Enhanced Stability of Polymeric Micelles Based on Postfunctionalized Poly(ethylene glycol)-b-poly(γ-propargyl l-glutamate): The Substituent Effect
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Author(s)
Zhao, Xiaoyong
Poon, Zhiyong
Engler, Amanda C.
Bonner, Daniel K.
Hammond, Paula T
Date Issued
May 2012
Journal
Biomacromolecules
Publisher
American Chemical Society
Citation
Zhao, Xiaoyong, Zhiyong Poon, Amanda C. Engler, Daniel K. Bonner, and Paula T. Hammond. Enhanced Stability of Polymeric Micelles Based on Postfunctionalized Poly(ethylene Glycol)-b-poly(γ-propargyl L-glutamate): The Substituent Effect. Biomacromolecules 13, no. 5 (May 14, 2012): 1315-1322.
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Author's final manuscript
Abstract
One of the major obstacles that delay the clinical translation of polymeric micelle drug delivery systems is whether these self-assembled micelles can retain their integrity in blood following intravenous (IV) injection. The objective of this study was to evaluate the impact of core functionalization on the thermodynamic and kinetic stability of polymeric micelles. The combination of ring-opening polymerization of N-carboxyanhydride (NCA) with highly efficient “click” coupling has enabled easy and quick access to a family of poly(ethylene glycol)-block-poly(γ-R-glutamate)s with exactly the same block lengths, for which the substituent “R” is tuned. The structures of these copolymers were carefully characterized by [superscript 1]H NMR, FT-IR, and GPC. When pyrene is used as the fluorescence probe, the critical micelle concentrations (CMCs) of these polymers were found to be in the range of 10[superscript –7]–10[superscript –6] M, which indicates good thermodynamic stability for the self-assembled micelles. The incorporation of polar side groups in the micelle core leads to high CMC values; however, micelles prepared from these copolymers are kinetically more stable in the presence of serum and upon SDS disturbance. It was also observed that these polymers could effectively encapsulate paclitaxel (PTX) as a model anticancer drug, and the micelles possessing better kinetic stability showed better suppression of the initial “burst” release and exhibited more sustained release of PTX. These PTX-loaded micelles exerted comparable cytotoxicity against HeLa cells as the clinically approved Cremophor PTX formulation, while the block copolymers showed much lower toxicity compared to the cremophor–ethanol mixture. The present work demonstrated that the PEG-b-PPLG can be a uniform block copolymer platform toward development of polymeric micelle delivery systems for different drugs through the facile modification of the PPLG block.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1021/bm201873u
