International Journal of Nanomedicine (Feb 2019)
Multifunctional PLGA-based nanoparticles as a controlled release drug delivery system for antioxidant and anticoagulant therapy
Abstract
Pei-Chi Lee,1 Bo-Shen Zan,1 Li-Ting Chen,1 Tze-Wen Chung1,2 1Department of Biomedical Engineering, National Yang Ming University, Taipei 112, Taiwan; 2Drug Delivery Department, Center for Advanced Pharmaceutics and Drug Delivery Research, National Yang Ming University, Taipei 112, Taiwan Background: Ischemia/reperfusion (I/R) injury causes the generation of many ROS such as H2O2 and leads to vascular thrombosis, which causes tissue damage. Purpose: In this investigation, poly (lactideco-glycolide) (PLGA)-based nanoparticles are used for their anticoagulant and antioxidant properties in vascular therapy. Methods: Both heparin and glutathione are entrapped on PLGA-stearylamine nanoparticles by layer-by-layer interactions. Results: The drug release rate is successfully controlled with only 10.3% of the heparin released after 96 hours. An H2O2-responsive platform is also developed by combining silk fibroin and horse peroxidase to detect H2O2 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. Conclusion: 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. Keywords: ischemia/reperfusion, I/R, heparin, glutathione, anticoagulant, antioxidant, human bone marrow mesenchymal stem cells, hBMSCs
