Preparation, Effect, and Mechanism Exploration of Hyaluronic Acid Microneedle Patch with Rapamycin Nanocrystals

Abstract

Transplant vein restenosis is the main complication affecting the long-term graft patency after coronary artery bypass grafting, mainly caused by VSMC proliferation and migration (initiating factors), leading to intimal hyperplasia and restenosis. Transplant vein restenosis has seriously affected the surgical efficacy of CABG, and the degree of transplant vein restenosis determines the patient’s survival time. Therefore, a solution to this problem is urgent. Rapamycin is a cell cycle drug that can inhibit VSMC proliferation and migration but its systemic toxicity is high. In recent years, microneedle drug delivery systems have become a research hotspot with broad clinical application prospects. These systems are capable of achieving sustained, safe, and painless local drug release. In cardiovascular applications, MNs can maximize local drug effects and reduce systemic side effects. We speculate that the MN drug delivery system can be used to target transplanted veins, suppress restenosis by inhibiting SMC proliferation, reduce the incidence of restenosis after coronary artery bypass grafting, and delay the occurrence of restenosis. Therefore, this study developed a hyaluronic acid MN patch loaded with rapamycin and conducted preliminary physicochemical experiments. The study was conducted in in vitro and in vivo experiments using a jugular vein transplantation model to evaluate the safety, efficacy, biocompatibility, and targeting of the MN system. The results indicate that the MN system has excellent physical properties, safety, effectiveness, biocompatibility, and strong targeting, which can act on HIF-1 and effectively inhibit the proliferation, migration, and intimal hyperplasia of SMC. This provides a foundation for future research on inhibiting CABG restenosis throughout the entire process to ensure the patency of transplanted blood vessels.