A Novel Transdermal Protein Delivery Strategy via Electrohydrodynamic Coating of PLGA Microparticles onto Microneedles
Transdermal delivery of biological therapeutics is emerging as a potent alternative to intravenous or subcutaneous injections. The latter possess major challenges including patient discomfort, the necessity for trained personnel, specialized sharps disposal, and risk of infection. The microneedle (M...
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Veröffentlicht in: | ACS applied materials & interfaces 2020-03, Vol.12 (11), p.12478-12488 |
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creator | Angkawinitwong, Ukrit Courtenay, Aaron J Rodgers, Aoife M Larrañeta, Eneko McCarthy, Helen O Brocchini, Steve Donnelly, Ryan F Williams, Gareth R |
description | Transdermal delivery of biological therapeutics is emerging as a potent alternative to intravenous or subcutaneous injections. The latter possess major challenges including patient discomfort, the necessity for trained personnel, specialized sharps disposal, and risk of infection. The microneedle (MN) technology circumvents many of the abovementioned challenges, delivering biological materials directly into the skin and allowing sustained release of the active ingredient both in animal models and in humans. This study describes the use of electrohydrodynamic atomization (EHDA) to coat ovalbumin (OVA)-loaded PLGA nanoparticles onto hydrogel-forming MN arrays. The particles showed extended release of OVA over ca. 28 days. Microscopic analysis demonstrated that EHDA could generate a uniform particle coating on the MNs, with 30% coating efficiency. Furthermore, the coated MN array manifested similar mechanical characteristics and insertion properties to the uncoated system, suggesting that the coating should have no detrimental effects on the application of the MNs. The coated MNs resulted in no significant increase in anti-OVA-specific IgG titres in C57BL/6 mice in vivo as compared to the untreated mice (paired t-test, p > 0.05), indicating that the formulations are nonimmunogenic. The approach of using EHDA to coat an MN array thus appears to have potential as a novel noninvasive protein delivery strategy. |
doi_str_mv | 10.1021/acsami.9b22425 |
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The latter possess major challenges including patient discomfort, the necessity for trained personnel, specialized sharps disposal, and risk of infection. The microneedle (MN) technology circumvents many of the abovementioned challenges, delivering biological materials directly into the skin and allowing sustained release of the active ingredient both in animal models and in humans. This study describes the use of electrohydrodynamic atomization (EHDA) to coat ovalbumin (OVA)-loaded PLGA nanoparticles onto hydrogel-forming MN arrays. The particles showed extended release of OVA over ca. 28 days. Microscopic analysis demonstrated that EHDA could generate a uniform particle coating on the MNs, with 30% coating efficiency. Furthermore, the coated MN array manifested similar mechanical characteristics and insertion properties to the uncoated system, suggesting that the coating should have no detrimental effects on the application of the MNs. The coated MNs resulted in no significant increase in anti-OVA-specific IgG titres in C57BL/6 mice in vivo as compared to the untreated mice (paired t-test, p > 0.05), indicating that the formulations are nonimmunogenic. The approach of using EHDA to coat an MN array thus appears to have potential as a novel noninvasive protein delivery strategy.</description><identifier>ISSN: 1944-8244</identifier><identifier>EISSN: 1944-8252</identifier><identifier>DOI: 10.1021/acsami.9b22425</identifier><identifier>PMID: 32066234</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Administration, Cutaneous ; Animals ; Cells, Cultured ; Coated Materials, Biocompatible - administration & dosage ; Coated Materials, Biocompatible - chemistry ; Coated Materials, Biocompatible - pharmacokinetics ; Dendritic Cells ; Electrochemical Techniques - methods ; Female ; Humans ; Mice ; Mice, Inbred C57BL ; Microinjections - instrumentation ; Nanoparticles - administration & dosage ; Nanoparticles - chemistry ; Needles ; Ovalbumin - administration & dosage ; Ovalbumin - chemistry ; Ovalbumin - pharmacokinetics ; Polylactic Acid-Polyglycolic Acid Copolymer - administration & dosage ; Polylactic Acid-Polyglycolic Acid Copolymer - chemistry ; Polylactic Acid-Polyglycolic Acid Copolymer - pharmacokinetics</subject><ispartof>ACS applied materials & interfaces, 2020-03, Vol.12 (11), p.12478-12488</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a370t-1574ee178743ecb9f8775520ecfc8b42568f7aadc44ee198b205ba37ad135e073</citedby><cites>FETCH-LOGICAL-a370t-1574ee178743ecb9f8775520ecfc8b42568f7aadc44ee198b205ba37ad135e073</cites><orcidid>0000-0002-2651-7839 ; 0000-0002-0766-4147 ; 0000-0003-3710-0438 ; 0000-0002-3066-2860</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acsami.9b22425$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acsami.9b22425$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>315,781,785,2766,27077,27925,27926,56739,56789</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32066234$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Angkawinitwong, Ukrit</creatorcontrib><creatorcontrib>Courtenay, Aaron J</creatorcontrib><creatorcontrib>Rodgers, Aoife M</creatorcontrib><creatorcontrib>Larrañeta, Eneko</creatorcontrib><creatorcontrib>McCarthy, Helen O</creatorcontrib><creatorcontrib>Brocchini, Steve</creatorcontrib><creatorcontrib>Donnelly, Ryan F</creatorcontrib><creatorcontrib>Williams, Gareth R</creatorcontrib><title>A Novel Transdermal Protein Delivery Strategy via Electrohydrodynamic Coating of PLGA Microparticles onto Microneedles</title><title>ACS applied materials & interfaces</title><addtitle>ACS Appl. Mater. Interfaces</addtitle><description>Transdermal delivery of biological therapeutics is emerging as a potent alternative to intravenous or subcutaneous injections. The latter possess major challenges including patient discomfort, the necessity for trained personnel, specialized sharps disposal, and risk of infection. The microneedle (MN) technology circumvents many of the abovementioned challenges, delivering biological materials directly into the skin and allowing sustained release of the active ingredient both in animal models and in humans. This study describes the use of electrohydrodynamic atomization (EHDA) to coat ovalbumin (OVA)-loaded PLGA nanoparticles onto hydrogel-forming MN arrays. The particles showed extended release of OVA over ca. 28 days. Microscopic analysis demonstrated that EHDA could generate a uniform particle coating on the MNs, with 30% coating efficiency. Furthermore, the coated MN array manifested similar mechanical characteristics and insertion properties to the uncoated system, suggesting that the coating should have no detrimental effects on the application of the MNs. The coated MNs resulted in no significant increase in anti-OVA-specific IgG titres in C57BL/6 mice in vivo as compared to the untreated mice (paired t-test, p > 0.05), indicating that the formulations are nonimmunogenic. The approach of using EHDA to coat an MN array thus appears to have potential as a novel noninvasive protein delivery strategy.</description><subject>Administration, Cutaneous</subject><subject>Animals</subject><subject>Cells, Cultured</subject><subject>Coated Materials, Biocompatible - administration & dosage</subject><subject>Coated Materials, Biocompatible - chemistry</subject><subject>Coated Materials, Biocompatible - pharmacokinetics</subject><subject>Dendritic Cells</subject><subject>Electrochemical Techniques - methods</subject><subject>Female</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microinjections - instrumentation</subject><subject>Nanoparticles - administration & dosage</subject><subject>Nanoparticles - chemistry</subject><subject>Needles</subject><subject>Ovalbumin - administration & dosage</subject><subject>Ovalbumin - chemistry</subject><subject>Ovalbumin - pharmacokinetics</subject><subject>Polylactic Acid-Polyglycolic Acid Copolymer - administration & dosage</subject><subject>Polylactic Acid-Polyglycolic Acid Copolymer - chemistry</subject><subject>Polylactic Acid-Polyglycolic Acid Copolymer - pharmacokinetics</subject><issn>1944-8244</issn><issn>1944-8252</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1ULFOwzAUtBCIlsLKiDwjpdiOEydjVUpBKlCJMkeO81JcJXFlp5Hy97hK6cZ0T093994dQveUTClh9EkqJ2s9TXPGOIsu0JimnAcJi9jleeZ8hG6c2xESh4xE12jkIY5ZyMeom-EP00GFN1Y2rgBbywqvrWlBN_gZKt2B7fFXa2UL2x53WuJFBaq15qcvrCn6xp9XeG5kq5stNiVer5Yz_K6VNXtpW60qcNg0rRl2DUDhN7foqpSVg7sTTtD3y2Izfw1Wn8u3-WwVyFCQNqCR4ABUJIKHoPK0TISIIkZAlSrJfeA4KYWUheJHWprkPl7upbKgYQREhBM0HXz9aecslNne6lraPqMkOxaYDQVmpwK94GEQ7A95DcWZ_teYJzwOBC_MduZgG___f26_-hF9JQ</recordid><startdate>20200318</startdate><enddate>20200318</enddate><creator>Angkawinitwong, Ukrit</creator><creator>Courtenay, Aaron J</creator><creator>Rodgers, Aoife M</creator><creator>Larrañeta, Eneko</creator><creator>McCarthy, Helen O</creator><creator>Brocchini, Steve</creator><creator>Donnelly, Ryan F</creator><creator>Williams, Gareth R</creator><general>American Chemical Society</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><orcidid>https://orcid.org/0000-0002-2651-7839</orcidid><orcidid>https://orcid.org/0000-0002-0766-4147</orcidid><orcidid>https://orcid.org/0000-0003-3710-0438</orcidid><orcidid>https://orcid.org/0000-0002-3066-2860</orcidid></search><sort><creationdate>20200318</creationdate><title>A Novel Transdermal Protein