Biodistribution of newly synthesized PHEA-based polymer-coated SPION in Sprague Dawley rats as magnetic resonance contrast agent

Junsung Park,1,2,* Wonkyung Cho,1,2,* Hee Jun Park,1,2 Kwang-Ho Cha,1,2 Dae-Chul Ha,2,5 Youn-Woong Choi,5 Ha-Young Lee,3 Sun-Hang Cho,5 Sung-Joo Hwang1,4 1Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea; 2College of Pharmacy, Chungnam National University, D...

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Main Authors: Park J, Cho W, Park HJ, Cha KH, Ha DC, Choi YW, Lee HY, Cho SH, Hwang SJ
Format: Article
Language:English
Published: Dove Medical Press 2013-10-01
Series:International Journal of Nanomedicine
Online Access:http://www.dovepress.com/biodistribution-of-newly-synthesized-phea-based-polymer-coated-spion-i-a14837
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author Park J
Cho W
Park HJ
Cha KH
Ha DC
Choi YW
Lee HY
Cho SH
Hwang SJ
author_facet Park J
Cho W
Park HJ
Cha KH
Ha DC
Choi YW
Lee HY
Cho SH
Hwang SJ
author_sort Park J
collection DOAJ
description Junsung Park,1,2,* Wonkyung Cho,1,2,* Hee Jun Park,1,2 Kwang-Ho Cha,1,2 Dae-Chul Ha,2,5 Youn-Woong Choi,5 Ha-Young Lee,3 Sun-Hang Cho,5 Sung-Joo Hwang1,4 1Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea; 2College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea; 3Biomaterials Laboratory, Korea Research Institutes of Chemical Technology, Daejeon, Republic of Korea; 4College of Pharmacy, Yonsei University, Incheon, Republic of Korea; 5Korea United Pharm Inc, Seoul, Republic of Korea *These authors contributed equally to this work Objectives: The purpose of this study was to observe the pharmacokinetic behavior of newly synthesized biocompatible polymers based on polyhydroxyethylaspartamide (PHEA) to be used to coat an iron oxide core to make superparamagnetic iron oxide nanoparticles (SPION). Materials and methods: The isotopes [14C] and [59Fe] were used to label the polymer backbone (CLS) and iron oxide core (FLS), respectively. In addition, unradiolabeled cold superparamagnetic iron oxide nanoparticles (SPION/ULS) were synthesized to characterize particle size by dynamic light scattering, morphology by transmission electron microscopy, and in vivo magnetic resonance imaging (MRI). CLS and FLS were used separately to investigate the behavior of both the synthesized polymer and [Fe] in Sprague Dawley (SD) rats, respectively. Because radioactivity of the isotopes was different by β for CLS and γ for FLS, synthesis of the samples had to be separately prepared. Results: The mean particle size of the ULS was 66.1 nm, and the biodistribution of CLS concentrations in various organs, in rank order of magnitude, was liver > kidney > small intestine > other. The biodistribution of FLS concentrations was liver > spleen > lung > other. These rank orders show that synthesized SPION mainly accumulates in the liver. The differences in the distribution were caused by the SPION metabolism. Radiolabeled polymer was metabolized by the kidney and excreted mainly in the urine; [59Fe] was recycled for erythrocyte production in the spleen and excreted mainly in the feces. The MR image of the liver after intravenous injection demonstrated that [Fe] effectively accumulated in the liver and exhibited high-contrast enhancement on T2-weighted images. Conclusion: This newly synthesized, polymer-coated SPION appears to be a promising candidate for use as a liver-targeted, biocompatible iron oxide MR imaging agent. Keywords: SPION, radiolabeled, polyhydroxyethylaspartamide, pharmacokinetic, liver
