Kucka Jan, Hrubý Martin, Lebeda Ondrej
Nuclear Physics Institute of the Academy of Sciences of the Czech Republic, Husinec-Rez 130, Rez, CZ-250 68, Czech Republic.
Appl Radiat Isot. 2010 Jun;68(6):1073-8. doi: 10.1016/j.apradiso.2010.01.022. Epub 2010 Jan 15.
Drug delivery systems based on thermoresponsive polymers might serve as suitable carriers for local radiotherapy. We have, therefore, designed and synthesized a radioiodine-labellable thermoresponsive polymer. The polymer was synthesized by copolymerization of N-isopropylacrylamide with N-methacryloyl tyrosinamide in tetrahydrofuran, and then labelled by (131)I. The solution of this labelled polymer in dimethylsulfoxide (4.4 MBq/ml; 1.8 wt% polymer) was applied to femoral muscle of male Balb/C mice (50 microl per animal). The biodistribution and excretion of radioactivity was followed in 2h and 1, 7, 14, 28 and 42 d post injection (n=6 per time point). As expected, the labelled polymer was left on the application site (ca 90% 2h post injection), decreasing slowly to ca 80% within 14 d. At 28 d post injection, ca 70% of the injected activity was still found on the application site, decreasing to ca 60% at 42 d. No organ-specific accumulation of the radioactivity released from the application site, including thyroid, was observed. Majority of the released radioactivity was excreted via urine and faeces. This preliminary study suggests that thermoresponsive polymers could be used as an effective delivery system for localized radiotherapy.
基于热响应性聚合物的药物递送系统可能是局部放射治疗的合适载体。因此,我们设计并合成了一种可放射性碘标记的热响应性聚合物。该聚合物通过N-异丙基丙烯酰胺与N-甲基丙烯酰基酪氨酸酰胺在四氢呋喃中共聚合成,然后用(131)I进行标记。将这种标记聚合物在二甲基亚砜中的溶液(4.4 MBq/ml;1.8 wt%聚合物)应用于雄性Balb/C小鼠的股四头肌(每只动物50微升)。在注射后2小时以及1、7、14、28和42天跟踪放射性的生物分布和排泄情况(每个时间点n = 6)。正如预期的那样,标记聚合物留在应用部位(注射后2小时约为90%),在14天内缓慢降至约80%。注射后28天,在应用部位仍发现约70%的注射活性,在42天时降至约60%。未观察到从应用部位释放的放射性在包括甲状腺在内的任何器官特异性积累。大部分释放的放射性通过尿液和粪便排出。这项初步研究表明,热响应性聚合物可作为局部放射治疗的有效递送系统。