Design and Optimization of Thermosensitive Hydrogels Combined with Lipid Nanotechnology for Topical Curcumin Application.

A novel co-encapsulation platform based on curcumin-loaded liposomes (Cur-Lip) incorporated into thermosensitive hydrogels (TSH) was developed to address the physicochemical and biological limitations of topical curcumin (Cur) delivery. Response Surface Methodology (RSM) was used to optimize Pluronic® F-127, glycerol, and alginate concentrations with respect to gelation time and viscosity. The optimized formulation (22% Pluronic® F-127, 5% glycerol, and 0.5% alginate) exhibited rapid time sol-gel transition (~86 s), suitable viscosity (~377 mPa·s), excellent model fitting (R2 = 0.99) and prediction accuracy. Three formulations (TSH, Cur-TSH, and Cur-Lip-TSH) were subsequently prepared and displayed appropriate thermoresponsive behavior. The Cur-Lip system showed high encapsulation efficiency (~78%). Upon incorporation into the TSH, Cur-Lip-TSH displayed increased viscosity and mechanical strength at physiological temperature. In vitro studies confirmed its cytocompatibility toward human keratinocytes, significant antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa, and no irritation potential as assessed by the Hen's Egg Test on the Chorioallantoic Membrane assay (HET-CAM). Overall, Cur-Lip-TSH represents a safe and robust thermosensitive platform that provides a foundation for future studies on controlled curcumin release and topical performance.