Development and biological evaluation of a Cotinus coggygria extract-loaded Pluronic F127-HPMC buccal gel formulation

Cotinus coggygria Scop. is a polyphenol-rich medicinal plant traditionally used in topical preparations, and the formulation-dependent effects of its extracts on fibroblast behavior remain insufficiently characterized. In this study, a 60% ethanol extract of C. coggygria was prepared and chemically profiled by LC-HRMS, identifying 6-OH-luteolin-7-O-glucoside as a major constituent. In silico bioactivity prediction of this compound indicated the highest mean probability of activity within the membrane/barrier-associated category (mean Pa = 0.895). An optimized Pluronic F127-HPMC gel formulation incorporating the extract was developed and evaluated using human fibroblasts as an in vitro screening model. Intracellular ATP levels were measured to examine potential effects on cellular bioenergetics, and cell migration was assessed by scratch assay. Within the tested concentration range (5-15 µg/mL), treatment with the extract-loaded gel resulted in reduced intracellular ATP levels by 25% and decreased migration modestly, whereas the extract alone did not significantly alter these parameters, indicating a formulation-dependent modulation of cellular response. In an exploratory Caenorhabditis elegans assay, the extract exhibited a biphasic concentration-dependent response, with the lowest concentration tested (3 µg/mL) producing the greatest lifespan extension, whereas higher concentrations (3000-50 000 µg/mL) progressively reduced survival. Collectively, these findings demonstrate that incorporation of C. coggygria extract into a gel matrix alters cellular bioenergetics and motility.