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Issue 24, 2009
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Reversibly crosslinked temperature-responsive nano-sized polymersomes: synthesis and triggered drug release

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Abstract

Water-soluble temperature responsive triblock copolymers, poly(ethylene oxide)-b-poly(acrylic acid)-b-poly(N-isopropylacrylamide) (PEO-PAA-PNIPAM), were prepared in one pot by sequential reversible addition–fragmentation chain-transfer (RAFT) polymerization using a PEO–trithiocarbonate (PEO–S-1-dodecyl-S-(R,R-dimethyl-R-aceticacid) trithiocarbonate) as a macro chain transfer agent. The block copolymers with MnPEO of 5 kDa, MnPAA of 0.35–1.45 kDa, and MnPNIPAM varying from 11–39 kDa were freely soluble in water as unimers at room temperature, but quickly self-assembled into nano-sized vesicles (about 220 nm) when raising the solution temperature to 37 °C. The vesicular structure was confirmed by confocal scanning laser microscope (CSLM) and static light scattering (SLS) measurements. The size and size distribution of the polymersomes depended on the solution concentration, the molecular weight of PNIPAM, the equilibrium time and shaking. Interestingly, thus-formed vesicles could be readily cross-linked at the interface using cystamineviacarbodiimide chemistry. The crosslinked polymersomes, while showing remarkable stability against dilution, organic solvent, high salt conditions and change of temperature in water, were otherwise rapidly dissociated under reductive conditions mimicking intracellular environment. Notably, FITC–dextran, used as a model protein, was shown to be encapsulated into the polymersomes with an unprecedently high loading efficiency (>85 wt%). The release studies showed that most FITC–dextran was retained within the polymersomes after lowering the temperature to 25 °C. However, in the presence of 10 mM dithiothreitol (DTT), fast release of FITC–dextran was achieved. These reversibly crosslinked temperature responsive nano-sized polymersomes are highly promising as smart carriers for triggered intracellular delivery of biopharmaceutics such as pDNA, siRNA, pharmaceutical proteins and peptides.

Graphical abstract: Reversibly crosslinked temperature-responsive nano-sized polymersomes: synthesis and triggered drug release

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Supplementary files

Article information


Submitted
19 Jan 2009
Accepted
01 Apr 2009
First published
11 May 2009

J. Mater. Chem., 2009,19, 4183-4190
Article type
Paper

Reversibly crosslinked temperature-responsive nano-sized polymersomes: synthesis and triggered drug release

H. Xu, F. Meng and Z. Zhong, J. Mater. Chem., 2009, 19, 4183
DOI: 10.1039/B901141B

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