International Journal of Nanomedicine (Jul 2019)
Effects of PEGylation on capture of dextran-coated magnetic nanoparticles in microcirculation
Abstract
Chien-Yu Chiu,1,2 Tze-Wen Chung,3,4 Si-Yi Chen,2 Yunn-Hwa Ma2,51Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Guishan, Taoyuan City 33302, Taiwan, ROC; 2Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Guishan, Taoyuan City 33302, Taiwan, ROC; 3Department of Biomedical Engineering, National Yang-Ming University, Beitou, Taipei City 11221, Taiwan, ROC; 4Center for Advanced Pharmaceutical Research and Drug Delivery, National Yang-Ming University, Beitou, Taipei City 11221, Taiwan, ROC; 5Department of Neurology, Chang Gung Memorial Hospital, Guishan, Taoyuan City 33305, Taiwan, ROCBackground: Magnetic nanoparticles (MNPs) can be localized against hemodynamic forces in blood vessels with the application of an external magnetic field. In addition, PEGylation of nanoparticles may increase the half-life of nanocomposites in circulation. In this work, we examined the effect of PEGylation on the magnetic capture of MNPs in vivo.Methods: Laser speckle contrast imaging and capillaroscopy were used to assess the magnetic capture of dextran-coated MNPs and red blood cell (RBC) flow in cremaster microvessels of anesthetized rats. Magnetic capture of MNPs in serum flow was visualized with an in vitro circulating system. The effect of PEGylation on MNP-endothelial cell interaction was studied in cultured cells using an iron assay.Results: In microcirculation through cremaster muscle, magnet-induced retention of 250 nm MNPs was associated with a variable reduction in RBC flow, suggesting a dynamic coupling of hemodynamic and magnetic forces. After magnet removal, faster restoration of flow was observed in PEG(+) than PEG(–) group, which may be attributed to a reduced interaction with vascular endothelium. However, PEGylation appears to be required for magnetic capture of 50 nm MNPs in microvessels, which was associated with increased hydrodynamic diameter to 130±6 nm in serum, but independent of the ς-potential.Conclusion: These results suggest that PEGylation may enhance magnetic capture of smaller MNPs and dispersion of larger MNPs after magnet removal, which may potentially affect the targeting, pharmacokinetics and therapeutic efficacy.Keywords: polyethylene glycol, magnetic nanoparticles, hemodynamics, microcirculation, magnetic targeting
