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.
Abstract: The penetration behavior into human nails and animal hoof membranes of a novel antifungal agent (EV-086K) for the treatment of onychomycosis was investigated in this study. The new drug provides a high lipophilicity which is adverse for penetration into nails. Therefore, four different formulations were developed, with particular focus on a colloidal carrier system (CCS) due to its penetration enhancing properties. On the one hand, ex vivo penetration experiments on human nails were performed. Afterwards the human nail plates were cut by cryomicrotome in order to quantify the drug concentration in the dorsal, intermediate and ventral nail layer using high-performance liquid chromatography (HPLC) with UV detection. On the other hand, equine and bovine hoof membranes were used to determine the in vitro penetration of the drug into the acceptor compartment of an online diffusion cell coupled with Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy. In combination, both results should exhibit a correlation between the EV-086K penetration behavior in human nail plates and animal hoof membranes. The investigations showed that the developed CCS could increase drug delivery through the human nail most compared to other formulations (nail lacquer, solution and hydrogel). Using animal hooves in the online diffusion cell, we were able to calculate pharmacokinetic data of the penetration process, especially diffusion and permeability coefficients. Finally, a qualitative correlation between the penetration results of human nails and equine hooves was established.
Copyright © 2014 Elsevier B.V. All rights reserved.
Publication Date: 2014-02-18 PubMed ID: 24560884DOI: 10.1016/j.jconrel.2014.02.013Google Scholar: Lookup
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- Journal Article
Summary
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The research investigates the effectiveness of different formulations in delivering an antifungal drug (EV-086K) through human nails to treat onychomycosis. It found that a specially developed colloidal carrier system was most effective.
Introduction
- The researchers sought to explore how well a new antifungal agent, EV-086K, could penetrate human nails and animal hoof membranes. This drug has a high lipophilicity, meaning it is soluble in lipids and organic solvents, which is a hurdle for penetration into nails.
- They developed four different formulations of EV-086K, including a novel one called a colloidal carrier system (CCS), thought to enhance drug penetration.
Methodology
- The study used ex vivo penetration experiments on human nails. Post-penetration, the nails were sliced using a cryomicrotome and tested using high-performance liquid chromatography (HPLC) to determine drug concentration levels in different nail layers.
- Additionally, the absorption of EV-086K into horse and cow hoof membranes was tested in vitro. For this experiment, an online diffusion cell was used and results were analyzed using Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy.
Findings
- According to the results, the drug could be delivered more effectively through human nails with the CCS than the other three formulations (nail lacquer, solution and hydrogel).
- Using the animal hoof membranes in the online diffusion cell allowed researchers to calculate important pharmacokinetic data like diffusion and permeability coefficients of the penetration process.
- They found a correlation between the penetration results of human nails and horse hoof membranes. This suggests that animal hoof membranes could serve as a practical substitute for human nails in future research studies.
Conclusion
- The research confirmed that a well-formulated carrier system is crucial for the successful delivery of lipophilic drugs like EV-086K through the nail. The discovery that the CCS formulation provided superior nail penetration in comparison to other known drug carrier systems is an important development for onychomycosis treatment.
Cite This Article
APA
Naumann S, Meyer JP, Kiesow A, Mrestani Y, Wohlrab J, Neubert RH.
(2014).
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, 180, 60-70.
https://doi.org/10.1016/j.jconrel.2014.02.013 Publication
Researcher Affiliations
- Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Halle (Saale) Germany. Electronic address: sandy.naumann@pharmazie.uni-halle.de.
- Evolva Holding SA, Reinach, Switzerland.
- Fraunhofer Institute for Mechanics of Materials IWM, Halle (Saale), Germany.
- Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Halle (Saale) Germany.
- Department of Dermatology and Venereology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
- Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Halle (Saale) Germany. Electronic address: reinhard.neubert@pharmazie.uni-halle.de.
