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Oleic acid-containing semisolid dosage forms exhibit in vivo anti-inflammatory effect via glucocorticoid receptor in a UVB radiation-induced skin inflammation model

  • Natháli Schopf Pegoraro
  • Camila Camponogara
  • Mailine Gehrcke
  • Laura Minussi Giuliani
  • Dariane Trivisiol da Silva
  • Luana Haselein Maurer
  • Priscilla Dias
  • Tatiana Emanuelli
  • Letícia Cruz
  • Sara Marchesan OliveiraEmail author
Original Article
  • 27 Downloads

Abstract

The treatment of cutaneous inflammation with topical corticosteroids may cause adverse effects reinforcing the need for therapeutic alternatives to treat inflammatory skin disorders. We investigated the anti-inflammatory effect of oleic acid (OA), a fatty acid of the omega-9 (ω-9) family, and we point out it as an alternative to treat inflammatory skin disorders. OA was incorporated into Lanette®- or Pemulen® TR2-based semisolid preparations and the pH, spreadability, rheological behavior and in vivo anti-inflammatory performance in a UVB radiation-induced skin inflammation model in mice were assessed. The anti-inflammatory activity was verified after single or repeated treatment of the mouse ear following the UVB. The OA action on glucocorticoid receptors was investigated. Both semisolids presented pH values compatible with the deeper skin layers, appropriate spreadability factors, and non-Newtonian pseudoplastic rheological behavior. Pemulen® 3% OA inhibited ear edema with superior efficacy than Lanette® 3% OA and dexamethasone after a single treatment. Pemulen® 3% OA and dexamethasone also reduced inflammatory cell infiltration. After repeated treatments, all formulations decreased the ear edema at 24 h, 48 h and 72 h after UVB. OA in semisolids, especially Pemulen® TR2-based ones, presented suitable characteristics for cutaneous administration and its anti-inflammatory activity seems to occur via glucocorticoid receptors. OA was also capable to reduce croton oil-induced skin inflammation. Besides, the ex vivo skin permeation study indicated that OA reaches the receptor medium, which correlates with a systemic absorption in vivo. The natural compound OA could represent a promising alternative to those available to treat inflammatory skin disorders.

Graphic abstract

Keywords

Omega-9 fatty acid Skin inflammation Sunburn Croton oil Skin permeation Mifepristone 

Abbreviations

ANOVA

Analysis of variance

BSA

Bovine serum albumin

DMSO

Dimethylsulphoxide

Emax

Maximal effect

Imax

Maximum inhibition

Lanette® 0.3% OA

Lanette®-based semisolid containing 0.3% oleic acid

Lanette® 1% OA

Lanette®-based semisolid containing 1% oleic acid

Lanette® 3% OA

Lanette®-based semisolid containing 3% oleic acid

OA

Oleic acid

Pemulen® 0.3% OA

Pemulen® TR2-based semisolid containing 0.3% oleic acid

Pemulen® 1% OA

Pemulen® TR2-based semisolid containing 1% oleic acid

Pemulen® 3% OA

Pemulen® TR2-based semisolid containing 3% oleic acid

SD

Standard deviation

SDS

Sodium dodecyl sulfate

SEM

Standard error of the mean

TPA

12-O-Tetradecanoylphorbol-13-acetate

UVA

Ultraviolet radiation type A

UVB

Ultraviolet radiation type B

UVC

Ultraviolet radiation type C

UVR

Ultraviolet radiation

Notes

Acknowledgements

NSP thanks Frigorífico Avisui for porcine skin donation.

Funding

This study was supported by the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul-FAPERGS and by the Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq [Grant #16/2551-0000281-9]; and by FAPERGS [Grant #17/2551-0001082-5] (Brazil); and by the CNPq [process #406098/2018-2]; and by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES/PROEX [#23038.005848/2018-31 and 23038.004173/2019-93; Grant: 0493/019]. SMO is recipient of fellowship from CNPq [process #307220/2017-6) and NSP and CC are recipient of fellowship from CAPES/PROEX [process #88882.182128/2018-01; process #88882.182152/2018-01]. We thank CNPq and CAPES for their fellowship support.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Natháli Schopf Pegoraro
    • 1
  • Camila Camponogara
    • 1
  • Mailine Gehrcke
    • 2
  • Laura Minussi Giuliani
    • 2
  • Dariane Trivisiol da Silva
    • 3
  • Luana Haselein Maurer
    • 3
  • Priscilla Dias
    • 4
  • Tatiana Emanuelli
    • 3
  • Letícia Cruz
    • 2
  • Sara Marchesan Oliveira
    • 1
    Email author
  1. 1.Graduate Program in Biological Sciences: Biochemistry Toxicology, Center of Natural and Exact Sciences, Department of Biochemistry and Molecular BiologyFederal University of Santa MariaSanta MariaBrazil
  2. 2.Graduate Program in Pharmaceutical Sciences, Center of Health SciencesFederal University of Santa MariaSanta MariaBrazil
  3. 3.Graduate Program in Food Science and Technology, Center of Rural SciencesFederal University of Santa MariaSanta MariaBrazil
  4. 4.Graduate Program in Genetics and Biochemistry, Biotechnology InstituteFederal University of UberlândiaUberlândiaBrazil

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