Curcumin-Based Nanoformulations for Oral Health: Mechanistic Insights, Antimicrobial Efficacy, and Future Clinical Perspectives.

Background/Objectives: Oral diseases remain among the most prevalent noncommunicable conditions worldwide, with biofilm-driven dysbiosis playing a central role in dental caries, gingivitis, periodontitis, and oral candidiasis. Curcumin has attracted considerable interest because of its anti-inflammatory, antioxidant, antimicrobial, and regenerative properties. However, its clinical use remains limited by poor water solubility, chemical instability, rapid metabolism, and low bioavailability. This review aimed to provide a comprehensive analysis of curcumin-based nanoformulations for oral health applications, with emphasis on their mechanistic actions, antibiofilm activity, and translational relevance. Methods: This review examined representative nanocarrier systems developed for curcumin delivery in oral health. These included polymeric nanoparticles, nanomicelles and nanoemulsions, solid lipid nanoparticles and nanostructured lipid carriers, nanogels, hydrogels, mucoadhesive films, and metallic or hybrid nanosystems. The analysis focused on molecular mechanisms of action, antimicrobial and antibiofilm effects against major oral pathogens, and key translational challenges. Results/Findings: Across the reviewed studies, nanoformulations consistently improved curcumin solubility, stability, tissue penetration, mucosal retention, and controlled release. Mechanistically, they enhanced anti-inflammatory activity through inhibition of nuclear factor kappa B (NF-κB), strengthened antioxidant defenses via the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) axis, supported tissue repair and osteogenic responses, disrupted oral biofilms, and modulated local immune responses. Antimicrobial activity was reported against Streptococcus mutans, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Candida albicans, with reduced exopolysaccharide production, impaired adhesion, and improved biofilm penetration. Conclusions: Curcumin-based nanoformulations represent promising adjunctive platforms for oral healthcare. However, their clinical translation still requires improved stability in the oral-environment standardized manufacturing and characterization, rigorous safety evaluation, and well-designed controlled clinical studies.