Laser‐induced thermal coagulation enhances skin uptake of topically applied compounds

Background Ablative fractional laser (AFL) generates microchannels in skin surrounded by a zone of thermally altered tissue, termed the coagulation zone (CZ). The thickness of CZ varies according to applied wavelength and laser settings. It is well‐known that AFL channels facilitate uptake of topica...

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Veröffentlicht in:Lasers in surgery and medicine 2017-08, Vol.49 (6), p.582-591
Hauptverfasser: Haak, C.S., Hannibal, J., Paasch, U., Anderson, R.R., Haedersdal, M.
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container_issue 6
container_start_page 582
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creator Haak, C.S.
Hannibal, J.
Paasch, U.
Anderson, R.R.
Haedersdal, M.
description Background Ablative fractional laser (AFL) generates microchannels in skin surrounded by a zone of thermally altered tissue, termed the coagulation zone (CZ). The thickness of CZ varies according to applied wavelength and laser settings. It is well‐known that AFL channels facilitate uptake of topically applied compounds, but the importance of CZ is unknown. Methods Franz Cells were used to investigate skin uptake and permeation of fluorescent labeled polyethylene glycols (PEGs) with mean molecular weights (MW) of 350, 1,000, and 5,000 Da. Microchannels with CZ thicknesses ranging from 0 to 80 μm were generated from micro‐needles (0 μm, CZ‐0), and AFL (10,600 nm) applied to −80°C deep frozen skin (20 μm, CZ‐20) and skin equilibrated to room temperature (80 μm, CZ‐80). Channels penetrated into similar mid‐dermal skin depths of 600–700 μm, and number of channels per skin area was similar. At 4 hours incubation, skin uptake of PEGs into CZ and dermis was evaluated by fluorescence microscopy at specific skin depths of 150, 400, and 1,000 μm and the transcutaneous permeation was quantified by fluorescence of receptor fluids. Results Overall, the highest uptake of PEGs was reached through microchannels surrounded by CZ compared to channels with no CZ (CZ‐20 and CZ‐80>CZ‐0).The thickness of CZ affected PEG distribution in skin. A thin CZ‐20 favored significantly higher mean fluorescence intensities inside CZ areas compared to CZ‐80 (PEG 350, 1,000, and 5,000; P 
doi_str_mv 10.1002/lsm.22642
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The thickness of CZ varies according to applied wavelength and laser settings. It is well‐known that AFL channels facilitate uptake of topically applied compounds, but the importance of CZ is unknown. Methods Franz Cells were used to investigate skin uptake and permeation of fluorescent labeled polyethylene glycols (PEGs) with mean molecular weights (MW) of 350, 1,000, and 5,000 Da. Microchannels with CZ thicknesses ranging from 0 to 80 μm were generated from micro‐needles (0 μm, CZ‐0), and AFL (10,600 nm) applied to −80°C deep frozen skin (20 μm, CZ‐20) and skin equilibrated to room temperature (80 μm, CZ‐80). Channels penetrated into similar mid‐dermal skin depths of 600–700 μm, and number of channels per skin area was similar. At 4 hours incubation, skin uptake of PEGs into CZ and dermis was evaluated by fluorescence microscopy at specific skin depths of 150, 400, and 1,000 μm and the transcutaneous permeation was quantified by fluorescence of receptor fluids. Results Overall, the highest uptake of PEGs was reached through microchannels surrounded by CZ compared to channels with no CZ (CZ‐20 and CZ‐80&gt;CZ‐0).The thickness of CZ affected PEG distribution in skin. A thin CZ‐20 favored significantly higher mean fluorescence intensities inside CZ areas compared to CZ‐80 (PEG 350, 1,000, and 5,000; P &lt; 0.001). In dermis, the uptake through CZ‐20 channels was significantly higher than through CZ‐80 and CZ‐0 at all skin depths (PEG 350, 1,000 and 5,000, 150–1,000 μm; P &lt; 0.001). Correspondingly, transcutaneous permeation of PEG 350 was highest in CZ‐20 compared to CZ‐80 and CZ‐0 samples (P &lt; 0.001). Permeation of larger molecules (PEG 1,000 and PEG 5,000) was generally low. Conclusion Uptake of topical compounds is higher through microchannels surrounded by a CZ than without a CZ. Moreover, CZ thickness influences PEG distribution, with highest PEG uptake achieved from microchannels surrounded by a thin CZ. Lasers Surg. Med. 49:582–591, 2017. © 2017 Wiley Periodicals, Inc.