Ocular Soluble Microneedle Patch Loaded with Immunogenic Cell Death Inducer PKHB1 Peptide for Alleviating Herpes Simplex Keratitis.

Herpes simplex keratitis (HSK) is a chronic, sight-threatening ocular condition caused by herpes simplex virus type 1 (HSV-1). Due to the limited efficacy and significant side effects of current treatments, enhancing the host's immune response to clear the virus has emerged as a promising therapeutic strategy. However, ocular drug delivery is often hindered by physiological barriers, resulting in low bioavailability of topical eye drops. To address this, we developed a hyaluronic acid methacryloyl-based soluble microneedle (MN) patch for targeted delivery of the immunogenic cell death inducer PKHB1 peptide, offering a novel treatment approach for HSK. Characterization of PKHB1-MNs demonstrated sustained drug release, high bioavailability, and favorable biosafety profiles. In the HSK mouse model, PKHB1-MNs enhanced CD8+ T cell-mediated adaptive immunity by modulating ocular antigen-presenting cells, thereby reducing HSV-1 replication and effectively alleviating HSK-induced lesions. The MN patch represents a promising, minimally invasive strategy for treating HSK and holds potential for the management of other anterior segment diseases.