Size Dependent Biodistribution and SPECT Imaging of 111In-Labeled Polymersomes
Size Dependent Biodistribution and SPECT Imaging of 111In-Labeled Polymersomes
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DOI：
10.1021/bc200578s
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发表时间：
2012-05-01
影响因子：
4.7
通讯作者：
van Hest, Jan C. M.
中科院分区：
文献类型：
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作者：
Brinkhuis, Rene P.;Stojanov, Katica;van Hest, Jan C. M.
聚合物囊泡，自组装的嵌段共聚物聚丁二烯-嵌段-聚（乙二醇），制备具有良好定义的直径在90和250 nm之间。在聚合物囊泡外围存在类似于1%的二亚乙基三胺五乙酸允许将放射性In-111螯合到表面上，并确定小鼠中的生物分布作为聚合物囊泡尺寸和聚（乙二醇）冠厚度的函数（即，PEG分子量）。将PEG分子量从1 kg/mol加倍至2 kg/mol不会显著改变血液循环半衰期。然而，不同聚合物囊泡样品的大小确实对血液循环时间产生了巨大的影响。发现120 nm及更大的聚合物囊泡在4 h内大部分从血液中清除，推测是由于网状内皮系统的识别。相比之下，约90 nm的较小聚合物囊泡循环时间更长。24小时后，超过30%的注射剂量仍存在于血池中。由于尺寸导致的血液循环动力学的这种急剧转变比脂质体观察到的要突然得多，并且另外通过SPECT/CT成像可视化。这些研究结果应考虑在制定和设计的聚合物囊泡的生物医学应用。尺寸比脂质体大得多，将影响药代动力学，因此，长循环制剂应远低于100 nm。
Polymersomes, self-assembled from the block copolymer polybutadiene-block-poly(ethylene glycol), were prepared with well-defined diameters between 90 and 250 nm. The presence of similar to 1% of diethylene triamine penta acetic acid on the polymersome periphery allowed to chelate radioactive In-111 onto the surface and determine the biodistribution in mice as a function of both the polymersome size and poly(ethylene glycol) corona thickness (i.e., PEG molecular weight). Doubling the PEG molecular weight from 1 kg/mol to 2 kg/mol did not change the blood circulation half-life significantly. However, the size of the different polymersome samples did have a drastic effect on the blood circulation times. It was found that polymersomes of 120 nm and larger become mostly cleared from the blood within 4 h, presumably due to recognition by the reticuloendothelial system. In contrast, smaller polymersomes of around 90 nm circulated much longer. After 24 h more than 30% of the injected dose was still present in the blood pool. This sharp transition in blood circulation kinetics due to size is much more abrupt than observed for liposomes and was additionally visualized by SPECT/CT imaging. These findings should be considered in the formulation and design of polymersomes for biomedical applications. Size, much more than for liposomes, will influence the pharmacokinetics, and therefore, long circulating preparations should be well below 100 nm.