Abstract
Malignant melanoma is the most aggressive type of skin cancer. Despite the recent progress in the survival rates, the worldwide incidence has been rising annually at a more rapid rate as compared to any other type of cancer. Dacarbazine (DTIC) monotherapy is approved for first-line treatment for malignant cutaneous melanoma. Resveratrol (RES) is a natural polyphenol that has shown to induce growth inhibition and cell apoptosis in melanoma cells. However, there are several challenges associated with delivery of these drugs which include lack of selectivity for tumor tissue, poor bioavailability, high photosensitivity, and dose-limiting systemic toxicity specifically associated with DTIC that limits its therapeutic efficacy. Nanostructured lipid carriers (NLC) serve as a potential platform for coadministration and protection of encapsulated drugs from degradation, enhance their pharmacokinetic profile and therapeutic efficacy, improve cellular uptake and biodistribution to tumor cells, minimize systemic toxicity and enhance accumulation at target site. The premise of this study is to design and characterize a lipid based injectable nanoparticulate delivery system for targeted delivery of both agents for the treatment of cutaneous malignant melanoma.An HPLC method was developed that enabled the simultaneous quantification of DTIC and RES which was validated for its specificity, linearity, precision, and accuracy as per USP guidelines. Nanostructured lipid carriers loaded with DTIC and RES were successfully developed and characterized while keeping the drugs protected from degradation. Melt-emulsification and solvent evaporation method along with ultrasonication was used for the formulation of NLC. The NLC were less than 200 nm in size and lyophilized NLC showed a significant increase in particle size up to 350 nm on freeze drying. Entrapment of RES was seen to be higher than DTIC in the lipid matrix. Both drugs were present in a non-crystalline state in the lipid matrix and all formulations remained stable over a period of 60 days. The formulation was found to be safe for intravenous administration. Future studies for this drug delivery system needs to address its efficacy and uptake in various cell lines. The possible synergism of both drugs in the formulation needs future investigation.