期刊
JOURNAL OF CONTROLLED RELEASE
卷 112, 期 3, 页码 350-356出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2006.03.006
关键词
MRI; biodegradable macromolecular contrast agents; gadolinium; polydisulfide; blood pool contrast agents
资金
- NCI NIH HHS [CA095873] Funding Source: Medline
- NIBIB NIH HHS [EB00489] Funding Source: Medline
The purpose of this study is to investigate how the structures of polydisulfide Gd(III) complexes affect their pharmacokinctics 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. (c) 2006 Elsevier B.V. All rights reserved.
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