Transdermal drug delivery in horses: An in vitro comparison of skin structure and permeation of two model drugs at various anatomical sites

Bizley, SC; Dudhia, J; Smith, RKW; Williams, AC

Abstract

Background: Oral and parenteral drug delivery in horses can be difficult. Equine--specific transdermal drug formulations offer improved ease of treatment; development of such formulations requires a deeper understanding of the structural and chemical tissue barrier of horse skin. Hypothesis/Objectives: To compare the structural composition and barrier properties of equine skin. Animals: Six warmblood horses (two males, four females) with no skin diseases. Materials and Methods: Routine histological and microscopic analyses were carried out with image analysis for skin from six different anatomical locations. In vitro drug permeation was analysed using a standard Franz diffusion cell protocol coupled with reversed phase-high-performance liquid chromatography detailing flux, lag times and tissue partitioning ratios of two model drug compounds. Results: Epidermal and dermal thicknesses varied between sites. The dermal and epidermal thicknesses of the croup were 1764 +/- 115 mu m and 36 +/- 3.6 mu m, respectively, and were significantly different (p < 0.05) from the inner thigh thicknesses which were 824 +/- 35 mu m and 49 +/- 3.6 mu m. Follicular density and size also varied. The highest flux for the model hydrophilic molecule (caffeine) was for the flank (3.22 +/- 0.36 mu g/cm(2)/h), while that for the lipophilic molecule (ibuprofen) was for the inner thigh (0.12 +/- 0.02 mu g/cm(2)/ h). Conclusions and Clinical Relevance: Anatomical location differences in equine skin structure and small molecule permeability were demonstrated. These results can aid in the development of transdermal therapies for horses.

Citation

Bizley, S., Dudhia, J., Smith, R., & Williams, A. (2023). Transdermal drug delivery in horses: An in vitro comparison of skin structure and permeation of two model drugs at various anatomical sites. Veterinary Dermatology, 34(3), 235-245. https://doi.org/10.1111/vde.13162

• Journal Article Type: Article
• Acceptance Date: Mar 28, 2023
• Online Publication Date: Apr 26, 2023
• Publication Date: 2023
• Deposit Date: Feb 15, 2024
• Publicly Available Date: Feb 15, 2024
• Print ISSN: 0959-4493
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 34
• Issue: 3
• Pages: 235-245
• DOI: https://doi.org/10.1111/vde.13162
• Keywords: administration; cutaneous; equine; skin; transdermal absorption; REGIONAL DIFFERENCES; PENETRATION; QUANTIFICATION; HYDROCORTISONE; DICLOFENAC; ABSORPTION; SYSTEM; IMAGE