Transcutaneous Immunization Studies in Mice Using Diphtheria Toxoid-Loaded Vesicle Formulations and a Microneedle Array
Identifieur interne : 000173 ( Pmc/Curation ); précédent : 000172; suivant : 000174Transcutaneous Immunization Studies in Mice Using Diphtheria Toxoid-Loaded Vesicle Formulations and a Microneedle Array
Auteurs : Zhi Ding [Pays-Bas, République populaire de Chine] ; Suzanne M. Bal [Pays-Bas] ; Stefan Romeijn [Pays-Bas] ; Gideon F. A. Kersten [Pays-Bas] ; Wim Jiskoot [Pays-Bas] ; Joke A. Bouwstra [Pays-Bas]Source :
- Pharmaceutical Research [ 0724-8741 ] ; 2010.
Abstract
To determine the immunogenicity of diphtheria toxoid (DT) formulated in two types of vesicles following transcutaneous immunization (TCI) of mice onto microneedle array-treated skin.
DT-containing cationic liposomes or anionic surfactant-based vesicles were prepared by extrusion and sonication. The physicochemical properties were characterized in terms of size, ζ-potential, vesicle elasticity and antigen association. TCI was performed by applying formulations onto intact or microneedle array-pretreated mice skin, using cholera toxin as an adjuvant. Subcutaneous and intradermal immunizations were as control. Immune responses were evaluated by IgG and neutralizing antibody titers, and the immune-stimulatory properties were assessed using cultured dendritic cells.
Stable DT-containing cationic liposomes (∼150 nm) and anionic vesicles (∼100 nm) were obtained. Incorporation of Span 80 increased liposome elasticity. About 90% and 77% DT was associated with liposomes and vesicles, respectively. TCI of all formulations resulted in substantial antibody titers only if microneedle pretreatment was applied. Co-administration of cholera toxin further augmented the immune responses of TCI. However, vesicle formulations didn’t enhance the immunogenicity on either intact or microneedle-treated skin and showed low stimulatory activity on dendritic cells.
Microneedle pretreatment and cholera toxin, but not antigen association to vesicles, enhances the immunogenicity of topically applied DT.
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DOI: 10.1007/s11095-010-0093-y
PubMed: 20237826
PubMed Central: 3003783
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Transcutaneous Immunization Studies in Mice Using Diphtheria Toxoid-Loaded Vesicle Formulations and a Microneedle Array</title><author><name sortKey="Ding, Zhi" sort="Ding, Zhi" uniqKey="Ding Z" first="Zhi" last="Ding">Zhi Ding</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff3">State Key Laboratory of Pharmaceutical Biotechnology, Biochemistry Department, Nanjing University, 210093 Nanjing, People’s Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pharmaceutical Biotechnology, Biochemistry Department, Nanjing University, 210093 Nanjing</wicri:regionArea></affiliation></author><author><name sortKey="Bal, Suzanne M" sort="Bal, Suzanne M" uniqKey="Bal S" first="Suzanne M." last="Bal">Suzanne M. Bal</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden</wicri:regionArea></affiliation></author><author><name sortKey="Romeijn, Stefan" sort="Romeijn, Stefan" uniqKey="Romeijn S" first="Stefan" last="Romeijn">Stefan Romeijn</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden</wicri:regionArea></affiliation></author><author><name sortKey="Kersten, Gideon F A" sort="Kersten, Gideon F A" uniqKey="Kersten G" first="Gideon F. 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Kersten</name><affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Research and Development, Netherlands Vaccine Institute, 3720 BA Bilthoven, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Research and Development, Netherlands Vaccine Institute, 3720 BA Bilthoven</wicri:regionArea></affiliation></author><author><name sortKey="Jiskoot, Wim" sort="Jiskoot, Wim" uniqKey="Jiskoot W" first="Wim" last="Jiskoot">Wim Jiskoot</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden</wicri:regionArea></affiliation></author><author><name sortKey="Bouwstra, Joke A" sort="Bouwstra, Joke A" uniqKey="Bouwstra J" first="Joke A." last="Bouwstra">Joke A. Bouwstra</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20237826</idno><idno type="pmc">3003783</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003783</idno><idno type="RBID">PMC:3003783</idno><idno type="doi">10.1007/s11095-010-0093-y</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">000173</idno><idno