Optimization and in-vitro assessment of the effectiveness of carvedilol-loaded proniosomal gels as a promising therapeutic approach for the topical treatment of skin cancer

Abstract

In the present study, proniosomal gels containing carvedilol (CAR) were formulated, using various non-ionic surfactants (NISs) in combination with cholesterol. The prepared proniosomal gel formulae were examined for the colloidal properties: vesicle size, size distribution (PDI), zeta potential (Z.pot) and entrapment efficiency (%EE). On the optimized formulae, visualization using TEM, ex-vivo skin permeability and deposition investigation, in-vitro cytotoxicity study using Human Melanoma cell line (A375) and in-vitro free radical scavenging activity using DPPH were performed. Results revealed that the prepared vesicles had a relatively high CAR entrapment efficiency and were in the nano-size range. Ex-vivo skin permeability and deposition results demonstrated the superiority of CAR proniosomal gel over free drug dispersions. The optimized CAR-loaded proniosomal gel showed a prominent cytotoxic activity on human melanoma cell line (A375), which was further confirmed by the results of DPPH free radical scavenging activity. Findings of this study suggest that the proniosomal gel F12(20 mg) comprised of Span 40, Tween 80 and cholesterol in a 3:6:1 ratio and loaded with 20 mg CAR displayed enhanced skin deposition, potent antioxidant properties and significant cytotoxic activity, suggesting it to be a propitious and effective topical delivery system for treating melanoma.