Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA.
Pharm Res. 2004 Mar;21(3):476-83. doi: 10.1023/B:PHAM.0000019302.26097.cc.
To determine the in vivo biodistribution for differently charged poly(amidoamine) (PAMAM) dendrimers in B16 melanoma and DU145 human prostate cancer mouse tumor model systems.
Neutral (NSD) and positive surface charged (PSD) generation 5 (d = 5 nm) PAMAM dendrimers were synthesized by using 3H-labeled acetic anhydride and tested in vivo. Dendrimer derivatives were injected intravenously, and their biodistribution was determined via liquid scintillation counting of tritium in tissue and excretory samples. Mice were also monitored for acute toxicity.
Both PSD and NSD localized to major organs and tumor. Dendrimers cleared rapidly from blood, with deposition peaking at 1 h for most organs and stabilizing from 24 h to 7 days postinjection. Maximal excretion occurred via urine within 24 h postinjection. Neither dendrimer showed acute toxicity.
Changes in the net surface charge of polycationic PAMAMs modify their biodistribution. PSD deposition into tissues is higher than NSD, although the biodistribution trend is similar. Highest levels were found in lungs, liver, and kidney, followed by those in tumor, heart, pancreas, and spleen, while lowest levels were found in brain. These nanoparticles could have future utility as systemic biomedical delivery devices.
在 B16 黑色素瘤和 DU145 人前列腺癌小鼠肿瘤模型系统中，确定不同带电多臂聚酰胺-胺（PAMAM）树枝状聚合物的体内生物分布。
通过使用 3H 标记的乙酸酐合成中性（NSD）和正表面带电（PSD）第 5 代（d = 5nm）PAMAM 树枝状聚合物，并进行体内测试。树枝状聚合物衍生物经静脉注射，通过组织和排泄样品中氚的液体闪烁计数来确定其生物分布。还监测了小鼠的急性毒性。
PSD 和 NSD 均定位于主要器官和肿瘤。树枝状聚合物从血液中迅速清除，大多数器官在 1 小时达到沉积峰值，并在注射后 24 小时至 7 天内稳定。最大排泄发生在注射后 24 小时内通过尿液。两种树枝状聚合物均无急性毒性。
聚阳离子 PAMAM 净表面电荷的变化改变了它们的生物分布。PSD 进入组织的沉积量高于 NSD，尽管生物分布趋势相似。在肺部、肝脏和肾脏中发现的水平最高，其次是肿瘤、心脏、胰腺和脾脏，而在大脑中发现的水平最低。这些纳米粒子将来可能作为全身生物医学给药装置具有应用潜力。