type="wicri:Area/Pmc/Curation">000173</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Transcutaneous Immunization Studies in Mice Using Diphtheria Toxoid-Loaded Vesicle Formulations and a Microneedle Array</title><author><name sortKey="Ding, Zhi" sort="Ding, Zhi" uniqKey="Ding Z" first="Zhi" last="Ding">Zhi Ding</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff3">State Key Laboratory of Pharmaceutical Biotechnology, Biochemistry Department, Nanjing University, 210093 Nanjing, People’s Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Pharmaceutical Biotechnology, Biochemistry Department, Nanjing University, 210093 Nanjing</wicri:regionArea></affiliation></author><author><name sortKey="Bal, Suzanne M" sort="Bal, Suzanne M" uniqKey="Bal S" first="Suzanne M." last="Bal">Suzanne M. Bal</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden</wicri:regionArea></affiliation></author><author><name sortKey="Romeijn, Stefan" sort="Romeijn, Stefan" uniqKey="Romeijn S" first="Stefan" last="Romeijn">Stefan Romeijn</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden</wicri:regionArea></affiliation></author><author><name sortKey="Kersten, Gideon F A" sort="Kersten, Gideon F A" uniqKey="Kersten G" first="Gideon F. A." last="Kersten">Gideon F. A. Kersten</name><affiliation wicri:level="1"><nlm:aff id="Aff2">Department of Research and Development, Netherlands Vaccine Institute, 3720 BA Bilthoven, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Research and Development, Netherlands Vaccine Institute, 3720 BA Bilthoven</wicri:regionArea></affiliation></author><author><name sortKey="Jiskoot, Wim" sort="Jiskoot, Wim" uniqKey="Jiskoot W" first="Wim" last="Jiskoot">Wim Jiskoot</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden</wicri:regionArea></affiliation></author><author><name sortKey="Bouwstra, Joke A" sort="Bouwstra, Joke A" uniqKey="Bouwstra J" first="Joke A." last="Bouwstra">Joke A. Bouwstra</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden</wicri:regionArea></affiliation></author></analytic><series><title level="j">Pharmaceutical Research</title><idno type="ISSN">0724-8741</idno><idno type="eISSN">1573-904X</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>ABSTRACT</title><sec><title>Purpose</title><p>To determine the immunogenicity of diphtheria toxoid (DT) formulated in two types of vesicles following transcutaneous immunization (TCI) of mice onto microneedle array-treated skin.</p></sec><sec><title>Methods</title><p>DT-containing cationic liposomes or anionic surfactant-based vesicles were prepared by extrusion and sonication. The physicochemical properties were characterized in terms of size, ζ-potential, vesicle elasticity and antigen association. TCI was performed by applying formulations onto intact or microneedle array-pretreated mice skin, using cholera toxin as an adjuvant. Subcutaneous and intradermal immunizations were as control. Immune responses were evaluated by IgG and neutralizing antibody titers, and the immune-stimulatory properties were assessed using cultured dendritic cells.</p></sec><sec><title>Results</title><p>Stable DT-containing cationic liposomes (∼150 nm) and anionic vesicles (∼100 nm) were obtained. Incorporation of Span 80 increased liposome elasticity. About 90% and 77% DT was associated with liposomes and vesicles, respectively. TCI of all formulations resulted in substantial antibody titers only if microneedle pretreatment was applied. Co-administration of cholera toxin further augmented the immune responses of TCI. However, vesicle formulations didn’t enhance the immunogenicity on either intact or microneedle-treated skin and showed low stimulatory activity on dendritic cells.</p></sec><sec><title>Conclusions</title><p>Microneedle pretreatment and cholera toxin, but not antigen association to vesicles, enhances the immunogenicity of topically applied DT.