负载西地那非的血小板膜包裹聚乳酸-乙醇酸纳米粒用于静脉移植物内膜增生的靶向治疗
Platelet Membrane-Encapsulated Poly(lactic--glycolic acid) Nanoparticles Loaded with Sildenafil for Targeted Therapy of Vein Graft Intimal Hyperplasia.
作者信息
Yang Fajing, Qiu Yihui, Xie Xueting, Zhou Xingjian, Wang Shunfu, Weng Jialu, Wu Lina, Ma Yizhe, Wang Ziyue, Jin Wenzhang, Chen Bicheng
机构信息
Department of Vascular Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China.
Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, PR China.
出版信息
Int J Pharm X. 2024 Aug 17;8:100278. doi: 10.1016/j.ijpx.2024.100278. eCollection 2024 Dec.
Autologous vein grafts have attracted widespread attention for their high transplantation success rate and low risk of immune rejection. However, this technique is limited by the postoperative neointimal hyperplasia, recurrent stenosis and vein graft occlusion. Hence, we propose the platelet membrane-coated Poly(lactic--glycolic acid) (PLGA) containing sildenafil (PPS). Platelet membrane (PM) is characterised by actively targeting damaged blood vessels. The PPS can effectively target the vein grafts and then slowly release sildenafil to treat intimal hyperplasia in the vein grafts, thereby preventing the progression of vein graft restenosis. PPS effectively inhibits the proliferation and migration of vascular smooth muscle cell (VSMCs) and promotes the migration and vascularisation of human umbilical vein endothelial cells (HUVECs). In a New Zealand rabbit model of intimal hyperplasia in vein grafts, the PPS significantly suppressed vascular stenosis and intimal hyperplasia at 14 and 28 days after surgery. Thus, PPS represents a nanomedicine with therapeutic potential for treating intimal hyperplasia of vein grafts.
自体静脉移植物因其高移植成功率和低免疫排斥风险而受到广泛关注。然而,该技术受到术后新生内膜增生、复发性狭窄和静脉移植物闭塞的限制。因此,我们提出了含西地那非的血小板膜包被聚乳酸-乙醇酸共聚物(PPS)。血小板膜(PM)的特点是能主动靶向受损血管。PPS可有效靶向静脉移植物,然后缓慢释放西地那非以治疗静脉移植物中的内膜增生,从而防止静脉移植物再狭窄的进展。PPS能有效抑制血管平滑肌细胞(VSMC)的增殖和迁移,并促进人脐静脉内皮细胞(HUVEC)的迁移和血管生成。在新西兰兔静脉移植物内膜增生模型中,PPS在术后14天和28天显著抑制了血管狭窄和内膜增生。因此,PPS是一种具有治疗静脉移植物内膜增生潜力的纳米药物。