Enhanced brain delivery and antiproliferative activity of resveratrol using milk-derived exosomes
The polyphenol resveratrol (RSV) undergoes extensive phase II metabolism, which limits its bioavailability and bioactivity, including anticancer effects. Growing preclinical evidence reinforces milk-derived exosomes (EXOs) as promising nanocarrier drugs and bioactives delivery systems. Herein, to ov...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | Journal of Agriculture and Food Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666154324004071 |
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| author | María Ángeles Ávila-Gálvez Beatriz Garay-Mayol Juan Antonio Giménez-Bastida María del Carmen López de las Hazas Carmen Mazarío-Gárgoles Maria Alexandra Brito Alberto Dávalos Juan Carlos Espín Antonio González-Sarrías |
| author_facet | María Ángeles Ávila-Gálvez Beatriz Garay-Mayol Juan Antonio Giménez-Bastida María del Carmen López de las Hazas Carmen Mazarío-Gárgoles Maria Alexandra Brito Alberto Dávalos Juan Carlos Espín Antonio González-Sarrías |
| author_sort | María Ángeles Ávila-Gálvez |
| collection | DOAJ |
| description | The polyphenol resveratrol (RSV) undergoes extensive phase II metabolism, which limits its bioavailability and bioactivity, including anticancer effects. Growing preclinical evidence reinforces milk-derived exosomes (EXOs) as promising nanocarrier drugs and bioactives delivery systems. Herein, to overcome the mentioned RSV's drawbacks, EXOs were loaded with RSV (EXO-RSV) to evaluate its brain delivery in Sprague-Dawley rats and its in vitro antiproliferative effects against human neuroblastoma SH-SY5Y and glioblastoma U-87MG cancer cells compared with non-encapsulated RSV. Pharmacokinetic analyses in perfused brains showed RSV detection only after EXO-RSV administration, not after non-encapsulated RSV administration. Encapsulation also resulted in lower concentrations of phase II-derived RSV metabolites in circulation. Additionally, blood-brain barrier (BBB) transport assays using human brain microvascular endothelial cells (HBMECs) corroborated that encapsulation enhanced RSV transport efficiency and protected it from cellular metabolism. In vitro and in silico analyses of phase-II conjugates, primarily RSV 3-glucuronide, showed lower capacity than RSV to cross the BBB. Finally, EXO-RSV (47−750 nM) showed an increased dose-dependent antiproliferative efficacy on both cancer cell lines compared with the non-encapsulated RSV (10 μM), which was ineffective after 72 h of treatment. Our findings suggest that EXOs protect RSV from phase II metabolism and enhance its brain delivery and antiproliferative activity. |
| format | Article |
| id | doaj-art-369671571ba04b79a3dfb9c8c8e5ccd2 |
| institution | DOAJ |
| issn | 2666-1543 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Agriculture and Food Research |
| spelling | doaj-art-369671571ba04b79a3dfb9c8c8e5ccd22025-08-20T02:49:05ZengElsevierJournal of Agriculture and Food Research2666-15432024-12-011810137010.1016/j.jafr.2024.101370Enhanced brain delivery and antiproliferative activity of resveratrol using milk-derived exosomesMaría Ángeles Ávila-Gálvez0Beatriz Garay-Mayol1Juan Antonio Giménez-Bastida2María del Carmen López de las Hazas3Carmen Mazarío-Gárgoles4Maria Alexandra Brito5Alberto Dávalos6Juan Carlos Espín7Antonio González-Sarrías8Laboratory of Food and Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, Dept. Food Science and Technology, CEBAS-CSIC, 30100 Campus de Espinardo, Murcia, SpainLaboratory of Food and Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, Dept. Food Science and Technology, CEBAS-CSIC, 30100 Campus de Espinardo, Murcia, SpainLaboratory of Food and Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, Dept. Food Science and Technology, CEBAS-CSIC, 30100 Campus de Espinardo, Murcia, SpainLaboratory of Epigenetics of Lipid Metabolism, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, 