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spelling doaj.art-fe96b659cfd744bab8c41633ec92e5c42022-12-21T20:36:22ZengDove Medical PressInternational Journal of Nanomedicine1176-91141178-20132013-10-012013Issue 140774089Biodistribution of newly synthesized PHEA-based polymer-coated SPION in Sprague Dawley rats as magnetic resonance contrast agentPark JCho WPark HJCha KHHa DCChoi YWLee HYCho SHHwang SJJunsung Park,1,2,* Wonkyung Cho,1,2,* Hee Jun Park,1,2 Kwang-Ho Cha,1,2 Dae-Chul Ha,2,5 Youn-Woong Choi,5 Ha-Young Lee,3 Sun-Hang Cho,5 Sung-Joo Hwang1,4 1Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea; 2College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea; 3Biomaterials Laboratory, Korea Research Institutes of Chemical Technology, Daejeon, Republic of Korea; 4College of Pharmacy, Yonsei University, Incheon, Republic of Korea; 5Korea United Pharm Inc, Seoul, Republic of Korea *These authors contributed equally to this work Objectives: The purpose of this study was to observe the pharmacokinetic behavior of newly synthesized biocompatible polymers based on polyhydroxyethylaspartamide (PHEA) to be used to coat an iron oxide core to make superparamagnetic iron oxide nanoparticles (SPION). Materials and methods: The isotopes [14C] and [59Fe] were used to label the polymer backbone (CLS) and iron oxide core (FLS), respectively. In addition, unradiolabeled cold superparamagnetic iron oxide nanoparticles (SPION/ULS) were synthesized to characterize particle size by dynamic light scattering, morphology by transmission electron microscopy, and in vivo magnetic resonance imaging (MRI). CLS and FLS were used separately to investigate the behavior of both the synthesized polymer and [Fe] in Sprague Dawley (SD) rats, respectively. Because radioactivity of the isotopes was different by β for CLS and γ for FLS, synthesis of the samples had to be separately prepared. Results: The mean particle size of the ULS was 66.1 nm, and the biodistribution of CLS concentrations in various organs, in rank order of magnitude, was liver > kidney > small intestine > other. The biodistribution of FLS concentrations was liver > spleen > lung > other. These rank orders show that synthesized SPION mainly accumulates in the liver. The differences in the distribution were caused by the SPION metabolism. Radiolabeled polymer was metabolized by the kidney and excreted mainly in the urine; [59Fe] was recycled for erythrocyte production in the spleen and excreted mainly in the feces. The MR image of the liver after intravenous injection demonstrated that [Fe] effectively accumulated in the liver and exhibited high-contrast enhancement on T2-weighted images. Conclusion: This newly synthesized, polymer-coated SPION appears to be a promising candidate for use as a liver-targeted, biocompatible iron oxide MR imaging agent. Keywords: SPION, radiolabeled, polyhydroxyethylaspartamide, pharmacokinetic, liverhttp://www.dovepress.com/biodistribution-of-newly-synthesized-phea-based-polymer-coated-spion-i-a14837
spellingShingle Park J
Cho W
Park HJ
Cha KH
Ha DC
Choi YW
Lee HY
Cho SH
Hwang SJ
Biodistribution of newly synthesized PHEA-based polymer-coated SPION in Sprague Dawley rats as magnetic resonance contrast agent
International Journal of Nanomedicine
title Biodistribution of newly synthesized PHEA-based polymer-coated SPION in Sprague Dawley rats as magnetic resonance contrast agent
title_full Biodistribution of newly synthesized PHEA-based polymer-coated SPION in Sprague Dawley rats as magnetic resonance contrast agent
title_fullStr Biodistribution of newly synthesized PHEA-based polymer-coated SPION in Sprague Dawley rats as magnetic resonance contrast agent
title_full_unstemmed Biodistribution of newly synthesized PHEA-based polymer-coated SPION in Sprague Dawley rats as magnetic resonance contrast agent
title_short Biodistribution of newly synthesized PHEA-based polymer-coated SPION in Sprague Dawley rats as magnetic resonance contrast agent
title_sort biodistribution of newly synthesized phea based polymer coated spion in sprague dawley rats as magnetic resonance contrast agent
url http://www.dovepress.com/biodistribution-of-newly-synthesized-phea-based-polymer-coated-spion-i-a14837
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