{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T17:22:15Z","timestamp":1792430535875,"version":"4.5.0"},"reference-count":246,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T00:00:00Z","timestamp":1713744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lebanese International University (LIU)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Overcoming the limited bioavailability and extensive metabolism of effective in vitro drugs remains a challenge that limits the translation of promising drugs into clinical trials. Resveratrol, despite its well-reported therapeutic benefits, is not metabolically stable and thus has not been utilized as an effective clinical drug. This is because it needs to be consumed in large amounts to overcome the burdens of bioavailability and conversion into less effective metabolites. Herein, we summarize the more relevant approaches to modify resveratrol, aiming to increase its biological and therapeutic efficacy. We discuss combination therapies, derivatization, and the use of resveratrol nanoparticles. Interestingly, the combination of resveratrol with established chemotherapeutic drugs has shown promising therapeutic effects on colon cancer (with oxaliplatin), liver cancer (with cisplatin, 5-FU), and gastric cancer (with doxorubicin). On the other hand, derivatizing resveratrol, including hydroxylation, amination, amidation, imidation, methoxylation, prenylation, halogenation, glycosylation, and oligomerization, differentially modifies its bioavailability and could be used for preferential therapeutic outcomes. Moreover, the encapsulation of resveratrol allows its trapping within different forms of shells for targeted therapy. Depending on the nanoparticle used, it can enhance its solubility and absorption, increasing its bioavailability and efficacy. These include polymers, metals, solid lipids, and other nanoparticles that have shown promising preclinical results, adding more \u201chype\u201d to the research on resveratrol. This review provides a platform to compare the different approaches to allow directed research into better treatment options with resveratrol.<\/jats:p>","DOI":"10.3390\/pharmaceutics16040569","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T09:53:52Z","timestamp":1713779632000},"page":"569","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":114,"title":["Enhancing the Bioavailability of Resveratrol: Combine It, Derivatize It, or Encapsulate It?"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4744-0954","authenticated-orcid":false,"given":"Mohamed","family":"Salla","sequence":"first","affiliation":[{"name":"Department of Biological and Chemical Sciences, School of Arts and Sciences, Lebanese International University, Khiyara\u2014West Bekaa, Bayrut P.O. Box 146404, Lebanon"},{"name":"Department of Biochemistry, Faculty of Medicine & Dentistry, University of Alberta, 113 Street 87 Avenue, Edmonton, AB T6G 2E1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Karaki","sequence":"additional","affiliation":[{"name":"Department of Biological and Chemical Sciences, School of Arts and Sciences, Lebanese International University, Khiyara\u2014West Bekaa, Bayrut P.O. Box 146404, Lebanon"},{"name":"Department of Chemistry and Biochemistry, Faculty of Arts and Sciences, Lebanese University, Zahl\u00e9 1801, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belal","family":"El Kaderi","sequence":"additional","affiliation":[{"name":"Department of Biological and Chemical Sciences, School of Arts and Sciences, Lebanese International University, Khiyara\u2014West Bekaa, Bayrut P.O. Box 146404, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abeer J.","family":"Ayoub","sequence":"additional","affiliation":[{"name":"Department of Biological and Chemical Sciences, School of Arts and Sciences, Lebanese International University, Khiyara\u2014West Bekaa, Bayrut P.O. Box 146404, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0443-0326","authenticated-orcid":false,"given":"Samar","family":"Younes","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Pharmacy, Lebanese International University, Khiyara\u2014West Bekaa, Bayrut P.O. Box 146404, Lebanon"},{"name":"INSPECT-LB (National Institute of Public Health, Clinical Epidemiology and Toxicology-Lebanon (INSPECT-LB)), Beirut 1103, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6352-4122","authenticated-orcid":false,"given":"Maya N.","family":"Abou Chahla","sequence":"additional","affiliation":[{"name":"Department of Biological and Chemical Sciences, School of Arts and Sciences, Lebanese International University, Khiyara\u2014West Bekaa, Bayrut P.O. Box 146404, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3822-6286","authenticated-orcid":false,"given":"Shairaz","family":"Baksh","sequence":"additional","affiliation":[{"name":"BioImmuno Designs, 4747 154 Avenue, Edmonton, AB T5Y 0C2, Canada"},{"name":"Bio-Stream Diagnostics, 2011 94 Street, Edmonton, AB T6H 1N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3611-3288","authenticated-orcid":false,"given":"Sami","family":"El Khatib","sequence":"additional","affiliation":[{"name":"Department of Biological and Chemical Sciences, School of Arts and Sciences, Lebanese International University, Khiyara\u2014West Bekaa, Bayrut P.O. Box 146404, Lebanon"},{"name":"Department of Biomedical Sciences, School of Arts and Sciences, Lebanese International University, Khiyara\u2014West Bekaa, Bayrut P.O. Box 146404, Lebanon"},{"name":"Center for Applied Mathematics and Bioinformatics (CAMB), Gulf University for Science and Technology, Mubarak Al-Abdullah 32093, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Salehi, B., Mishra, A.P., Nigam, M., Sener, B., Kilic, M., Sharifi-Rad, M., Fokou, P.V.T., Martins, N., and Sharifi-Rad, J. (2018). Resveratrol: A Double-Edged Sword in Health Benefits. Biomedicines, 6.","DOI":"10.3390\/biomedicines6030091"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zhang, L.-X., Li, C.-X., Kakar, M.U., Khan, M.S., Wu, P.-F., Amir, R.M., Dai, D.-F., Naveed, M., Li, Q.-Y., and Saeed, M. (2021). Resveratrol (RV): A Pharmacological Review and Call for Further Research. Biomed. 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