Tags

Type your tag names separated by a space and hit enter

Long-term stability of influenza vaccine in a dissolving microneedle patch.
Drug Deliv Transl Res 2017; 7(2):195-205DD

Abstract

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.

Authors+Show Affiliations

School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive, Atlanta, GA, 30332-0100, USA.Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech and Emory University, Georgia Institute of Technology, 313 Ferst Drive, Atlanta, GA, 30332-0100, USA.Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1518 Clifton Road, Atlanta, GA, 30322, USA.Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1518 Clifton Road, Atlanta, GA, 30322, USA.Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1518 Clifton Road, Atlanta, GA, 30322, USA.School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive, Atlanta, GA, 30332-0100, USA. School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA, 30332-0400, USA.School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive, Atlanta, GA, 30332-0100, USA. prausnitz@gatech.edu. Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech and Emory University, Georgia Institute of Technology, 313 Ferst Drive, Atlanta, GA, 30332-0100, USA. prausnitz@gatech.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

26926241

Citation

Mistilis, Matthew J., et al. "Long-term Stability of Influenza Vaccine in a Dissolving Microneedle Patch." Drug Delivery and Translational Research, vol. 7, no. 2, 2017, pp. 195-205.
Mistilis MJ, Joyce JC, Esser ES, et al. Long-term stability of influenza vaccine in a dissolving microneedle patch. Drug Deliv Transl Res. 2017;7(2):195-205.
Mistilis, M. J., Joyce, J. C., Esser, E. S., Skountzou, I., Compans, R. W., Bommarius, A. S., & Prausnitz, M. R. (2017). Long-term stability of influenza vaccine in a dissolving microneedle patch. Drug Delivery and Translational Research, 7(2), pp. 195-205. doi:10.1007/s13346-016-0282-2.
Mistilis MJ, et al. Long-term Stability of Influenza Vaccine in a Dissolving Microneedle Patch. Drug Deliv Transl Res. 2017;7(2):195-205. PubMed PMID: 26926241.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term stability of influenza vaccine in a dissolving microneedle patch. AU - Mistilis,Matthew J, AU - Joyce,Jessica C, AU - Esser,E Stein, AU - Skountzou,Ioanna, AU - Compans,Richard W, AU - Bommarius,Andreas S, AU - Prausnitz,Mark R, PY - 2016/3/2/pubmed PY - 2017/10/27/medline PY - 2016/3/2/entrez KW - Influenza vaccine KW - Microneedle KW - Solid dosage form KW - Transdermal delivery KW - Vaccine delivery KW - Vaccine formulation KW - Vaccine stability SP - 195 EP - 205 JF - Drug delivery and translational research JO - Drug Deliv Transl Res VL - 7 IS - 2 N2 - 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. SN - 2190-3948 UR - https://www.unboundmedicine.com/medline/citation/26926241/Long_term_stability_of_influenza_vaccine_in_a_dissolving_microneedle_patch_ L2 - https://dx.doi.org/10.1007/s13346-016-0282-2 DB - PRIME DP - Unbound Medicine ER -