Biodistribution, clearance, and biocompatibility of iron oxide magnetic nanoparticles in rats
Biodistribution, clearance, and biocompatibility of iron oxide magnetic nanoparticles in rats
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DOI：
10.1021/mp7001285
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发表时间：
2008-03-01
影响因子：
4.9
通讯作者：
Labhasetwar, Vinod
中科院分区：
文献类型：
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作者：
Jain, Tapan K.;Reddy, Maram K.;Labhasetwar, Vinod
磁性纳米粒子的生物分布、清除率和生物相容性是确保其安全临床应用的关键。我们使用新型氧化铁MNP制剂研究了这些方面，该制剂可用作磁共振成像（MRI）剂和药物载体系统。对大鼠静脉内给予MNP后3周内分析血清和组织铁水平的变化。血清丙氨酸氨基转移酶（ALT），天冬氨酸氨基转移酶（AST），碱性磷酸酶（AKP）水平，和总铁结合力（TIBC）也随着时间的推移，以评估对肝功能的影响MNP。还分析了所选组织的氧化应激，并进行了组织学研究，以确定MNP的生物相容性。血清铁水平逐渐增加，长达1周，但此后水平缓慢下降。铁在各种身体组织中的生物分布随时间而变化，但注射的铁在肝脏和脾脏中的比例大于在脑、心脏、肾脏和肺中的比例。肝脏和脾脏样品的磁化强度测量显示3周内稳定下降，表明颗粒降解。血清显示在MNP注射后6-24小时内ALT、AST、AKP水平和TIBC短暂升高。氧化应激的增加是组织依赖性的，在3天左右达到峰值，然后缓慢下降。在第1天和第7天采集的肝脏、脾脏和肾脏样本的组织学分析显示无明显异常变化。总之，我们的MNP不会引起肝酶水平的长期变化或诱导氧化应激，因此可以安全地用于药物递送和成像应用。
It is essential to determine the biodistribution, clearance, and biocompatibility of magnetic nanoparticles (MNPs) for in vivo biomedical applications to ensure their safe clinical use. We have studied these aspects with our novel iron oxide MNP formulation, which can be used as a magnetic resonance imaging (MRI) agent and a drug carrier system. Changes in serum and tissue iron levels were analyzed over 3 weeks after intravenous administration of MNPs to rats. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP) levels, and total iron-binding capacity (TIBC) were also measured with time to assess the effect of MNPs on liver function. Selected tissues were also analyzed for oxidative stress and studied histologically to determine biocompatibility of MNPs. Serum iron levels gradually increased for up to 1 week but levels slowly declined thereafter. Biodistribution of iron in various body tissues changed with time but greater fraction of the injected iron localized in the liver and spleen than in the brain, heart, kidney, and lung. Magnetization measurements of the liver and spleen samples showed a steady decrease over 3 weeks, suggesting particle degradation. Serum showed a transient increase in ALT, AST, AKP levels, and TIBC over a period of 6-24 h following MNP injection. The increase in oxidative stress was tissue dependent, reaching a peak at similar to 3 days and then slowly declining thereafter. Histological analyses of liver, spleen, and kidney samples collected at 1 and 7 days showed no apparent abnormal changes. In conclusion, our MNPs did not cause long-term changes in the liver enzyme levels or induce oxidative stress and thus can be safely used for drug delivery and imaging applications.