Document Detail


Micelles based on biodegradable poly(L-glutamic acid)-b-polylactide with paramagnetic Gd ions chelated to the shell layer as a potential nanoscale MRI-visible delivery system.
MedLine Citation:
PMID:  18047289     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
There is much interest in the development of a nanoscale drug delivery system with MRI visibility to optimize the delivery efficiency and therapeutic efficacy under image guidance. Here we report on the successful fabrication of nanoscale micelles based on biodegradable poly( L-glutamic acid)- b-polylactide (PG- b-PLA) block copolymer with paramagnetic Gd3+ ions chelated to their shell. PG- b-PLA was synthesized by sequential polymerization reactions: anionic polymerization of L-lactide followed by ring-opening polymerization of benzyl glutamate N-carboxylic anhydride. The metal chelator p-aminobenzyldiethylenetriaminepenta(acetic acid) (DTPA) was readily conjugated to the side chain carboxylic acids of poly( L-glutamic acid). The resulting copolymer formed spherical micelles in aqueous solution with an average diameter of 230 nm at pH 7.4. The size of PG(DTPA)- b-PLA micelles decreased with increasing pH value. DTPA-Gd chelated to the shell layer of the micelles exhibited significantly higher spin-lattice relaxivity (r1) than a small-molecular-weight MRI contrast agent, indicating that water molecules could readily access the Gd ions in the micelles. Because of the presence of multiple carboxylic acid functional groups in the shell layer, polymeric micelles based on biodegradable PG(DTPA-Gd)- b-PLA may be a suitable platform for the development of MRI-visible, targeted nanoscale drug delivery systems.
Authors:
Guodong Zhang; Rui Zhang; Xiaoxia Wen; Li Li; Chun Li
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-11-30
Journal Detail:
Title:  Biomacromolecules     Volume:  9     ISSN:  1526-4602     ISO Abbreviation:  Biomacromolecules     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-14     Completed Date:  2008-03-31     Revised Date:  2013-08-29    
Medline Journal Info:
Nlm Unique ID:  100892849     Medline TA:  Biomacromolecules     Country:  United States    
Other Details:
Languages:  eng     Pagination:  36-42     Citation Subset:  IM    
Affiliation:
Department of Experimental Diagnostic Imaging, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biocompatible Materials*
Gadolinium / chemistry*
Lactic Acid / chemistry*
Magnetic Resonance Spectroscopy / methods*
Mice
Micelles*
Microscopy, Electron, Transmission
NIH 3T3 Cells
Nanotechnology*
Polyglutamic Acid / chemistry*
Polymers / chemistry*
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Spectrophotometry, Infrared
Grant Support
ID/Acronym/Agency:
R01 CA119387/CA/NCI NIH HHS; R01 CA119387/CA/NCI NIH HHS; R01 CA119387-01/CA/NCI NIH HHS; R01 CA119387-02/CA/NCI NIH HHS; R01 CA119387-03/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Biocompatible Materials; 0/Micelles; 0/Polymers; 25513-46-6/Polyglutamic Acid; 26100-51-6/poly(lactic acid); 50-21-5/Lactic Acid; 7440-54-2/Gadolinium
Comments/Corrections

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