Natural Baicalin Compound Microneedle: A Novel Therapeutic Strategy for Critical Limb Ischemia Through the Promotion of Muscle Differentiation.

Critical limb ischemia (CLI) results from inadequate blood perfusion in the extremities, leading to accelerated muscle cell apoptosis in mild cases and lower limb claudication in severe cases. It can therefore significantly reduce the quality of life of patients. In this study, baicalin (BA), a representative flavonoid, is shown to induce myogenic differentiation thus alleviating CLI. The underlying mechanism of action of BA primarily involves the direct activation of the Wnt/β-catenin signaling pathway and the drug metabolism enzyme cytochrome P450 (Cyp1a1) in muscle cells. To address the challenging aqueous solubility of flavonoids for in vivo applications, we designed an innovative composite microneedle patch (GEL+PUE+BA MNs). This delivery strategy not only overcomes the solubility limitations of flavonoids in vivo but also promotes the repair of ischemic muscle through localized intervention. It efficiently delivers BA to the ischemic site, stimulates the associated muscle cells, and induces their differentiation into skeletal muscle. This process markedly reduces the apoptotic cells and muscle loss in the lower extremities. Our study underscores the significant therapeutic effects of GEL+PUE+BA MNs as a biomaterial for treating hindlimb ischemia and highlights its considerable potential in managing CLI.