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

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.

The study aimed to develop and optimize QUR-loaded invasomes (QUR-INV) for topical administration.

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.

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).

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.