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

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 ~4-fold increment in plasma RV Cmax and ~2-fold 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.

Resveratrol Delivery from Implanted Cyclodextrin Polymers Provides Sustained Antioxidant Effect on Implanted Neural Probes

“…Previous work demonstrated various formulations of cyclodextrin ability to improve resveratrol biodistribution, utilizing the CD/resveratrol inclusion complex to overcome resveratrol's low aqueous solubility and bioavailability [53][54][55]. However, the majority of these formulations incorporated the monomer form of CD (either natural or modified), which unfortunately has limited translational use due to nephrotoxicity concerns and hastened delivery kinetics [56,57].…”

An Innovative Strategy for Oral Biofilm Control in Early Childhood Based on a Resveratrol-Cyclodextrin Nanotechnology Approach

“…RV-HPβCD complexation has already been described [ 18 , 19 ]. The mouthwash was obtained as follows: RV (0.318% w / v , purchased from Fagron, Bologna, Italy) and HPβCD (0.318% w / v , purchased from Roquette, Lestrem, France) were mixed with deionized water in a clean and sterile recipient by means of a dissolver operated to shake at low speed without swirling for 5 h.…”

“…Indeed, the complexation of RV with 2-hydroxypropyl-β-CD (HPβCD), a semisynthetic CD, has been proved effective in enhancing RV water solubility, bioavailability and efficacy [ 17 , 18 ]. A recent study in a mouse model demonstrated that the oral administration of RV-HPβCD increased two-fold the RV tissue bioavailability than when delivered into aqueous nanosuspension [ 19 ]. Furthermore, HPβCD has an excellent safety profile, resulting neither in local nor in systemic toxic effect on oral tissues after ingestion [ 18 , 20 ].…”

Inclusion Complex of Resveratrol with γ-Cyclodextrin as a Functional Ingredient for Lemon Juices

“…Interestingly, the solubilizing effect of γ-CD on RSV is similar to that exhibited by α-CD [15,16]. RSV is also described to form inclusion complexes with several chemically modified CDs, including the randomly methylated derivatives of α-CD (RAMEA) [19] and of β-CD (RAMEB) [19,20], the 2,6-permethylated derivative of β-CD (DIMEB) [19], sulfobutylether-β-CD [21] and the randomly (2-hydroxy)propylated derivative of β-CD (HP-β-CD) [10][11][12]22,23]. HP-β-CD, in a comparative study, was demonstrated to have the strongest binding affinity to RSV, followed by RAMEB [24].…”