Chitosan-Coated Nanoemulsion for Quercetin Delivery: Formulation Optimisation and Pharmacokinetic Evaluation

Objective: The present study aimed to develop a chitosan-coated quercetin nanoemulsion (CS-QCT-NE) and to assess its pharmacokinetic performance following oral administration. Methods: A nanoemulsion was formulated using oleic acid as the oil phase, Tween-20 as surfactant, and PEG-200 as cosurfactant. A rotatable central composite design (CCD) with an α value of 1.414 was employed to optimise the nanoemulsion formulation by investigating the influence of organic phase concentration (30-50%), sonication amplitude (20-24%), and sonication time (0-160 s) on globule size (GS), polydispersity index (PDI), and entrapment efficiency (EE). The selected QCT-NE was subsequently coated with low-and medium-molecular-weight chitosan at concentrations of 0.5%, 1.0%, and 1.5% for comparative evaluation, and the 1.5% LMW-coated formulation was empirically selected for further characterisation. It was analysed using transmission electron microscopy (TEM), in vitro drug release testing, and pharmacokinetic and biodistribution studies. Results: The selected CS-QCT-NE exhibited a globule size of 135.4±2.39 nm, PDI of 0.254±0.001, and zeta potential of+26.8±5.97 mV. TEM analysis confirmed spherical droplets with a uniform size distribution. In vitro drug release studies showed 83.72% cumulative drug release in pH 7.4 phosphate buffer within 48 h. Pharmacokinetic assessment showed approximately a 2.43-fold higher systemic exposure, as indicated by AUC0-24, for CS-QCT-NE compared with QCT-PD, corresponding to an exploratory relative oral exposure of 242.8%. Conclusion: The 1.5% LMW chitosan-coated nanoemulsion resulted in higher systemic quercetin (QCT) exposure following oral administration. These pharmacokinetic results are preliminary, and additional studies with a fully validated bioanalytical method are necessary to verify the observed differences.