Development of a dissolvable microneedle influenza vaccine patch

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.

The Great Book of Ireland - Leabhar Mór na hÉireann

The Great Book of Ireland, Leabhar Mór na hÉireann, is an extraordinary modern vellum manuscript in a single volume which comprises the original work of 120 artists, 140 poets and nine composers. Produced in Dublin between 1989 and 1991, it has been acquired by University College Cork to be preserved in posterity on behalf of the Irish people. Conceived originally as a venture to create a saleable artefact which would help to fund the development plans of two arts organizations in Ireland, the original architects of the idea and editors of the end product were Theo Dorgan of Poetry Ireland and Gene Lambert of Clashganna Mills, with Eamonn Martin as business manager. Out of their initial meeting in March 1989 came the first tentative idea of producing an original artefact that would raise substantial funds for their charitable-status arts organizations, while at the same time being a venture worthwhile in itself. What was to emerge was a project of breath-taking ambition and scale – The Great Book of Ireland, Leabhar Mór na hÉireann, completed in 1991. Artists, poets, and composers were asked to contribute in their own medium what they believed represented their hopes, fears, dreams, or imaginings in the Ireland of that particular time, and which would have resonance in a thousand years - as the longevity of vellum allows. Each page of The Great Book is a unique artefact in itself, often multi-layered or palimpsestial in nature. The whole “united” in design by the work of the scribe, Denis Brown. This paper will describes the creation process of the book, its subsequent history, and future plans for the book at University College Cork.