Multifunctional Microneedle Patches for Perivascular Gene Delivery and Treatment of Vascular Intimal Hyperplasia

Gene therapy has emerged as a promising approach to address
challenging
cardiovascular diseases. Extensive efforts have been focused on developing
highly efficient gene vectors with precise delivery techniques to
enhance its effectiveness. In this study, we present multifunctional
dopamine-gelatin microneedle patches with gene therapy capabilities
to achieve perivascular gene delivery for intimal hyperplasia treatment.
These patches that were fabricated through freeze-drying of gelatin
are with recombinant adeno-associated virus (rAAVs)-carrying tips
and dopamine coating backing layers. The lyophilized gelatin could
not only effectively preserve the therapeutic activity of rAAVs but
could also demonstrate the capability to penetrate the adventitia
for efficient delivery. The incorporation of dopamine facilitated
patch adhesion and extended the release duration. Based on these advantages,
we have demonstrated that the rAAVs-loaded microneedle patches (AMNPs)
behave satisfactorily in perivascular gene delivery to inhibit carotid
artery restenosis in rats. These features indicate that the AMNPs
are clinically valuable in the treatment of vascular intimal hyperplasia
diseases.

基因治疗已成为应对难治性心血管疾病的极具前景的治疗策略。学界已开展大量研究，致力于开发具备精准递送技术的高效基因载体，以提升基因治疗的疗效。本研究中，我们开发了兼具基因治疗功能的多功能多巴胺-明胶微针贴片，用于实现血管周围基因递送以治疗内膜增生。该贴片采用明胶冷冻干燥法制备，针体负载重组腺相关病毒（recombinant adeno-associated virus, rAAVs），背衬层带有多巴胺涂层。冻干明胶不仅可有效维持rAAVs的治疗活性，还能够穿透血管外膜，实现高效递送。多巴胺的引入不仅增强了贴片的黏附能力，还延长了药物释放时长。基于上述优势，我们证实负载重组腺相关病毒的微针贴片（AMNPs）可在大鼠模型中实现优异的血管周围基因递送效果，有效抑制颈动脉再狭窄。上述特性表明，AMNPs在血管内膜增生类疾病的临床治疗中具有较高的应用价值。