Thermoresponsive curcumin-loaded solid lipid nanoparticle hydrogel for periodontitis: In vitro, ex vivo, and pilot clinical evaluation

Periodontitis (PD) is a chronic inflammatory disease caused by oral dysbiosis, aggravated by oxidative stress, leading to gum recession, periodontal pocket formation, clinical attachment loss, alveolar bone loss and eventually tooth loss. Curcumin, possesses antioxidant, antimicrobial, and anti-inflammatory properties making it suitable for periodontitis control, but its clinical efficacy is limited by poor solubility and instability. Curcumin-loaded solid lipid nanoparticles (C-SLNs), previously optimised to improve solubility, stability, and permeability, were formulated for periodontal pocket application. C-SLNs showed 62.8–83.9% in vitro biofilm inhibition against clinical sub-gingival plaque isolates, at 1500 and 2000 μg/mL, respectively. EPS matrix fragmentation, dispersion and bacterial cell lysis were observed in biofilms grown ex vivo on dentine discs treated with 1500 μg/mL of C-SLNs, indicating biofilm penetration. Confocal microscopy showed a 38-fold greater cellular uptake of fluorescein isothiocyanate loaded F-SLNs than free fluorescein isothiocyanate in human epithelial carcinoma cells. The C-SLNs dispersion was lyophilized and incorporated into a thermoresponsive Carbopol–poloxamer hydrogel to improve its structural integrity, adhesion, and retention in periodontal pockets. C-SLN hydrogel (particle size 618 nm) containing 0.6% w/v curcumin, exhibited gelation temperature of 32.7 ± 0.52 °C, acceptable syringeability and desirable consistency, > 70% cell viability and sustained release for seven days. In a randomized, parallel-arm pilot clinical trial (30 patients) C-SLN hydrogel when applied concomitantly with scaling and root planing, produced significantly greater improvements in probing pocket depth (2.7 times; p < 0.001) and clinical attachment level (1.5 times; P = 0.004) at 3 month in comparison to results at 1 month, than SRP alone treatment, supporting its potential as a non- antibiotic adjunctive strategy for periodontitis. Larger, adequately powered controlled clinical studies are however warranted.