A Core-Shell Structured Microneedle Patch With Adjustable Release of Kinetically for the Treatment of Melasma.

Melasma is a facial hyperpigmentation disease that significantly impacts patients' quality of life. Clinical treatment is limited by the short half-lives and hydrophilicity of drugs, necessitating release curve optimization to maintain a stable therapeutic concentration for an extended period. This article utilizes natural biomaterials to design a core-shell structured microneedle, combining the "immediate release" and "delayed release" module to achieve programmed drug release. Silk fibroin with a crystalline structure is used as the shell to ensure the harmlessness of the accessible areas, which can provide a release channel for 24 h. The cellulose in the core layer undergoes acetylation treatment, endowing it with the ability to regulate the diffusion flux of hydrophilic drugs. Further, the release kinetics can be tuned based on the crystallinity of the shell layer and the degree of acetylation in the core layer. In the melasma model, glutathione and tranexamic acid play a major role at 0-4 h and 4-24 h, respectively, with bioavailability increased to 264% and 172%. The synergistic effect reduces the generation and transfer of melanin, and restores skin color to near normal. Therefore, this core-shell structure microneedle patch is expected to promote the long-term clinical treatment of melasma.