Micronized/ultramicronized palmitoylethanolamide displays superior oral efficacy compared to nonmicronized palmitoylethanolamide in a rat model of inflammatory pain

Journal of Neuroinflammation

Salvatore Cuzzocrea¹  Emanuela Esposito²  Rosalba Siracusa²  Rosalia Crupi²  Marika Cordaro²  Giuseppe Bruschetta²  Daniela Impellizzeri² 

[1] Manchester Biomedical Research Centre, Manchester Royal Infirmary, University of Manchester, Manchester, Oxford Rd, Manchester M13 9WL, UK;Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D¿Alcontres, no 31, Messina 98166, Italy

关键词: Ultramicronized;    Palmitoylethanolamide;    Pain;    Oral administration;    Micronized;    Inflammation;    Hyperalgesia;    Edema;   

Others  :  1151067
DOI  :  10.1186/s12974-014-0136-0

 received in 2014-06-27, accepted in 2014-07-25,  发布年份 2014

【 摘 要 】

Background

The fatty acid amide palmitoylethanolamide (PEA) has been studied extensively for its anti-inflammatory and neuroprotective actions. The lipidic nature and large particle size of PEA in the native state may limit its solubility and bioavailability when given orally, however. Micronized formulations of a drug enhance its rate of dissolution and reduce variability of absorption when orally administered. The present study was thus designed to evaluate the oral anti-inflammatory efficacy of micronized/ultramicronized versus nonmicronized PEA formulations.

Methods

Micronized/ultramicronized PEA was produced by the air-jet milling technique, and the various PEA preparations were subjected to physicochemical characterization to determine particle size distribution and purity. Each PEA formulation was then assessed for its anti-inflammatory effects when given orally in the carrageenan-induced rat paw model of inflammation, a well-established paradigm of edema formation and thermal hyperalgesia.

Results

Intraplantar injection of carrageenan into the right hind paw led to a marked accumulation of infiltrating inflammatory cells and increased myeloperoxidase activity. Both parameters were significantly decreased by orally given micronized PEA (PEA-m; 10 mg/kg) or ultramicronized PEA (PEA-um; 10 mg/kg), but not nonmicronized PeaPure (10 mg/kg). Further, carrageenan-induced paw edema and thermal hyperalgesia were markedly and significantly reduced by oral treatment with micronized PEA-m and ultramicronized PEA-um at each time point compared to nonmicronized PeaPure. However, when given by the intraperitoneal route, all PEA formulations proved effective.

Conclusions

These findings illustrate the superior anti-inflammatory action exerted by orally administered, micronized PEA-m and ultramicronized PEA-um, versus that of nonmicronized PeaPure, in the rat paw carrageenan model of inflammatory pain.

【 授权许可】

   
2014 Impellizzeri et al.; licensee BioMed Central Ltd.

【 图 表 】

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