Intradermal Administration of Influenza Vaccine with Trehalose and Pullulan-Based Dissolving Microneedle Arrays

Most influenza vaccines are administered via intramuscular injection which has several disadvantages that might jeopardize the compliance of vaccinees. Intradermal administration of dissolving-microneedle-arrays (dMNAs) could serve as minimal invasive alternative to needle injections. However, during the production process of dMNAs antigens are subjected to several stresses, which may reduce their potency. Moreover, the needles need to have sufficient mechanical strength to penetrate the skin and subsequently dissolve effectively to release the incorporated antigen. Here, we investigated whether blends of trehalose and pullulan are suitable for the production of stable dMNA fulfilling these criteria. Our results demonstrate that production of trehalose/pullulan-based dMNAs rendered microneedles that were sharp and stiff enough to pierce into ex vivo human skin and subsequently dissolve within 15 min. The mechanical properties of the dMNAs were maintained well even after four weeks of storage at temperatures up to 37 degrees C. In addition, immunization of mice with influenza antigens via both freshly prepared dMNAs and dMNAs after storage (four weeks at 4 degrees C or 37 degrees C) resulted in antibody titers of similar magnitude as found in intramuscularly injected mice and partially protected mice from influenza virus infection. Altogether, our results demonstrate the potential of trehalose/pullulan-based dMNAs as alternative dosage form for influenza vaccination.(c) 2022 The Authors. Published by Elsevier Inc. on behalf of American Pharmacists Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Automated summary

This study demonstrates the potential of trehalose/pullulan-based dissolving-microneedle-arrays (dMNAs) as an alternative dosage form for influenza vaccination. The produced dMNAs have sufficient mechanical strength and stability to penetrate ex vivo human skin and dissolve within a short period of time to release antigens. Immunization of mice with influenza antigens via freshly prepared or stored dMNAs resulted in antibody titers comparable to intramuscularly injected mice, providing partial protection against influenza virus infection.