMBA-croton oil-induced skin cancer model in mice. Results and discussion: Significant reduction in the number of papillomas was observed in skin cancer-bearing mice on treatment with nanovesicular formulation (51.4 +/- 3.2%) in comparison with marketed formulation (21.3 +/- 2.1%) of 5-FU. Tumor volume was found to be reduced to 46.3 +/- 3.5% with prepared formulation, whereas the marketed formulation-treated group showed the reduction of 18.6 +/- 1.8% in comparison with the control (untreated) group. Conclusion: The results of present study demonstrated that nanovesicular formulation of 5-FU possessed the enhanced anticancer activity which could be attributed to better intracellular uptake, cellular retention, and sustained release of drug.