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

• Published in: Nature communications 2024-01, Vol.15 (1), p.820-15, Article 820
• Main Authors: Zhu, Wenjun, Wei, Ting, Xu, Yuchun, Jin, Qiutong, Chao, Yu, Lu, Jiaqi, Xu, Jun, Zhu, Jiafei, Yan, Xiaoying, Chen, Muchao, Chen, Qian, Liu, Zhuang
• Format: Article
• Language: English
• Subjects: 13/1; 13/21; 13/31; 14; 14/1; 14/19; 14/34; 14/63; 140/125; 140/131; 147/143; 631/250/590/2294; 631/61/2297; 631/67/580; 639/925/352/152; 64/60; Animals; Antibodies; Antigens; Biocompatibility; Cell-mediated immunity; Chitosan; COVID-19 Vaccines; Drug delivery; Drug Delivery Systems; Drug development; Female; Females; Humanities and Social Sciences; Humans; Humoral immunity; Immune checkpoint inhibitors; Immune response; Immunity; Immunological memory; Immunosuppressive agents; Immunotherapy; Injection; Melanoma; Melanoma - drug therapy; Mice; multidisciplinary; Perfluorocarbons; Rabbits; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Skin; Swine; Toxicity; Transdermal medication; Vaccines; Viral Vaccines
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-45158-6

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. Different approaches have been described for the transdermal delivery of drugs. Here the authors report the design of a fluorocarbon modified chitosan-based non-invasive transdermal platform for the delivery of biomacromolecules, such as viral antigens for vaccines or immune checkpoint inhibitors for melanoma immunotherapy.