Novel curcumin formulations for the therapy of oral cancer: a comprehensive review of mechanisms, delivery systems, and translational prospects

Oral cancer, particularly oral squamous cell carcinoma, represents a major global health challenge with high rates of morbidity and mortality. Current treatments often encounter limitations such as toxicity and drug resistance. Curcumin, a natural polyphenol derived from turmeric, has shown significant promise as a therapeutic agent due to its anti-inflammatory, antioxidant, and broad-spectrum anticancer activities. However, its clinical application has been limited by poor solubility, rapid metabolism, and low bioavailability. This review examines the potential of novel curcumin formulations developed to address these challenges in oral cancer treatment. It explores advanced delivery systems including nanoparticle-based carriers, liposomes, niosomes, and hybrid technologies that enhance bioavailability and enable targeted delivery. Additionally, the review discusses synthetic curcumin analogues that offer improved stability and potency. These innovative approaches demonstrate enhanced anticancer effects through pro-apoptotic, anti-proliferative, and anti-angiogenic mechanisms, often exhibiting synergistic activity with conventional therapies. This review aims to synthesize current evidence on the mechanisms and efficacy of these advanced curcumin-based strategies and provide future perspectives on their role as safe and effective options in oral oncology.