Thermostabilization of influenza vaccine in microneedle patches
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Mistilis, Matthew Joseph
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Abstract
Vaccine delivery to the skin via microneedles confers several advantages over the traditional hypodermic needle and syringe. This work focuses on developing microneedles as a thermostable delivery method for the influenza vaccine that can be completely removed from the cold-chain, thus minimizing cost and wastage during storage and transportation. Microneedle formulations were screened for their effect on influenza vaccine activity during drying. A number of excipients, particularly the combination of arginine and heptagluconate, successfully stabilized influenza vaccine during storage in the dried state and in microneedle patches at ambient or elevated temperatures for up to eighteen months. Influenza vaccine microneedle patches were shown to be resistant against several stresses and remained immunogenic in a mouse model after long-term storage. The primary mechanism of influenza vaccine activity loss during drying was aggregation, which can be mitigated by stabilizing excipients.
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2016-01-13
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Dissertation