28049, Madrid, SpainLaboratory of Epigenetics of Lipid Metabolism, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, 28049, Madrid, SpainResearch Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal; Department of Pharmaceutical Sciences and Medicines, Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, PortugalLaboratory of Epigenetics of Lipid Metabolism, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, 28049, Madrid, Spain; Consorcio CIBER de la Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III (ISCIII), Madrid, 28029, SpainLaboratory of Food and Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, Dept. Food Science and Technology, CEBAS-CSIC, 30100 Campus de Espinardo, Murcia, Spain; Corresponding author.Laboratory of Food and Health, Research Group on Quality, Safety and Bioactivity of Plant Foods, Dept. Food Science and Technology, CEBAS-CSIC, 30100 Campus de Espinardo, Murcia, Spain; Corresponding author.The polyphenol resveratrol (RSV) undergoes extensive phase II metabolism, which limits its bioavailability and bioactivity, including anticancer effects. Growing preclinical evidence reinforces milk-derived exosomes (EXOs) as promising nanocarrier drugs and bioactives delivery systems. Herein, to overcome the mentioned RSV's drawbacks, EXOs were loaded with RSV (EXO-RSV) to evaluate its brain delivery in Sprague-Dawley rats and its in vitro antiproliferative effects against human neuroblastoma SH-SY5Y and glioblastoma U-87MG cancer cells compared with non-encapsulated RSV. Pharmacokinetic analyses in perfused brains showed RSV detection only after EXO-RSV administration, not after non-encapsulated RSV administration. Encapsulation also resulted in lower concentrations of phase II-derived RSV metabolites in circulation. Additionally, blood-brain barrier (BBB) transport assays using human brain microvascular endothelial cells (HBMECs) corroborated that encapsulation enhanced RSV transport efficiency and protected it from cellular metabolism. In vitro and in silico analyses of phase-II conjugates, primarily RSV 3-glucuronide, showed lower capacity than RSV to cross the BBB. Finally, EXO-RSV (47−750 nM) showed an increased dose-dependent antiproliferative efficacy on both cancer cell lines compared with the non-encapsulated RSV (10 μM), which was ineffective after 72 h of treatment. Our findings suggest that EXOs protect RSV from phase II metabolism and enhance its brain delivery and antiproliferative activity.http://www.sciencedirect.com/science/article/pii/S2666154324004071ExosomeNanocarrierPolyphenolResveratrolBrain cancerBlood-brain barrier |
| spellingShingle | María Ángeles Ávila-Gálvez Beatriz Garay-Mayol Juan Antonio Giménez-Bastida María del Carmen López de las Hazas Carmen Mazarío-Gárgoles Maria Alexandra Brito Alberto Dávalos Juan Carlos Espín Antonio González-Sarrías Enhanced brain delivery and antiproliferative activity of resveratrol using milk-derived exosomes Journal of Agriculture and Food Research Exosome Nanocarrier Polyphenol Resveratrol Brain cancer Blood-brain barrier |
| title | Enhanced brain delivery and antiproliferative activity of resveratrol using milk-derived exosomes |
| title_full | Enhanced brain delivery and antiproliferative activity of resveratrol using milk-derived exosomes |
| title_fullStr | Enhanced brain delivery and antiproliferative activity of resveratrol using milk-derived exosomes |
| title_full_unstemmed | Enhanced brain delivery and antiproliferative activity of resveratrol using milk-derived exosomes |
| title_short | Enhanced brain delivery and antiproliferative activity of resveratrol using milk-derived exosomes |
| title_sort | enhanced brain delivery and antiproliferative activity of resveratrol using milk derived exosomes |
| topic | Exosome Nanocarrier Polyphenol Resveratrol Brain cancer Blood-brain barrier |
| url | http://www.sciencedirect.com/science/article/pii/S2666154324004071 |
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