</description><identifier>ISSN: 0196-8092</identifier><identifier>EISSN: 1096-9101</identifier><identifier>DOI: 10.1002/lsm.22642</identifier><identifier>PMID: 28181673</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Ablation ; ablative fractional laser ; Administration, Cutaneous ; Animals ; Balancing ; Blood Coagulation ; Cells, Cultured ; Channels ; Coagulation ; coagulation zone ; Dermatologic Agents - administration &amp; dosage ; Dermatologic Agents - pharmacokinetics ; Dermis ; Drug Delivery Systems ; Female ; Fluorescence ; Fluorescence microscopy ; Franz cell ; Hypodermic needles ; Lasers ; Microchannels ; Microscopy ; Microscopy, Fluorescence ; Needles ; Penetration ; Polyethylene glycol ; Polyethylene Glycols - administration &amp; dosage ; Polyethylene Glycols - pharmacokinetics ; Polyethylenes ; Random Allocation ; Skin ; Skin - diagnostic imaging ; Skin - metabolism ; Swine ; Temperature effects ; topical drug delivery</subject><ispartof>Lasers in surgery and medicine, 2017-08, Vol.49 (6), p.582-591</ispartof><rights>2017 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3902-c6fd893fdf9a4e0d03f5723b1fefb83b83e1c04e0abef472f73f56648dbae9483</citedby><cites>FETCH-LOGICAL-c3902-c6fd893fdf9a4e0d03f5723b1fefb83b83e1c04e0abef472f73f56648dbae9483</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Flsm.22642$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Flsm.22642$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28181673$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Haak, C.S.</creatorcontrib><creatorcontrib>Hannibal, J.</creatorcontrib><creatorcontrib>Paasch, U.</creatorcontrib><creatorcontrib>Anderson, R.R.</creatorcontrib><creatorcontrib>Haedersdal, M.</creatorcontrib><title>Laser‐induced thermal coagulation enhances skin uptake of topically applied compounds</title><title>Lasers in surgery and medicine</title><addtitle>Lasers Surg Med</addtitle><description>Background Ablative fractional laser (AFL) generates microchannels in skin surrounded by a zone of thermally altered tissue, termed the coagulation zone (CZ). The thickness of CZ varies according to applied wavelength and laser settings. It is well‐known that AFL channels facilitate uptake of topically applied compounds, but the importance of CZ is unknown. Methods Franz Cells were used to investigate skin uptake and permeation of fluorescent labeled polyethylene glycols (PEGs) with mean molecular weights (MW) of 350, 1,000, and 5,000 Da. Microchannels with CZ thicknesses ranging from 0 to 80 μm were generated from micro‐needles (0 μm, CZ‐0), and AFL (10,600 nm) applied to −80°C deep frozen skin (20 μm, CZ‐20) and skin equilibrated to room temperature (80 μm, CZ‐80). Channels penetrated into similar mid‐dermal skin depths of 600–700 μm, and number of channels per skin area was similar. At 4 hours incubation, skin uptake of PEGs into CZ and dermis was evaluated by fluorescence microscopy at specific skin depths of 150, 400, and 1,000 μm and the transcutaneous permeation was quantified by fluorescence of receptor fluids. Results Overall, the highest uptake of PEGs was reached through microchannels surrounded by CZ compared to channels with no CZ (CZ‐20 and CZ‐80&gt;CZ‐0).The thickness of CZ affected PEG distribution in skin. A thin CZ‐20 favored significantly higher mean fluorescence intensities inside CZ areas compared to CZ‐80 (PEG 350, 1,000, and 5,000; P &lt; 0.001). In dermis, the uptake through CZ‐20 channels was significantly higher than through CZ‐80 and CZ‐0 at all skin depths (PEG 350, 1,000 and 5,000, 150–1,000 μm; P &lt; 0.001). Correspondingly, transcutaneous permeation of PEG 350 was highest in CZ‐20 compared to CZ‐80 and CZ‐0 samples (P &lt; 0.001). Permeation of larger molecules (PEG 1,000 and PEG 5,000) was generally low. Conclusion Uptake of topical compounds is higher through microchannels surrounded by a CZ than without a CZ. Moreover, CZ thickness influences PEG distribution, with highest PEG uptake achieved from microchannels surrounded by a thin CZ. Lasers Surg. Med. 49:582–591, 2017. © 2017 Wiley Periodicals, Inc.