Abstract
Resveratrol (3,5,4′-trihydroxystilbene; RSV) is a natural nonflavonoid polyphenol present in many species of plants, particularly in grapes, blueberries, and peanuts. Several in vitro and in vivo studies have shown that in addition to antioxidant, anti-inflammatory, cardioprotective and neuroprotective actions, it exhibits antitumor properties. In mammalian models, RSV is extensively metabolized and rapidly eliminated and therefore it shows a poor bioavailability, in spite it of its lipophilic nature. During the past decade, in order to improve RSV low aqueous solubility, absorption, membrane transport, and its poor bioavailability, various methodological approaches and different synthetic derivatives have been developed. In this review, we will describe the strategies used to improve pharmacokinetic characteristics and then beneficial effects of RSV. These methodological approaches include RSV nanoencapsulation in lipid nanocarriers or liposomes, nanoemulsions, micelles, insertion into polymeric particles, solid dispersions, and nanocrystals. Moreover, the biological results obtained on several synthetic derivatives containing different substituents, such as methoxylic, hydroxylic groups, or halogens on the RSV aromatic rings, will be described. Results reported in the literature are encouraging but require additional in vivo studies, to support clinical applications.
Highlights
Natural products have recently aroused interest within the scientific community for their beneficial effects on several diseases
The biological results obtained on several synthetic derivatives containing different substituents, such as methoxylic, hydroxylic groups, or halogens on the RSV aromatic rings, will be described
Similar results were obtained by incorporation of grape peel extract (GPE) into a solid dispersion delivery system or dripping pill (DP) (GPEDP) oral delivery system and testing effects on rats [58]
Summary
Several reports confirmed that RSV possesses health beneficial effects, this compound shows peculiar pharmacokinetic characteristics that limit its use. RSV is absorbed at the intestinal level by passive diffusion or by membrane transporters and released in the bloodstream where it can be detected as unmodified or metabolized molecule [45]. It has been reported that the majority of plasma RSV metabolites are RSV-3-O-sulfate, RSV-4 -O-glucuronide, and RSV-3-O-glucuronide, all with very little bioactivity, even if RSV-3-O-sulfate possesses estrogen receptor α-preferential antagonistic activity [48]. Glucuronide, all with very little bioactivity, even if RSV-3-O-sulfate possesses estrogen receptor αpreferential antagonistic activity [48]. SSiinnccee RRSSVV hhaass aa lliimmiitteedd ddiissssoolluuttiioonn rraattee iinn tthhee aaqquueeoouuss eennvviirroonnmmeenntt,, aa ssmmaallll iinnccrreeaassee iinn ssoolluubbiilliittyy mmaayy ssiiggnniifificcaannttllyy eennhhaannccee iittss bbiiooaavvaaiillaabbiilliittyy [[5577]]. Nanonization of the drug particles producing nanocrystals represents a very promising strategy that improves solubility, dissolution rate of insoluble drugs, physical and chemical stability, compatibility in oral forms of dosage, and oral bioavailability [61]
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