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 a solvent injection method. Quality-by-Design (QbD) was applied to optimize and obtain a final formulation with the desired quality attributes, and within an 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 a dacarbazine concentration of 0.5 µg/mL, while Dacarbazine Solution showed only 10.20% cytotoxicity at the same concentration. The number of late apoptotic cells was also found to be much higher (45.16% vs. 8.43%). Furthermore, migration assay and proliferation study also revealed significantly higher inhibition of cell migration and proliferation by Coated-Dacarbazine Eugenol Liposomes, signifying its potential against metastasis. Thus, surface-functionalized dacarbazine- and eugenol-loaded liposomes hold great promise against resistant and aggressive metastatic melanoma, with much less unwanted cytotoxicity and reduced doses of the chemotherapeutic agent.
Highlights
Melanocytes, while, on the one hand, protecting the skin from harmful ultraviolet radiation in their normal state, form one of the deadliest cancers when undergoing malignant growth on the other.Melanoma, which is the cancer of melanocytes, is a highly aggressive cancer, and causes up to 60–80% of skin cancer-related deaths [1,2]
The major challenge associated with melanoma treatment is the resistance of melanoma cells chemotherapy, which can lead to the failure of the treatment, along with poor response and survival rates [5,6]
When the organic solvent is completely diffused in the external aqueous phase, vesicle formation takes place consequent to self-assembly of bilayer planar fragments (BPFs)
Summary
Melanocytes, while, on the one hand, protecting the skin from harmful ultraviolet radiation in their normal state, form one of the deadliest cancers when undergoing malignant growth on the other.Melanoma, which is the cancer of melanocytes, is a highly aggressive cancer, and causes up to 60–80% of skin cancer-related deaths [1,2]. It is reported that inhibiting the function of survivin in melanoma cells can spontaneously cause apoptosis, impairing the growth of the tumor [12]. Downregulation of survivin has been found to inhibit migration, metastasis, and proliferation of cancer cells, both in vitro and in vivo [13]. The fact that it is overexpressed in most cancer cells, but hardly expressed at all in any normal tissue, makes it an attractive target for targeted anti-cancer therapies [14]
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