Hyaluronan molecular weight: effects on dissolution time of dissolving microneedles in the skin and on immunogenicity of antigen

Loading...
Thumbnail Image
Files
12171.pdf(1.36 MB)
Accepted version
Date
2020-02-18
Authors
Leone, Mara
Romeijn, Stefan
Slütter, Bram
O'Mahony, Conor
Kersten, Gideon
Bouwstra, Joke A.
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Research Projects
Organizational Units
Journal Issue
Abstract
Biomaterials used as matrix for dissolving microneedles (dMNs) may affect the manufacturing process as well as the potency of the active pharmaceutical ingredient, e.g. the immunogenicity of incorporated vaccine antigens. The aim of this study was to investigate the effect of the molecular weight of hyaluronan, a polymer widely used in the fabrication of dMNs, ranging in molecular weight from 4.8 kDa to 1.8 MDa, on the dissolution of microneedles in the skin in time as well as the antibody response in mice and T-cell activation in vitro. Hyaluronan molecular weight (HA-MWs) did not affect antibody responses (when lower than 150 kDa) nor CD4+ T-cell responses against model antigen ovalbumin. However, the HA-MWs had an effect on the fabrication of dMNs. The 1.8 MDa HA was not suitable for the fabrication of dMNs. Similarly, the 4.8 kDa HA generated dMN arrays less robust compared to the other HA-MWs requiring optimization of the drying conditions. Finally, higher HA-MWs led to longer application time of dMN arrays for a complete dissolution of microneedles into the skin. Specifically, we identified 20 kDa HA as the optimal HA-MW for the fabrication of dMNs as with this MW the dMNs are robust and dissolve fast in the skin without affecting immunogenicity.
Description
Keywords
Dissolving microneedles , Hyaluronan , Molecular weight , Immune response , Dermal vaccine delivery
Citation
Leone, M., Romeijn, S., Slütter, B., O'Mahony, C., Kersten, G. and Bouwstra, J. A. (2020) 'Hyaluronan molecular weight: effects on dissolution time of dissolving microneedles in the skin and on immunogenicity of antigen', European Journal of Pharmaceutical Sciences, 105269. doi: 10.1016/j.ejps.2020.105269