Co-delivery of eugenol and dacarbazine by hyaluronic acid-coated liposomes for targeted inhibition of survivin in treatment of resistant metastatic 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 inhibitsurvivin protein in breast cancer cells. Survivin is also overexpressed by melanoma cells, andis known to impart resistance to them against chemotherapy-induced apoptosis. To be able tofight resistant melanoma, we formulated hyaluronic acid (HA)-coated liposomes loaded with an effective combination of anti-melanoma agents (Dacarbazine and Eugenol), using a solvent injectionmethod. Quality-by-Design (QbD) was applied to optimize and obtain a final formulation withthe desired quality attributes, and within an acceptable size range. The optimized formulationwas then subjected to performance analysis in cell lines. Coated-Dacarbazine Eugenol Liposomeswere found to possess 95.08% cytotoxicity at a dacarbazine concentration of 0.5 μg/mL, whileDacarbazine Solution showed only 10.20% cytotoxicity at the same concentration. The number oflate apoptotic cells was also found to be much higher (45.16% vs. 8.43%). Furthermore, migrationassay and proliferation study also revealed significantly higher inhibition of cell migration andproliferation by Coated-Dacarbazine Eugenol Liposomes, signifying its potential against metastasis.Thus, surface-functionalized dacarbazine- and eugenol-loaded liposomes hold great promise againstresistant and aggressive metastatic melanoma, with much less unwanted cytotoxicity and reduceddoses of the chemotherapeutic agent.