Noninvasive visualization of in vivo drug delivery of poly(L-glutamic acid) using contrast-enhanced MRI.
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.
Ye
Furong
F
Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84108, USA.
Ke
Tianyi
T
Jeong
Eun-Kee
EK
Wang
Xuli
X
Sun
Yongen
Y
Johnson
Melody
M
Lu
Zheng-Rong
ZR
D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D008970:Molecular Weight; D011099:Polyglutamic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
D003287:Contrast Media; D011099:Polyglutamic Acid