A smart MMP-9-responsive hydrogel releasing quercetin for psoriasis therapy.

Introduction: Psoriasis is an autoimmune disease characterized primarily by chronic inflammation, with suboptimal clinical therapeutic outcomes. Quercetin, a bio-safe plant secondary metabolite, exerts anti-inflammatory effects by modulating multiple signaling pathways and holds promise as a therapeutic candidate for psoriasis. Methods: Our preliminary studies demonstrated that silk protein (SF) derived from silkworm cocoons exhibits excellent biocompatibility and can form hydrogels, serving as an ideal drug carrier for skin applications. We loaded quercetin into the SF hydrogel system and systematically investigated the therapeutic efficacy of this composite formulation (QSF) against imiquimod-induced psoriasis models through in vitro and in vivo experiments. Results: The hydrogel exhibited desirable enzyme-responsive properties. When exposed to an in vitro microenvironment containing 10 nM MMP-9, the hydrogel network rapidly disintegrated, achieving a cumulative quercetin release of 58.26% ± 7.64% within 24 h. The enriched quercetin in lesion tissues markedly reduced the positive expression levels of IL-17, TNF-α, and IL-1β, with inhibition rates of 32.14%, 20.25%, and 33.71%, respectively, which effectively interrupted the inflammatory cascade and obviously alleviated skin desquamation and pruritus. Discussion: Collectively, the fabricated QSF hydrogel presents anti-inflammatory and symptomatic relief effects, providing a feasible strategy and experimental basis for the development of novel topical preparations for psoriasis treatment.