Department of Biomedical Engineering, National Yang Ming University, Taipei 112, Taiwan,
Drug Delivery Department, Center for Advanced Pharmaceutics and Drug Delivery Research, National Yang Ming University, Taipei 112, Taiwan,
Int J Nanomedicine. 2019 Feb 26;14:1533-1549. doi: 10.2147/IJN.S174962. eCollection 2019.
Ischemia/reperfusion (I/R) injury causes the generation of many ROS such as HO and leads to vascular thrombosis, which causes tissue damage.
In this investigation, poly (lactideco-glycolide) (PLGA)-based nanoparticles are used for their anticoagulant and antioxidant properties in vascular therapy.
Both heparin and glutathione are entrapped on PLGA-stearylamine nanoparticles by layer-by-layer interactions.
The drug release rate is successfully controlled with only 10.3% of the heparin released after 96 hours. An HO-responsive platform is also developed by combining silk fibroin and horse peroxidase to detect HO in this drug delivery system. Besides, hyaluronic acid was decorated on the surface of nanoparticles to target the human bone marrow mesenchymal stem cells (hBMSCs) for cell therapy. The results of an in vitro study indicate that the nanoparticles could be taken up by hBMSCs within 2 hours and exocytosis occurred 6 hours after cellular uptake.
We propose that the multifunctional nanoparticles that are formed herein can be effectively delivered to the site of an I/R injury via the hBMSC homing effect. The proposed approach can potentially be used to treat vascular diseases, providing a platform for hBMSCs for the controlled delivery of a wide range of drugs.
缺血/再灌注(I/R)损伤会产生大量的活性氧物种(ROS),如 HO,导致血管血栓形成,进而引起组织损伤。
本研究中,聚(乳酸-共-乙醇酸)(PLGA)基纳米粒子因其在血管治疗中的抗凝和抗氧化特性而被用于研究。
通过层层相互作用,将肝素和谷胱甘肽包封在 PLGA-硬脂胺纳米粒子中。
药物释放率得到了有效控制,仅在 96 小时后就有 10.3%的肝素释放。通过将丝素蛋白和马过氧化物酶结合,开发了一个 HO 响应平台,用于在该药物输送系统中检测 HO。此外,还在纳米粒子表面修饰了透明质酸,以靶向人骨髓间充质干细胞(hBMSCs)进行细胞治疗。体外研究结果表明,纳米粒子可以在 2 小时内被 hBMSCs 摄取,并在细胞摄取后 6 小时发生外排。
我们提出,本文所形成的多功能纳米粒子可以通过 hBMSC 归巢效应有效递送至 I/R 损伤部位。该方法可能为血管疾病的治疗提供了一个平台,为 hBMSCs 提供了一个用于控制输送各种药物的平台。