Hyaluronan molecular weight: effects on dissolution time of dissolving microneedles in the skin and on immunogenicity of antigen

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dc.contributor.authorLeone, Mara
dc.contributor.authorRomeijn, Stefan
dc.contributor.authorSlütter, Bram
dc.contributor.authorO'Mahony, Conor
dc.contributor.authorKersten, Gideon
dc.contributor.authorBouwstra, Joke A.
dc.date.accessioned2020-02-24T15:48:01Z
dc.date.available2020-02-24T15:48:01Z
dc.date.issued2020-02-18
dc.date.updated2020-02-24T15:43:18Z
dc.description.abstractBiomaterials used as matrix for dissolving microneedles (dMNs) may affect the manufacturing process as well as the potency of the active pharmaceutical ingredient, e.g. the immunogenicity of incorporated vaccine antigens. The aim of this study was to investigate the effect of the molecular weight of hyaluronan, a polymer widely used in the fabrication of dMNs, ranging in molecular weight from 4.8 kDa to 1.8 MDa, on the dissolution of microneedles in the skin in time as well as the antibody response in mice and T-cell activation in vitro. Hyaluronan molecular weight (HA-MWs) did not affect antibody responses (when lower than 150 kDa) nor CD4+ T-cell responses against model antigen ovalbumin. However, the HA-MWs had an effect on the fabrication of dMNs. The 1.8 MDa HA was not suitable for the fabrication of dMNs. Similarly, the 4.8 kDa HA generated dMN arrays less robust compared to the other HA-MWs requiring optimization of the drying conditions. Finally, higher HA-MWs led to longer application time of dMN arrays for a complete dissolution of microneedles into the skin. Specifically, we identified 20 kDa HA as the optimal HA-MW for the fabrication of dMNs as with this MW the dMNs are robust and dissolve fast in the skin without affecting immunogenicity.en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid105269en
dc.identifier.citationLeone, M., Romeijn, S., Slütter, B., O'Mahony, C., Kersten, G. and Bouwstra, J. A. (2020) 'Hyaluronan molecular weight: effects on dissolution time of dissolving microneedles in the skin and on immunogenicity of antigen', European Journal of Pharmaceutical Sciences, 105269. doi: 10.1016/j.ejps.2020.105269en
dc.identifier.doi10.1016/j.ejps.2020.105269en
dc.identifier.endpage21en
dc.identifier.issn0928-0987
dc.identifier.journaltitleEuropean Journal of Pharmaceutical Sciencesen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/9693
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urihttp://www.sciencedirect.com/science/article/pii/S0928098720300580
dc.rights© 2020 Published by Elsevier B.V. under a Creative Commons licenseen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectDissolving microneedlesen
dc.subjectHyaluronanen
dc.subjectMolecular weighten
dc.subjectImmune responseen
dc.subjectDermal vaccine deliveryen
dc.titleHyaluronan molecular weight: effects on dissolution time of dissolving microneedles in the skin and on immunogenicity of antigenen
dc.typeArticle (peer-reviewed)en
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