Noninvasive Visualization of in Vivo Drug Delivery of Poly(L-glutamic acid) Using Contrast-Enhanced MRI

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• 作者：Furong Ye ; Tianyi Ke ; Eun-Kee Jeong ; Xuli Wang ; Yongen Sun ; Melody Johnson ; Zheng-Rong Lu
• 刊名：Molecular Pharmaceutics
• 出版年：2006
• 出版时间：October 2006
• 年：2006
• 卷：3
• 期：5
• 页码：507 - 515
• 全文大小：428K
• 年卷期：v.3,no.5(October 2006)
• ISSN：1543-8392

文摘

Biomedical imaging is valuable for noninvasive investigation of in vivo drug deliverywith polymer conjugates. It can provide real-time information on pharmacokinetics, biodistribution,and drug delivery efficiency of the conjugates. Noninvasive visualization of in vivo drug deliveryof polymer conjugates with contrast-enhanced magnetic resonance imaging (MRI) was studiedwith paramagnetically labeled poly(L-glutamic acid) in an animal tumor model. Poly(L-glutamicacid) 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 bearingMDA-MB-231 human breast cancer xenografts. Contrast-enhanced MRI resulted in real-timeand three-dimensional visualization of blood circulation, pharmacokinetics, biodistribution, andtumor 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 tumoraccumulation. The conjugates with higher molecular weights exhibited a more prolonged bloodcirculation and higher tumor accumulation. The difference between the conjugates of 87 and50 kDa was not significant. Contrast-enhanced MRI is effective for noninvasive real-timevisualization of in vivo drug delivery of paramagnetically labeled polymer conjugates.