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. <i>In vitro</i>, SFN enhanced shikonin uptake, suppressing keratinocyte hyperproliferation and promoting apoptosis, while SeHA scavenged ROS, mitigating oxidative stress and inflammation. <i>In vivo</i>, 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.