Improving Transungual Permeation Study Design by Increased Bovine Hoof Membrane Thickness and Subsequent Infection
Ungual formulations are regularly tested using human nails or animal surrogates in Franz diffusion cell experiments. Membranes sometimes less than 100 µm thick are used, disregarding the higher physiological thickness of human nails and possible fungal infection. In this study, bovine hoof membranes...
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MDPI AG
2021-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/12/2098 |
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| author | Sebastian Kappes Thilo Faber Lotta Nelleßen Tanju Yesilkaya Udo Bock Alf Lamprecht |
| author_facet | Sebastian Kappes Thilo Faber Lotta Nelleßen Tanju Yesilkaya Udo Bock Alf Lamprecht |
| author_sort | Sebastian Kappes |
| collection | DOAJ |
| description | Ungual formulations are regularly tested using human nails or animal surrogates in Franz diffusion cell experiments. Membranes sometimes less than 100 µm thick are used, disregarding the higher physiological thickness of human nails and possible fungal infection. In this study, bovine hoof membranes, healthy or infected with <i>Trichophyton rubrum</i>, underwent different imaging techniques highlighting that continuous pores traversed the entire membrane and infection resulted in fungal growth, both superficial, as well as in the membrane’s matrix. These membrane characteristics resulted in substantial differences in the permeation of the antifungal model substance bifonazole, depending on the dosage forms. Increasing the thickness of healthy membranes from 100 µm to 400 µm disproportionally reduced the permeated amount of bifonazole from the liquid and semisolid forms and allowed for a more pronounced assessment of the effects by excipients, such as urea as the permeation enhancer. Similarly, an infection of 400-µm membranes drastically increased the permeated amount. Therefore, the thickness and infection statuses of the membranes in the permeation experiments were essential for a differential readout, and standardized formulation-dependent experimental setups would be highly beneficial. |
| first_indexed | 2024-03-10T03:19:51Z |
| format | Article |
| id | doaj.art-d7ce3b32e7e24b8b96da04fc38ed7d76 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T03:19:51Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-d7ce3b32e7e24b8b96da04fc38ed7d762023-11-23T10:05:52ZengMDPI AGPharmaceutics1999-49232021-12-011312209810.3390/pharmaceutics13122098Improving Transungual Permeation Study Design by Increased Bovine Hoof Membrane Thickness and Subsequent InfectionSebastian Kappes0Thilo Faber1Lotta Nelleßen2Tanju Yesilkaya3Udo Bock4Alf Lamprecht5Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Gerhard-Domagk-Str. 3, 53121 Bonn, GermanyDepartment of Pharmaceutics, Institute of Pharmacy, University of Bonn, Gerhard-Domagk-Str. 3, 53121 Bonn, GermanyDepartment of Pharmaceutics, Institute of Pharmacy, University of Bonn, Gerhard-Domagk-Str. 3, 53121 Bonn, GermanyBayer Vital GmbH, 51373 Leverkusen, GermanyBock Project Management, 54456 Tawern, GermanyDepartment of Pharmaceutics, Institute of Pharmacy, University of Bonn, Gerhard-Domagk-Str. 3, 53121 Bonn, GermanyUngual formulations are regularly tested using human nails or animal surrogates in Franz diffusion cell experiments. Membranes sometimes less than 100 µm thick are used, disregarding the higher physiological thickness of human nails and possible fungal infection. In this study, bovine hoof membranes, healthy or infected with <i>Trichophyton rubrum</i>, underwent different imaging techniques highlighting that continuous pores traversed the entire membrane and infection resulted in fungal growth, both superficial, as well as in the membrane’s matrix. These membrane characteristics resulted in substantial differences in the permeation of the antifungal model substance bifonazole, depending on the dosage forms. Increasing the thickness of healthy membranes from 100 µm to 400 µm disproportionally reduced the permeated amount of bifonazole from the liquid and semisolid forms and allowed for a more pronounced assessment of the effects by excipients, such as urea as the permeation enhancer. Similarly, an infection of 400-µm membranes drastically increased the permeated amount. Therefore, the thickness and infection statuses of the membranes in the permeation experiments were essential for a differential readout, and standardized formulation-dependent experimental setups would be highly beneficial.https://www.mdpi.com/1999-4923/13/12/2098ungual permeation modelonychomycosisbovine hoofbifonazolescanning electron microscopy |
| spellingShingle | Sebastian Kappes Thilo Faber Lotta Nelleßen Tanju Yesilkaya Udo Bock Alf Lamprecht Improving Transungual Permeation Study Design by Increased Bovine Hoof Membrane Thickness and Subsequent Infection Pharmaceutics ungual permeation model onychomycosis bovine hoof bifonazole scanning electron microscopy |
| title | Improving Transungual Permeation Study Design by Increased Bovine Hoof Membrane Thickness and Subsequent Infection |
| title_full | Improving Transungual Permeation Study Design by Increased Bovine Hoof Membrane Thickness and Subsequent Infection |
| title_fullStr | Improving Transungual Permeation Study Design by Increased Bovine Hoof Membrane Thickness and Subsequent Infection |
| title_full_unstemmed | Improving Transungual Permeation Study Design by Increased Bovine Hoof Membrane Thickness and Subsequent Infection |
| title_short | Improving Transungual Permeation Study Design by Increased Bovine Hoof Membrane Thickness and Subsequent Infection |
| title_sort | improving transungual permeation study design by increased bovine hoof membrane thickness and subsequent infection |
| topic | ungual permeation model onychomycosis bovine hoof bifonazole scanning electron microscopy |
| url | https://www.mdpi.com/1999-4923/13/12/2098 |
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