{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T02:08:09Z","timestamp":1768097289910,"version":"3.49.0"},"reference-count":57,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T00:00:00Z","timestamp":1613779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Progetto Operativo Nazionale","award":["PON01_02512"],"award-info":[{"award-number":["PON01_02512"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Palmitoylethanolamide (PEA) is an endogenous anti-inflammatory lipid mediator and a widely used nutraceutical. In this study, we designed, realized, and tested a drug-carrier conjugate between PEA (the active drug) and glucuronic acid (the carrier). The conjugate, named GLUPEA, was characterized for its capability of increasing PEA levels and exerting anti-inflammatory activity both in vitro and in vivo. GLUPEA treatment, compared to the same concentration of PEA, resulted in higher cellular amounts of PEA and the endocannabinoid 2-arachidonoyl glycerol (2-AG), and increased 2-AG-induced transient receptor potential vanilloid type 1 (TRPV1) channel desensitization to capsaicin. GLUPEA inhibited pro-inflammatory monocyte chemoattractant protein 2 (MCP-2) release from stimulated keratinocytes, and it was almost as efficacious as ultra-micronized PEA at reducing colitis in dinitrobenzene sulfonic acid (DNBS)-injected mice when using the same dose. GLUPEA is a novel pro-drug able to efficiently mimic the anti-inflammatory and endocannabinoid enhancing actions of PEA.<\/jats:p>","DOI":"10.3390\/cells10020450","type":"journal-article","created":{"date-parts":[[2021,2,21]],"date-time":"2021-02-21T21:15:01Z","timestamp":1613942101000},"page":"450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Glucuronic Acid-Palmitoylethanolamide Conjugate (GLUPEA) Is an Innovative Drug Delivery System and a Potential Bioregulator"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7394-020X","authenticated-orcid":false,"given":"Emiliano","family":"Manzo","sequence":"first","affiliation":[{"name":"Istituto di Chimica Biomolecolare, CNR, 80078 Pozzuoli, Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aniello","family":"Schiano Moriello","sequence":"additional","affiliation":[{"name":"Istituto di Chimica Biomolecolare, CNR, 80078 Pozzuoli, Napoli, Italy"},{"name":"Endocannabinoid Research Group, 80078 Pozzuoli, Napoli, Italy"},{"name":"Epitech Group S.p.A., 35030 Saccolongo, Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Tinto","sequence":"additional","affiliation":[{"name":"Istituto di Chimica Biomolecolare, CNR, 80078 Pozzuoli, Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Verde","sequence":"additional","affiliation":[{"name":"Istituto di Chimica Biomolecolare, CNR, 80078 Pozzuoli, Napoli, Italy"},{"name":"Endocannabinoid Research Group, 80078 Pozzuoli, Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Allar\u00e0","sequence":"additional","affiliation":[{"name":"Istituto di Chimica Biomolecolare, CNR, 80078 Pozzuoli, Napoli, Italy"},{"name":"Endocannabinoid Research Group, 80078 Pozzuoli, Napoli, Italy"},{"name":"Epitech Group S.p.A., 35030 Saccolongo, Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6131-0470","authenticated-orcid":false,"given":"Luciano","family":"De Petrocellis","sequence":"additional","affiliation":[{"name":"Istituto di Chimica Biomolecolare, CNR, 80078 Pozzuoli, Napoli, Italy"},{"name":"Endocannabinoid Research Group, 80078 Pozzuoli, Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ester","family":"Pagano","sequence":"additional","affiliation":[{"name":"Endocannabinoid Research Group, 80078 Pozzuoli, Napoli, Italy"},{"name":"Dipartimento di Farmacia, Universit\u00e0 di Napoli Federico II, 80138 Naples, Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo A.","family":"Izzo","sequence":"additional","affiliation":[{"name":"Endocannabinoid Research Group, 80078 Pozzuoli, Napoli, Italy"},{"name":"Dipartimento di Farmacia, Universit\u00e0 di Napoli Federico II, 80138 Naples, Napoli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1490-3070","authenticated-orcid":false,"given":"Vincenzo","family":"Di Marzo","sequence":"additional","affiliation":[{"name":"Istituto di Chimica Biomolecolare, CNR, 80078 Pozzuoli, Napoli, Italy"},{"name":"Endocannabinoid Research Group, 80078 Pozzuoli, Napoli, Italy"},{"name":"Canada Excellence Research Chair on the Microbiome-Endocannabinoidome Axis in Metabolic Health, CRIUCPQ and INAF-Centre NUTRISS, Faculties of Medicine and Agriculture and Food Sciences, Universit\u00e9 Laval, Queb\u00e9c, QC G1V 0A6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Petrosino","sequence":"additional","affiliation":[{"name":"Istituto di Chimica Biomolecolare, CNR, 80078 Pozzuoli, Napoli, Italy"},{"name":"Endocannabinoid Research Group, 80078 Pozzuoli, Napoli, Italy"},{"name":"Epitech Group S.p.A., 35030 Saccolongo, Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1084\/jem.100.5.425","article-title":"The Effect of Egg Yolk in Diets on Anaphylactic Arthritis (Passive Arthus Phenomenon) in the Guinea Pig","volume":"100","author":"Coburn","year":"1954","journal-title":"J. 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