Microneedle Patch Delivery of PLCG1-siRNA Efficient Enhanced Temozolomide Therapy for Glioblastoma.

The blood-brain barrier (BBB) and drug resistance present challenges for chemotherapy of glioblastoma (GBM). A microneedle (MN) patch with excellent biocompatibility and biodegradability was designed to bypass the BBB and release temozolomide (TMZ) and PLCG1-siRNA directly into the tumor site for synergistic treatment of GBM. The codelivery of TMZ and PLCG1-siRNA enhanced DNA damage and apoptosis. The potential mechanism behind this enhancement is to knockdown of PLCG1 expression, which positively regulates the expression of signal transducer and activator of transcription 3 genes, thereby preventing DNA repair and enhancing the sensitivity of GBM to TMZ. The MN patch enables long-term sustainable drug release through implantation and increases local drug concentrations in diseased areas, significantly extending mouse survival time compared to other drug treatment groups. MN drug delivery provides a platform for the combination treatment of GBM and other central nervous system diseases.