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Pharmaceutics2022; 14(12); doi: 10.3390/pharmaceutics14122552

Comparative Ungual Drug Uptake Studies: Equine Hoof Membrane vs. Human Nail Plate.

Abstract: Human nail diseases, mostly caused by fungal infections, are common and difficult to treat. The development and testing of new drugs and drug delivery systems for the treatment of nail diseases is often limited by the lack of human nail material for permeation studies. Animal material is frequently used, but there are only few comparative data on the human nail plate, and there is neither a standardized test design nor a nail bed analogue to study drug uptake into the nail. In this study, a new permeation device was developed for permeation studies, and the permeation behavior of three model substances on the human nail plate and a model membrane from the horse hoof was investigated. A linear correlation was found between drug uptake by the human nail plate and the uptake by the equine hoof. The developed and established permeation device is suitable for investigations of ungual drug transport and enables the use of different membrane diameters and the use of a gel-based nail bed analog. The hydrogel-based acceptor medium used ensures adequate stabilization and hydration of the nail membrane.
Publication Date: 2022-11-22 PubMed ID: 36559046PubMed Central: PMC9781965DOI: 10.3390/pharmaceutics14122552Google Scholar: Lookup
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  • Journal Article

Summary

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The research article presents the development of a new permeation device designed to study drug uptake in treating human nail diseases, with a comparison between human nail plate and horse hoof membrane as reliable test materials.

Problem Statement

  • Human nail diseases, primarily arising from fungal infections, are common and complex to manage.
  • Developing new medications and delivery systems to treat these diseases is often hampered by a lack of human nail material for permeation studies.
  • Researchers commonly use animal material for such studies, but limited comparative data on human nail plates exists.
  • There is no standardized design for testing drug uptake on the nail bed, or a nail bed analogue to conduct these studies.

Research Objectives

  • The researchers aimed to develop a permeation device for such studies.
  • The study targeted the observation of the permeation behavior of three model substances on a human nail plate and a horse hoof membrane (serving as the model).
  • The intent was to determine if there’s a correlation between drug absorption by the human nail plate and the equine hoof.

Key Findings

  • The study found a linear correlation between drug uptake by the human nail plate and uptake by the equine hoof.
  • This suggests that the equine hoof membrane can serve as a reliable model for studying drug penetration into the human nail plate.

Significance of the Study

  • The permeation device developed can prove useful for investigating drug transport in ungual (relating to the nails) studies.
  • The device allows for manipulation of different membrane diameters and enables the use of a gel-based nail bed analog.
  • The utilized hydrogel-based acceptor medium ensures proper stabilization and hydration of the nail membrane, optimizing the conditions for study.

Cite This Article

APA
Dobler D, Gerber M, Schmidts TM, Runkel F, Schlupp P. (2022). Comparative Ungual Drug Uptake Studies: Equine Hoof Membrane vs. Human Nail Plate. Pharmaceutics, 14(12). https://doi.org/10.3390/pharmaceutics14122552

Publication

ISSN: 1999-4923
NlmUniqueID: 101534003
Country: Switzerland
Language: English
Volume: 14
Issue: 12

Researcher Affiliations

Dobler, Dorota
  • Technische Hochschule Mittelhessen, Institute of Bioprocess Engineering and Pharmaceutical Technology, 35390 Giessen, Germany.
Gerber, Mona
  • Technische Hochschule Mittelhessen, Institute of Bioprocess Engineering and Pharmaceutical Technology, 35390 Giessen, Germany.
Schmidts, Thomas M
  • Technische Hochschule Mittelhessen, Institute of Bioprocess Engineering and Pharmaceutical Technology, 35390 Giessen, Germany.
Runkel, Frank
  • Technische Hochschule Mittelhessen, Institute of Bioprocess Engineering and Pharmaceutical Technology, 35390 Giessen, Germany.
  • Faculty of Biology and Chemistry, Justus Liebig University, Ludwigstraße 23, 35390 Giessen, Germany.
  • Institute of Pharmaceutics and Biopharmaceutics, Philipps University, Robert-Koch-Straße 4, 35037 Marburg, Germany.
Schlupp, Peggy
  • Technische Hochschule Mittelhessen, Institute of Bioprocess Engineering and Pharmaceutical Technology, 35390 Giessen, Germany.

