Non-invasive in vivo evaluation of in situ forming PLGA implants by benchtop magnetic resonance imaging (BT-MRI) and EPR spectroscopy
Non-invasive in vivo evaluation of in situ forming PLGA implants by benchtop magnetic resonance imaging (BT-MRI) and EPR spectroscopy
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DOI：
10.1016/j.ejpb.2009.06.008
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发表时间：
2010-01-01
影响因子：
4.9
通讯作者：
Maeder, Karsten
中科院分区：
文献类型：
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作者：
Kempe, Sabine;Metz, Hendrik;Maeder, Karsten
在本研究中，我们使用台式磁共振成像（BT-MRI）对原位形成聚丙交酯乙交酯（PLGA）植入物进行非侵入性连续体内研究，无需使用造影剂。聚乙二醇（PEG）400被用作临床使用的NMP的替代溶剂。除了 BT-MRI 之外，我们还应用电子顺磁共振 (EPR) 光谱来表征体外和体内植入物形成和药物递送过程。我们能够通过 EPR 和 MPI 跟踪植入物形成的关键过程。由于 EPR 光谱对极性和迁移率敏感，因此我们能够跟踪溶剂/非溶剂交换和 PLGA 沉淀的动力学。由于 PEG 400 的高水亲和力，我们观察到种植体附近有短暂的水积聚。此外，我们通过 BT-MRI 检测到植入物的封装是生物系统对聚合物的反应，随后在两个月内降解。我们可以证明 MPI 总体上有潜力对原位形成植入物的体内命运获得新的见解。该研究还清楚地表明，BT-MRI 是超导 MRI 机器的一种新的可行且便宜得多的替代方案，用于监测小型哺乳动物体内的药物输送过程。 (C) 2009 Elsevier B.V. 保留所有权利。
In the present study, we used benchtop magnetic resonance imaging (BT-MRI) for non-invasive and continuous in vivo studies of in situ forming poly(lactide-co-glycolide) (PLGA) implants without the use of contrast agents. Polyethylene glycol (PEG) 400 was used as an alternative solvent to the clinically used NMP. In addition to BT-MRI, we applied electron paramagnetic resonance (EPR) spectroscopy to characterize implant formation and drug delivery processes in vitro and in vivo.We were able to follow key processes of implant formation by EPR and MPI. Because EPR spectra are sensitive to polarity and mobility, we were able to follow the kinetics of the solvent/non-solvent exchange and the PLGA precipitation. Due to the high water affinity of PEG 400, we observed a transient accumulation of water in the implant neighbourhood. Furthermore, we detected the encapsulation by BT-MRI of the implant as a response of the biological system to the polymer, followed by degradation over a period of two months. We could show that MPI in general has the potential to get new insights in the in vivo fate of in situ forming implants. The study also clearly shows that BT-MRI is a new viable and much less expensive alternative for superconducting MRI machines to monitor drug delivery processes in vivo in small mammals. (C) 2009 Elsevier B.V. All rights reserved.