Insertion Process of Ceramic Nanoporous Microneedles by Means of a Novel Mechanical Applicator Design
Identifieur interne : 003D71 ( Ncbi/Curation ); précédent : 003D70; suivant : 003D72Insertion Process of Ceramic Nanoporous Microneedles by Means of a Novel Mechanical Applicator Design
Auteurs : Xavier H. M. Hartmann ; Peter Van Der Linde [Pays-Bas] ; Erik F. G. A. Homburg ; Lambert C. A. Van Breemen ; Arthur M. De Jong ; Regina Luttge [Pays-Bas]Source :
- Pharmaceutics [ 1999-4923 ] ; 2015.
Abstract
Arrays of microneedles (MNAs) are integrated in an out-of-plane fashion with a base plate and can serve as patches for the release of drugs and vaccines. We used soft-lithography and micromolding to manufacture ceramic nanoporous (np)MNAs. Failure modes of ceramic npMNAs are as yet poorly understood and the question remained: is our npMNA platform technology ready for microneedle (MN) assembly into patches? We investigated npMNAs by microindentation, yielding average crack fracture forces above the required insertion force for a single MN to penetrate human skin. We further developed a thumb pressure-actuated applicator-assisted npMNA insertion method, which enables anchoring of MNs in the skin by an adhesive in one handling step. Using a set of simple artificial skin models, we found a puncture efficiency of this insertion method a factor three times higher than by applying thumb pressure on the npMNA base plate directly. In addition, this new method facilitated zero MN-breakage due to a well-defined force distribution exerted onto the MNs and the closely surrounding area prior to bringing the adhesive into contact with the skin. Owing to the fact that such parameter space exists, we can conclude that npMNAs by soft lithography are a platform technology for MN assembly into a patch.
Url:
DOI: 10.3390/pharmaceutics7040503
PubMed: 26593939
PubMed Central: 4695831
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Insertion Process of Ceramic Nanoporous Microneedles by Means of a Novel Mechanical Applicator Design</title><author><name sortKey="Hartmann, Xavier H M" sort="Hartmann, Xavier H M" uniqKey="Hartmann X" first="Xavier H. M." last="Hartmann">Xavier H. M. Hartmann</name><affiliation><nlm:aff id="af1-pharmaceutics-07-00503">Department of Mechanical Engineering, Microsystems Group, Materials Technology Institute (MaTe) and ICMS Institute for Complex Molecular Systems, Eindhoven University of Technology, Den Dolech 2, 5612 AZ Eindhoven, The Netherlands; E-Mails:<email>x.h.m.hartmann@student.tue.nl</email> (X.H.M.H.);<email>f.g.a.homburg@tue.nl</email> (E.F.G.A.H.)</nlm:aff></affiliation></author><author><name sortKey="Van Der Linde, Peter" sort="Van Der Linde, Peter" uniqKey="Van Der Linde P" first="Peter" last="Van Der Linde">Peter Van Der Linde</name><affiliation><nlm:aff id="af2-pharmaceutics-07-00503">MESA+ Institute for Nanotechnology, University of Twente, 7500 AE Enschede, The Netherlands; E-Mail:<email>p.vanderlinde@utwente.nl</email></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-pharmaceutics-07-00503">MyLife Technologies B.V., 7522 NH Enschede, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>MyLife Technologies B.V., 7522 NH Enschede</wicri:regionArea><wicri:noRegion>7522 NH Enschede</wicri:noRegion></affiliation></author><author><name sortKey="Homburg, Erik F G A" sort="Homburg, Erik F G A" uniqKey="Homburg E" first="Erik F. G. A." last="Homburg">Erik F. G. A. Homburg</name><affiliation><nlm:aff id="af1-pharmaceutics-07-00503">Department of Mechanical Engineering, Microsystems Group, Materials Technology Institute (MaTe) and ICMS Institute for Complex Molecular Systems, Eindhoven University of Technology, Den Dolech 2, 5612 AZ Eindhoven, The Netherlands; E-Mails:<email>x.h.m.hartmann@student.tue.nl</email> (X.H.M.H.);<email>f.g.a.homburg@tue.nl</email> (E.F.G.A.H.)