Development of a dissolvable microneedle influenza vaccine patch

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dc.contributor.advisor Crean, Abina en
dc.contributor.advisor Moore, Anne en Allen, Evin A. 2016-08-12T10:39:26Z 2016 2016
dc.identifier.citation Allen, E. 2016. Development of a dissolvable microneedle influenza vaccine patch. PhD Thesis, University College Cork. en
dc.description.abstract Delivery of large molecular weight biological molecules to the epidermis and dermis is constrained by the tough outer layer of the epidermis, the stratum corneum (sc). Microneedle technologies attempt to overcome this physical barrier using sharp micron-size projections to penetrate the sc. Dissolvable microneedles (DMN), are a particular microneedle design whereby the needle structure is composed of a soluble matrix that upon application to the skin, dissolves releasing the vaccine load into skin. This thesis examines (1) the formulation and processing considerations around DMN fabrication, (2) the immunogenicity of DMN containing trivalent influenza vaccine (TIV) in pre-clinical mouse and pig models and (3) the thermostability of these DMN formulations during storage. The results demonstrate the importance of formulation for microneedle formation and mechanical strength. Trehalose and polyvinylalcohol based formulations produced optimal microneedle structures and were amenable to piezoelectric dispensing; allowing for precise multi-layered DMN to be fabricated. The effect of drying conditions was assessed and found to be critical for DMN mechanical strength and skin penetration. The antibody responses to TIV generated by DMN-mediated vaccination were comparable or greater to those induced by immunization with a commercial TIV via the IM route in mice. DMN mediated immunisation resulted in a significantly broader humoral response to heterotypic influenza viruses compared to IM delivery. Stored at 40°C, a licensed seasonal influenza vaccine incorporated into DMN array was thermostable for at least 6 month as determined by Single Radial Immunodiffusion and immunogenicity in mice. The thesis advances the field of DMN influenza vaccination by elucidating important processing and formulation considerations in the fabrication of highly reproducible DMN. It also demonstrated that DMN can induce broader, larger humoral responses than conventional IM administration while demonstrating enhanced accelerated stability. Crucially, this works advances an automated fabrication system that will allow for clinical translation of DMN. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2016, Evin Allen. en
dc.rights.uri en
dc.subject Microneedles en
dc.subject Vaccine en
dc.subject Influenza en
dc.title Development of a dissolvable microneedle influenza vaccine patch en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD (Medicine and Health) en
dc.internal.availability Full text not available en Restricted to everyone for one year en 10000-01-01
dc.description.version Accepted Version
dc.contributor.funder College of Medicine and Health, University College Cork en
dc.description.status Not peer reviewed en Pharmacy en
dc.check.type No Embargo Required
dc.check.reason Releasing this thesis would cause substantial prejudice to the commercial interests of University College Cork en
dc.check.opt-out Yes en
dc.thesis.opt-out true
dc.check.embargoformat Hard bound copy in Library only en
dc.internal.conferring Summer 2016 en

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© 2016, Evin Allen. Except where otherwise noted, this item's license is described as © 2016, Evin Allen.
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