Quercetin-loaded invasomal gel: preparation, optimization, in vitro evaluation and ex vivo skin permeation evaluation.

BACKGROUND: Skin cancer is one of the most common cancers, and effective topical delivery of therapeutic agents is limited by the skin barrier. Quercetin (QUR), a natural flavonoid with antioxidant and antiproliferative properties, has limited application due to its poor solubility and low skin permeability. OBJECTIVE: The study aimed to develop and optimize QUR-loaded invasomes (QUR-INV) for topical administration. METHODS: QUR-INV were prepared using the thin-film hydration method and optimized using a full factorial design, where characterization involve vesicles size, zeta potential, and entrapment efficiency (EE%). Evaluations included in-vitro release, ex-vivo skin permeation, dermatokinetics analysis, antioxidant activity, and cytotoxicity study. RESULTS: The optimized QUR-INV exhibited a vesicle size of 211.5 nm, low polydispersity index (PDI) of 0.219, high negative zeta potential of -37.1 mV, and entrapment efficiency of 89.5%. In-vitro release showed an initial burst release within 4 hr followed by sustained controlled release over 24hr. Ex-vivo skin permeation studies demonstrated ≈2-fold higher QUR permeation from QUR-INV gel than QUR-conventional gel; while dermatokinetic analysis confirming enhanced penetration to deeper skin layers. Antioxidant activity demonstrated that encapsulation of quercetin into invasomes preserves its intrinsic antioxidant functionality; cytotoxicity against A431 epidermoid carcinoma cells revealed significantly lower IC₅₀ for QUR-INV gel (27.96 µg/mL) versus QUR-conventional gel (52.02 µg/mL) and pure QUR (297.36 µg/mL). CONCLUSION: The study successfully developed and optimized the quercetin-loaded invasomal gel with desirable physicochemical characteristics and controlled drug release behaviour. The formulation demonstrated enhanced cytotoxic activity and improved skin permeation, indicating its potential topical delivery system.