MeSH Terms
- Animals
- Antifungal Agents / administration & dosage
- Antifungal Agents / pharmacokinetics
- Cattle
- Colloids / chemistry
- Colloids / metabolism
- Delayed-Action Preparations / chemistry
- Delayed-Action Preparations / metabolism
- Drug Carriers / chemistry
- Drug Carriers / metabolism
- Hoof and Claw / metabolism
- Horses
- Humans
- Nails / metabolism
Citations
This article has been cited 15 times.- Urso FG, Del Prete S, Foucher C, Barberis M, Carriero F, Bart A. Use of a 3D Model with Reconstructed Human Epidermis Infected with Fungi and Covered with a Bovine Nail to Simulate Onychomycosis and to Evaluate the Effects of Antifungal Agents. J Fungi (Basel) 2025 Apr 4;11(4).
- Baier J, Jansen B, Wenzel-Storjohann A, Tasdemir D, Peifer C. Novel Henna-Related Naphthazarine Photosensitizers for an Effective Photodynamic Therapy of Onychomycosis. ACS Pharmacol Transl Sci 2023 Dec 8;6(12):1958-1971.
- Gupta I, Adin SN, Rashid MA, Alhamhoom Y, Aqil M, Mujeeb M. Linalool-Incorporated Synergistically Engineered Modified Liposomal Nanocarriers for Enhanced Transungual Delivery of Terbinafine against Onychomycosis. Materials (Basel) 2023 Jun 16;16(12).
- Dobler D, Gerber M, Schmidts TM, Runkel F, Schlupp P. Comparative Ungual Drug Uptake Studies: Equine Hoof Membrane vs. Human Nail Plate. Pharmaceutics 2022 Nov 22;14(12).
- Puri V, Froelich A, Shah P, Pringle S, Chen K, Michniak-Kohn B. Quality by Design Guided Development of Polymeric Nanospheres of Terbinafine Hydrochloride for Topical Treatment of Onychomycosis Using a Nano-Gel Formulation. Pharmaceutics 2022 Oct 12;14(10).
- Krawczyk-Santos AP, Marreto RN, Concheiro A, Alvarez-Lorenzo C, Taveira SF. Poly(pseudo)rotaxanes formed by mixed micelles and α-cyclodextrin enhance terbinafine nail permeation to deeper layers. Int J Pharm X 2022 Dec;4:100118.
- Kappes S, Faber T, Nelleßen L, Yesilkaya T, Bock U, Lamprecht A. Improving Transungual Permeation Study Design by Increased Bovine Hoof Membrane Thickness and Subsequent Infection. Pharmaceutics 2021 Dec 6;13(12).
- Šveikauskaitė I, Briedis V. Potential of Naftifine Application for Transungual Delivery. Molecules 2020 Jul 3;25(13).
- Vikas A, Rashmin P, Mrunali P, Chavan RB, Kaushik T. Mechanistic Insights of Formulation Approaches for the Treatment of Nail Infection: Conventional and Novel Drug Delivery Approaches. AAPS PharmSciTech 2020 Jan 14;21(2):67.
- Lee BC, Pangeni R, Na J, Koo KT, Park JW. Preparation and in vivo evaluation of a highly skin- and nail-permeable efinaconazole topical formulation for enhanced treatment of onychomycosis. Drug Deliv 2019 Dec;26(1):1167-1177.
- Kreutz T, de Matos SP, Koester LS. Recent Patents on Permeation Enhancers for Drug Delivery Through Nails. Recent Pat Drug Deliv Formul 2019;13(3):203-218.
- Šveikauskaitė I, Pockevičius A, Briedis V. Potential of Chemical and Physical Enhancers for Transungual Delivery of Amorolfine Hydrochloride. Materials (Basel) 2019 Mar 28;12(7).
- Iermak I, da Silva AP, Kurachi C, Bagnato VS, Inada NM. Raman Microspectroscopy as a Tool to Elucidate the Efficacy of Topical Formulations Containing Curcumin. Pharmaceuticals (Basel) 2019 Mar 23;12(1).
- Akhtar N, Sharma H, Pathak K. Onychomycosis: Potential of Nail Lacquers in Transungual Delivery of Antifungals. Scientifica (Cairo) 2016;2016:1387936.
- Bhuptani RS, Deshpande KM, Patravale VB. Transungual permeation: current insights. Drug Deliv Transl Res 2016 Aug;6(4):426-39.
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