{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:51:44Z","timestamp":1788519104089,"version":"build-2803163510"},"reference-count":19,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T00:00:00Z","timestamp":1582761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Onychomycosis, or fungal nail infection, is a common fungal infection largely caused by dermatophyte fungi, such as <jats:italic>Trichophyton rubrum<\/jats:italic> or <jats:italic>Trichophyton mentagrophytes<\/jats:italic>, which affects a significant number of people. Treatment is either through oral antifungal medicines, which are efficacious but have significant safety concerns, or with topical antifungal treatments that require long treatment regimens and have only limited efficacy. Thus, an efficacious topical therapy remains an unmet medical need. Among the barriers to topical delivery through the nail are the physico-chemical properties of the antifungal drugs. Here, we explore the ability of a range of antifungal compounds with different hydrophilicities to penetrate the nail. Human nail discs were clamped within static diffusion (Franz) cells and dosed with equimolar concentrations of antifungal drugs. Using LC-MS\/MS we quantified the amount of drug that passed through the nail disc and that which remained associated with the nail. Our data identified increased drug flux through the nail for the more hydrophilic compounds (caffeine as a hydrophilic control and fluconazole, with LogP -0.07 and 0.5, respectively), while less hydrophilic efinaconazole, amorolfine and terbinafine (LogP 2.7, 5.6 and 5.9 respectively) had much lower flux through the nail. On the other hand, hydrophilicity alone did not account for the amount of drug associated with\/bound to the nail itself. While there are other factors that are likely to combine to dictate nail penetration, this work supports earlier studies that implicate compound hydrophilicity as a critical factor for nail penetration.<\/jats:p>","DOI":"10.1371\/journal.pone.0229414","type":"journal-article","created":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T18:33:03Z","timestamp":1582828383000},"page":"e0229414","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":28,"title":["Assessment of the nail penetration of antifungal agents, with different physico-chemical properties"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4715-3111","authenticated-orcid":true,"given":"H.","family":"Davies-Strickleton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Hannam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhys","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Gibbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Ridden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Ridden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Cook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,2,27]]},"reference":[{"issue":"5","key":"pone.0229414.ref001","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1111\/j.1365-2710.2009.01107.x","article-title":"Toenail onychomycosis: an important global disease burden","volume":"35","author":"J Thomas","year":"2010","journal-title":"J Clin Pharm Ther"},{"issue":"7","key":"pone.0229414.ref002","first-page":"10","article-title":"The role of topical antifungal therapy for onychomycosis and the emegernce of newer agents","volume":"7","author":"JQ Del Rosso","year":"2014","journal-title":"J Clin Aesthet Dermatol"},{"issue":"7","key":"pone.0229414.ref003","doi-asserted-by":"crossref","first-page":"0159661","DOI":"10.1371\/journal.pone.0159661","article-title":"Efficacy coefficients determined using nail permeability and antifungal activity in keratin-containing media are useful for predicting clinical efficacies of topical drugs for onychomycosis","volume":"11","author":"Y Matsuda","year":"2016","journal-title":"PLoS One"},{"issue":"1","key":"pone.0229414.ref004","doi-asserted-by":"crossref","first-page":"39","DOI":"10.2165\/00128071-200304010-00005","article-title":"Terbinafine: a review of its use in onychomycosis in adults","volume":"4","author":"MJ Darkes","year":"2003","journal-title":"Am J Clin Dermatol"},{"key":"pone.0229414.ref005","doi-asserted-by":"crossref","first-page":"24","DOI":"10.2174\/2211738507666190228104031","article-title":"Novel drug delivery strategies for the treatment of onychomycosis","volume":"7","author":"RK Dhamoon","year":"2019","journal-title":"Pharmaceutical Nanotechnology"},{"issue":"3","key":"pone.0229414.ref006","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1128\/CMR.11.3.415","article-title":"Onychomycosis: