N-Palmitoylethanolamine depot injection increased its tissue levels and those of other acylethanolamide lipids

Stephanie L. Grillo, Jantana Keereetaweep, Michael A. Grillo, Kent D. Chapman, Peter Koulen

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)747-752
Number of pages6
JournalDrug Design, Development and Therapy
Volume7
DOIs
StatePublished - Aug 9 2013

Fingerprint

Lipids
Injections
Retina
Delayed-Action Preparations
Inbred DBA Mouse
Corn Oil
Dimethyl Sulfoxide
palmidrol
N-acylethanolamines
Solubility
Oral Administration
Ethanol
Carbon
Water
Brain
Therapeutics
Serum

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Grillo, Stephanie L. ; Keereetaweep, Jantana ; Grillo, Michael A. ; Chapman, Kent D. ; Koulen, Peter. / N-Palmitoylethanolamine depot injection increased its tissue levels and those of other acylethanolamide lipids. In: Drug Design, Development and Therapy. 2013 ; Vol. 7. pp. 747-752.
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N-Palmitoylethanolamine depot injection increased its tissue levels and those of other acylethanolamide lipids. / Grillo, Stephanie L.; Keereetaweep, Jantana; Grillo, Michael A.; Chapman, Kent D.; Koulen, Peter.

In: Drug Design, Development and Therapy, Vol. 7, 09.08.2013, p. 747-752.

Research output: Contribution to journalArticle

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