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American journal of veterinary research2004; 65(3); 271-276; doi: 10.2460/ajvr.2004.65.271

Effect of topical application of diclofenac liposomal suspension on experimentally induced subcutaneous inflammation in horses.

Abstract: To determine whether 1% diclofenac liposomal suspension (DLS) ointment would be absorbed transdermally and attenuate experimentally induced subcutaneous inflammation in horses. Methods: 7 healthy adult horses. Methods: Inflammation was produced by injecting 1% sterile carrageenan into subcutaneously implanted tissue cages 8 hours before (time -8) and at the time of application of test ointment. A crossover design was used. Horses received 1 of 2 treatments (topically administered control or DLS ointments) during 48 hours of carrageenan-induced subcutaneous inflammation. A single application of test ointment (7.2 g) was applied over each tissue cage (time 0). Samples of transudate and blood were collected at -8, 0, 6, 12, 18, 24, 30, 36, and 48 hours. Plasma and transudate diclofenac concentrations were determined by use of high-performance liquid chromatography. Transudate concentrations of prostaglandin E2 (PGE2) were determined with a competitive enzyme immunoassay. Results: DLS was absorbed transdermally. The highest concentration (mean +/- SEM, 76.2 +/- 29 ng/mL) was detectable in tissue-cage fluid within 18 hours after application. Minimal concentrations of diclofenac were detectable in plasma. Application of DLS significantly decreased transudate concentrations of PGE2 at 6 and 30 hours. Decreases in PGE2 concentration were observed in the DLS group at all collection times. Conclusions: A single topical application of DLS resulted in concentrations of diclofenac in transudate within 6 hours and significantly attenuated carrageenan-induced local production of PGE2. Results of this study suggest that DLS is readily absorbed transdermally and may be efficacious for reducing subcutaneous inflammation in horses.
Publication Date: 2004-03-19 PubMed ID: 15027670DOI: 10.2460/ajvr.2004.65.271Google Scholar: Lookup
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  • Comparative Study
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The study investigates whether a 1% solution of diclofenac liposomal suspension ointment could be absorbed via skin and decrease induced inflammation under the skin layer in horses.

Research Methodology

  • Seven healthy adult horses were exposed to experimentally induced inflammation by injecting 1% sterile carrageenan into tissue cages that were implanted beneath the skin layer.
  • The inflammation was induced 8 hours prior to and during the application of the test ointment in a crossover study design.
  • The horses were administered either a control ointment or the diclofenac liposomal suspension (DLS). The ointments were applied topically over a period of 48 hours during which inflammation was induced by carrageenan.
  • Every horse received a single application of the test ointment (7.2 grams) over their respective tissue cages.
  • Samples of skin tissue (transudate) and blood were collected at 9 different time intervals over the period of 48 hours.
  • The concentrations of diclofenac in the plasma and transudate as well as the concentration of prostaglandin E2 in the transudate were determined.

Research Findings

  • It was observed that the DLS was successfully absorbed via the skin. The maximum concentration of DLS in the tissue-cage fluid was 76.2 ± 29 ng/mL which was detected within 18 hours after application.
  • Notably, the study found only minimal concentrations of diclofenac in the blood plasma.
  • Additionally, the use of DLS notably reduced the concentration of prostaglandin E2, a potent inflammation mediator, at the 6 and 30 hour marks. Reduced concentrations were observed at all time points in the DLS group.

Conclusion

  • A single topical application of DLS can result in noticeable concentrations of the solution in the transudate within a span of 6 hours and appreciably reduced locally produced prostaglandin E2 triggered by the carrageenan.
  • The results indicate that DLS can be efficiently absorbed via skin application and could be useful in managing subcutaneous inflammation in horses.

Cite This Article

APA
Caldwell FJ, Mueller PO, Lynn RC, Budsberg SC. (2004). Effect of topical application of diclofenac liposomal suspension on experimentally induced subcutaneous inflammation in horses. Am J Vet Res, 65(3), 271-276. https://doi.org/10.2460/ajvr.2004.65.271

Publication

ISSN: 0002-9645
NlmUniqueID: 0375011
Country: United States
Language: English
Volume: 65
Issue: 3
Pages: 271-276

Researcher Affiliations

Caldwell, Fred J
  • Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
Mueller, P O Eric
    Lynn, Randy C
      Budsberg, Steven C

        MeSH Terms

        • Administration, Topical
        • Animals
        • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
        • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
        • Carrageenan
        • Chromatography, High Pressure Liquid
        • Cross-Over Studies
        • Diclofenac / administration & dosage
        • Diclofenac / therapeutic use
        • Horse Diseases / drug therapy
        • Horses
        • Immunoenzyme Techniques
        • Inflammation / drug therapy
        • Inflammation / veterinary
        • Liposomes
        • Subcutaneous Tissue

        Citations

        This article has been cited 4 times.
        1. Munn R, Whittem T, Woodward AP. The Surface Area to Volume Ratio Changes the Pharmacokinetic and Pharmacodynamic Parameters in the Subcutaneous Tissue Cage Model: As Illustrated by Carprofen in Sheep. Front Vet Sci 2022;9:905797.
          doi: 10.3389/fvets.2022.905797pubmed: 35847628google scholar: lookup
        2. Cooper DL, Harirforoosh S. Design and optimization of PLGA-based diclofenac loaded nanoparticles. PLoS One 2014;9(1):e87326.
          doi: 10.1371/journal.pone.0087326pubmed: 24489896google scholar: lookup
        3. Kayasuga-Kariya Y, Iwanaga S, Fujisawa A, Lin LS, Suzuki S, Chung UI, Sasaki N, Shimohata N, Mochizuki M. Dermal cell damage induced by topical application of non-steroidal anti-inflammatory drugs is suppressed by trehalose co-lyophilization in ex vivo analysis. J Vet Med Sci 2013 Dec 30;75(12):1619-22.
          doi: 10.1292/jvms.12-0502pubmed: 23884023google scholar: lookup
        4. Lohmann-Menezes B, Giarolla J, da Silva-Santos Y, Petri G, Epiphanio S. Canis lupus familiaris and diclofenac: understanding the potential risks of this association. Front Vet Sci 2024;11:1507390.
          doi: 10.3389/fvets.2024.1507390pubmed: 39717786google scholar: lookup