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Engineering of antigen-saving dissolving microneedles for intradermal vaccine delivery

The intradermal administration route is attractive for vaccine delivery, because of the highly populated antigen-presenting cells in the skin. However, the skin’s main physical barrier, the stratum corneum, prevents vaccines from entering the skin.

J. Lee
29 november 2023
Thesis in Leiden Repository

To overcome this barrier, dissolving microneedle arrays (dMNAs) have been developed, miniaturized needles that enter the skin without reaching the blood vessels and pain receptors. After entering, they dissolve and leave the vaccine in the skin, leaving no sharps waste behind. The dissolution is achieved effectively because dMNAs are composed of sugar or biodegradable polymers. For vaccination purposes, such microneedles have another huge potential, as antigens are stored in a dry form that improves thermal stability. This includes that dMNAs ensure antigen stability at room- and elevated temperatures, thereby circumventing the cold chain requirement for storage. Furthermore, since dMNAs don't require qualified medical personnel for application, self-administration is feasible.Currently, the most frequently used fabrication approach (centrifugation method) results in major antigen waste. As antigens are generally very expensive, the current method is not suitable for the cost-effective fabrication of dMNAs. Therefore, a novel dMNA production technology that lowers antigen loss is required. In the thesis, the engineering of a novel dMNA production system based on a dispensing approach that minimizes antigen loss was presented. Furthermore, a comparison was made between the two production approaches (centrifugation and dispensing methods) for vaccine delivery via dMNAs. In additional studies, this novel method has been used to deliver influenza vaccine into the skin leading successfully to a high and protective immune response. In conclusion, a dispensing system for dMNAs production, as opposed to the centrifugation process, is a promising method for the cost-effective fabrication of dMNAs.

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