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Home / Equine Research Bank / Vet Dermatol / Transdermal drug delivery in horses: An in vitro comparison ...
Veterinary dermatology2023; doi: 10.1111/vde.13162

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

Abstract: 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. Objective: To compare the structural composition and barrier properties of equine skin. Methods: Six warmblood horses (two males, four females) with no skin diseases. 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/cm /h), while that for the lipophilic molecule (ibuprofen) was for the inner thigh (0.12 ± 0.02 μg/cm /h). Conclusions: 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. Background: L'administration de médicaments par voie orale et parentérale chez les chevaux peut être difficile. Les formulations de médicaments transdermiques spécifiques aux équidés offrent une meilleure facilité de traitement; le développement de telles formulations nécessite une compréhension plus approfondie de la structure de la barrière tissulaire physique et chimique de la peau de cheval. HYPOTHÈSES/OBJECTIFS: Comparer la composition structurale et les propriétés barrières de la peau équine. Unassigned: Six chevaux à sang chaud (deux mâles, quatre femelles) sans affection cutanée MATÉRIELS ET MÉTHODES: Une analyse histologique et microscopique de routine est effectuée pour six emplacements cutanés différents. La perméation in vitro du médicament a été analysée à l'aide d'un protocole standard de cellule de diffusion de Franz couplé à une chromatographie liquide à haute performance en phase inversée (RP-HPLC) détaillant le flux, les temps de latence et les taux de partitionnement tissulaire de deux médicaments modèles. RÉSULTATS: L'épaisseur de l'épiderme et du derme varie d'un site à l'autre. L’épaisseur du derme et de l’épiderme de la croupe est respectivement de 1.764 ± 115 μm et de 36 ± 3.6 μm et elle diffère significativement (p < 0.05) de celle de l'intérieur de la cuisse variant de 824 ± 35 μm et de 49 ± 3.6 μm. La densité et la taille des follicules varient également. Le flux le plus élevé pour la molécule hydrophile modèle (caféine) est observé sur le flanc (3.22 ± 0.36 μg/cm /h), tandis que celui de la molécule lipophile (ibuprofène) est à l'intérieur de la cuisse (0.12 ± 0.02 μg/cm /h). Unassigned: Des différences dans la structure de la peau équine et la perméabilité aux petites molécules sont obsercées selon la localisation anatomique. Ces résultats peuvent aider au développement de thérapies transdermiques destinées aux chevaux. INTRODUCCIÓN: la administración de fármacos por vía oral y parenteral en caballos puede ser difícil. Las formulaciones de fármacos transdérmicos específicos para equinos ofrecen una mayor facilidad de tratamiento; el desarrollo de tales formulaciones requiere una comprensión más profunda de la barrera estructural y química del tejido de la piel del caballo. HIPÓTESIS/OBJETIVOS: Comparar la composición estructural y propiedades de barrera de la piel equina. ANIMALES: Seis caballos de sangre caliente (warmblood) (dos machos, cuatro hembras) sin enfermedades de la piel. MATERIALES Y MÉTODOS: Se realizaron análisis histológicos y microscópicos de rutina con análisis de imagen para piel de seis localizaciones anatómicas diferentes. La permeación del fármaco in vitro se analizó utilizando un protocolo estándar de Franz de difusión en celdilla junto con cromatografía líquida de alto rendimiento de fase inversa (RP-HPLC) que detalla el flujo, tiempos de retraso y las proporciones de partición en tejidos de dos compuestos farmacológicos modelo. RESULTADOS: Los grosores epidérmico y dérmico variaron entre sitios. Los grosores dérmico y epidérmico de la grupa fueron 1764 ± 115 μm y 36 ± 3.6 μm, respectivamente, y fueron significativamente diferentes (p < 0.05) de los grosores de la cara interna del muslo, que fueron 824 ± 35 μm y 49 ± 3.6 μm. La densidad y el tamaño folicular también variaron. El mayor flujo para la molécula hidrofílica modelo (cafeína) fue para el flanco (3.22 ± 0.36 μg/cm /h), mientras que para la molécula lipofílica (ibuprofeno) fue para la cara interna del muslo (0.12 ± 0.02 μg/cm /h). CONCLUSIONES Y RELEVANCIA CLÍNICA: Se demostraron diferencias de ubicación anatómica en la estructura de la piel equina y la permeabilidad de moléculas pequeñas. Estos resultados pueden ayudar en el desarrollo de terapias transdérmicas para caballos. Unassigned: Orale und parenterale Medikamentenverabreichung kann bei Pferden schwierig sein. Pferde-spezifische transdermale Wirkstoff-Formulierungen ermöglichen eine einfachere Behandlung; für die Entwicklung dieser Formulierungen ist ein tieferes Verständnis der Strukturen und der chemischen Gewebebarrieren der Pferdehaut