Cotinus coggygria Flower Extract-Loaded Liposomes: Physicochemical Characterization, Antimicrobial Activity, Biocompatibility, and Rheological Evaluation of the Developed Topical Emulgel

Background/Objectives: Cotinus coggygria Scop. is a polyphenol-rich medicinal plant with antioxidant and antimicrobial properties. This study aimed to develop a liposomal formulation containing aqueous C. coggygria flower extract, evaluate its physicochemical characteristics, antimicrobial activity, and in vitro biocompatibility, and incorporate it into a topical emulgel. Methods: The aqueous extract was characterized by HPLC analysis and subsequently incorporated into soybean phospholipid liposomes prepared by an in situ method followed by membrane extrusion. Vesicle size, polydispersity index (PDI), and zeta potential were determined. Antimicrobial activity was evaluated against clinically relevant skin-associated bacterial and fungal isolates, while biocompatibility was assessed in MRC-5 fibroblasts and HaCaT keratinocytes using the MTT assay. The liposomal dispersion was subsequently incorporated into an emulgel and characterized with respect to organoleptic properties, pH, and rheological behavior. Results: The aqueous extract was particularly rich in gallic acid (74.52 mg/g DW). The developed liposomes showed a mean diameter of 127.48 ± 1.33 nm, PDI of 0.224 ± 0.008, and zeta potential of −29.39 ± 0.95 mV. Extract-loaded liposomes exhibited antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Citrobacter koseri, Proteus mirabilis, and Candida albicans, with measurable activity retained during prolonged incubation. Empty liposomes were non-cytotoxic, while extract-loaded liposomes maintained cell viability above the cytotoxicity threshold across the entire tested concentration range in both cell lines. The final emulgel was homogeneous, mildly acidic, shear-thinning, predominantly elastic, and structurally more resistant than the placebo formulation. Conclusions: The developed C. coggygria flower extract-loaded liposomal emulgel combines nanoscale delivery, relevant antimicrobial activity, excellent in vitro biocompatibility, and suitable topical rheology. These findings support further investigation of the developed system as a multifunctional topical formulation.