{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T10:19:21Z","timestamp":1784110761568,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T00:00:00Z","timestamp":1653004800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["P41EB015903"],"award-info":[{"award-number":["P41EB015903"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Lasers Surg Med"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>The ability of ablative fractional lasers (AFL) to enhance topical drug uptake is well established. After AFL\u00a0delivery, however, drug clearance by local vasculature is poorly understood. Modifications in vascular clearance may enhance AFL\u2010assisted drug concentrations and prolong drug dwell time in the skin. Aiming to assess the role and modifiability of vascular clearance after AFL\u2010assisted delivery, this study examined the impact of vasoregulative interventions on AFL\u2010assisted 5\u2010fluorouracil (5\u2010FU) concentrations in in vivo skin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>5\u2010FU uptake was assessed in intact\u00a0and AFL\u2010exposed skin in a live pig model. After fractional CO<jats:sub>2<\/jats:sub> laser exposure (15\u2009mJ\/microbeam, 5% density), vasoregulative intervention using topical brimonidine cream, epinephrine solution, or pulsed dye laser (PDL) was performed in designated treatment areas, followed by a single 5% 5\u2010FU cream application. At 0, 1, 4, 48, and 72\u2009h, 5\u2010FU concentrations were measured in 500 and 1500\u2009\u03bcm skin layers by mass spectrometry (<jats:italic>n<\/jats:italic>\u2009=\u20096). A supplemental assessment of blood flow following AFL\u2009\u00b1\u2009vasoregulation was performed using optical coherence tomography (OCT) in a human volunteer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to intact skin, AFL facilitated a prompt peak in 5\u2010FU delivery that remained elevated up to 4\u2009hours\u00a0(1500\u2009\u03bcm: 1.5 vs. 31.8\u2009ng\/ml [1\u2009hour,\u00a0<jats:italic>p<\/jats:italic>\u2009=\u20090.002]; 5.3 vs. 14.5\u2009ng\/ml [4\u2009hours, <jats:italic>p<\/jats:italic>\u2009=\u20090.039]). However, AFL's impact was transient, with 5\u2010FU concentrations comparable to intact skin at later time points. Overall, vasoregulative intervention with brimonidine or PDL led to significantly higher peak 5\u2010FU concentrations, prolonging the drug's dwell time in the skin versus AFL delivery alone. As such, brimonidine and PDL led to twofold higher 5\u2010FU concentrations than AFL alone in both skin layers by 1\u2009hour\u00a0(e.g., 500\u2009\u03bcm: 107\u2009ng\/ml [brimonidine]; 96.9\u2009ng\/ml [PDL], 46.6\u2009ng\/ml [AFL alone],\u00a0<jats:italic>p<\/jats:italic>\u2009\u2264\u20090.024), and remained significantly elevated at 4\u2009hours\u00a0(<jats:italic>p<\/jats:italic>\u2009\u2264\u20090.024). A similar pattern was observed for epinephrine, although trends remained nonsignificant (<jats:italic>p<\/jats:italic>\u2009\u2265\u20090.09). Prolonged 5\u2010FU delivery was provided by PDL, resulting in sustained drug deposition compared to AFL alone at both 48 and 72\u2009hours\u00a0in the superficial skin layer (<jats:italic>p<\/jats:italic>\u2009\u2264\u20090.024). Supporting drug delivery findings, OCT revealed that increases in local blood flow after AFL were mitigated in test areas also exposed to PDL, brimonidine, or epinephrine, with PDL providing the greatest, sustained reduction in flow over 48\u2009hours.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Vasoregulative intervention in conjunction with AFL\u2010assisted delivery enhances and prolongs 5\u2010FU deposition in in vivo skin.<\/jats:p><\/jats:sec>","DOI":"10.1002\/lsm.23558","type":"journal-article","created":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T07:23:03Z","timestamp":1653031383000},"page":"1288-1297","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Local vasoregulative interventions impact drug concentrations in the skin after topical laser\u2010assisted delivery"],"prefix":"10.1002","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5928-5042","authenticated-orcid":false,"given":"Emily","family":"Wenande","sequence":"first","affiliation":[{"name":"Wellman Center for Photomedicine Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"},{"name":"Department of Dermatology, Bispebjerg Hospital University of Copenhagen Copenhagen NV Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3231-0762","authenticated-orcid":false,"given":"Sarat Chandra","family":"Gundavarapu","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1649-3888","authenticated-orcid":false,"given":"Joshua","family":"Tam","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"},{"name":"Department of Dermatology Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2517-0033","authenticated-orcid":false,"given":"Brijesh","family":"Bhayana","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina N.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0972-485X","authenticated-orcid":false,"given":"William A.","family":"Farinelli","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6623-3515","authenticated-orcid":false,"given":"Benjamin J.","family":"Vakoc","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"},{"name":"Department of Dermatology Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4966-3035","authenticated-orcid":false,"given":"R. 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