Protein‐Capturing Microgel‐Integrated Microneedle Array Patches for Enhanced Tip‐Loading, Storage Stability, and Transdermal Delivery of Recombinant Proteins

Protein‐Capturing Microgel‐Integrated Microneedle Array Patches for Enhanced Tip‐Loading, Storage Stability, and Transdermal Delivery of Recombinant Proteins

Small

10.1002/smll.202512624

https://doi.org/10.1002/smll.202512624

Ki Hyun Bae, Kun Liang, Brandon Y. L. Seow, Jia Min Loh, Li Li, Fritz Lai, Qingfeng Chen, Motoichi Kurisawa, Steven T. G. Thng, Yi Yan Yang

23 January 2026

Bae, K. H., Liang, K., Seow, B. Y. L., Loh, J. M., Li, L., Lai, F., Chen, Q., Kurisawa, M., Thng, S. T. G., & Yang, Y. Y. (2026). Protein‐Capturing Microgel‐Integrated Microneedle Array Patches for Enhanced Tip‐Loading, Storage Stability, and Transdermal Delivery of Recombinant Proteins. Small. Portico. https://doi.org/10.1002/smll.202512624

ABSTRACT Microneedles have gained increasing attention as an ideal device for transdermal drug delivery; however, their application to proteins has been a challenging task because of their inadequate tip‐loading and unsatisfactory stability. Herein, we report the development of a microgel‐integrated microneedle array patch (MI‐MAP) capable of not only localizing protein cargoes in the tip portion but also stabilizing them via protein‐phenolic interactions. Incorporation of protein‐capturing microgels allows enrichment of protein cargoes within the tip region of microneedles, resulting in a significant enhancement in their transdermal delivery performance. MI‐MAP enables more effective stabilization of labile recombinant proteins, such as botulinum neurotoxin, human interferon alpha‐2a, and SARS‐CoV‐2 spike receptor‐binding domain (RBD), during storage at 25 °C for 28 days compared to the counterpart lacking the microgels (HA‐MAP). Transdermal delivery of CpG‐adjuvanted RBD using MI‐MAP elicits a more rapid neutralizing antibody response and germinal center B‐cell proliferation in mice than HA‐MAP and subcutaneous injection, without causing any severe inflammation. This study presents a potential strategy for improving tip‐loading and storage stability of recombinant proteins within microneedle structures.

Publisher Copyright

This research / project is supported by the Agency for Science, Technology and Research (A*STAR) - Career Development Fund
Grant Reference no. : C210812012

This research / project is supported by the Lee Kong Chian School of Medicine - Start Up Grant
Grant Reference no. : NA

This is the peer reviewed version of the following article: Bae, K. H., Liang, K., Seow, B. Y. L., Loh, J. M., Li, L., Lai, F., Chen, Q., Kurisawa, M., Thng, S. T. G., & Yang, Y. Y. (2026). Protein‐Capturing Microgel‐Integrated Microneedle Array Patches for Enhanced Tip‐Loading, Storage Stability, and Transdermal Delivery of Recombinant Proteins. Small. Portico, which has been published in final form at https://doi.org/10.1002/smll.202512624. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.

https://oar.a-star.edu.sg/communities-collections/articles/22766

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Bioprocessing Technology Institute