The clearance and biodistribution of magnetic composite nanoparticles in healthy and osteoarthritic rat knees.
The clearance and biodistribution of magnetic composite nanoparticles in healthy and osteoarthritic rat knees.
复制标题
磁性复合纳米粒子在健康及骨关节炎大鼠膝关节的清除及生物分布。
DOI：
10.1016/j.jconrel.2020.01.052
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发表时间：
2020-05-10
期刊：
影响因子：
--
通讯作者：
Allen KD
中科院分区：
文献类型：
--
作者：
Partain BD;Unni M;Rinaldi C;Allen KD
关节内注射是治疗骨关节炎(OA)的最直接途径，但药物载体在关节内的分布仍未得到充分研究。为此，我们开发了一种磁性复合纳米颗粒，可以通过体内成像系统(IVIS)进行体内荧光跟踪，并通过电子顺磁共振(EPR)光谱进行体外定量。使用该颗粒，在内侧半月板横断模型(5、10和15月龄雄性Lewis大鼠)中，评估了年龄和OA发病机制对颗粒清除和分布的影响。半月板切断后9周，注射复合纳米颗粒，通过IVIS评估关节间隙。注射后2周处死动物，用电子顺磁共振波谱分析颗粒在体内的分布。IVIS和EPR波谱数据表明，14天后关节内仍有大量颗粒。EPR波谱数据表明，与对侧对照相比，膝盖骨关节炎的颗粒清除更慢，15月龄大鼠的颗粒清除速度比5月龄和10月龄大鼠的慢。这项研究证明了在评估纳米颗粒关节内给药时，将年龄和骨关节炎作为因素的重要性。
Intra-articular injections are the most direct route for administering osteoarthritis (OA) therapies, yet how drug carriers distribute within the joint remains understudied. To this end, we developed a magnetic composite nanoparticle that can be tracked with fluorescence in vivo via an in vivo imaging system (IVIS), and quantified ex vivo via electron paramagnetic resonance (EPR) spectroscopy. Using this particle, the effects of age and OA pathogenesis on particle clearance and distribution were evaluated in the medial meniscus transection model of OA (5-, 10-, and 15-month old male Lewis rats). At 9 weeks after meniscus transection, composite nanoparticles were injected and joint clearance was assessed via IVIS. At 2 weeks after injection, animals were euthanized and particle distribution was quantified ex vivo via EPR spectroscopy. IVIS and EPR spectroscopy data indicate a predominant amount of particles remained in the joint after 14 days. EPR spectroscopy data suggests particles cleared more slowly from OA knees than from the contralateral control, with particles clearing more slowly from 15-month old rats than from 5- and 10-month old rats. This study demonstrates the importance of including both age and OA as factors when evaluating nanoparticles for intra-articular drug delivery.
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