Design and evaluation of targeted nanoliposomes for combinatorial approach against melanoma

Abstract

While melanoma remains a challenge for oncologists, possibilities are being continuously explored to fight resistant metastatic melanoma more effectively. Eugenol is reported to inhibit survivin protein in breast cancer cells. Survivin is also overexpressed by melanoma cells and is known to impart resistance to them against chemotherapy induced apoptosis. To be able to fight resistant melanoma, we formulated hyaluronic acid (HA) coated liposomes loaded with an effective combination of anti-melanoma agents (Dacarbazine and Eugenol) using solvent injection method. QbD was applied to optimize and obtain a final formulation with desired quality attributes and within acceptable size range. The optimized formulation was then subjected to performance analysis in cell lines. Coated-Dacarbazine Eugenol Liposomes were found to possess 95.08 % cytotoxicity at dacarbazine concentration of 0.5 and#956;g/ml, while Dacarbazine Solution showed only 10.20 % cytotoxicity at same concentration. The number of late apoptotic cells was also found to be much higher (45.16 % vs 8.43 %). Further, migration assay and proliferation study also revealed significantly greater inhibition of cell migration and proliferation by Coated-Dacarbazine Eugenol Liposomes, signifying its potential against metastasis. newlineIn melanoma induced C57BL/6 mice, significant difference between the tumor volumes was seen among control group and groups receiving dacarbazine solution (DS), coated liposomes of dacarbazine (DLC) and coated liposomes of dacarbazine and eugenol (DELC). Tumor volume in DELC treated group was least at the end of the treatment. Histopathological analysis revealed more necrosis in tumor and less damage in liver and lungs in DELC treated group. Also, the coated liposomes were found to be more accumulated in tumor, while drug solution led to a much higher concentration in liver. Coated liposomes also stayed longer in systemic circulation as compared to solution and uncoated liposomes.