Sjöholm I, Edman P
J Pharmacol Exp Ther. 1979 Dec;211(3):656-62.
Microspheres of 14C-labeled highly cross-linked polyacrylamide (mean diameter 0.25-0.30 micron) have been prepared by emulsion polymerization. The label was introduced in the polymer via the cross-linking monomer. N,N'-[14C]methylenebisacrylamide. The microparticles were used to follow qualitatively and quantitatively the distribution and the fate of polyacrylamide in mouse and rat after i.v. and i.p. injection. The polyacrylamide particles are rapidly cleared from the circulation (t 1/2 in rat approximately 40 min) by macrophages of the reticuloendothelial system. They are mainly (about 80%) found in the liver and spleen both after i.v. and i.p. injection (4.1 mg given totally to mice weighing 20-25 g). They can also be detected early (1 hr after i.v. injection) in the bone marrow, and particle aggregates are also initially found in the lungs, although no respiratory problems were noted. After about 16 weeks, the radioactivity rapidly decreases in the liver and spleen, with t 1/2 10 to 14 weeks and 15 to 24 weeks, respectively, depending on the route of administration. Radioactivity in the gut and gut walls detected 2 months after injection suggests that the polyacrylamide is slowly metabolized. No toxic effects-apart from transient hepatospleenomegaly-were detected in mice 45 weeks after they were given a total of 9.8 mg of polyacrylamide.
通过乳液聚合制备了14C标记的高度交联聚丙烯酰胺微球(平均直径0.25 - 0.30微米)。标记物通过交联单体N,N'-[14C]亚甲基双丙烯酰胺引入聚合物中。这些微粒用于定性和定量追踪静脉注射和腹腔注射后聚丙烯酰胺在小鼠和大鼠体内的分布及归宿。聚丙烯酰胺颗粒通过网状内皮系统的巨噬细胞迅速从循环中清除(大鼠的半衰期约为40分钟)。静脉注射和腹腔注射后(给体重20 - 25克的小鼠总共注射4.1毫克),它们主要(约80%)分布在肝脏和脾脏中。静脉注射后1小时也能在骨髓中早期检测到它们,并且最初在肺部也能发现颗粒聚集体,尽管未观察到呼吸问题。大约16周后,肝脏和脾脏中的放射性迅速下降,根据给药途径不同,半衰期分别为10至14周和15至24周。注射2个月后在肠道和肠壁中检测到的放射性表明聚丙烯酰胺在缓慢代谢。给小鼠总共注射9.8毫克聚丙烯酰胺45周后,除了短暂的肝脾肿大外,未检测到其他毒性作用。