Dacarbazine-Loaded Lipid Polymer Hybrid Nanoparticles for Management of Skin Melanoma: Optimization and Anticancer Studies

Dacarbazine is an anticancer drug used in the treatment of skin melanoma. However, its systemic administration results in various side effects. These constraints might be alleviated by topical dacarbazine administration for the treatment of skin melanoma, although it is confined by the drug's limited skin permeability. To improve dacarbazine efficacy against skin cancer and minimize its systemic side effects, it was loaded in lipid polymer hybrid nanoparticle (LPHN)-based topical delivery system. LPHNs were prepared using emulsification solvent evaporation method employing experimental design for the optimization of independent variables. Optimized LPHNs showed particle size, entrapment efficiency, and zeta potential of 202.7 nm, 70.29 +/- 0.97%, and - 24.89 mV, respectively. Further, optimized formulation was incorporated in gel and was evaluated for ex vivo permeability. Studies revealed enhanced permeability following Higuchi diffusion kinetics. Flux was observed to be 15.93 +/- 1.61 mu g center dot cm-2 center dot h-1. Anticancer efficacy studies on melanoma cell line exhibited enhanced cytotoxicity of drug. Accelerated stability studies indicated stability of drug for at least six months. These results confirm the potential of topical dacarbazine LPHNs to enhance the efficacy against skin melanoma.