Tip-retained hydrated silk fibroin microneedles for sustained local delivery of TNF-α antagonist in psoriasis treatment.

Psoriasis is a chronic immune-mediated inflammatory skin disease characterized by keratinocyte hyperproliferation and cytokine-driven immune activation, in which TNF-α plays a central pathogenic role. We developed a layered hydrated silk fibroin (SF) microneedle system (ETA@Hyd MN) with SF tips loaded with etanercept (ETA, a TNF-α inhibitor for psoriasis), for local cutaneous delivery to reduce systemic exposure and rapidly dissolving polyvinyl alcohol (PVA) bases that facilitate retention of the SF tips within the skin. Hydration markedly slowed ETA release, with approximately 80% released at 48 h compared with approximately 75% released within 1 h from microneedles without hydration. In HaCaT cell scratch assays, release media from ETA@Hyd MN attenuated the accelerated wound closure response, resulting in a greater remaining scratch width than that in the model group at 48 h. In an IMQ-induced psoriasis-like mouse model, ETA@Hyd MN improved clinical symptoms, reduced PASI scores, alleviated spleen enlargement, and suppressed epidermal hyperplasia and TNF-α/IL-6 expression. These results demonstrate that ETA@Hyd MN enables sustained ETA release and effectively suppresses inflammation, highlighting its potential for treating inflammatory skin diseases.