使用对比增强磁共振成像对聚(L-谷氨酸)体内药物递送进行无创可视化。
Noninvasive visualization of in vivo drug delivery of poly(L-glutamic acid) using contrast-enhanced MRI.
作者信息
Ye Furong, Ke Tianyi, Jeong Eun-Kee, Wang Xuli, Sun Yongen, Johnson Melody, Lu Zheng-Rong
机构信息
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84108, USA.
出版信息
Mol Pharm. 2006 Sep-Oct;3(5):507-15. doi: 10.1021/mp060052g.
Biomedical imaging is valuable for noninvasive investigation of in vivo drug delivery with polymer conjugates. It can provide real-time information on pharmacokinetics, biodistribution, and drug delivery efficiency of the conjugates. Noninvasive visualization of in vivo drug delivery of polymer conjugates with contrast-enhanced magnetic resonance imaging (MRI) was studied with paramagnetically labeled poly(L-glutamic acid) in an animal tumor model. Poly(L-glutamic acid) is a biocompatible and biodegradable drug carrier for diagnostics and therapeutics. Poly(L-glutamic acid)-1,6-hexanediamine--(Gd-DO3A) conjugates with molecular weights of 87, 50, and 28 kDa and narrow molecular weight distributions were prepared and studied in mice bearing MDA-MB-231 human breast cancer xenografts. Contrast-enhanced MRI resulted in real-time and three-dimensional visualization of blood circulation, pharmacokinetics, biodistribution, and tumor accumulation of the conjugates, and the size effect on these pharmaceutics properties. The conjugate of 28 kDa rapidly cleared from the circulation and had a relatively lower tumor accumulation. The conjugates with higher molecular weights exhibited a more prolonged blood circulation and higher tumor accumulation. The difference between the conjugates of 87 and 50 kDa was not significant. Contrast-enhanced MRI is effective for noninvasive real-time visualization of in vivo drug delivery of paramagnetically labeled polymer conjugates.
生物医学成像对于使用聚合物偶联物进行体内药物递送的非侵入性研究具有重要价值。它可以提供有关偶联物的药代动力学、生物分布和药物递送效率的实时信息。在动物肿瘤模型中,利用顺磁性标记的聚(L-谷氨酸)研究了通过对比增强磁共振成像(MRI)对聚合物偶联物体内药物递送进行的非侵入性可视化。聚(L-谷氨酸)是一种用于诊断和治疗的生物相容性和可生物降解的药物载体。制备了分子量分别为87、50和28 kDa且分子量分布狭窄的聚(L-谷氨酸)-1,6-己二胺-(钆-二乙三胺五乙酸)偶联物,并在携带MDA-MB-231人乳腺癌异种移植瘤的小鼠中进行了研究。对比增强MRI实现了对偶联物的血液循环、药代动力学、生物分布和肿瘤蓄积以及这些药学性质的尺寸效应的实时三维可视化。28 kDa的偶联物迅速从循环中清除,肿瘤蓄积相对较低。分子量较高的偶联物表现出更长的血液循环时间和更高的肿瘤蓄积。87 kDa和50 kDa偶联物之间的差异不显著。对比增强MRI对于顺磁性标记的聚合物偶联物体内药物递送的非侵入性实时可视化是有效的。