Zong Yuda, Guo Junyu, Ke Tianyi, Mohs Aaron M, Parker Dennis L, Lu Zheng-Rong
Department of Pharmaceutics and Pharmaceutical Chemistry, University of UT, Salt Lake City, Utah, USA.
J Control Release. 2006 May 30;112(3):350-6. doi: 10.1016/j.jconrel.2006.03.006. Epub 2006 May 2.
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.
本研究的目的是探究作为可生物降解大分子磁共振成像（MRI）造影剂的多硫化物钆（III）配合物的结构如何影响其药代动力学和体内造影增强效果。制备并表征了带负电荷的多硫化物钆（III）配合物（钆-二乙三胺五乙酸-胱氨酸共聚物，GDCP）和中性试剂（钆-二乙三胺五乙酸-胱氨酸二乙酯共聚物，GDCEP），它们具有不同的分子量。在小鼠体内研究了这些试剂的MRI造影增强效果。中性的GDCEP在血浆中的降解速度比带负电荷的GDCP更快。因此，与GDCEP相比，GDCP在血池和肝脏中产生了更显著且持久的造影增强效果。由于从血液循环中快速降解和清除，GDCEP的尺寸对其体内造影增强效果没有显著影响。GDCP分子量的增加导致血池中体内造影增强效果延长。多硫化物钆（III）配合物的结构修饰产生了具有不同降解性和体内造影增强效果的可生物降解大分子MRI造影剂。
