DEVELOPMENT AND CHARACTERISATION OF QUERCETIN PHYTOSOMES FOR ENHANCED ANTIOXIDANT ACTIVITY

Abstract

Quercetin is a naturally occurring flavonoid with well-established antioxidant, anti-inflammatory, and therapeutic potential; however, its clinical application is significantly limited by poor aqueous solubility, low oral bioavailability, and rapid metabolism. The present study aimed to develop and optimize a quercetin phytosomal formulation using phosphatidylcholine to enhance its physicochemical characteristics and antioxidant performance. Quercetin phytosomes were prepared by the solvent evaporation (thin-film hydration) technique, and formulation variables including phospholipid concentration, drug concentration, and stirring time were systematically Optimised. The Optimised formulation (P6) with a drug-to-phospholipid ratio of 1:2 exhibited the most desirable physicochemical characteristics, including a particle size of 218.4 ± 12.6 nm, zeta potential of −29.6 ± 1.7 mV, porosity of 61.8 ± 2.5%, and an entrapment efficiency of 93.8 ± 1.9%, indicating efficient molecular complexation and excellent colloidal stability. Differential Scanning Calorimetry (DSC) demonstrated the disappearance of the characteristic crystalline melting peak of quercetin, confirming successful formation of the quercetin–phosphatidylcholine molecular complex and reduced drug crystallinity. In vitro drug release studies revealed a sustained release profile, achieving 82.9% cumulative drug release over 24 h, with release kinetics best described by the Higuchi diffusion model and Korsmeyer–Peppas analysis indicating a nonFickian diffusion mechanism. Furthermore, the Optimised phytosomal formulation exhibited concentrationdependent antioxidant activity, demonstrating significantly greater free radical scavenging than free quercetin at equivalent concentrations, with 72.80 ± 0.65% DPPH inhibition at 100 µg/mL compared with 65.40 ± 0.75% for free quercetin. The enhanced antioxidant activity was attributed to improved aqueous dispersibility, higher drug entrapment, and sustained release from the phospholipid matrix. Overall, the developed quercetin phytosomal system effectively overcame the inherent limitations of quercetin by improving drug encapsulation, physicochemical stability, controlled release, and antioxidant efficacy. These findings demonstrate the potential of phytosomal technology as a promising lipid-based delivery platform for enhancing the therapeutic performance of poorly water-soluble flavonoids and support its further evaluation for pharmaceutical applications.