Department of General Biophysics, University of Lodz, Lodz, Poland.
J Biomed Mater Res A. 2011 Nov;99(2):261-8. doi: 10.1002/jbm.a.33196. Epub 2011 Aug 16.
Dendrimers are highly branched macromolecules with the potential to be used for biomedical applications. Several dendrimers are toxic owing to their positively charged surfaces. However, this toxicity can be reduced by coating these peripheral cationic groups with carbohydrate residues. In this study, the toxicity of three types of 4th generation poly (propyleneimine) dendrimers were investigated in vivo; uncoated (PPI-g4) dendrimers, and dendrimers in which 25% or 100% of surface amino groups were coated with maltotriose (PPI-g4-25%m or PPI-g4-100%m), were administered to Wistar rats. Body weight, food and water consumption, and urine excretion were monitored daily. Blood was collected to investigate biochemical and hematological parameters, and the general condition and behavior of the animals were analyzed. Unmodified PPI dendrimers caused changes in the behavior of rats, a decrease in food and water consumption, and lower body weight gain. In the case of PPI-g4 and PPI-g4-25%m dendrimers, disturbances in urine and hematological and biochemical profiles returned to normal during the recovery period. PPI-g4-100%m was harmless to rats. The PPI dendrimers demonstrated dose- and sugar-modification-degree dependent toxicity. A higher dose of uncoated PPI dendrimers caused toxicity, but surface modification almost completely abolished this toxic effect.
树状聚合物是具有潜在生物医学应用的高度支化大分子。由于其带正电荷的表面，一些树状聚合物具有毒性。然而，通过用碳水化合物残基覆盖这些外围阳离子基团，可以降低这种毒性。在这项研究中，体内研究了三种类型的第四代聚（丙烯亚胺）树状聚合物的毒性；未涂层（PPI-g4）树状聚合物，以及其中 25%或 100%表面氨基被麦芽糖三糖覆盖的树状聚合物（PPI-g4-25%m 或 PPI-g4-100%m），被施用于 Wistar 大鼠。每天监测体重、食物和水的消耗以及尿液排泄情况。采集血液以研究生化和血液学参数，并分析动物的一般状况和行为。未修饰的 PPI 树状聚合物导致大鼠行为改变、食物和水消耗减少以及体重增加减少。在 PPI-g4 和 PPI-g4-25%m 树状聚合物的情况下，尿液和血液学及生化特征的紊乱在恢复期恢复正常。PPI-g4-100%m 对大鼠无害。PPI 树状聚合物表现出剂量和糖修饰程度依赖性毒性。未涂层 PPI 树状聚合物的较高剂量会引起毒性，但表面修饰几乎完全消除了这种毒性作用。
