A Glucuronic Acid-Palmitoylethanolamide Conjugate (GLUPEA) Is an Innovative Drug Delivery System and a Potential Bioregulator
Open Access
- 20 February 2021
- Vol. 10 (2), 450
- https://doi.org/10.3390/cells10020450
Abstract
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.Funding Information
- Progetto Operativo Nazionale (PON01_02512)
This publication has 59 references indexed in Scilit:
- Increased levels of palmitoylethanolamide and other bioactive lipid mediators and enhanced local mast cell proliferation in canine atopic dermatitisBMC Veterinary Research, 2014
- Protective role of palmitoylethanolamide in contact allergic dermatitisAllergy, 2010
- Levels of endocannabinoids and palmitoylethanolamide and their pharmacological manipulation in chronic granulomatous inflammation in ratsPharmacological Research, 2010
- ‘Entourage’ effects of N‐palmitoylethanolamide and N‐oleoylethanolamide on vasorelaxation to anandamide occur through TRPV1 receptorsBritish Journal of Pharmacology, 2008
- Microglia produce and hydrolyze palmitoylethanolamideNeuropharmacology, 2008
- The orphan receptor GPR55 is a novel cannabinoid receptorBritish Journal of Pharmacology, 2007
- Histidine-conjugated poly(amino acid) derivatives for the novel endosomolytic delivery carrier of doxorubicinJournal of Controlled Release, 2006
- Inhibitory effect of palmitoylethanolamide on gastrointestinal motility in miceBritish Journal of Pharmacology, 2001
- Endocannabinoids control spasticity in a multiple sclerosis modelThe FASEB Journal, 2000
- N-acylethanolamine accumulation in infarcted myocardiumBiochemical and Biophysical Research Communications, 1979