Development and Evaluation of Quercetin-Loaded Invasomal Gel for Enhanced Dermal Drug Delivery

Abstract

Quercetin is a naturally occurring polyphenolic flavonoid widely present in fruits, vegetables and medicinal plants and is known for its potent antioxidant, anti-inflammatory, anticancer and cardioprotective activities. However, its therapeutic potential is significantly limited by poor aqueous solubility, low bioavailability and inadequate permeability across biological membranes. In topical applications, the stratum corneum acts as a major barrier, restricting effective drug penetration and reducing therapeutic efficiency. The present study aims to develop and evaluate a quercetin-loaded invasomal gel to enhance dermal delivery and improve the stability and bioavailability of quercetin. Quercetin-loaded invasomes were prepared using the thin-film hydration method employing phospholipids, ethanol and terpenes as key components to enhance vesicle deformability and skin penetration. The optimized invasomal dispersion was subsequently incorporated into a Carbopol-based hydrogel to obtain a stable topical formulation. The prepared formulations were evaluated for physicochemical parameters such as colour, clarity, homogeneity, pH, viscosity and spreadability. Drug-related parameters including entrapment efficiency, drug content and stability were also assessed. Further evaluation involved in vitro drug release studies, ex vivo permeation studies using egg membrane and antioxidant activity using the DPPH radical scavenging assay. The optimized invasomal gel demonstrated good physical stability, acceptable pH suitable for skin application, uniform drug distribution and excellent spreadability. The formulation showed higher drug release and improved permeation compared to conventional quercetin gel formulations. The antioxidant studies confirmed that the formulation retained the free radical scavenging activity of quercetin. Overall, the invasomal gel system significantly enhanced the solubility, stability and dermal penetration of quercetin. Thus, the developed quercetin invasomal gel represents a promising nanocarrier-based topical delivery system for improving the therapeutic efficacy of poorly soluble phytoconstituents. The formulation is stable, cost-effective and suitable for topical application, indicating its potential for the management of oxidative stress-related and inflammatory skin disorders.