Precision Engineered Dissolving Microneedles Enable Green–Light Activated Chemo–Photodynamic Therapy for Psoriasis

Psoriasis exhibits limited response to monotherapy, and customized combination strategies for synergistic treatment are constrained by skin permeability and insufficient control of drug activation. This study proposes a dissolving microneedle (MN) platform that integrates photodynamic therapy and chemotherapy for synergistic psoriasis treatment. The platform utilizes high-precision projection microstereolithography (PμSL) combined with a template replication strategy, coloading methotrexate (MTX) and a novel photosensitizer, 8-Phenyl-2,6-diiodo-1,3,5,7-tetramethyl BODIPY (I-BDP), into a poly(vinylpyrrolidone) (PVP) matrix to construct MTX/I-BDP@PVP MNs. The MNs efficiently penetrate the stratum corneum, enabling precise drug delivery to the lesion site, which matches the optimal penetration depth of green light. Upon green-light irradiation, I-BDP generates reactive oxygen species, synergizing with MTX to suppress keratinocyte hyperproliferation and induce apoptosis in HaCaT cells, with an apoptosis rate of 82.4%. The spatially confined activation minimizes off-target damage to healthy tissue. This synergistic MN platform offers a safe, controllable, and effective strategy for the treatment of psoriasis and other inflammatory skin diseases.