title: N-Palmitoylethanolamine depot injection increased its tissue levels and those of other acylethanolamide lipids.
abstract: N-Palmitoylethanolamine (NAE 16:0) is an endogenous lipid signaling molecule that has limited water solubility, and its action is short-lived due to its rapid metabolism. This poses a problem for use in vivo as oral administration requires a high concentration for significant levels to reach target tissues, and injection of the compound in a dimethyl sulfoxide- or ethanol-based vehicle is usually not desirable during long-term treatment. A depot injection of NAE 16:0 was successfully emulsified in sterile corn oil (10 mg/kg) and administered in young DBA/2 mice in order to elevate baseline levels of NAE 16:0 in target tissues. NAE 16:0 levels were increased in various tissues, particularly in the retina, 24 and 48 hours following injections. Increases ranged between 22% and 215% (above basal levels) in blood serum, heart, brain, and retina and induced an entourage effect by increasing levels of other 18 carbon N-Acylethanolamines (NAEs), which ranged between 31% and 117% above baseline. These results indicate that NAE 16:0 can be used as a depot preparation, avoiding the use of inadequate vehicles, and can provide the basis for designing tissue-specific dosing regimens for therapies involving NAEs and related compounds.
authors: Vision Research Center, Department of Ophthalmology, School of Medicine, University of Missouri-Kansas City, MO 64108, USA.
authors: Stephanie L
authors: SL
authors: Grillo
authors: Jantana
authors: J
authors: Keereetaweep
authors: Michael A
authors: MA
authors: Grillo
authors: Kent D
authors: KD
authors: Chapman
authors: Peter
authors: P
authors: Koulen
mesh_terms: D000577:Amides; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism; D003314:Corn Oil / Q000737:chemistry; D003692:Delayed-Action Preparations; D063388:Endocannabinoids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004983:Ethanolamines / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010169:Palmitic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014677:Pharmaceutical Vehicles / Q000737:chemistry; D012160:Retina / Q000378:metabolism; D012995:Solubility; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000577:Amides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D063388:Endocannabinoids; D004983:Ethanolamines; C022203:N-acylethanolamines; D010169:Palmitic Acids; D014677:Pharmaceutical Vehicles; C005958:palmidrol; D003314:Corn Oil
keywords: DBA/2 mice; cannabinoid receptor; gas chromatography; lipid extraction; mass spectrometry; vanilloid receptor
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