Intensification of quercetin nanobubble formulation and performance by multi-factor optimization and interaction analysis.

The natural flavonoid Quercetin (QT) showed a potential for various health benefits, but its pharmaceutical applications are hindered by low solubility, permeability, and limited bioavailability. This research aimed to synthesize, develop and optimize polylactic acid co-glycolic acid (PLGA) nanobubbles using solvent evaporation method as a sustained delivery system for QT, thus improving stability and bioavailability. Through a four-factor, three-level Box Behnken Design, 29 experimental runs were carried out to optimize QT-PLGA nanobubbles. An optimized formulation consisted of 50 mg QT, 250 mg PLGA, and 1.89% PVA. The nanobubbles displayed a particle size of 139.5 ± 6.24 nm, polydispersity index of 0.296 ± 0.19, and zeta potential of -23.0 ± 3.44 mV, with an entrapment efficiency of 59.24 ± 3.08%. Analysis through Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction confirmed no drug-polymer interaction, while scanning electron microscopy revealed a uniform spherical nanoparticle. studies exhibited an excellent drug release, and stability studies showed no significant changes after one month. studies in rats demonstrated increased (3.03) and (5.84), indicating an improved sustained release and absorption. These findings underscored a potential of QT-loaded PLGA nanobubbles to enhance the drug kinetics and bioavailability, offering possibilities for targeted drug delivery and improved therapeutic outcomes.