Preclinical pharmacokinetics comparison between resveratrol 2-hydroxypropyl-β-cyclodextrin complex and resveratrol suspension after oral administration

Trans-Resveratrol (RV) is a natural polyphenol characterized by interesting pleiotropic potentials and health benefits, but its administration is hampered by a unsatisfactory pharmacokinetics. Various approaches have been identified to circumvent it: among them, 2-hydroxypropyl-beta-cyclodextrins (HP beta CD) are valuable strategy. Here, we compare the employment of HP beta CD based formulation with a resveratrol nanosupension (obtained by diluting a RV ethanol solution with PBS, added of 0.05 % hydroxyethylcellulose) to improve RV bioavailability after oral administration to mice. The inclusion of RV in HP beta CD was confirmed by differential scanning calorimetry, Fourier transformed infrared spectroscopy, and phase solubility study. The two formulations were orally administered to BALB-c mice. RV concentrations in plasma and tissues were detected at different time (0-120 min) by HPLC method. HP beta CD complexation mediate a approximately fourfold increment in plasma RV C-max and approximately twofold augment of RV AUC(0-120) in comparison with RV nanosuspension. Similar increased concentrations were observed in heart, liver, kidney and gut. In particular, HP beta CD mediated a 5.5-folds increase of resveratrol concentration in the intestine, in comparison to the nanosuspension. In conclusion, based on our results, HP beta CD complexation is a promising approach to increase the oral bioavailability of RV. Moreover, the achievement of high concentrations in gut suggested a potential employment of oral RV-HP beta CD as anti-inflammatory/chemopreventive agent in this tissue.