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

Guodong Zhang, Rui Zhang, Xiaoxia Wen, Li Li, Chun Li

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)36-42
Number of pages7
JournalBiomacromolecules
Volume9
Issue number1
DOIs
StatePublished - Jan 2008

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

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