期刊
JOURNAL OF CONTROLLED RELEASE
卷 172, 期 1, 页码 77-85出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2013.07.027
关键词
Fluorine-18 labeling; HPMA; PEG; PET; Structure-property relationships; Walker 256 mammary carcinoma
资金
- Max-Planck Graduate Center (MPGC)
- Graduate School Materials Science in Mainz (Excellence Initiative) [DFG/GSC 266]
- DFG [RO 985/30-1, TH 482/4-1, ZE 230/21-1]
- SAMT Initiative Mainz
This paper reports the body distribution of block copolymers (made by controlled radical polymerization) with N-(2-hydroxypropyl)methacrylamide (HPMA) as hydrophilic block and laurylmethacrylate (LMA) as hydrophobic block. They form micellar aggregates in aqueous solution. For this study the hydrophilic/hydrophobic balance was varied by incorporation of differing amounts of poly(ethylene glycol) (PEG) side chains into the hydrophilic block, while keeping the degree of polymerization of both blocks constant. PEGylation reduced the size of the micellar aggregates (R-h = 113 to 38 nm) and led to a minimum size of 7% PEG side chains. Polymers were labeled with the positron emitter F-18, which enables to monitor their biodistribution pattern for up to 4 h with high spatial resolution. These block copolymers were investigated in Sprague-Dawley rats bearing the Walker 256 mammary carcinoma in vivo. Organ/tumor uptake was quantified by ex vivo biodistribution as well as small animal positron emission tomography (PET). All polymers showed renal clearance with time. Their uptake in liver and spleen decreased with size of the aggregates. This made PEGylated polymers - which form smaller aggregates - attractive as they show a higher blood pool concentration. Within the studied polymers, the block copolymer of 7% PEGylation exhibited the most favorable organ distribution pattern, showing highest blood-circulation level as well as lowest hepatic and splenic uptake. Most remarkably, the in vivo results revealed a continuous increase in tumor accumulation with PEGylation (independent of the blood pool concentration) - starting from lowest tumor uptake for the pure block copolymer to highest enrichment with 11% PEG side chains. These findings emphasize the need for reliable (non-invasive) in vivo techniques revealing overall polymer distribution and helping to identify drug carrier systems for efficient therapy. (C) 2013 Published by Elsevier B.V.
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