期刊
BIOMACROMOLECULES
卷 9, 期 11, 页码 3321-3331出版社
AMER CHEMICAL SOC
DOI: 10.1021/bm800867n
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资金
- University of New South Wales
- CRC-P (Cooperative Research Center for Polymers)
- ARC (Australian Research Council)
A nucleosides containing block copolymer, poly(polyethylene glycol methyl ether methacrylate)-block-poly(5'-O-methacryloyluridine) (PPEGMEMA(30)-b-PMAU(80)) was self-assembled in aqueous medium and cross-linked via RAFT polymerization at 60 degrees C to afford core-cross-linked micelles exhibiting a PPEGMEMA corona and a polynucleotide core. A disulfide cross-linking agent, bis(2-methacryloyloxyethyl)disulfide, was employed to cross-link the structure via the RAFT process resulting in core-shell nanoparticles, which can degrade under reductive conditions. The resulting core-cross-linked micelles readily hydrolyzed into free block copolymers in the presence of dithiothreitol (DTT) in less than 1 h, depending on the concentration of the reducing agent and the amount of cross-linker in the micelle. A small fraction of permanently cross-linked micelle was found as the result of conventional chain transfer to disulfide containing compounds. A model drug, vitamin B-2, was loaded into the micelle. The loading capacity increased with increasing cross-linking degree. The amount of drug released reached 60-70% after 7 h in the presence of DTT (0.65 mM), while the cross-linked micelle in the absence of dithiothreitol shows only a delayed drug release. Cytotoxicity tests confirmed the biocompatibility of the polymers and the residues after reduction.
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