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

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 μm and 36 ± 3.6 μm, respectively, and were significantly different (p < 0.05) from the inner thigh thicknesses which were 824 ± 35 μm and 49 ± 3.6 μm. Follicular density and size also varied. The highest flux for the model hydrophilic molecule (caffeine) was for the flank (3.22 ± 0.36 μg/cm2/h), while that for the lipophilic molecule (ibuprofen) was for the inner thigh (0.12 ± 0.02 μg/cm2/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.