Non-invasive transdermal delivery of biomacromolecules with fluorocarbon-modified chitosan for melanoma immunotherapy and viral vaccines

Wenjun Zhu, Ting Wei, Yuchun Xu, Qiutong Jin, Yu Chao, Jiaqi Lu, Jun Xu, Jiafei Zhu, Xiaoying Yan, Muchao Chen, Qian Chen () and Zhuang Liu ()
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Wenjun Zhu: Soochow University
Ting Wei: Soochow University
Yuchun Xu: Soochow University
Qiutong Jin: Soochow University
Yu Chao: Soochow University
Jiaqi Lu: Soochow University
Jun Xu: Soochow University
Jiafei Zhu: Soochow University
Xiaoying Yan: Soochow University
Muchao Chen: Soochow University
Qian Chen: Soochow University
Zhuang Liu: Soochow University

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Transdermal drug delivery has been regarded as an alternative to oral delivery and subcutaneous injection. However, needleless transdermal delivery of biomacromolecules remains a challenge. Herein, a transdermal delivery platform based on biocompatible fluorocarbon modified chitosan (FCS) is developed to achieve highly efficient non-invasive delivery of biomacromolecules including antibodies and antigens. The formed nanocomplexes exhibits effective transdermal penetration ability via both intercellular and transappendageal routes. Non-invasive transdermal delivery of immune checkpoint blockade antibodies induces stronger immune responses for melanoma in female mice and reduces systemic toxicity compared to intravenous injection. Moreover, transdermal delivery of a SARS-CoV-2 vaccine in female mice results in comparable humoral immunity as well as improved cellular immunity and immune memory compared to that achieved with subcutaneous vaccine injection. Additionally, FCS-based protein delivery systems demonstrate transdermal ability for rabbit and porcine skins. Thus, FCS-based transdermal delivery systems may provide a compelling opportunity to overcome the skin barrier for efficient transdermal delivery of bio-therapeutics.

Date: 2024
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DOI: 10.1038/s41467-024-45158-6

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