caa a22 4500 445312726 CHVBK 20180317142635.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s11095-011-0507-5 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0507-5 Ocular Pharmacokinetic Study Using T1 Mapping and Gd-Chelate- Labeled Polymers [Elektronische Daten] [Xianfeng Shi, Xin Liu, Xueming Wu, Zheng-Rong Lu, S. Li, Eun-Kee Jeong] ABSTRACT: Purpose: Recent advances in drug discovery have led to the development of a number of therapeutic macromolecules for treatment of posterior eye diseases. We aimed to investigate the clearance of macromolecular contrast probes (polymers conjugated with Gd-chelate) in the vitreous after intravitreal injections with the recently developed ms-DSEPI-T12 MRI and to examine the degradation of disulfide-containing biodegradable polymers in the vitreous humor in vivo. Methods: Intravitreal injections of model contrast agents poly[N-(2-hydroxypropyl)methacrylamide]-GG-1,6-hexanediamine-(Gd-DO3A), biodegradable (Gd-DTPA)-cystine copolymers, and MultiHance were performed in rabbits; their distribution and elimination from the vitreous after injections were determined by MRI. Results: Times for macromolecular contrast agents to decrease to half their initial concentrations in the vitreous ranged from 0.4-1.3days post-injection. Non-biodegradable polymers demonstrated slower vitreal clearance than those of disulfide-biodegradable polymers. Biodegradable polymers had similar clearance as MultiHance. Conclusions: Usefulness of T1 mapping and ms-DSEPI-T12 MRI to study ocular pharmacokinetics was demonstrated. Results suggest an enzymatic degradation mechanism for the disulfide linkage in polymers in the vitreous leading to breakup of polymers in vitreous humor over time. Springer Science+Business Media, LLC, 2011 biodegradable polymer nationallicence MRI nationallicence ms-DSEPI-T12 nationallicence ocular pharmacokinetics nationallicence vitreous humors nationallicence Shi Xianfeng Department of Radiology Utah Center for Advanced Imaging Research, University of Utah, 729 Arapeen Dr., 84108, Salt Lake City, Utah, USA aut Liu Xin Department of Radiology Utah Center for Advanced Imaging Research, University of Utah, 729 Arapeen Dr., 84108, Salt Lake City, Utah, USA aut Wu Xueming Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA aut Lu Zheng-Rong Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA aut Li S. Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, Ohio, USA aut Jeong Eun-Kee Department of Radiology Utah Center for Advanced Imaging Research, University of Utah, 729 Arapeen Dr., 84108, Salt Lake City, Utah, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3180-3188 0724-8741 28:12<3180 2011 28 11095 https://doi.org/10.1007/s11095-011-0507-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0507-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Shi Xianfeng Department of Radiology Utah Center for Advanced Imaging Research, University of Utah, 729 Arapeen Dr., 84108, Salt Lake City, Utah, USA aut NATIONALLICENCE 700 1- Liu Xin Department of Radiology Utah Center for Advanced Imaging Research, University of Utah, 729 Arapeen Dr., 84108, Salt Lake City, Utah, USA aut NATIONALLICENCE 700 1- Wu Xueming Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA aut NATIONALLICENCE 700 1- Lu Zheng-Rong Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA aut NATIONALLICENCE 700 1- Li S. Division of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, Ohio, USA aut NATIONALLICENCE 700 1- Jeong Eun-Kee Department of Radiology Utah Center for Advanced Imaging Research, University of Utah, 729 Arapeen Dr., 84108, Salt Lake City, Utah, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3180-3188 0724-8741 28:12<3180 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer