{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T02:55:04Z","timestamp":1783133704387,"version":"3.54.6"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,8,17]],"date-time":"2015-08-17T00:00:00Z","timestamp":1439769600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Lasers Surg Med"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec><jats:title>Background and Objective<\/jats:title><jats:p>Ablative fractional laser (AFXL) is rapidly evolving as one of the foremost techniques for cutaneous drug delivery. While AFXL has effectively improved topical drug\u2010induced clearance rates of actinic keratosis, treatment of basal cell carcinomas (BCCs) has been challenging, potentially due to insufficient drug uptake in deeper skin layers. This study sought to investigate a standardized method to actively fill laser\u2010generated channels by altering pressure, vacuum, and pressure (PVP), enquiring its effect on (i) relative filling of individual laser channels; (ii) cutaneous deposition and delivery kinetics; (iii) biodistribution and diffusion pattern, estimated by mathematical simulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Franz diffusion chambers (FCs) were used to evaluate the PVP\u2010technique, comparing passive (AFXL) and active (AFXL\u2009+\u2009PVP) channel filling. A fractional CO<jats:sub>2<\/jats:sub>\u2010laser generated superficial (225\u2009\u00b5m;17.5\u2009mJ\/channel) and deep (1200\u2009\u00b5m; 130.5\u2009mJ\/channel) channels, and PVP was delivered as a 3\u2010minutes cycle of 1 minute pressure (+1.0\u2009atm), 1 minute vacuum (\u22121.0\u2009atm), and 1 minute pressure (+1.0\u2009atm). Filling of laser channels was visualized with a colored biomarker liquid (<jats:italic>n<\/jats:italic>\u2009=\u200912 FCs, <jats:italic>n<\/jats:italic>\u2009=\u2009588 channels). Nuclear magnetic resonance quantified intracutaneous deposition of topically applied polyethylene glycol (PEG400) over time (10 minutes, 1 hour, and 4 hours), investigated with (<jats:italic>n<\/jats:italic>\u2009=\u200936 FCs) and without (<jats:italic>n<\/jats:italic>\u2009=\u200930 FCs) PVP\u2010filling. Two\u2010dimensional mathematical simulation was used to simulate intradermal biodistribution and diffusion at a depth of 1,000\u2009\u00b5m.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Active filling with application of PVP increased the number of filled laser channels. At a depth of 1,000\u2009\u00b5m, filling increased from 44% (AFXL) to 94% with one PVP cycle (AFXL\u2009+\u2009PVP; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01). Active filling greatly enhanced intracutaneous deposition of PEG400, resulting in a rapid delivery six\u2010folding uptake at 10 minutes (AFXL 54\u2009\u00b5g\/ml vs. AFXL\u2009+\u2009PVP 303\u2009\u00b5g\/ml, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01). AFXL alone generated an inhomogeneous uptake of PEG400, which greatly improved with active filling, resulting in a uniform uptake within the entire tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Active filling with PVP secures filling of laser channels and induces a deeper, greater, more rapid delivery than conventional AFXL. This delivery technique has promise to improve treatment efficacy for medical treatments of dermally invasive lesions, such as BCCs. Lasers Surg. Med. 48:116\u2013124, 2016. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/lsm.22374","type":"journal-article","created":{"date-parts":[[2015,8,17]],"date-time":"2015-08-17T14:14:18Z","timestamp":1439820858000},"page":"116-124","source":"Crossref","is-referenced-by-count":40,"title":["Fractional laser\u2010assisted drug delivery: Active filling of laser channels with pressure and vacuum alteration"],"prefix":"10.1002","volume":"48","author":[{"given":"Andr\u00e9s M.","family":"Erlendsson","sequence":"first","affiliation":[{"name":"Wellman Center for Photomedicine, Massachusetts General Hospital Harvard Medical School Boston Massachusetts 02114"},{"name":"Department of Dermatology Bispebjerg University Hospital Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apostolos G.","family":"Doukas","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine, Massachusetts General Hospital Harvard Medical School Boston Massachusetts 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Farinelli","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine, Massachusetts General Hospital Harvard Medical School Boston Massachusetts 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brijesh","family":"Bhayana","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine, Massachusetts General Hospital Harvard Medical School Boston Massachusetts 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Rox","family":"Anderson","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine, Massachusetts General Hospital Harvard Medical School Boston Massachusetts 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merete","family":"Haedersdal","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine, Massachusetts General Hospital Harvard Medical School Boston Massachusetts 02114"},{"name":"Department of Dermatology Bispebjerg University Hospital Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,8,17]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/10717540500455975"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/dsu.12111"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/lsm.22227"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/DSS.0000000000000207"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/lsm.20048"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/lsm.20405"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/lsm.20860"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2010.03.017"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2011.03.015"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2011.03.006"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/lsm.22102"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.12507"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2012.10893.x"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.13222"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/lsm.22228"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/lsm.21130"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2010.07.032"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.13166"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.1998.00415.x"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2003.10.031"},{"issue":"3","key":"e_1_2_6_22_1","doi-asserted-by":"crossref","first-page":"200","DOI":"10.2340\/000155555573200202","article-title":"Effect of pressure on in vitro percutaneous absorption of caffeine","volume":"73","author":"Treffel P","year":"1993","journal-title":"Acta Derm Venereol"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12533356"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-024924-4.50005-5"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4362.1983.tb02187.x"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(90)91288-H"},{"key":"e_1_2_6_27_1","doi-asserted-by":"crossref","unstructured":"KositratnaG MansteinD.Rapid fibrin plug formation within ablative fractional CO2 laser lesions. 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