Dual action microneedle patch for psoriasis

[Fred]

This study presents a dual action microneedle therapy for psoriasis that alleviates psoriasis by modulating keratinocyte ferroptosis and scavenging cfDNA to restore inflammatory homeostasis.

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Psoriasis is a chronic inflammatory skin disorder characterized by dysregulated epithelial-immune interactions. Emerging evidence implicates keratinocyte ferroptosis as a critical pathological mechanism, whereby oxidative epidermal damage and elevated levels of cell-free DNA (cfDNA) amplify immune dysregulation and sustain chronic psoriatic inflammation.

Here, we developed a dual-action microneedle system (CAD), with needle tips composed of guanidine-functionalized chitosan and deferoxamine (DFO), designed to eliminate pro-inflammatory cfDNA while locally releasing DFO for iron chelation. In an imiquimod-induced psoriasis mouse model, CAD markedly alleviated psoriatic symptoms, reducing the psoriasis area and severity index score by approximately 50% compared with the model group and demonstrating superior therapeutic efficacy to clinically used calcipotriol.

Further studies revealed that CAD depleted accumulated iron and inflammatory cfDNA in lesioned skin, alleviating oxidative stress and suppressing ferroptosis, inhibiting the inflammatory cascade, and maintaining immune homeostasis for effective psoriasis treatment. This study presents a dual-action microneedle therapy for psoriasis that alleviates psoriasis by modulating keratinocyte ferroptosis and scavenging cfDNA to restore inflammatory homeostasis, providing a promising foundation for the development of mechanism-guided combination therapies for psoriasis.

Future work will further optimize the formulation for clinical translation and explore its therapeutic potential for other ferroptosis-related inflammatory skin disorders.

Source: onlinelibrary.wiley.com

*Funding:
National Natural Science Foundation of China. Natural Science Foundation of Fujian Province of China. Open Foundation of Hubei Key Laboratory of Regenerative Medicine and Multi-disciplinary Translational Research. Scientific Research Foundation of State Key Laboratory of Vaccines for Infectious Diseases Xiang'An Biomedicine Laboratory. MOE Key Laboratory of Macromolecular Synthesis and Functionalization Zhejiang University.