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Investigating novel manufacturing methods for vaccine-containing dissolvable microneedle patches for skin immunisation
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Date
2025
Authors
Moore, Lyndsey E.
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Publisher
University College Cork
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Abstract
Global vaccine uptake is constrained by accessibility and acceptability. The requirement for cold chain distribution and the need for injection-based immunisation, by trained healthcare workers, are two dominant reasons for reduced access. This research focuses on the development of vaccine-containing dissolvable microneedle (DMN) skin patches, as a solution to these issues. DMN patches, sometimes called microneedle array patches (MAP), have micron-scale protrusions called “microneedles”, on an adhesive backing layer, which are applied to the body, generally the skin. These microneedles consist of the vaccine embedded in stabilising excipients which, when inserted into a body surface, dissolve and release the vaccine into the body. These skin patches are therefore easy-to-administer and are designed to be thermostable out of cold chain. Although demonstrating strong potential to solve critical immunisation campaign issues, a number to technical issues remain to be resolved. This research aimed to identify innovative solutions that could solve some of these MAP issues and, in the long-term, contribute to addressing vaccine accessibility.
Firstly, improving the amount of vaccine delivered into skin was addressed. The tapered shape of a DMN patch means that most of its volume is located at the adhesive base, furthest away from the tip and least likely to be productively inserted into skin. This can be overcome by producing a two-layer DMN, where the vaccine is concentrated to the sugar/polymer tip and the base of the microneedle is composed of an inactive second formulation. The solubility properties of the two different microneedle layers were exploited by using polyvinylpyrrolidone-co-vinyl acetate (PVPVA), an amphiphilic polymer, in an ethanol-based backing layer, which prevented the backflow of the active pharmaceutical ingredient (API) from the hydrophilic tip layer. A novel, stable two-layer DMN was developed which was able to penetrate skin. These DMN were demonstrated to deliver a significantly higher amount of active material to skin, compared to single layer DMN.
Most human vaccines are delivered in a liquid volume of 0.5mL, whereas the total volume of a DMN patch is in the low microlitre range. This can cause challenges around concentrating the bulk antigen to deliver the necessary dose. In this thesis, the problem of low volume was addressed by investigating microneedle height and density to increase the total volume, while retaining other physical attributes of the patch such as strength and penetration efficiency. A meta-analysis review defined the most common microneedle geometries. Using these results, 3 patch templates: 600μm tall conical, pyramidal, and obelisk templates with 100 microneedles (MN) per 1cm2 area were 3D printed using a moderate-resolution, stereolithography-based 3D printer. These higher density arrays demonstrated 5.5 to 6.5-fold increase in volume within a 1cm2 area while retaining necessary physical DMN patch characteristics. Production of DMN patches using these templates demonstrated that a moderate-resolution 3D printer was compatible with the desired DMN characteristics, despite having tip diameters of approximately 85μm.
Current methods of producing DMN patches have several steps, some of which can be potentially automated and/or removed. Automated liquid dispensing was investigated for its ability to substitute for the manual mould-filling process, with the aim of identifying critical process and formulation parameters to obtain successful DMN patches. The design space of these parameters, required to produce high quality DMN patches, were identified using a Design of Experiments approach. This research demonstrates that automated liquid dispensing can be used to produce successful DMN patches, involving fewer processing steps compared to the conventional process. This automated system can work for both low-density, conventional MN mould and the 3D printed high-density MN moulds.
Currently, some vaccines are lyophilised to facilitate improved stability within the vaccine cold chain, but lyophilisation is expensive, time-consuming, and requires extensive expert knowledge to successfully implement. Photocuring, or hardening polymers using near-ultraviolet light, was investigated as an alternative method for drying vaccines. This research addressed identifying biocompatible formulations that were both compatible with photocuring, using a commonly reported biomedical photoinitiator, and prevented vaccine degradation during the fabrication process. Five polymers were identified from the literature that were suitable for photocuring and could be compatible to stabilise vaccines. Further development of this method has potential benefits with respect to time, consistency, and efficiency to dry vaccines into solid forms.
Finally, developing improved vaccine technologies is fruitless if the public are hesitant to consent to vaccination. Therefore, it is important to understand why people accept, refuse or are hesitant about vaccines, so that public health information can be appropriately developed. University students, usually aged 18-24, are a unique demographic due to living on their own for the first time, and their lifestyles. University students absorb health information differently than other demographics, such as parents, immunocompromised individuals, and the elderly populations. Therefore, a survey of University College Cork students’ vaccine uptake and confidence was conducted. Social media had no significant impact on their willingness to accept vaccines. However, students’ behaviour on social media and their living environments significantly impacted their vaccine attitudes. Fear of needles was not a significant driver of vaccine acceptance. The findings from this survey underlie future work to better target information on immunisation programmes to improve vaccine uptake.
In summary, novel findings in this research contribute to the field insights on DMN design and production processes. The key findings relate to improvements in microneedle patch design with regards to dose loading and bioavailability, and novel patch production and drying methods that have scalable potential. These advances will support the progression of microneedle technology towards their successful final global use as an injection-free, easy-to-administer vaccine delivery technology.
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Keywords
Dissolvable microneedle , Vaccine , Skin delivery , Additive manufacturing , Microneedle design , Vaccine hesitancy
Citation
Moore, L. E. 2025. Investigating novel manufacturing methods for vaccine-containing dissolvable microneedle patches for skin immunisation. PhD Thesis, University College Cork.