Vismodegib (VMD) is a hedgehog inhibitor which indicated for basal cell skin cancer (BCC). This work focuses on investigating the influence of isopropyl alcohol additive for topical delivering and targeting of VMD-loaded binary ethosomes for BCC treatment. Different binary ethosome formulae were prepared based on Box-Behnken design using different concentrations of phospholipid (A), cholesterol (B) and isopropyl alcohol/total alcohol ratio (C). The prepared formulae were characterized for %entrapment efficiency (R1), vesicle size (R2), %release (R3) and steady-state flux (R4). Increasing A, B and C resulted in significant increase of R1 and R2 and significant decrease of R3 and R4. The optimization was achieved and the optimum formula was selected to investigate its anti-tumour efficacy in vivo. The optimum formula showed a localized VMD and consequently a significant anti-tumour activity compared with oral VMD. Briefly, VMD-loaded binary ethosome gel could be an effective treatment of BCC with lower side effects. Graphical abstract.
Keywords: basal cell carcinoma; ethosomes; histopathology; isopropyl alcohol; vismodegib.