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 28 references
  1. de Berker D.A.R., Baran R.. Baran & Dawber’s Diseases of the Nails and Their Management. John Wiley & Sons; Hoboken, NJ, USA: 2018. Science of the Nail Apparatus; pp. 1–50.
    doi: 10.1002/9781118286715.ch1google scholar: lookup
  2. Kobayashi Y., Miyamoto M., Sugibayashi K., Morimoto Y.. Drug permeation through the three layers of the human nail plate. J. Pharm. Pharmacol. 1999;51:271–278.
    doi: 10.1211/0022357991772448pubmed: 10344627google scholar: lookup
  3. Wollina U., Nenoff P., Haroske G., Haenssle H.A.. The Diagnosis and Treatment of Nail Disorders. Dtsch. Arztebl. Int. 2016;113:509–518.
    doi: 10.3238/arztebl.2016.0509pmc: PMC5527843pubmed: 27545710google scholar: lookup
  4. Kushwaha A.S., Sharma P., Shivakumar H.N., Rappleye C., Zukiwski A., Proniuk S., Murthy S.N.. Trans-ungual Delivery of AR-12, A Novel Antifungal Drug. AAPS PharmSciTech 2017;18:2702–2705.
    doi: 10.1208/s12249-017-0752-ypubmed: 28289970google scholar: lookup
  5. Lusiana, Reichl S., Müller-Goymann C.C.. Keratin film made of human hair as a nail plate model for studying drug permeation. Eur. J. Pharm. Biopharm. 2011;78:432–440.
    doi: 10.1016/j.ejpb.2011.01.022pubmed: 21791369google scholar: lookup
  6. Sil B.C., Patel A., Crowther J.M., Moore D.J., Hadgraft J., Hilton S.T., Lane M.E.. A Preliminary Investigation of Additive Manufacture to Fabricate Human Nail Plate Surrogates for Pharmaceutical Testing. Pharmaceutics 2019;11:250.
  7. Mertin D., Lippold B.C.. In-vitro permeability of the human nail and of a keratin membrane from bovine hooves: Influence of the partition coefficient octanol/water and the water solubility of drugs on their permeability and maximum flux. J. Pharm. Pharmacol. 1997;49:30–34.
  8. Khengar R.H., Jones S.A., Turner R.B., Forbes B., Brown M.B.. Nail swelling as a pre-formulation screen for the selection and optimisation of ungual penetration enhancers. Pharm. Res. 2007;24:2207–2212.
    doi: 10.1007/s11095-007-9368-3pubmed: 17665289google scholar: lookup
  9. Nogueiras-Nieto L., Gómez-Amoza J.L., Delgado-Charro M.B., Otero-Espinar F.J.. Hydration and N-acetyl-l-cysteine alter the microstructure of human nail and bovine hoof: Implications for drug delivery. J. Control. Release. 2011;156:337–344.
    doi: 10.1016/j.jconrel.2011.08.021pubmed: 21906642google scholar: lookup
  10. Monti D., Saccomani L., Chetoni P., Burgalassi S., Saettone M.F., Mailland F.. In vitro transungual permeation of ciclopirox from a hydroxypropyl chitosan-based, water-soluble nail lacquer. Drug Dev. Ind. Pharm. 2005;31:11–17.
    doi: 10.1081/DDC-43935pubmed: 15704853google scholar: lookup
  11. Täuber A., Müller-Goymann C.C.. In vitro permeation and penetration of ciclopirox olamine from poloxamer 407-based formulations—Comparison of isolated human stratum corneum, bovine hoof plates and keratin films. Int. J. Pharm. 2015;489:73–82.
    doi: 10.1016/j.ijpharm.2015.04.043pubmed: 25895717google scholar: lookup
  12. Joshi M., Sharma V., Pathak K.. Matrix based system of isotretinoin as nail lacquer to enhance transungal delivery across human nail plate. Int. J. Pharm. 2015;478:268–277.
    doi: 10.1016/j.ijpharm.2014.11.050pubmed: 25445993google scholar: lookup
  13. Schlupp P., Weber M., Schmidts T., Geiger K., Runkel F.. Development and validation of an alternative disturbed skin model by mechanical abrasion to study drug penetration. Results Pharma Sci. 2014;4:26–33.
