Effect of size and charge on pharmacokinetics and in vivo MRI contrast enhancement of biodegradable polydisulfide Gd(III) complexes.
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.
Zong
Yuda
Y
Department of Pharmaceutics and Pharmaceutical Chemistry, University of UT, Salt Lake City, Utah, USA.
Guo
Junyu
J
Ke
Tianyi
T
Mohs
Aaron M
AM
Parker
Dennis L
DL
Lu
Zheng-Rong
ZR
D000818:Animals; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics*; D004220:Disulfides / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D005682:Gadolinium / Q000737:chemistry / Q000493:pharmacokinetics*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D017207:Rats, Sprague-Dawley; D055672:Static Electricity
D003287:Contrast Media; D004220:Disulfides; D005682:Gadolinium