Zhu Wenjun, Wei Ting, Xu Yuchun, Jin Qiutong, Chao Yu, Lu Jiaqi, Xu Jun, Zhu Jiafei, Yan Xiaoying, Chen Muchao, Chen Qian, Liu Zhuang
Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou, 215123, China.
Suzhou InnoBM Pharmaceutics Co. Ltd., Suzhou, Jiangsu, 215213, China.
Nat Commun. 2024 Jan 27;15(1):820. 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.
经皮给药已被视为口服给药和皮下注射的一种替代方式。然而，生物大分子的无针经皮给药仍然是一个挑战。在此，开发了一种基于生物相容性氟碳修饰壳聚糖（FCS）的经皮给药平台，以实现包括抗体和抗原在内的生物大分子的高效非侵入性给药。形成的纳米复合物通过细胞间和经附属器途径展现出有效的经皮渗透能力。与静脉注射相比，免疫检查点阻断抗体的非侵入性经皮给药在雌性小鼠中对黑色素瘤诱导更强的免疫反应，并降低全身毒性。此外，与皮下注射疫苗相比，雌性小鼠经皮递送严重急性呼吸综合征冠状病毒2（SARS-CoV-2）疫苗产生了相当的体液免疫以及改善的细胞免疫和免疫记忆。此外，基于FCS的蛋白质递送系统对兔皮和猪皮显示出经皮能力。因此，基于FCS的经皮递送系统可能为克服皮肤屏障以实现生物治疗药物的高效经皮递送提供一个极具吸引力的机会。