  14. Gunt H.B., Kasting G.B.. Effect of hydration on the permeation of ketoconazole through human nail plate in vitro. Eur. J. Pharm. Sci. 2007;32:254–260.
    doi: 10.1016/j.ejps.2007.07.009pubmed: 17928205google scholar: lookup
  15. Kunugi A.. Photolysis of Sorbic Acid and Interaction of Sorbic Acid with Sulfur-containing Amino Acids. Food Hyg. Saf. Sci. (Shokuhin Eiseigaku Zasshi) 1984;25:246–250_241.
    doi: 10.3358/shokueishi.25.246google scholar: lookup
  16. Thatai P., Sapra B.. Transungual delivery: Deliberations and creeds. Int. J. Cosmet. Sci. 2014;36:398–411.
    doi: 10.1111/ics.12142pubmed: 24888698google scholar: lookup
  17. Shanbhag P.P., Jani U.. Drug delivery through nails: Present and future. New Horiz. Transl. Med. 2017;3:252–263.
  18. Mertin D., Lippold B.C.. In-vitro permeability of the human nail and of a keratin membrane from bovine hooves: Prediction of the penetration rate of antimycotics through the nail plate and their efficacy. J. Pharm. Pharmacol. 1997;49:866–872.
  19. Baden H.P., Goldsmith L.A., Fleming B.. A comparative study of the physicochemical properties of human keratinized tissues. Biochim. Biophys. Acta. 1973;322:269–278.
    doi: 10.1016/0005-2795(73)90303-6pubmed: 4765091google scholar: lookup
  20. Davies-Strickleton H., Cook J., Hannam S., Bennett R., Gibbs A., Edwards D., Ridden C., Ridden J., Cook D.. Assessment of the nail penetration of antifungal agents, with different physico-chemical properties. PLoS ONE 2020;15:e0229414.
  21. Elsayed M.M.A.. Development of topical therapeutics for management of onychomycosis and other nail disorders: A pharmaceutical perspective. J. Control. Release. 2015;199:132–144.
    doi: 10.1016/j.jconrel.2014.11.017pubmed: 25481439google scholar: lookup
  22. Kobayashi Y., Komatsu T., Sumi M., Numajiri S., Miyamoto M., Kobayashi D., Sugibayashi K., Morimoto Y.. In vitro permeation of several drugs through the human nail plate: Relationship between physicochemical properties and nail permeability of drugs. Eur. J. Pharm. Sci. 2004;21:471–477.
    doi: 10.1016/j.ejps.2003.11.008pubmed: 14998577google scholar: lookup
  23. Reddy N., Zhou W., Ma M.. Keratin-Based Materials. De Gruyter; Berlin, Germany: 2020. Chapter 1 Introduction to keratin; pp. 1–24.
    doi: 10.1515/9781501511769-001google scholar: lookup
  24. Marshall R.C.. Genetic variation in the proteins of human nail. J. Investig. Dermatol. 1980;75:264–269.
    doi: 10.1111/1523-1747.ep12523296pubmed: 6157756google scholar: lookup
  25. Baden H.P., Kubilus J.. Fibrous proteins of bovine hoof. J. Investig. Dermatol. 1983;81:220–224.
    doi: 10.1111/1523-1747.ep12518002pubmed: 6411826google scholar: lookup
  26. Marshall R.C.. Nail, Claw, Hoof and Horn Keratin. In: Bereiter-Hahn J., Matoltsy A.G., Richards K.S., editors. Biology of the Integument: 2 Vertebrates. Springer; Berlin/Heidelberg, Germany: 1986. pp. 722–738.
  27. Gunt H.B., Kasting G.B.. Equilibrium water sorption characteristics of the human nail. J. Cosmet. Sci. 2007;58:1–9.
  28. Naumann S., Meyer J.-P., Kiesow A., Mrestani Y., Wohlrab J., Neubert R.H.H.. Controlled nail delivery of a novel lipophilic antifungal agent using various modern drug carrier systems as well as in vitro and ex vivo model systems. J. Control. Release. 2014;180:60–70.
    doi: 10.1016/j.jconrel.2014.02.013pubmed: 24560884google scholar: lookup