Improved antidiabetic potential of quercetin-loaded chitosan–lecithin nanoparticles for effective glycaemic control

Diabetes mellitus is a major global health challenge, causing significant morbidity and mortality. Quercetin (QTN), a natural flavonoid, has potential antidiabetic and insulin-sensitising effects. However, its clinical use is limited by poor solubility and bioavailability. We developed the QTN loaded chitosan–lecithin nanoparticles (QTN/LCHS-NPs) to enhance its therapeutic profile. QTN/LCHS-NPs were synthesised using a 20:1 lecithin:chitosan ratio. Characterisation included encapsulation efficiency (�), particle size and zeta potential (ZP). <i>In vitro</i>, drug release studies were conducted to evaluate release kinetics. <i>In vivo,</i> pharmacokinetic and pharmacodynamic studies were performed in male Wistar rats to assess bioavailability, antidiabetic activity and lipid-modulating effects. The optimised QTN/LCHS-NP formulation exhibited 79.72% �, diameter of 130.1 nm, and a ZP of 23.46 mV. <i>In vitro</i> release studies showed a biphasic pattern, with an initial burst release followed by a sustained release of 86.10% over 24 h. Bioavailability (area under the curve, AUC: 167.22 h⋅µg/mL) exceeded free QTN (AUC: 26.2 h⋅µg/mL). Fasting blood glucose decreased from 292.9 to 107.7 mg/dL, along with improved lipid profiles. QTN/LCHS-NPs significantly enhanced the oral bioavailability of QTN and improved its antidiabetic and antihyperlipidaemic effects, demonstrating their potential as an effective delivery system for addressing metabolic disorders.