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 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.

Development of BSA conjugated on modified surface of quercetin- loaded lipid nanocarriers for breast cancer treatment

“…From the image, it is revealed that the morphology of the formulation changed, evidencing the successful conjugation of BSA with Q-LNs. The SEM image BSA conjugated Q-loaded LNs is validated using reported image of surface-modified LNs (Mishra et al 2019) and (Sana et al 2017).…”

Recent Advances in Nanotechnology for the Treatment of Melanoma

“…In the same year Mishra and coworkers formulated hyaluronic acid (HA)-coated liposomes and loaded with an effective combination of Dacarbazine and Eugenol two anti-melanoma agents, through a solvent injection method [ 44 ]. Coated-Dacarbazine Eugenol Liposomes showed 95.08% cytotoxicity at a dacarbazine concentration of 0.5 µg/mL with respect to dacarbazine solution that showed only 10.20% cytotoxicity at the same concentration.…”

Essential Oils and Their Main Chemical Components: The Past 20 Years of Preclinical Studies in Melanoma

“…Even if a direct effect on melanoma angiogenesis has not yet been reported, several EOs or their components have been found to affect in vitro endothelial functions and/or in vivo neovascularisation. Among them, EOs from Hypericum perforatum [187] and Myristica fragrans [56] should be mentioned, together with coated-dacarbazine eugenol liposomes, for their ability to reduce proliferation and migration of endothelial-like cells [188]. Citrus lemon EO nanoemulsions have been found to decrease angiogenesis in CAM [189].…”

“…The used in vitro and in vivo models are also listed. Salvia officinalis -Infected wound model (BALB/c) [190] Tridax procumbens -B16-F10 (C57BL/6) [86] Curcumol HUVEC [199] Eugenol EAhy.926 [188] Perillyl Alcohol BLMVEC, HUVEC, B16-F10 [198] Zerumbone HUVEC, CAM, rat aortic ring assay [195,196] β-Caryophyllene B16-F10 (C57BL/6N) [140] β-Elemene CAM, rat aortic ring assay, B16-F10 (C57BL/6) [120,152] Human Umbilical Vein Endothelial Cells (HUVEC), transformed human umbilical vein endothelial cells produced by fusion of A549/8 lung adenocarcinoma with human umbilical endothelial cells (EAhy.926), Bovine Lung Microvascular Endothelial Cells (BLMVEC), chick embryo chorioallantoic membrane (CAM). Where not reported, EO active components were not available in the cited paper.…”

“…Liposomes loaded with dacarbazine and eugenol, and coated with hyaluronic acid in order to enable the active targeting of the CD44 receptor that is overexpressed by tumor cells [211], have been reported to inhibit proliferation of both human (SK-MEL-28) and mouse (B16-F10) melanoma cells and to induce both apoptosis and necrosis. The authors suggested the use of this liposome formulation to reduce dacarbazine dose during chemotherapy and consequently toxicity on normal cells [188].…”