nötig. Unassigned: Ein Vergleich der strukturellen Zusammensetzung und der Eigenschaften der Hautbarriere der Pferdehaut. Unassigned: Sechs Warmblüter (zwei männlich, vier weiblich) ohne Hauterkrankungen. Unassigned: Es wurde eine histologische und mikroskopische Analyse mittels Bildanalyse der Haut in sechs unterschiedlichen Lokalisationen durchgeführt. Die in vitro Durchlässigkeit der Wirkstoffe wurde mittels Standard Franz Diffusionsprotokoll gekoppelt mit Umkehrphasen Hochleistungsflüssigkeitschromatografie (RP-HPLC) analysiert, wobei Fluss, Verzögerungszeiten und der Anteil der Gewebsverteilung zweier Wirkstoffkomponenten als Modell detailliert dargestellt wurden. Unassigned: Die epidermale und dermale Dicke variierte zwischen den Körperstellen. Die dermale und epidermale Dicke der Krupp betrug 1,764 ± 115 μm bzw 36 ± 3.6 μm und war signifikant verschieden (p < 0.05) von der Dicke der inneren Schenkel, die 824 ± 35 μm bzw 49 ± 3.6 μm betrug. Die Follikeldichte und Größe variierten ebenfalls. Der höchste Fluss für das hydrophile Modellmolekül (Koffein) war im Bereich der Flanke (322 ± 0.36 μg/cm /h) zu finden, während jenes für das lipophile Molekül (Ibuprofen) im Bereich der Innenschenkel am höchsten war (0.12 ± 0.02 μg/cm /h). Unassigned: Es wurden die Unterschiede der anatomischen Lokalisationen der Struktur der Pferdehaut und der Durchlässigkeit kleiner Moleküle gezeigt. Diese Ergebnisse können bei der Entwicklung transdermaler Therapien für Pferde helfen. 背景: 馬の経口および非経口薬物送達は困難である。馬に特化した経皮吸収型製剤により、治療が容易になる。このような製剤の開発には、馬の皮膚の構造的および化学的な組織バリアに関する深い理解が必要である。 仮説/目的: 本研究の目的は、馬の皮膚の構造組成およびバリア性を比較することであった。 対象動物: 皮膚疾患のないウォームブラッド6頭(雄2頭、雌4頭)。 材料と方法: 6つの解剖学的部位から採取した皮膚について、画像解析を用いて通常の組織学的および顕微鏡的解析を実施した。In vitroにおける薬物透過性を、標準的なフランツ型拡散セルプロトコルおよび逆相高速液体クロマトグラフィ(RP-HPLC)を用いて、2種類のモデル化合物のフラックス、ラグタイム、組織分配比を詳細に解析した。 結果: 表皮および真皮の厚さは部位によって異なる。臀部の真皮および表皮の厚さは、それぞれ1,764 ± 115 μmおよび36 ± 3.6 μmであり、内腿の真皮および表皮の厚さは824 ± 35 μmおよび49 ± 3.6 μmであり、有意差(p < 0.05) があった。毛包密度およびサイズも変化した。親水性分子(カフェイン)のフラックスが最も高かったのは脇腹(3.22 ± 0.36 μg/cm /h)であり、親油性分子(イブプロフェン)のフラックスが最も高かったのは内腿(0.12 ± 0.02 μg/cm /h)であった。 結論と臨床的関連性: 馬の皮膚構造と低分子化合物の透過性に解剖学的部位の違いがあることが示された。これらの結果は、馬の経皮治療薬の開発に役立つと考えられた。. 背景: 马的口服和非肠道给药可能很困难。马特异性透皮药物制剂提高了治疗的简易性；这种配方的开发需要对马皮的结构和化学组织屏障有更深入的了解。 假设/目的: 比较马皮肤的结构组成和屏障功能。 动物: 六匹没有皮肤病的温血马(两只雄性，四只雌性)。 材料和方法: 对来自六个不同解剖位置的皮肤进行常规组织学和显微镜分析，并进行图像分析。使用标准Franz扩散池方案结合反相高效液相色谱(RP-HPLC)分析体外药物渗透，详细说明两种模型药物化合物的通透量、滞后时间和组织分配比。 结果: 不同部位的表皮和真皮厚度不同。臀部的真皮和表皮厚度分别为1764 ± 115 μm和36 ± 3.6 μm，与大腿内侧824 ± 35 μm和49 ± 3.6 μm.毛囊密度和大小也不同，差异显著(p < 0.05)。体侧的亲水分子模型(咖啡因)通透量最高(3.22 ± 0.36 μg/cm /h)，而亲脂性分子(布洛芬)的最高通透量为大腿内侧(0.12 ± 0.02 μg/cm /h)。 结论和临床相关性: 马的皮肤结构和小分子通透性在解剖学位置上存在差异。这些结果有助于开发马匹的透皮疗法。. Unassigned: Administração oral e parenteral de medicações para cavalos pode ser difícil. Formulações transdermais específicas para equinos facilitam o tratamento; o desenvolvimento destas formulações requer maior conhecimento na barreira tecidual química e estrutural da pele equina. HIPÓTESE/OBJETIVOS: Comparar a composição estrutural e as propriedades da barreira cutânea de equinos. MATERIAIS E MÉTODOS: Realizou-se análise histológica e microscópica de rotina a partir de imagens da pele seis locais anatômicos diferentes. A permeabilidade in vitro foi avaliada utilizando o protocolo de difusão celular de Franz padrão pareado com fluxo detalhado de cromatografia líquida de fase reversa de alta performance (RP-HPLC), tempos de atraso e taxas de partição tecidual de dois compostos de fármacos modelo. Results: As espessuras epidérmica e dérmica variaram entre os locais. As espessuras dérmica e epidérmica da garupa foram 1.764 ± 115 μm e 36 ± 3.6 μm, respectivamente, e foram significativamente diferentes (p < 0.05) das espessuras da parte interna da coxa que foram 824 ± 35 μm e 49 ± 3.6 μm. A densidade e o tamanho foliculares também variaram. O maior fluxo para o modelo de molécula hidrofílica (cafeína) foi para o flanco (3.22 ± 0.36 μg/cm /h), enquanto para o modelo de molécula lipofílica (ibuprofeno) foi para a parte interna da coxa (0.12 ± 0.02.μg/cm /h). CONCLUSÕES E RELEVÂNCIA CLÍNICA: Foram demonstradas diferenças regionais anatômicas na estrutura e permeabilidade a pequenas moléculas na pele equina. Estes resultados podem auxiliar no desenvolvimento de terapias transdermais para equinos.
© 2023 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of ESVD and ACVD.
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Publication Date: 2023-04-26 PubMed ID: 37185892DOI: 10.1111/vde.13162Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates the potential for transdermal drug delivery in horses, comparing the structure and drug permeability of equine skin at different anatomical locations. The study highlights location-dependent differences, paving the way for the development of targeted transdermal treatments.

