Body distribution of poly(D,L-lactide-co-glycolide) copolymer degradation products in rats
Body distribution of poly(D,L-lactide-co-glycolide) copolymer degradation products in rats
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DOI：
10.1007/s10856-008-3460-z
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发表时间：
2008-10-01
影响因子：
3.7
通讯作者：
Sun, Jiao
中科院分区：
文献类型：
--
作者：
Hua, Nan;Sun, Jiao
聚（D，L-丙交酯-共-乙交酯）（PLGA）共聚物是少数几种批准用于人体的合成聚合物之一，但PLGA衍生的低聚物和颗粒的生物相容性仍然存在疑问。在此，用I-125的氯仿溶液对高分子量PLGA（Mw = 32，000）进行放射性标记，并在Sprague道利大鼠背部皮下植入圆形I-125-PLGA薄膜后，检查PLGA共聚物降解产物的体内分布。在2、4、6、8、10和12周拍摄的PLGA植入物的放射自显影图像显示，膜的中心部分比边缘部分降解得更快。在这些时间点检查体室分布，发现超过一半的放射性从皮肤中回收。剩余放射性集中在血液、肝脏和肾脏中。放射性稳定地出现在血液中，并在植入后12周内保持升高，而肝脏至肾脏的分布在6周后开始减少。这些结果累积表明，植入部位降解颗粒和碎片的清除极其延迟。此外，降解产物从植入部位释放到血流中后，降解颗粒和碎片选择性地集中在肝脏和肾脏中。
Poly (D,L-lactide-co-glycolide) (PLGA) copolymers are among the few synthetic polymers approved for human use, but the biocompatibility of PLGA-derived oligomers and particles remains questionable. Here, high molecular weight PLGA (Mw = 32,000) was radiolabeled with I-125 in chloroform solution, and the body distribution of PLGA copolymer degradation products was examined following subcutaneous implantation of round I-125-PLGA films on the back of Sprague Dawley rats. Autoradiographic images of the PLGA implant taken at 2, 4, 6, 8, 10, and 12 weeks revealed that the central portion of the film degraded much more rapidly than the marginal portions. Examination of the body compartment distribution at these time points revealed that over one-half of the radioactivity was recovered from skin. The remaining radioactivity was concentrated in the blood, liver, and kidneys. Radioactivity steadily appeared in the blood and remained elevated up to 12 weeks after implantation, while the liver to kidney distribution began to decrease after 6 weeks. Cumulatively, these results indicate that the clearance of degraded particles and fragments from the implantation site is extremely delayed. Moreover, the degraded particles and fragments were selectively concentrated in the liver and kidneys, following release of degraded products into the bloodstream from the implantation site.