Shell-cross-linked micelles containing cationic polymers synthesized via the RAFT process: Toward a more biocompatible gene delivery system

Zhang, L., Nguyen, T. L. U., Bernard, J., Davis, T. P., Barner-Kowollik, C., & Stenzel, M. H. (2007) Shell-cross-linked micelles containing cationic polymers synthesized via the RAFT process: Toward a more biocompatible gene delivery system. Biomacromolecules, 8(9).

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Abstract

Block copolymers poly(2-(dimethylamino) ethyl methacrylate)-b-poly(polyethylene glycol methacrylate) (PD-MAEMA-b-P(PEGMA)) were prepared via reversible addition fragmentation chain transfer polymerization (RAFT). The polymerization was found to proceed with the expected living behavior resulting in block copolymers with varying block sizes of low polydispersity (PDI < 1.3). The resulting block copolymer was self-assembled in an aqueous environment, leading to the formation of pH-responsive micelles. Further stabilization of the micellar system was performed in water using ethylene glycol dimethacrylate and the RAFT process to cross-link the shell. The cross-linked micelle was found to have properties significantly different from those of the uncross-linked block copolymer micelle. While a distinct critical micelle concentration (CMC) was observed using block copolymers, the CMC was absent in the cross-linked system. In addition, a better stability against disintegration was observed when altering the ionic strength such as the absence of changes of the hydrodynamic diameter with increasing NaCI concentration. Both cross-linked and uncross-linked micelles displayed good binding ability for genes. However, the cross-linked system exhibited a slightly superior tendency to bind oligonucleotides. Cytotoxicity tests confirmed a significant improvement of the biocompatibility of the synthesized cross-linked micelle compared to that of the highly toxic PDMAEMA. The cross-linked micelles were taken up by cells without causing any signs of cell damage, while the PDMAEMA homopolymer clearly led to cell death. © 2007 American Chemical Society.

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ID Code: 99164
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By :90
Export Date: 5 September 2016
CODEN: BOMAF
Correspondence Address: Stenzel, M.H.; Centre for Advanced Macromolecular Design (CAMD), School of Chemical Science and Engineering, The University of New South Wales, Sydney, NSW 2052, Australia; email: camd@unsw.edu.au
Chemicals/CAS: ethylene glycol, 107-21-1; methacrylic acid, 18358-13-9, 79-41-4; sodium chloride, 7647-14-5; 2-(dimethylamino)ethyl methacrylate, 2867-47-2; Acrylic Resins; Biocompatible Materials; Methacrylates; Micelles; Polyethylene Glycols; poly(2-(dimethylamino) ethyl methacrylate)-b-poly(polyethylene glycol methacrylate); polyethylene glycol methacrylate
Keywords: Ethylene glycol dimethacrylate, Reversible addition fragmentation chain transfer, Biocompatibility, Block copolymers, Critical micelle concentration, Crosslinking, Cytotoxicity, Micelles, Oligonucleotides, Polyethylene glycols, Polymerization, Polymethyl methacrylates, Genes, copolymer, ethylene glycol, methacrylic acid, oligonucleotide, poly(polyethylene glycol methacrylate), poly[2 (dimethylamino)ethyl methacrylate], sodium chloride, unclassified drug, animal cell, article, binding affinity, cell death, controlled study, cross linking, cytotoxicity test, gel permeation chromatography, gene delivery system, hydrodynamics, ionic strength, light scattering, micelle, mouse, nonhuman, nuclear magnetic resonance spectroscopy, pH, priority journal, surface tension, synthesis, transmission electron microscopy, Acrylic Resins, Biocompatible Materials, Gene Transfer Techniques, Hydrogen-Ion Concentration, Methacrylates, Molecular Structure
DOI: 10.1021/bm070370g10.1016/ j.polymer.2007.06.048Barner, L., Davis, T.P., Stenzel, M.H., Barner-Kowollik, C., (2007) Macromol. R
ISSN: 15257797
Divisions: Current > Schools > School of Chemistry, Physics & Mechanical Engineering
Current > Institutes > Institute for Future Environments
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Deposited On: 22 Sep 2016 04:50
Last Modified: 11 Oct 2016 04:40

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