Delivery Strategy via Electrohydrodynamic Coating of PLGA Microparticles onto Microneedles</title><author>Angkawinitwong, Ukrit ; Courtenay, Aaron J ; Rodgers, Aoife M ; Larrañeta, Eneko ; McCarthy, Helen O ; Brocchini, Steve ; Donnelly, Ryan F ; Williams, Gareth R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a370t-1574ee178743ecb9f8775520ecfc8b42568f7aadc44ee198b205ba37ad135e073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Administration, Cutaneous</topic><topic>Animals</topic><topic>Cells, Cultured</topic><topic>Coated Materials, Biocompatible - administration & dosage</topic><topic>Coated Materials, Biocompatible - chemistry</topic><topic>Coated Materials, Biocompatible - pharmacokinetics</topic><topic>Dendritic Cells</topic><topic>Electrochemical Techniques - methods</topic><topic>Female</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microinjections - instrumentation</topic><topic>Nanoparticles - administration & dosage</topic><topic>Nanoparticles - chemistry</topic><topic>Needles</topic><topic>Ovalbumin - administration & dosage</topic><topic>Ovalbumin - chemistry</topic><topic>Ovalbumin - pharmacokinetics</topic><topic>Polylactic Acid-Polyglycolic Acid Copolymer - administration & dosage</topic><topic>Polylactic Acid-Polyglycolic Acid Copolymer - chemistry</topic><topic>Polylactic Acid-Polyglycolic Acid Copolymer - pharmacokinetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Angkawinitwong, Ukrit</creatorcontrib><creatorcontrib>Courtenay, Aaron J</creatorcontrib><creatorcontrib>Rodgers, Aoife M</creatorcontrib><creatorcontrib>Larrañeta, Eneko</creatorcontrib><creatorcontrib>McCarthy, Helen O</creatorcontrib><creatorcontrib>Brocchini, Steve</creatorcontrib><creatorcontrib>Donnelly, Ryan F</creatorcontrib><creatorcontrib>Williams, Gareth R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>ACS applied materials & interfaces</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Angkawinitwong, Ukrit</au><au>Courtenay, Aaron J</au><au>Rodgers, Aoife M</au><au>Larrañeta, Eneko</au><au>McCarthy, Helen O</au><au>Brocchini, Steve</au><au>Donnelly, Ryan F</au><au>Williams, Gareth R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Novel Transdermal Protein Delivery Strategy via Electrohydrodynamic Coating of PLGA Microparticles onto Microneedles</atitle><jtitle>ACS applied materials & interfaces</jtitle><addtitle>ACS Appl. Mater. Interfaces</addtitle><date>2020-03-18</date><risdate>2020</risdate><volume>12</volume><issue>11</issue><spage>12478</spage><epage>12488</epage><pages>12478-12488</pages><issn>1944-8244</issn><eissn>1944-8252</eissn><abstract>Transdermal delivery of biological therapeutics is emerging as a potent alternative to intravenous or subcutaneous injections. The latter possess major challenges including patient discomfort, the necessity for trained personnel, specialized sharps disposal, and risk of infection. The microneedle (MN) technology circumvents many of the abovementioned challenges, delivering biological materials directly into the skin and allowing sustained release of the active ingredient both in animal models and in humans. This study describes the use of electrohydrodynamic atomization (EHDA) to coat ovalbumin (OVA)-loaded PLGA nanoparticles onto hydrogel-forming MN arrays. The particles showed extended release of OVA over ca. 28 days. Microscopic analysis demonstrated that EHDA could generate a uniform particle coating on the MNs, with 30% coating efficiency. Furthermore, the coated MN array manifested similar mechanical characteristics and insertion properties to the uncoated system, suggesting that the coating should have no detrimental effects on the application of the MNs. The coated MNs resulted in no significant increase in anti-OVA-specific IgG titres in C57BL/6 mice in vivo as compared to the untreated mice (paired t-test, p > 0.05), indicating that the formulations are nonimmunogenic. 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subjects | Administration, Cutaneous Animals Cells, Cultured Coated Materials, Biocompatible - administration & dosage Coated Materials, Biocompatible - chemistry Coated Materials, Biocompatible - pharmacokinetics Dendritic Cells Electrochemical Techniques - methods Female Humans Mice Mice, Inbred C57BL Microinjections - instrumentation Nanoparticles - administration & dosage Nanoparticles - chemistry Needles Ovalbumin - administration & dosage Ovalbumin - chemistry Ovalbumin - pharmacokinetics Polylactic Acid-Polyglycolic Acid Copolymer - administration & dosage Polylactic Acid-Polyglycolic Acid Copolymer - chemistry Polylactic Acid-Polyglycolic Acid Copolymer - pharmacokinetics |
title | A Novel Transdermal Protein Delivery Strategy via Electrohydrodynamic Coating of PLGA Microparticles onto Microneedles |
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