33
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Progress to Improve Oral Bioavailability and Beneficial Effects of Resveratrol

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Most cited references171

          • Record: found
          • Abstract: found
          • Article: not found

          High absorption but very low bioavailability of oral resveratrol in humans.

          The dietary polyphenol resveratrol has been shown to have chemopreventive activity against cardiovascular disease and a variety of cancers in model systems, but it is not clear whether the drug reaches the proposed sites of action in vivo after oral ingestion, especially in humans. In this study, we examined the absorption, bioavailability, and metabolism of 14C-resveratrol after oral and i.v. doses in six human volunteers. The absorption of a dietary relevant 25-mg oral dose was at least 70%, with peak plasma levels of resveratrol and metabolites of 491 +/- 90 ng/ml (about 2 microM) and a plasma half-life of 9.2 +/- 0.6 h. However, only trace amounts of unchanged resveratrol (<5 ng/ml) could be detected in plasma. Most of the oral dose was recovered in urine, and liquid chromatography/mass spectrometry analysis identified three metabolic pathways, i.e., sulfate and glucuronic acid conjugation of the phenolic groups and, interestingly, hydrogenation of the aliphatic double bond, the latter likely produced by the intestinal microflora. Extremely rapid sulfate conjugation by the intestine/liver appears to be the rate-limiting step in resveratrol's bioavailability. Although the systemic bioavailability of resveratrol is very low, accumulation of resveratrol in epithelial cells along the aerodigestive tract and potentially active resveratrol metabolites may still produce cancer-preventive and other effects.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Bioavailability of resveratrol.

            This paper reviews our current understanding of the absorption, bioavailability, and metabolism of resveratrol, with an emphasis on humans. The oral absorption of resveratrol in humans is about 75% and is thought to occur mainly by transepithelial diffusion. Extensive metabolism in the intestine and liver results in an oral bioavailability considerably less than 1%. Dose escalation and repeated dose administration of resveratrol does not appear to alter this significantly. Metabolic studies, both in plasma and in urine, have revealed major metabolites to be glucuronides and sulfates of resveratrol. However, reduced dihydroresveratrol conjugates, in addition to highly polar unknown products, may account for as much as 50% of an oral resveratrol dose. Although major sites of metabolism include the intestine and liver (as expected), colonic bacterial metabolism may be more important than previously thought. Deconjugation enzymes such as β-glucuronidase and sulfatase, as well as specific tissue accumulation of resveratrol, may enhance resveratrol efficacy at target sites. Resveratrol analogs, such as methylated derivatives with improved bioavailability, may be important in future research. © 2011 New York Academy of Sciences.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Improving drug solubility for oral delivery using solid dispersions.

              C Leuner (2000)
              The solubility behaviour of drugs remains one of the most challenging aspects in formulation development. With the advent of combinatorial chemistry and high throughput screening, the number of poorly water soluble compounds has dramatically increased. Although solid solutions have tremendous potential for improving drug solubility, 40 years of research have resulted in only a few marketed products using this approach. With the introduction of new manufacturing technologies such as hot melt extrusion, it should be possible to overcome problems in scale-up and for this reason solid solutions are enjoying a renaissance. This article begins with an overview of the historical background and definitions of the various systems including eutectic mixtures, solid dispersions and solid solutions. The remainder of the article is devoted to the production, the different carriers and the methods used for the characterization of solid dispersions.
                Bookmark

                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                19 March 2019
                March 2019
                : 20
                : 6
                : 1381
                Affiliations
                [1 ]Department of Pharmacy and Health and Nutritional Sciences University of Calabria, Via Pietro Bucci, Arcavacata di Rende, 87036 Cosenza, Italy; francesca.deamicis@ 123456unical.it (F.D.A.); rosa.sirianni@ 123456unical.it (R.S.); s.sinicropi@ 123456unical.it (M.S.S.); francesco.puoci@ 123456unical.it (F.P.); ivan.casaburi@ 123456unical.it (I.C.)
                [2 ]Department of Science, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100 Potenza, Italy; carmela.saturnino@ 123456unibas.it
                Author notes
                [* ]Correspondence: adele.chimento@ 123456unical.it (A.C.); v.pezzi@ 123456unical.it (V.P.); Tel.: +39-0984-493184 (A.C.); +39-0984-493148 (V.P.)
                [†]

                These authors contributed equally to this work (co-first authors).

                Author information
                https://orcid.org/0000-0003-2435-8931
                https://orcid.org/0000-0002-5963-6762
                https://orcid.org/0000-0003-2311-2286
                Article
                ijms-20-01381
                10.3390/ijms20061381
                6471659
                30893846
                5e412ae2-9c46-41ee-8798-316c8660e51d
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 February 2019
                : 13 March 2019
                Categories
                Review

                Molecular biology
                resveratrol,resveratrol bioavailability,resveratrol delivery systems,resveratrol derivatives

                Comments

                Comment on this article