Phytosomes against melanoma: disrupting molecular pathways with targeted phytochemical delivery

Melanoma is still the most lethal form of skin cancer causing approximately 56,000 fatalities annually. This cancer is primarily caused by molecular variations in the MAPK, PI3K/AKT, Wnt/β-catenin, p53, and immune signalling pathways. Even though immunotherapies and targeted agents have extended survival, resistance to therapy, toxicity, and limited accessibility still hinder progress worldwide. Various phytoconstituents obtained from natural sources, incorporating flavonoids, terpenoids, alkaloids, and polyphenols, have shown potent antiproliferative, pro-apoptotic, anti-inflammatory, and anti-metastatic effects in melanoma. However, their clinical use is limited by rapid metabolism, minimal systemic stability, poor absorption, and lack of tumor targeting despite attractive preclinical data. A significant improvement in phytochemical delivery in the form of nanoliposomes has emerged, introducing phytosome technology. This technology overcomes the drawbacks by producing stable phospholipid complexes with phytochemicals, thereby enhancing their solubility, bioavailability, membrane-permeability, and pharmacokinetic parameters. This comprehensive study covers the cellular mechanisms of melanoma, the drawbacks of existing therapies, the benefits of nanotechnology-based strategies and the increasing importance of phytosomes as a delivery vehicle for anticancer phytochemicals. It explains the progress in preparation methods, therapeutic effects, preclinical investigations, and the challenges in translating phytosome-based drug delivery for cutaneous melanoma.