title: Long-term stability of influenza vaccine in a dissolving microneedle patch.
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.affiliation: School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive, Atlanta, GA, 30332-0100, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Mistilis
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech and Emory University, Georgia Institute of Technology, 313 Ferst Drive, Atlanta, GA, 30332-0100, USA.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Joyce
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1518 Clifton Road, Atlanta, GA, 30322, USA.
authors.forename: E Stein
authors.initials: ES
authors.lastname: Esser
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1518 Clifton Road, Atlanta, GA, 30322, USA.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Skountzou
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, 1518 Clifton Road, Atlanta, GA, 30322, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Compans
authors.affiliation: 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.
authors.forename: Andreas S
authors.initials: AS
authors.lastname: Bommarius
authors.affiliation: 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.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Prausnitz
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D004355:Drug Stability; D005260:Female; D006388:Hemagglutinins / Q000378:metabolism; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000737:chemistry; D008807:Mice, Inbred BALB C; D008845:Microinjections; D009339:Needles; D013696:Temperature; D057968:Transdermal Patch
chemical_list: D006388:Hemagglutinins; D007252:Influenza Vaccines
keywords: Influenza vaccine; Microneedle; Solid dosage form; Transdermal delivery; Vaccine delivery; Vaccine formulation; Vaccine stability