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Simerska, P" uniqKey="Simerska P">P Simerska</name></author><author><name sortKey="Moyle, Pm" uniqKey="Moyle P">PM Moyle</name></author><author><name sortKey="Olive, C" uniqKey="Olive C">C Olive</name></author><author><name sortKey="Toth, I" uniqKey="Toth I">I Toth</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mikszta, Ja" uniqKey="Mikszta J">JA Mikszta</name></author><author><name sortKey="Laurent, Pe" uniqKey="Laurent P">PE 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Pharm Res</journal-id><journal-title-group><journal-title>Pharmaceutical Research</journal-title></journal-title-group><issn pub-type="ppub">0724-8741</issn><issn pub-type="epub">1573-904X</issn><publisher><publisher-name>Springer US</publisher-name><publisher-loc>Boston</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">20237826</article-id><article-id pub-id-type="pmc">3003783</article-id><article-id pub-id-type="publisher-id">93</article-id><article-id pub-id-type="doi">10.1007/s11095-010-0093-y</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Paper</subject></subj-group></article-categories><title-group><article-title>Transcutaneous Immunization Studies in Mice Using Diphtheria Toxoid-Loaded Vesicle Formulations and a Microneedle Array</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Ding</surname><given-names>Zhi</given-names></name><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Bal</surname><given-names>Suzanne M.</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Romeijn</surname><given-names>Stefan</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Kersten</surname><given-names>Gideon F. A.</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Jiskoot</surname><given-names>Wim</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Bouwstra</surname><given-names>Joke A.</given-names></name><address><phone>+31-71-5274208</phone><fax>+31-71-5274565</fax><email>bouwstra@lacdr.leidenuniv.nl</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><aff id="Aff1"><label>1</label>Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands</aff><aff id="Aff2"><label>2</label>Department of Research and Development, Netherlands Vaccine Institute, 3720 BA Bilthoven, The Netherlands</aff><aff id="Aff3"><label>3</label>State Key Laboratory of Pharmaceutical Biotechnology, Biochemistry Department, Nanjing University, 210093 Nanjing, People’s Republic of China</aff></contrib-group><pub-date pub-type="epub"><day>17</day><month>3</month><year>2010</year></pub-date><pub-date pub-type="pmc-release"><day>17</day><month>3</month><year>2010</year></pub-date><pub-date pub-type="ppub"><month>1</month><year>2011</year></pub-date><volume>28</volume><issue>1</issue><fpage>145</fpage><lpage>158</lpage><history><date date-type="received"><day>14</day><month>10</month><year>2009</year></date><date date-type="accepted"><day>11</day><month>2</month><year>2010</year></date></history><permissions><copyright-statement>© The Author(s) 2010</copyright-statement></permissions><abstract><title>ABSTRACT</title><sec><title>Purpose</title><p>To determine the immunogenicity of diphtheria toxoid (DT) formulated in two types of vesicles following transcutaneous immunization (TCI) of mice onto microneedle array-treated skin.</p></sec><sec><title>Methods</title><p>DT-containing cationic liposomes or anionic surfactant-based vesicles were prepared by extrusion and sonication. The physicochemical properties were characterized in terms of size, ζ-potential, vesicle elasticity and antigen association. TCI was performed by applying formulations onto intact or microneedle array-pretreated mice skin, using cholera toxin as an adjuvant. Subcutaneous and intradermal immunizations were as control. Immune responses were evaluated by IgG and neutralizing antibody titers, and the immune-stimulatory properties were assessed using cultured dendritic cells.</p></sec><sec><title>Results</title><p>Stable DT-containing cationic liposomes (∼150 nm) and anionic vesicles (∼100 nm) were obtained. Incorporation of Span 80 increased liposome elasticity. About 90% and 77% DT was associated with liposomes and vesicles, respectively. TCI of all formulations resulted in substantial antibody titers only if microneedle pretreatment was applied. Co-administration of cholera toxin further augmented the immune responses of TCI. However, vesicle formulations didn’t enhance the immunogenicity on either intact or microneedle-treated skin and showed low stimulatory activity on dendritic cells.</p></sec><sec><title>Conclusions</title><p>Microneedle pretreatment and cholera toxin, but not antigen association to vesicles, enhances the immunogenicity of topically applied DT.</p></sec></abstract><kwd-group><title>KEY WORDS</title><kwd>cholera toxin</kwd><kwd>diphtheria toxoid</kwd><kwd>microneedle array</kwd><kwd>transcutaneous immunization</kwd><kwd>vesicles</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© Springer Science+Business Media, LLC 2010</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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