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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

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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.

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Abbreviations

ANOVA:

Analysis of variance

BSA:

Bovine serum albumin

DMSO:

Dimethylsulphoxide

E max :

Maximal effect

I max :

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

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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.

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Authors and Affiliations

  1. Graduate Program in Biological Sciences: Biochemistry Toxicology, Center of Natural and Exact Sciences, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria, Av. Roraima 1000, Camobi, Santa Maria, RS, 97105-900, Brazil

    Natháli Schopf Pegoraro, Camila Camponogara & Sara Marchesan Oliveira

  2. Graduate Program in Pharmaceutical Sciences, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil

    Mailine Gehrcke, Laura Minussi Giuliani & Letícia Cruz

  3. Graduate Program in Food Science and Technology, Center of Rural Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil

    Dariane Trivisiol da Silva, Luana Haselein Maurer & Tatiana Emanuelli

  4. Graduate Program in Genetics and Biochemistry, Biotechnology Institute, Federal University of Uberlândia, Uberlândia, MG, Brazil

    Priscilla Dias

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  1. Natháli Schopf Pegoraro
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  2. Camila Camponogara
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Pegoraro, N.S., Camponogara, C., Gehrcke, M. et al. Oleic acid-containing semisolid dosage forms exhibit in vivo anti-inflammatory effect via glucocorticoid receptor in a UVB radiation-induced skin inflammation model. Inflammopharmacol 28, 773–786 (2020). https://doi.org/10.1007/s10787-019-00675-5

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