Development of chitosan, pullulan, and alginate based drug-loaded nano-emulsions as a potential malignant melanoma delivery platform

Abstract

Melanoma is the most aggressive form of skin cancer and various treatments have been investigated to treat this disease, but drug resistance remains an important factor in the failure of conventional therapeutics. Here we describe the development, optimisation and characterisation of alginate, chitosan, pullulan, and their combined nano-emulsions as drug delivery platforms for potential application for melanoma. A novel nano-emulsion delivery system was designed and assessed by determining in vitro drug release, cell viability (MTT), cellular apoptosis (ELISA) and confocal microscopy. A comparative analysis of the effect of the nano-emulsions on BRAF-mutant melanoma (A375) and keratinocyte (HaCaT) cells was conducted, with the “pullulan-chitosan” nano-emulsion chosen as an approach for melanoma drug delivery. Increased apoptosis induction of melanoma cells was recorded as 90% after 72 h of treatment with doxorubicin-loaded optimal nano-emulsion. Similarly, in the same treatment, the viability of melanoma cells was decreased by 70%. More importantly, A375 cells treated with naïve doxorubicin were 100% viable compared to cells treated with doxorubicin-loaded nano-emulsion which were only 30%viable. Achieved results are indicating the importance of the drug carrier's polymeric combination and the impact of the drug release pattern on the efficiency of the treatment. This offers potential for the abrogation of drug-efflux-related chemo-resistance.