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

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Abstract

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-β-cyclodextrins (HPβCD) are valuable strategy. Here, we compare the employment of HPβCD 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 HPβCD 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. HPβCD complexation mediate a approximately fourfold increment in plasma RV Cmax and  approximately twofold augment of RV AUC0-120 in comparison with RV nanosuspension. Similar increased concentrations were observed in heart, liver, kidney and gut. In particular, HPβCD mediated a 5.5-folds increase of resveratrol concentration in the intestine, in comparison to the nanosuspension. In conclusion, based on our results, HPβCD 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-HPβCD as anti-inflammatory/chemopreventive agent in this tissue.

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Acknowledgments

This work was supported by private grants generously funded by “Ordre International des Anysetiers, Commanderie du Piemont”.

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    Authors and Affiliations

    1. Dipartimento di Scienze Cliniche e Biologiche, Università degli Studi di Torino, Regione Gonzole, 10, 10043, Orbassano, Italy

      Zhiqian Yang, Paolina Salamone, Elisa Pirro, Andrea E. Sprio, Federica Di Scipio, Maria E. Carere & Giovanni N. Berta

    2. Department of Drug Sciences and Technology, Università degli Studi di Torino, Via P. Giuria, 9, 10125, Turin, Italy

      Monica Argenziano & Roberta Cavalli

    3. Department of Molecular Biotechnology and Health Sciences, Università degli Studi di Torino, Via Nizza, 52, 10126, Turin, Italy

      Elena Quaglino & Federica Cavallo

    4. National Institute of Cardiovascular Researches, Via Irnerio, 48, 40126, Bologna, Italy

      Giovanni N. Berta

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    1. Zhiqian Yang
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    2. Monica Argenziano
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    Roberta Cavalli and Giovanni N. Berta have contributed equally at this work.

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    Yang, Z., Argenziano, M., Salamone, P. et al. Preclinical pharmacokinetics comparison between resveratrol 2-hydroxypropyl-β-cyclodextrin complex and resveratrol suspension after oral administration. J Incl Phenom Macrocycl Chem 86, 263–271 (2016). https://doi.org/10.1007/s10847-016-0657-5

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