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<p>Addressing mucosal inflammatory disorders in the ocular surface or respiratory system remains a formidable challenge owing to the limited penetration of biological therapeutics across epithelial barriers. In this study, we explored the potential of human single-domain antibodies (UdAbs) as topical therapeutics for the targeted modulation of interleukin-33 (IL-33) in two mucosal-associated inflammatory disorders. The anti-IL-33 UdAb A12 demonstrated potent inhibition of the IL-33-mediated signaling pathway, despite not potently blocking the IL-33 receptor interaction. Compared with the anti-IL-33 control IgG itepekimab, the topical delivery of A12 resulted in significantly elevated corneal concentrations in vivo, which resulted in negligible ocular penetration. Moreover, A12 considerably ameliorated dry eye disease severity by exerting anti-inflammatory effects. Furthermore, in another murine model of allergic asthma, inhaled A12 substantially reduced overall lung inflammation. Our findings revealed the capacity of UdAbs to penetrate mucosal barriers following noninvasive localized delivery, highlighting their potential as an innovative therapeutic strategy for modulating mucosal inflammation.</p>

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Topical delivery of a human single-domain antibody targeting IL-33 to inhibit mucosal inflammation

  • 期刊论文

  • 发表日期：

    2025年6月11日

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  • Keke Huang,
  • Yuqing Wu,
  • Yu Kong,
  • Qingyuan Xu,
  • Mingwei Lv,
  • Yirou Zhang,
  • Yiteng Lu,
  • Quanxiao Li,
  • Cheng Li,
  • Wenping Song,
  • Xiaoyi Zhu,
  • Zhenlin Yang,
  • Changchang Xin,
  • Xujiao Zhou,
  • Tianlei Ying,
  • Yanling Wu,
  • Jiaxu Hong

摘要

Addressing mucosal inflammatory disorders in the ocular surface or respiratory system remains a formidable challenge owing to the limited penetration of biological therapeutics across epithelial barriers. In this study, we explored the potential of human single-domain antibodies (UdAbs) as topical therapeutics for the targeted modulation of interleukin-33 (IL-33) in two mucosal-associated inflammatory disorders. The anti-IL-33 UdAb A12 demonstrated potent inhibition of the IL-33-mediated signaling pathway, despite not potently blocking the IL-33 receptor interaction. Compared with the anti-IL-33 control IgG itepekimab, the topical delivery of A12 resulted in significantly elevated corneal concentrations in vivo, which resulted in negligible ocular penetration. Moreover, A12 considerably ameliorated dry eye disease severity by exerting anti-inflammatory effects. Furthermore, in another murine model of allergic asthma, inhaled A12 substantially reduced overall lung inflammation. Our findings revealed the capacity of UdAbs to penetrate mucosal barriers following noninvasive localized delivery, highlighting their potential as an innovative therapeutic strategy for modulating mucosal inflammation.