Engineering Thermoresponsive In Situ Gels Incorporating Nutraceutical-Laden Nanostructured Lipid Carriers for...

Periodontitis is a chronic inflammatory disease marked by the progressive destruction of periodontal tissues, where conventional therapies often fail to maintain adequate drug levels at the target site. This study reports the development and characterization of a thermosensitive gel containing nanostructured lipid carriers (NLC) for controlled local periodontal delivery. Apigenin (AP)-loaded NLC were prepared using AP as active agent and clove essential oil (CEO) as liquid lipid subsequently incorporated into Poloxamer 407 (5-15% w/w) hydrogels. The formulations were evaluated in relation to particle size, morphology, thermal and rheological behavior, mucoadhesion, in vitro release, antibacterial activity, and stability. Optimized nanoscale NLC showed a high entrapment efficiency, and uniform morphology. Raman analysis confirmed successful AP incorporation and homogeneous distribution in the gel without incompatibility. NLC-loaded gels exhibited sol-gel transition at physiological temperature with improved viscoelasticity and enhanced mucoadhesion. The drug release was sustained for 48 h and followed the Korsmeyer-Peppas model, indicating diffusion-based and anomalous transport. The antibacterial assessment demonstrated the pronounced inhibitory activity of the NLC formulations against key periodontal pathogens, with the formulation-dependent modulation of antimicrobial efficacy observed following the gel incorporation. Stability studies showed preserved nanoparticle structure and uniform dispersion. Overall, the thermoresponsive NLC-hydrogel system offers a promising strategy for prolonged, localized periodontal therapy.