Objective and Methodology

  • The aim of the research was to analyse the structural composition and barrier properties of equine skin, particularly focusing on the possibilities for transdermal drug delivery.
  • The study used a sample of six warmblood horses, free from skin diseases.
  • The researchers gathered samples from six different anatomical locations on each horse.
  • Standard histological and microscopic examinations were carried out on collected skin samples.
  • In vitro drug permeation was assessed using a standard Franz diffusion cell protocol coupled with reversed phase-high-performance liquid chromatography (RP-HPLC).
  • The flux, lag times and tissue partitioning ratios of two model drug compounds, caffeine (a hydrophilic molecule) and ibuprofen (a lipophilic molecule), were carefully examined.

Findings

  • Significant variations were found in the epidermal and dermal thicknesses among different sites. The thickest skin was found on the croup, while the inner thigh skin was significantly thinner.
  • The density and size of hair follicles also varied across the different locations.
  • The highest flux for the caffeine molecule was found on the flank of the horse, while the inner thigh area showed the highest flux for the ibuprofen molecule.
  • These observations indicated that the anatomical location significantly affects the permeability of small molecules, influencing the effectiveness of transdermal drug delivery.

Conclusion

  • The findings highlighted the need for further research on equine skin structure to improve the development and effectiveness of transdermal drug delivery in horses.
  • This study provides a fundamental resource for developing therapies for horse treatments, specifically those based on transdermal drug delivery systems.

Cite This Article

APA
Bizley SC, Dudhia J, Smith RKW, Williams AC. (2023). Transdermal drug delivery in horses: An in vitro comparison of skin structure and permeation of two model drugs at various anatomical sites. Vet Dermatol. https://doi.org/10.1111/vde.13162

Publication

Veterinary dermatology
ISSN: 1365-3164
NlmUniqueID: 9426187
Country: England
Language: English

Researcher Affiliations

Bizley, Samuel C
  • Clinical Science and Services, The Royal Veterinary College, Hatfield, Hertfordshire, UK.
Dudhia, Jayesh
  • Clinical Science and Services, The Royal Veterinary College, Hatfield, Hertfordshire, UK.
Smith, Roger K W
  • Clinical Science and Services, The Royal Veterinary College, Hatfield, Hertfordshire, UK.
Williams, Adrian C
  • School of Pharmacy, University of Reading, Reading, Berkshire, UK.

Grant Funding

  • vet/prj/777 / Horserace Betting Levy Board

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