Encapsulation of silibinin in ginger oil-based nanoemulsions for melanoma treatment

Melanoma is a highly lethal form of skin cancer that develops from genetic mutations in melanocytes. Although it accounts for only 1% of malignant skin tumours, melanoma is responsible for the majority of skin cancer-related deaths, largely due to the limited efficacy of current treatments for metastatic disease. Recent studies have highlighted silibinin's anticancer potential, due to the ability to modulate key signalling pathways involved in tumour progression, proliferation, and metastasis [1]. Silibinin is a natural flavonoid extracted from milk thistle, extensively known for its antioxidant and anti-inflammatory properties. Recent studies have shown that silibinin also exhibits promising anticancer activity, in melanoma [2]. Nevertheless, it shows low water solubility and poor bioavailability, limiting its therapeutic utility. In this context, employing nanocarriers may overcome these drawbacks and improve its therapeutic performance. Among the different nanoscale delivery systems, nanoemulsions are emerging as an interesting option in cancer therapeutics [3]. Nanoemulsions are composed of heterogeneous nanometer droplets dispersed in an immiscible liquid, which leads to high stability and solubility. Nanoemulsions offer significant advantages as a delivery system for different therapeutic agents, including essential oils. Their nanometric droplet size increases solubility and stability, enhances absorption and facilitates the targeted delivery of hydrophobic substances, thereby improving bioavailability. The small size of nanoemulsions increases their surface area, promoting better interaction with biological membranes and enabling controlled release. These features amplify the therapeutic efficacy of encapsulated agents. Specifically, nanoemulsions incorporating essential oils have demonstrated enhanced anticancer activity compared to the oils in their free form, which is attributed to improved cellular uptake and sustained release profiles [4]. Recent studies have explored the potential of combining essential oils with chemotherapeutic agents to enhance anticancer efficacy through synergistic effects. Ginger essential oil (Zingiber officinale) has shown promising results, with its major active compound, 6-gingerol, demonstrating synergistic anticancer activity when coadministered with drugs like paclitaxel and methotrexate in various cancer cell lines [5]. In addition to its anticancer properties, ginger oil has antiinflammatory, antioxidant and skin-soothing effects, making it particularly relevant for treating skin conditions. Based on these considerations, we develop ginger oil-based nanoemulsions for the delivery of silibinin. Our objective was to assess whether combining these two approaches could generate a new therapeutic effect for cancer management. In consideration of its dermatoactive properties and documented synergism with chemotherapeutics, ginger oil may constitute a valuable component in innovative topical strategies for treating melanoma. In this work, nanoemulsions were obtained by the solvent displacement technique and optimised through the construction of a ternary phase diagram to obtain the appropriate components and the concentration ranges of essential oil, surfactants, co-surfactant, and water. In particular, the following emulsifying agents: poloxamer 188, tween 80, sucrose ester 70 and soy phosphatidylcholine were investigated. All nanoemulsions were characterised for droplet size, zeta potential and PDI using DLS, and stability wasevaluated. References [1] Arghidash F, et al. Exploring the multifaceted effects of silymarin on melanoma: Focusing on the role of lipid-based nanocarriers. J Drug Deliv Sci Technol. 2024;99:105950. [2] Lee MH, et al. Direct targeting of MEK1/2 and RSK2 by silybin induces cell-cycle arrest and inhibits melanoma cell growth. Cancer Prev Res (Phila). 2013;6(5):455–65. [3] Sánchez-López E, et al. Current applications of nanoemulsions in cancer therapeutics. Nanomaterials. 2019;9(6):821. [4] Panyajai P, et al. Anticancer activity of Zingiber ottensii essential oil and its nanoformulations. PLoS One. 2022;17(1):e0262335. [5] Wala K, et al. Anticancer efficacy of 6-gingerol with paclitaxel against wild-type of human breast adenocarcinoma. Molecules. 2022;27(9):2693.