Platelet Membrane-Encapsulated Poly(lactic- co-glycolic acid) Nanoparticles Loaded with Sildenafil for Targeted Therapy of Vein Graft Intimal Hyperplasia

血小板膜包裹聚乳酸-乙醇酸纳米粒子载西地那非用于静脉移植内膜增生的靶向治疗

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作者:Fajing Yang, Yihui Qiu, Xueting Xie, Xingjian Zhou, Shunfu Wang, Jialu Weng, Lina Wu, Yizhe Ma, Ziyue Wang, Wenzhang Jin, Bicheng Chen

Abstract

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-co-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.

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