This study tested the hypothesis that optimized microneedle patch formulations can stabilize trivalent subunit influenza vaccine during long-term storage outside the cold chain and when exposed to potential stresses found during manufacturing and storage. Formulations containing combinations of trehalose/sucrose, sucrose/arginine, and arginine/heptagluconate were successful at retaining most or all vaccine activity during storage at 25 °C for up to 24 months as determined by ELISA assay. The best formulation of microneedle patches contained arginine/heptagluconate, which showed no significant loss of vaccine activity during the study. To validate these in vitro findings, mice were immunized using trivalent influenza vaccine stored in microneedle patches for more than 1 year at 25 °C, which elicited antibody titers greater than or equal to fresh liquid vaccine delivered by intradermal injection, indicating the retention of immunogenicity during storage. Finally, influenza vaccine in microneedle patches lost no significant activity during exposure to 60 °C for 4 months, multiple freeze-thaw cycles, or electron beam irradiation. We conclude that optimally formulated microneedle patches can retain influenza vaccine activity during extended storage outside the cold chain and during other environmental stresses, which suggests the possibility of microneedle patch storage on pharmacy shelves without refrigeration.
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We thank Novartis for generously providing monovalent influenza vaccine stock. This work was supported in part by the National Institutes of Health. We thank Polo Gaputan and Miraj Desai for their work on this project. The work was carried out in the Center for Drug Design, Development, and Delivery and the Institute for Bioengineering and Bioscience at the Georgia Institute of Technology. Matthew Mistilis, Andreas Bommarius, and Mark Prausnitz are inventors of patent(s) that have been or may be licensed to companies developing microneedle-based products, and Mark Prausnitz is a paid advisor to companies developing microneedle-based products and is a founder/shareholder of companies developing microneedle-based products. This potential conflict of interest has been disclosed and is overseen by Georgia Tech and Emory University.
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Mistilis, M.J., Joyce, J.C., Esser, E.S. et al. Long-term stability of influenza vaccine in a dissolving microneedle patch. Drug Deliv. and Transl. Res. 7, 195–205 (2017). https://doi.org/10.1007/s13346-016-0282-2
- Vaccine delivery
- Transdermal delivery
- Vaccine stability
- Vaccine formulation
- Solid dosage form
- Influenza vaccine