</description><subject>Ablation</subject><subject>ablative fractional laser</subject><subject>Administration, Cutaneous</subject><subject>Animals</subject><subject>Balancing</subject><subject>Blood Coagulation</subject><subject>Cells, Cultured</subject><subject>Channels</subject><subject>Coagulation</subject><subject>coagulation zone</subject><subject>Dermatologic Agents - administration &amp; dosage</subject><subject>Dermatologic Agents - pharmacokinetics</subject><subject>Dermis</subject><subject>Drug Delivery Systems</subject><subject>Female</subject><subject>Fluorescence</subject><subject>Fluorescence microscopy</subject><subject>Franz cell</subject><subject>Hypodermic needles</subject><subject>Lasers</subject><subject>Microchannels</subject><subject>Microscopy</subject><subject>Microscopy, Fluorescence</subject><subject>Needles</subject><subject>Penetration</subject><subject>Polyethylene glycol</subject><subject>Polyethylene Glycols - administration &amp; dosage</subject><subject>Polyethylene Glycols - pharmacokinetics</subject><subject>Polyethylenes</subject><subject>Random Allocation</subject><subject>Skin</subject><subject>Skin - diagnostic imaging</subject><subject>Skin - metabolism</subject><subject>Swine</subject><subject>Temperature effects</subject><subject>topical drug delivery</subject><issn>0196-8092</issn><issn>1096-9101</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10M9KHTEUBvBQWur12kVfoAx0o4u5niRjJlmK-KcwxYWKy5DJnNTRzGSczCB310foM_ZJjI7tolAIJJDf-Th8hHymsKEA7NDHbsOYKNg7sqKgRK4o0PdkBTS9JSi2Q3ZjvAcAzqD8SHaYpJKKkq_IbWUijr9__mr7ZrbYZNMdjp3xmQ3mx-zN1IY-w_7O9BZjFh_aPpuHyTxgFlw2haG1xvttZobBt2nahm4Ic9_EPfLBGR_x09u9Jjdnp9cnF3l1ef7t5LjKLVfAcitcIxV3jVOmQGiAu6OS8Zo6dLXk6SC1kH5Mja4omSsTEKKQTW1QFZKvyf6SO4zhccY46a6NFr03PYY5aiqFEFJRfpTo13_ofZjHPm2nqaKqgJIXLKmDRdkxxDii08PYdmbcagr6pW2d2tavbSf75S1xrjts_so_9SZwuICn1uP2_0m6uvq-RD4DbuSLDw</recordid><startdate>201708</startdate><enddate>201708</enddate><creator>Haak, C.S.</creator><creator>Hannibal, J.</creator><creator>Paasch, U.</creator><creator>Anderson, R.R.</creator><creator>Haedersdal, M.</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>M7Z</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201708</creationdate><title>Laser‐induced thermal coagulation enhances skin uptake of topically applied compounds</title><author>Haak, C.S. ; Hannibal, J. ; Paasch, U. ; Anderson, R.R. ; Haedersdal, M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3902-c6fd893fdf9a4e0d03f5723b1fefb83b83e1c04e0abef472f73f56648dbae9483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Ablation</topic><topic>ablative fractional laser</topic><topic>Administration, Cutaneous</topic><topic>Animals</topic><topic>Balancing</topic><topic>Blood Coagulation</topic><topic>Cells, Cultured</topic><topic>Channels</topic><topic>Coagulation</topic><topic>coagulation zone</topic><topic>Dermatologic Agents - administration &amp; dosage</topic><topic>Dermatologic Agents - pharmacokinetics</topic><topic>Dermis</topic><topic>Drug Delivery Systems</topic><topic>Female</topic><topic>Fluorescence</topic><topic>Fluorescence microscopy</topic><topic>Franz cell</topic><topic>Hypodermic needles</topic><topic>Lasers</topic><topic>Microchannels</topic><topic>Microscopy</topic><topic>Microscopy, Fluorescence</topic><topic>Needles</topic><topic>Penetration</topic><topic>Polyethylene glycol</topic><topic>Polyethylene Glycols - administration &amp; dosage</topic><topic>Polyethylene Glycols - pharmacokinetics</topic><topic>Polyethylenes</topic><topic>Random Allocation</topic><topic>Skin</topic><topic>Skin - diagnostic imaging</topic><topic>Skin - metabolism</topic><topic>Swine</topic><topic>Temperature effects</topic><topic>topical drug delivery</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Haak, C.S.