Lipid-Coated Nanocrystals as a Tool for Improving the Antioxidant Activity of Resveratrol

Abstract

Trans-resveratrol, a polyphenolic phytoalexin found in various plant sources, has been the focus of increasing attention in recent years because of its role in the prevention of many human diseases, and particularly because of its antioxidant properties. However, the in vivo effect of trans-resveratrol after oral administration is negligible when compared to its efficacy in vitro, due to its low bioavailability. Moreover, it presents stability issues as it is an extremely photosensitive compound when exposed to light. This work aims to develop lipid-coated nanocrystals in order to improve the antioxidant activity and bioavailability of trans-resveratrol. Lipid-coated trans-resveratrol nanocrystals with sizes lower than 500 nm, spherical shapes and smooth surfaces were obtained via a milling method. They showed a faster dissolution rate than the coarse trans-resveratrol powder. The antioxidant properties of trans-resveratrol were not impaired by the milling process. The in vivo pharmacokinetics of lipid-coated trans-resveratrol nanocrystals were evaluated after oral administration to rats, with a commercial Phytosome^® formulation being used for comparison purposes. An increase in the trans-resveratrol area under the curve was observed and the lipid-coated nanocrystal formulation led to an enhancement in the oral bioavailability of the compound.

Keywords: lipid coating; nanocrystals; oral bioavailability; trans-resveratrol.

Figure 1

Chemical structures of trans-resveratrol and cis-resveratrol.

Figure 2

SEM images of raw resveratrol (A), trans-resveratrol nanocrystals (B) and lipid-coated nanocrystals (C).

Figure 3

In vitro dissolution profiles of the trans-resveratrol NCs (RV-NC) and lipid-coated trans-resveratrol NCs (LC RV-NC) in comparison with the coarse resveratrol powder (RV) and RV Phytosome^®.

Figure 4

(A) Differential scanning calorimetry (DSC) thermograms of (a) trans-resveratrol (RV), (b) RV nanocrystals (RV-NC), (c) lipid-coated RV nanocrystals (LC RV-NC), (d) RV Phytosome^® and (e) phosphatidylcholine. (B) FTIR spectra of the coarse trans-resveratrol powder (RV), trans-resveratrol nanocrystals (RV-NC), lipid-coated trans-resveratrol nanocrystals (LC RV-NC) and phosphatidylcholine (PC).

Figure 5

(A) In vitro antioxidant activity of trans-resveratrol nanocrystals (RV-NC), lipid-coated trans-resveratrol nanocrystals (LC RV-NC), RV Phytosome^® and the coarse RV suspension (RV) at different concentrations, expressed as DPPH radical scavenging percentage. (B) Lipid peroxidation inhibition activity of trans-resveratrol nanocrystals (RV-NC), lipid coated trans-resveratrol nanocrystals (LC RV-NC), RV Phytosome^® and the coarse RV suspension (RV), evaluated in a TBA assay. The experiments were conducted in triplicate and data are presented as means ± standard deviation (SD).

Figure 6

Plasma concentrations of trans-resveratrol vs. time after the oral administration of RV coarse powder (RV), lipid-coated RV nanocrystals (LC RV-NC) and RV Phytosome^®.