</nlm:aff></affiliation></author><author><name sortKey="Van Breemen, Lambert C A" sort="Van Breemen, Lambert C A" uniqKey="Van Breemen L" first="Lambert C. A." last="Van Breemen">Lambert C. A. Van Breemen</name><affiliation><nlm:aff id="af4-pharmaceutics-07-00503">Department of Mechanical Engineering, Polymer Technology Group and Materials Technology Institute (MaTe), Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands; E-Mail:<email>l.c.a.v.breemen@tue.nl</email></nlm:aff></affiliation></author><author><name sortKey="De Jong, Arthur M" sort="De Jong, Arthur M" uniqKey="De Jong A" first="Arthur M." last="De Jong">Arthur M. De Jong</name><affiliation><nlm:aff id="af5-pharmaceutics-07-00503">Department of Applied Physics, Molecular Biosensing for Medical Diagnostics and ICMS Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands; E-Mail:<email>a.m.de.jong@tue.nl</email></nlm:aff></affiliation></author><author><name sortKey="Luttge, Regina" sort="Luttge, Regina" uniqKey="Luttge R" first="Regina" last="Luttge">Regina Luttge</name><affiliation><nlm:aff id="af1-pharmaceutics-07-00503">Department of Mechanical Engineering, Microsystems Group, Materials Technology Institute (MaTe) and ICMS Institute for Complex Molecular Systems, Eindhoven University of Technology, Den Dolech 2, 5612 AZ Eindhoven, The Netherlands; E-Mails:<email>x.h.m.hartmann@student.tue.nl</email> (X.H.M.H.);<email>f.g.a.homburg@tue.nl</email> (E.F.G.A.H.)</nlm:aff></affiliation><affiliation><nlm:aff id="af2-pharmaceutics-07-00503">MESA+ Institute for Nanotechnology, University of Twente, 7500 AE Enschede, The Netherlands; E-Mail:<email>p.vanderlinde@utwente.nl</email></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-pharmaceutics-07-00503">MyLife Technologies B.V., 7522 NH Enschede, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>MyLife Technologies B.V., 7522 NH Enschede</wicri:regionArea><wicri:noRegion>7522 NH Enschede</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26593939</idno><idno type="pmc">4695831</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695831</idno><idno type="RBID">PMC:4695831</idno><idno type="doi">10.3390/pharmaceutics7040503</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">000370</idno><idno type="wicri:Area/Pmc/Curation">000370</idno><idno type="wicri:Area/Pmc/Checkpoint">000508</idno><idno type="wicri:Area/Ncbi/Merge">003D71</idno><idno type="wicri:Area/Ncbi/Curation">003D71</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Insertion Process of Ceramic Nanoporous Microneedles by Means of a Novel Mechanical Applicator Design</title><author><name sortKey="Hartmann, Xavier H M" sort="Hartmann, Xavier H M" uniqKey="Hartmann X" first="Xavier H. M." last="Hartmann">Xavier H. M. Hartmann</name><affiliation><nlm:aff id="af1-pharmaceutics-07-00503">Department of Mechanical Engineering, Microsystems Group, Materials Technology Institute (MaTe) and ICMS Institute for Complex Molecular Systems, Eindhoven University of Technology, Den Dolech 2, 5612 AZ Eindhoven, The Netherlands; E-Mails:<email>x.h.m.hartmann@student.tue.nl</email> (X.H.M.H.);<email>f.g.a.homburg@tue.nl</email> (E.F.G.A.H.)</nlm:aff></affiliation></author><author><name sortKey="Van Der Linde, Peter" sort="Van Der Linde, Peter" uniqKey="Van Der Linde P" first="Peter" last="Van Der Linde">Peter Van Der Linde</name><affiliation><nlm:aff id="af2-pharmaceutics-07-00503">MESA+ Institute for Nanotechnology, University of Twente, 7500 AE Enschede, The Netherlands; E-Mail:<email>p.vanderlinde@utwente.nl</email></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-pharmaceutics-07-00503">MyLife Technologies B.V., 7522 NH Enschede, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>MyLife Technologies B.V., 7522 NH Enschede</wicri:regionArea><wicri:noRegion>7522 NH Enschede</wicri:noRegion></affiliation></author><author><name sortKey="Homburg, Erik F G A" sort="Homburg, Erik F G A" uniqKey="Homburg E" first="Erik F. G. A." last="Homburg">Erik F. G. A. Homburg</name><affiliation><nlm:aff id="af1-pharmaceutics-07-00503">Department of Mechanical Engineering, Microsystems Group, Materials Technology Institute (MaTe) and ICMS Institute for Complex Molecular Systems, Eindhoven University of Technology, Den Dolech 2, 5612 AZ Eindhoven, The Netherlands; E-Mails:<email>x.h.m.hartmann@student.tue.nl</email> (X.H.M.H.);<email>f.g.a.homburg@tue.nl</email> (E.F.G.A.H.)