Tissue distribution and pharmacokinetics of stable polyacrylamide nanoparticles following intravenous injection in the rat.
Tissue distribution and pharmacokinetics of stable polyacrylamide nanoparticles following intravenous injection in the rat.
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大鼠静脉注射后稳定的聚丙烯酰胺纳米颗粒的组织分布和药代动力学。
DOI：
10.1016/j.taap.2010.11.017
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发表时间：
2011-03-15
影响因子：
3.8
通讯作者：
Philbert MA
中科院分区：
文献类型：
--
作者：
Wenger Y;Schneider RJ 2nd;Reddy GR;Kopelman R;Jolliet O;Philbert MA
各种聚合物纳米颗粒（NP）正在开发用于成像和治疗用途。然而，人们对他们的行为知之甚少。本研究检查了稳定的聚丙烯酰胺（PAA）纳米颗粒（平均直径约31 nm）的药代动力学、分布和消除。将PAA-NP和聚乙二醇涂覆的PAA-NP注射到健康雄性大鼠的尾静脉中。在5分钟至120小时的时间范围内采集血液、组织和排泄物，并对其放射性含量进行定量。然后应用数学模型分析两种NP的分布动态。血液中的消除可以通过快速但有限的迁移到主要器官（约20%，半衰期为0.6至1.3小时）和较慢的分布到尸体（约70%，半衰期为35至43小时）来解释。尿排泄水平与血药浓度相关。在120 h时，合并累积尿和粪便排出量占剂量的6%以下。与其他五种聚合物纳米颗粒相比，所研究的颗粒具有最高的半衰期和曲线下面积（4000至5000%-h）。当纳米颗粒尺寸从30 nm增加到250 nm时，这两个参数降低了三个数量级。对于类似的尺寸，聚乙二醇化的纳米颗粒在血液中比非聚乙二醇化的纳米颗粒更持久，但这种差异在30 nm和相对高的剂量范围内比在100 nm以上小得多。PAA NP的持久性与通过炎症和细胞损伤的典型血清标志物测量的急性毒性体征无关。
A variety of polymer nanoparticles (NP) are under development for imaging and therapeutic use. However, little is known about their behavior. This study examined pharmacokinetics, distribution and elimination of stable polyacrylamide (PAA) nanoparticles (~31 nm average diameter). PAA-NPs and polyethylene glycol-coated PAA-NPs were injected into the tail veins of healthy male rats. Blood, tissues and excreta were collected at times ranging from 5 minutes to 120 hours and their radioactive content was quantified. A mathematical model was then applied to analyze the distribution dynamics of both NPs. Elimination from the blood could be accounted for by a quick but finite relocation to the major organs (about 20%, 0.6 to 1.3h half-lives), and a slower distribution to the carcass (about 70%, 35 to 43h half-lives). Excreted urinary levels correlated with blood concentrations. Combined cumulative urinary and fecal output accounted for less than 6% of the dose at 120h. Compared to five other polymeric nanoparticles, the studied particles are at the highest half-lives and Area Under the Curve (4000 to 5000 %-h). These two parameters decrease by three orders of magnitude when nanoparticle size increases from the 30 nm range up to 250 nm. For similar sizes, pegylated nanoparticles are more persistent in the blood than non pegylated ones, but this difference is much smaller in the 30 nm and relatively high dose range than above 100 nm. Persistence of PAA NPs is not associated with acute toxicity signs as measured by typical serum markers of inflammation and cellular damage.
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影响因子：
2.7
作者：
Kopelman, R;Koo, YEL;Ross, BD
通讯作者：
Ross, BD
影响因子：
2.8
作者：
Moffat, Bradford A;Reddy, G Ramachandra;Ross, Brian D
通讯作者：
Ross, Brian D
影响因子：
4.9
作者：
Li, Shyh-Dar;Huang, Leaf
通讯作者：
Huang, Leaf
影响因子：
7.4
作者：
Clark, HA;Kopelman, R;Philbert, MA
通讯作者：
Philbert, MA
影响因子：
4.5
作者：
Kreuter, J;Shamenkov, D;Alyautdin, R
通讯作者：
Alyautdin, R