Issue 20, 2023

Efficient fabrication of thermo-stable dissolving microneedle arrays for intradermal delivery of influenza whole inactivated virus vaccine

Abstract

Dissolving microneedle arrays (dMNAs) can be used to deliver vaccines via the intradermal route. Fabrication of dMNAs using centrifugation is the most common preparation method of dMNAs, but it results in a substantial loss of antigens. In order to solve the issue of antigen waste, we engineered an automatic dispensing system for dMNA preparation. Here, we report on the fabrication of influenza whole inactivated virus (WIV) vaccine-loaded dMNAs (WIV dMNAs) by using the automatic dispensing system. Prior to the dispensing process, polydimethylsiloxane (PDMS) moulds were treated with oxygen plasma to increase surface hydrophilicity. WIV dMNAs were prepared with 1% (w/v) trehalose and pullulan (50 : 50 weight ratio). During the dispensing process, reduced pressure was applied to the PDMS mould via a vacuum chamber to make microneedle cavities airless. After producing dMNAs, WIV was quantified and 1.9 μg of WIV was loaded per dMNA, of which 1.3 μg was in the microneedle tips. Compared to the centrifugation method, this automatic dispensing system resulted in a 95% reduction of antigen waste. A hemagglutination assay confirmed that WIV dMNA maintained the stability of the antigen for at least four weeks of storage, even at room temperature or at 37 °C. The WIV dMNAs displayed 100% penetration efficiency in human skin, and 83% of the microneedle volume was dissolved in the skin within 10 minutes. In a vaccination study, mice immunised with WIV dMNAs showed similar IgG levels to those that received WIV intramuscularly. In conclusion, using the automatic dispensing system for dMNA production strongly reduced antigen waste and yielded dMNAs with excellent physical, mechanical, and immunological properties.

Graphical abstract: Efficient fabrication of thermo-stable dissolving microneedle arrays for intradermal delivery of influenza whole inactivated virus vaccine

  • This article is part of the themed collection: Microneedles

Article information

Article type
Paper
Submitted
02 mars 2023
Accepted
10 août 2023
First published
11 août 2023

Biomater. Sci., 2023,11, 6790-6800

Efficient fabrication of thermo-stable dissolving microneedle arrays for intradermal delivery of influenza whole inactivated virus vaccine

J. Lee, M. Beukema, O. A. Zaplatynska, C. O'Mahony, W. L. J. Hinrichs, A. L. W. Huckriede, J. A. Bouwstra and K. van der Maaden, Biomater. Sci., 2023, 11, 6790 DOI: 10.1039/D3BM00377A

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