</creatorcontrib><creatorcontrib>Hannibal, J.</creatorcontrib><creatorcontrib>Paasch, U.</creatorcontrib><creatorcontrib>Anderson, R.R.</creatorcontrib><creatorcontrib>Haedersdal, M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Lasers in surgery and medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Haak, C.S.</au><au>Hannibal, J.</au><au>Paasch, U.</au><au>Anderson, R.R.</au><au>Haedersdal, M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Laser‐induced thermal coagulation enhances skin uptake of topically applied compounds</atitle><jtitle>Lasers in surgery and medicine</jtitle><addtitle>Lasers Surg Med</addtitle><date>2017-08</date><risdate>2017</risdate><volume>49</volume><issue>6</issue><spage>582</spage><epage>591</epage><pages>582-591</pages><issn>0196-8092</issn><eissn>1096-9101</eissn><abstract>Background Ablative fractional laser (AFL) generates microchannels in skin surrounded by a zone of thermally altered tissue, termed the coagulation zone (CZ). The thickness of CZ varies according to applied wavelength and laser settings. It is well‐known that AFL channels facilitate uptake of topically applied compounds, but the importance of CZ is unknown. Methods Franz Cells were used to investigate skin uptake and permeation of fluorescent labeled polyethylene glycols (PEGs) with mean molecular weights (MW) of 350, 1,000, and 5,000 Da. Microchannels with CZ thicknesses ranging from 0 to 80 μm were generated from micro‐needles (0 μm, CZ‐0), and AFL (10,600 nm) applied to −80°C deep frozen skin (20 μm, CZ‐20) and skin equilibrated to room temperature (80 μm, CZ‐80). Channels penetrated into similar mid‐dermal skin depths of 600–700 μm, and number of channels per skin area was similar. At 4 hours incubation, skin uptake of PEGs into CZ and dermis was evaluated by fluorescence microscopy at specific skin depths of 150, 400, and 1,000 μm and the transcutaneous permeation was quantified by fluorescence of receptor fluids. Results Overall, the highest uptake of PEGs was reached through microchannels surrounded by CZ compared to channels with no CZ (CZ‐20 and CZ‐80&gt;CZ‐0).The thickness of CZ affected PEG distribution in skin. A thin CZ‐20 favored significantly higher mean fluorescence intensities inside CZ areas compared to CZ‐80 (PEG 350, 1,000, and 5,000; P &lt; 0.001). In dermis, the uptake through CZ‐20 channels was significantly higher than through CZ‐80 and CZ‐0 at all skin depths (PEG 350, 1,000 and 5,000, 150–1,000 μm; P &lt; 0.001). Correspondingly, transcutaneous permeation of PEG 350 was highest in CZ‐20 compared to CZ‐80 and CZ‐0 samples (P &lt; 0.001). Permeation of larger molecules (PEG 1,000 and PEG 5,000) was generally low. Conclusion Uptake of topical compounds is higher through microchannels surrounded by a CZ than without a CZ. Moreover, CZ thickness influences PEG distribution, with highest PEG uptake achieved from microchannels surrounded by a thin CZ. Lasers Surg. Med. 49:582–591, 2017. © 2017 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28181673</pmid><doi>10.1002/lsm.22642</doi><tpages>10</tpages></addata></record>
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subjects Ablation
ablative fractional laser
Administration, Cutaneous
Animals
Balancing
Blood Coagulation
Cells, Cultured
Channels
Coagulation
coagulation zone
Dermatologic Agents - administration & dosage
Dermatologic Agents - pharmacokinetics
Dermis
Drug Delivery Systems
Female
Fluorescence
Fluorescence microscopy
Franz cell
Hypodermic needles
Lasers
Microchannels
Microscopy
Microscopy, Fluorescence
Needles
Penetration
Polyethylene glycol
Polyethylene Glycols - administration & dosage
Polyethylene Glycols - pharmacokinetics
Polyethylenes
Random Allocation
Skin
Skin - diagnostic imaging
Skin - metabolism
Swine
Temperature effects
topical drug delivery
title Laser‐induced thermal coagulation enhances skin uptake of topically applied compounds
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