Effect of size and charge on pharmacokinetics and in vivo MRI contrast enhancement of biodegradable polydisulfide Gd(III) complexes

Journal of Controlled Release : Official Journal of the Controlled Release Society
Yuda ZongZheng-Rong Lu

Abstract

The purpose of this study is to investigate how the structures of polydisulfide Gd(III) complexes affect their pharmacokinetics and in vivo contrast enhancement as biodegradable macromolecular MRI contrast agents. A negatively charged polydisulfide Gd(III) complex, (Gd-DTPA)-cystine copolymers (GDCP), and a neutral agent, (Gd-DTPA)-cystine diethyl ester copolymers (GDCEP), with different molecular weights were prepared and characterized. The MRI contrast enhancement of the agents was studied in mice. Neutral GDCEP showed more rapid degradation than negatively charged GDCP in the blood plasma. Consequently, GDCP resulted in more significant and prolonged contrast enhancement in the blood pool and liver than GDCEP. The size of GDCEP did not significantly affect its in vivo contrast enhancement due to rapid degradation and clearance from the blood circulation. The increase in the molecular weight of GDCP resulted in prolonged in vivo contrast enhancement in the blood pool. The structural modification of polydisulfide Gd(III) complexes resulted in biodegradable macromolecular MRI contrast agents with different degradability and in vivo contrast enhancement.

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Citations

Jun 22, 2011·Pharmaceutical Research·Xianfeng ShiEun-Kee Jeong
Jan 2, 2013·Chemical Reviews·Venkat Ratnam DevadasuM N V Ravi Kumar
Jun 5, 2012·Molecular Pharmaceutics·Eric SchopfAdah Almutairi
Aug 13, 2009·European Radiology·Monique R BernsenGabriel P Krestin
Feb 10, 2009·Biomaterials·Fenghua MengZhiyuan Zhong
Jul 31, 2007·Journal of Controlled Release : Official Journal of the Controlled Release Society·Zheng-Rong LuAnagha Vaidya
Nov 26, 2008·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Yi FengZheng-Rong Lu
Jul 31, 2007·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Aaron M MohsZheng-Rong Lu
Oct 28, 2011·Journal of Magnetic Resonance Imaging : JMRI·Zhen YeZheng-Rong Lu
Dec 19, 2012·International Journal of Pharmaceutics·István HajduJános Borbély
Sep 17, 2013·Chemical Communications : Chem Comm·Gemma-Louise DaviesJason J Davis
Aug 1, 2020·ChemMedChem·Giulia BononiFilippo Minutolo
Aug 28, 2014·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Weiren ChengYe Liu

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