Selenium-functionalized hyaluronic acid dissolvable microneedle patch synergistic herbal shikonin-loaded tetrahedral framework nucleic acids for psoriasis therapy

Psoriasis is a complex, chronic inflammatory skin disease for which current therapies are limited by systemic toxicity, rapid relapse, and incomplete resolution. Despite advances in microneedle (MN)-assisted transdermal drug delivery, conventional systems often suffer from suboptimal pharmacokinetics and limited therapeutic versatility. Here, we engineered a dissolvable MN patch composed of selenium-functionalized hyaluronic acid (SeHA) integrated with shikonin-loaded tetrahedral framework nucleic acids (SFN) to enable sustained drug release while modulating the reactive oxygen species (ROS)-rich psoriatic microenvironment. The SeHA-SFN MNs exhibited robust mechanical properties, permitting efficient penetration of hyperkeratotic epidermis, followed by rapid dissolution and targeted SFN delivery. In vitro, SFN enhanced shikonin uptake, suppressing keratinocyte hyperproliferation and promoting apoptosis, while SeHA scavenged ROS, mitigating oxidative stress and inflammation. In vivo, the system ameliorated psoriatic phenotypes in an imiquimod-induced murine model, attenuating epidermal thickening, systemic inflammation, and pathological microenvironmental cues. Biosafety assessments confirmed excellent biocompatibility. By synergizing antioxidative SeHA with SFN-mediated shikonin delivery, this platform presents a promising and versatile approach for localized and targeted management of psoriasis, potentially extending to other inflammatory skin disorders.