</nlm:aff></affiliation></author><author><name sortKey="Van Breemen, Lambert C A" sort="Van Breemen, Lambert C A" uniqKey="Van Breemen L" first="Lambert C. A." last="Van Breemen">Lambert C. A. Van Breemen</name><affiliation><nlm:aff id="af4-pharmaceutics-07-00503">Department of Mechanical Engineering, Polymer Technology Group and Materials Technology Institute (MaTe), Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands; E-Mail:<email>l.c.a.v.breemen@tue.nl</email></nlm:aff></affiliation></author><author><name sortKey="De Jong, Arthur M" sort="De Jong, Arthur M" uniqKey="De Jong A" first="Arthur M." last="De Jong">Arthur M. De Jong</name><affiliation><nlm:aff id="af5-pharmaceutics-07-00503">Department of Applied Physics, Molecular Biosensing for Medical Diagnostics and ICMS Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands; E-Mail:<email>a.m.de.jong@tue.nl</email></nlm:aff></affiliation></author><author><name sortKey="Luttge, Regina" sort="Luttge, Regina" uniqKey="Luttge R" first="Regina" last="Luttge">Regina Luttge</name><affiliation><nlm:aff id="af1-pharmaceutics-07-00503">Department of Mechanical Engineering, Microsystems Group, Materials Technology Institute (MaTe) and ICMS Institute for Complex Molecular Systems, Eindhoven University of Technology, Den Dolech 2, 5612 AZ Eindhoven, The Netherlands; E-Mails:<email>x.h.m.hartmann@student.tue.nl</email> (X.H.M.H.);<email>f.g.a.homburg@tue.nl</email> (E.F.G.A.H.)</nlm:aff></affiliation><affiliation><nlm:aff id="af2-pharmaceutics-07-00503">MESA+ Institute for Nanotechnology, University of Twente, 7500 AE Enschede, The Netherlands; E-Mail:<email>p.vanderlinde@utwente.nl</email></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-pharmaceutics-07-00503">MyLife Technologies B.V., 7522 NH Enschede, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>MyLife Technologies B.V., 7522 NH Enschede</wicri:regionArea><wicri:noRegion>7522 NH Enschede</wicri:noRegion></affiliation></author></analytic><series><title level="j">Pharmaceutics</title><idno type="eISSN">1999-4923</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Arrays of microneedles (MNAs) are integrated in an out-of-plane fashion with a base plate and can serve as patches for the release of drugs and vaccines. We used soft-lithography and micromolding to manufacture ceramic nanoporous (np)MNAs. Failure modes of ceramic npMNAs are as yet poorly understood and the question remained: is our npMNA platform technology ready for microneedle (MN) assembly into patches? We investigated npMNAs by microindentation, yielding average crack fracture forces above the required insertion force for a single MN to penetrate human skin. We further developed a thumb pressure-actuated applicator-assisted npMNA insertion method, which enables anchoring of MNs in the skin by an adhesive in one handling step. Using a set of simple artificial skin models, we found a puncture efficiency of this insertion method a factor three times higher than by applying thumb pressure on the npMNA base plate directly. In addition, this new method facilitated zero MN-breakage due to a well-defined force distribution exerted onto the MNs and the closely surrounding area prior to bringing the adhesive into contact with the skin. Owing to the fact that such parameter space exists, we can conclude that npMNAs by soft lithography are a platform technology for MN assembly into a patch.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Boks, M A" uniqKey="Boks M">M.A. Boks</name></author><author><name sortKey="Unger, W W J" uniqKey="Unger W">W.W.J. Unger</name></author><author><name sortKey="Engels, S" uniqKey="Engels S">S. Engels</name></author><author><name sortKey="Ambrosini, M" uniqKey="Ambrosini M">M. Ambrosini</name></author><author><name sortKey="Van Kooyk, Y" uniqKey="Van Kooyk Y">Y. van Kooyk</name></author><author><name sortKey="Luttge, R" uniqKey="Luttge R">R. 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Verpoorten</name></author><author><name sortKey="Van Den Berg, A" uniqKey="Van Den Berg A">A. van den Berg</name></author><author><name sortKey="Luttge, R" uniqKey="Luttge R">R. Luttge</name></author><author><name sortKey="Bouwstra, J A" uniqKey="Bouwstra J">J.A. Bouwstra</name></author></analytic></biblStruct></listBibl></div1></back></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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