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.
Url:
DOI: 10.1007/s11095-010-0093-y
PubMed: 20237826
PubMed Central: 3003783
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<author><name sortKey="Ding, Zhi" sort="Ding, Zhi" uniqKey="Ding Z" first="Zhi" last="Ding">Zhi Ding</name>
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<author><name sortKey="Jiskoot, Wim" sort="Jiskoot, Wim" uniqKey="Jiskoot W" first="Wim" last="Jiskoot">Wim Jiskoot</name>
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<author><name sortKey="Bouwstra, Joke A" sort="Bouwstra, Joke A" uniqKey="Bouwstra J" first="Joke A." last="Bouwstra">Joke A. Bouwstra</name>
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<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>
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<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>
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<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>
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<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>
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<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>
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<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>
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<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>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<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>
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