Objective To prepare galangin-whey protein-nanoparticles (Gal-WP-NPs), and study its oral pharmacokinetic behavior and protective effect on the hepatic ischemia reperfusion injury in vivo. Methods Single-factor experiments were conducted to investigate the effects of various formulation processes on Gal-WP-NPs. Box-Behnken design-response surface methodology (BBD-RSM) was used to obtain its optimal prescriptions. Entrapment efficiency, drug loading, particle size and ζ potential were determined. Gal-WP-NPs powder was prepared by freeze-drying method. Transmission electron microscopy (TEM) was used to observe the microstructure of Gal-WP-NPs. Galangin crystal in Gal-WP-NPs powder was analyzed by X-ray powder diffraction (XRPD). Solubility of galangin and Gal-WP-NPs powder were compared, and drug release behavior of Gal-WP-NPs in gastrointestinal fluid was determined. SD rats were administered galangin and Gal-WP-NPs via ig at a dose of 150 mg/kg (calculated as galangin), the main pharmacokinetic parameters and relative bioavailability of Gal-WP-NPs were calculated. The model of hepatic ischemia reperfusion injury was established, and then the protective effects of galangin and Gal-WP-NPs were compare on the hepatic ischemia reperfusion injury. Results Optimal formulation processes of Gal-WP-NPs: the volume ratio of the anti-solvent phase to the solvent phase was 15.40:1, the amounts ratio of whey protein to galangin was 15.05:1, and the ultrasonic power was 82.00 W. Envelopment efficiency, drug loading, particle size and ζ potential were (94.07 ± 0.98)%, (5.76 ± 0.09)%, (197.39 ± 4.46) nm and (-23.79 ± 0.75) mV, respectively. Gal-WP-NPs are spherical nanoparticles. Galangin existed as an amorphous state in Gal-WP-NPs powder. Solubility of galangin was significantly increased (P < 0.01), and the release process of Gal-WP-NPs in vitro conformed to the Weibull model. The peak time (t_max) of Gal-WP-NPs was delayed to (2.17 ± 0.64) h, half-life period (t_1/2) was increased to (5.11 ± 0.95) h, and oral relative bioavailability was increased to 6.58 times. Gal-WP-NPs significantly enhanced the protective effect of galangin on the hepatic ischemia reperfusion injury. Conclusion Gal-WP-NPs significantly increased the oral relative bioavailability of galangin and enhanced the protective effect on the hepatic ischemia reperfusion injury.

galangin  /  whey protein  /  nanoparticles  /  Box-Behnken design-response surface methodology  /  pharmacokinetics  /  bioavailability  /  hepatic ischemia reperfusion injury