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Review
. 2019 Jul 25;8(8):244.
doi: 10.3390/antiox8080244.

Strategies to Improve Resveratrol Systemic and Topical Bioavailability: An Update

Sebastiano Intagliata  1 , Maria N Modica  1 , Ludovica M Santagati  1 , Lucia Montenegro  2
Affiliations
Review

Strategies to Improve Resveratrol Systemic and Topical Bioavailability: An Update

Sebastiano Intagliata et al. Antioxidants (Basel). .

Abstract

In recent years, a great deal of attention has been paid to natural compounds due to their many biological effects. Polyphenols are a class of plant derivatives that have been widely investigated for preventing and treating many oxidative stress-related pathological conditions, such as neurodegenerative and cardiovascular diseases, cancer, diabetes mellitus and inflammation. Among these polyphenols, resveratrol (RSV) has attracted considerable interest owing to its high antioxidant and free radical scavenging activities. However, the poor water solubility and rapid metabolism of RSV lead to low bioavailability, thus limiting its clinical efficacy. After discussing the main biochemical mechanisms involved in RSV biological activities, this review will focus on the strategies attempted to improve RSV effectiveness, both for systemic and for topical administration. In particular, technological approaches involving RSV incorporation into different delivery systems such as liposomes, polymeric and lipid nanoparticles, microemulsions and cyclodextrins will be illustrated, highlighting their potential clinical applications. In addition, chemical modifications of this antioxidant aimed at improving its physicochemical properties will be described along with the results of in vitro and in vivo studies.

Keywords: cyclodextrins; drug delivery systems; lipid nanoparticles; liposomes; microemulsions; polymeric nanoparticles; prodrugs; resveratrol.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structure of trans-RSV (3,5,4′-trihydroxy-trans-stilbene).
Figure 2
Figure 2
General structures of RSV prodrugs and RSV analogs.
Figure 3
Figure 3
Schematic representation of drug delivery systems.
Figure 4
Figure 4
Chemical structures of RSV triacetate (1), RSV tri-mPEG1900 (2), RVS trimesylate (3), and 3,5,4′-tri(α-d-glucose-3-O-succinyl)-resveratrol (4).
Figure 5
Figure 5
Chemical structures of PEG-resveratrol prodrugs 5a–f, 6a–l, and 7a–l. * = chiral center
Figure 6
Figure 6
Chemical structures of RSV-3,5-di-O-β-d-glucopyranoside (8), RSV-3-O-(6′-O-butanoyl)-β-d-glucopyranoside (9), RSV-3-O-(6′-O-octanoyl)-β-d-glucopyranoside (10).
Figure 7
Figure 7
Chemical structures of acetal derivatives of RSV (11–13).
Figure 8
Figure 8
Chemical structures of N,N-disubstituted carbamoyl-RSV derivatives 14, and 15.
Figure 9
Figure 9
General formula of N-monosubstituted carbamoyl-RSV derivatives, and chemical structure of 16.
Figure 10
Figure 10
Chemical structures of methoxy-oligo(ethylene glycol)-carbamate substituted prodrugs, 17–19.
Figure 11
Figure 11
Chemical structures of N-monosubstituted carbamate amino acidic prodrugs 20–23, and 24a–i.
Figure 12
Figure 12
Chemical structures of RSV-triphenylphosphonium derivatives 25–30.
Figure 13
Figure 13
Chemical structures of 3,5-O-digalloylresveratrol (DIG) 31, RSV-aspirin hybrid (RAH) 32, and compound 33.
Figure 14
Figure 14
Chemical structures of 4′-RSV ester derivatives 34–38, and mono and diester RSV derivatives 39a–l.
Figure 15
Figure 15
Chemical structures of RSV triphosphate (40) and RSV triglycolate (41).
Figure 16
Figure 16
Chemical structures of RSV 4′-isobutyrate (37), RSV 4′-butyrate (38), RSV 4′-palmitoate (42), RSV 3-acetate (43), and RSV 3,5-diacetate (44).
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