pathogenesis, diagnosis, and management","volume":"11","author":"BE Elewski","year":"1998","journal-title":"Clin Microbiol Rev"},{"key":"pone.0229414.ref007","first-page":"950358","article-title":"Hydroxypropyl-\u03b2-cyclodextrin: A novel transungual permeation enhancer for development of topical drug delivery system for onychomycosis","author":"P Chouhan","year":"2014","journal-title":"J Drug Deliv"},{"key":"pone.0229414.ref008","first-page":"252","article-title":"Drug delivery through nails: Present and future","volume":"3","author":"PP Shanbhag","year":"2017","journal-title":"New horizons in Translational Medicine"},{"key":"pone.0229414.ref009","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2009.10.002","article-title":"Transungual drug delivery: Current Status","volume":"384","author":"R Elkeeb","year":"2010","journal-title":"International Journal of Pharmaceutics"},{"key":"pone.0229414.ref010","first-page":"604","article-title":"Different physicochemical properties of antimycotic agents are relevant for penetration into and through human nails","volume":"61","author":"RHH Neubert","year":"2006","journal-title":"Pharmazie"},{"key":"pone.0229414.ref011","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1211\/0022357991772448","article-title":"Drug permeation through the three layers of the human nail plate","volume":"51","author":"Y Kobayashi","year":"1999","journal-title":"J. Pharm. Pharmacol"},{"key":"pone.0229414.ref012","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.2042-7158.1983.tb04258.x","article-title":"Physicochemical characterization of the human nail\u2014permeation pattern for water and the homologous alcohols and differences with respect to the stratum-corneum","volume":"35","author":"KA Walters","year":"1983","journal-title":"J. Pharm. Pharmacol"},{"key":"pone.0229414.ref013","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.ejpb.2016.03.008","article-title":"An investigation of how fungal infection influences drug penetration through onychomycosis patient\u2019s nail plates","volume":"102","author":"WJ McAuley","year":"2016","journal-title":"Eur J Pharm Biopharm"},{"key":"pone.0229414.ref014","unstructured":"Human tissue authority [Internet]. Relevant material under the Human Tissue Act 2004. Available from: https:\/\/www.hta.gov.uk\/policies\/relevant-material-under-human-tissue-act-2004"},{"key":"pone.0229414.ref015","unstructured":"Health Research Authority [Internet]. Do I need NHS REC approval? Available from: http:\/\/www.hra-decisiontools.org.uk\/ethics\/"},{"issue":"1","key":"pone.0229414.ref016","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1080\/10717544.2019.1687612","article-title":"Preparation and in vivo evaluation of a highly skin- and nail-permeable efinaconazole topical formulation for enhanced treatment of onychomycosis","volume":"26","author":"B Chun Lee","year":"2019","journal-title":"Drug Delivery"},{"key":"pone.0229414.ref017","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.jpba.2009.08.019","article-title":"A direct LC\/MS\/MS method for the determination of ciclopirox penetration across human nail plate in in vitro penetration studies","volume":"51","author":"W Bu","year":"2010","journal-title":"J Pharm Biomed Anal"},{"issue":"1","key":"pone.0229414.ref018","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.00779-17","article-title":"In vitro human onychopharmacokinetic and pharmacodynamic analyses of ME111, a new tppical agent in onychomycosis","volume":"62","author":"N Kubota-Ishida","year":"2018","journal-title":"Antimicrob Agents Chemother"},{"issue":"2","key":"pone.0229414.ref019","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1080\/13693780410001731583","article-title":"In vitro activities of posaconazole, ravuconazole, terbinafine, itraconazole and fluconazole against dermatophyte, yeast and non-dermatophyte species","volume":"43","author":"AK Gupta","year":"2005","journal-title":"Medical Mycology"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0229414","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T18:04:32Z","timestamp":1747418672000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0229414"}},"subtitle":[],"editor":[{"given":"Siew Hua","family":"Gan,","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,2,27]]},"references-count":19,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,2,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0229414","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,27]]}}}