{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T10:32:22Z","timestamp":1775817142909,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,12,30]],"date-time":"2017-12-30T00:00:00Z","timestamp":1514592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Ultrasound Medicine"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>The aim of our study was to determine the effectiveness of using ultrasound (US) to increase the permeability of the nail, with the goal of improving outcomes in the treatment of onychomycosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Porcine nails were used because of their similarity to human nails. A hydrophilic blue dye was used as a drug\u2010mimicking compound. Two sets of experiments were performed: luminosity experiments to assess the dye levels inside the nail after US and sham treatments and diffusion cell experiments for determination of changes in nail permeability due to US application. In both sets of experiments, planar US transducers were used to sonicate the nails at frequencies of 400, 600, and 800 kHz and 1 MHz, an intensity of 1 W\/cm<jats:sup>2<\/jats:sup>, and a duration of 5\u2009min in a continuous mode. Modeling studies were also performed to assess the safety of US application to the human toe for later clinical studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the luminosity experiments, application of US at frequencies of 600 and 800 kHz led to statistically significant results (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.05), with an increase in dye delivery into the nail of up to 95% compared to control values. The diffusion cell results found statistical significance (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.05) at all applied frequencies, with up to a 70% increase in the nail permeability compared to the control. Safety modeling studies found a maximal temperature increase of 4.4\u2009\u00b0C in the bone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our proposed US method may offer an alternative for improved treatment of onychomycosis. The current maximal temperature increase was found to be at the safety limit, and so pulsing and other alternatives will be investigated to minimize this temperature increase.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jum.14526","type":"journal-article","created":{"date-parts":[[2017,12,30]],"date-time":"2017-12-30T11:42:42Z","timestamp":1514634162000},"page":"1743-1752","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Ultrasound\u2010Enhanced Drug Delivery for Treatment of Onychomycosis"],"prefix":"10.1002","volume":"37","author":[{"given":"Alina","family":"Kline\u2010Schoder","sequence":"first","affiliation":[{"name":"Departments of Biomedical Engineering George Washington University Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zung","family":"Le","sequence":"additional","affiliation":[{"name":"Podiatry, Medical Faculty Associates George Washington University Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7572-3922","authenticated-orcid":false,"given":"Vesna","family":"Zderic","sequence":"additional","affiliation":[{"name":"Departments of Biomedical Engineering George Washington University Washington DC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,12,30]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2006.12.019"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0190-9622(98)70199-9"},{"key":"e_1_2_6_4_1","first-page":"8","article-title":"Psychosocial perception of adults with onychomycosis: a blinded, controlled comparison of 1017 adult Hong Kong residents with or without onychomycosis","volume":"1","author":"Chan HH","year":"2014","journal-title":"Biopsychosoc Med"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0507.2008.01618.x"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000080853"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1992.tb00009.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11046-009-9265-x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp0804878"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.7547\/87507315-90-10-495"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2012.10.013"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.20757"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.7863\/jum.2011.30.12.1723"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.4155\/tde.14.32"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425247.2012.739603"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1109\/ICCME.2007.4381938"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1121\/1.1433811"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/1520-6017(200105)90:5<545::AID-JPS1012>3.0.CO;2-H"},{"key":"e_1_2_6_19_1","first-page":"101","article-title":"Nail drug delivery system: a review","volume":"2","author":"Basini P","year":"2012","journal-title":"J Adv Pharm Technol Res"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1997.tb06788.x"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.21711"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1081\/DDC-43935"},{"key":"e_1_2_6_23_1","volume-title":"The Nature of Color Subtraction: A Guided Inquiry Experience","author":"Orvis J","year":"2007"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.3109\/02656736.2013.823672"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1118\/1.4929553"},{"key":"e_1_2_6_26_1","volume-title":"Ultrasonic Bio\u2010instrumentation","author":"Christensen DA","year":"1988"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ultrasmedbio.2017.01.007"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1121\/1.3257547"},{"key":"e_1_2_6_29_1","first-page":"32","volume-title":"Exposure Criteria for Medical Diagnostic Ultrasound, I: Criteria Based on Thermal Mechanisms","author":"National Council on Radiation Protection and Measurements","year":"1992"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-5629(97)00027-6"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.2519\/jospt.1995.22.4.142"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-5629(98)00111-2"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1258\/ult.2010.100003"},{"key":"e_1_2_6_34_1","unstructured":"American Institute of Ultrasound in Medicine.Statement on mammalian biological effects of ultrasound in vivo. 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