期刊
BIOMACROMOLECULES
卷 12, 期 1, 页码 145-155出版社
AMER CHEMICAL SOC
DOI: 10.1021/bm101080p
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资金
- Canadian Institutes of Health Research (CIHR)
- Natural Sciences and Engineering Research Council of Canada
- Michael Smith Foundation for Health Research
- Canadian Blood Services
- Canada Foundation for Innovation
- CIHR/CBS
- Centre for Drug Research and Development
Hyperbranched polyglycerols (HPGs) with hydrophobic cores and derivatized with methoxy poly(ethylene glycol) were synthesized and further functionalized with carboxylate groups to bind and deliver cisplatin. Low and high levels of carboxylate were conjugated to HPGs (HPG-C-8/10-MePEG(6.5)-COOH113 and HPG-C-8/10-MePEG(6.5)-COOH348) and their structures were confirmed through NMR and FTIR spectroscopy and potentiometric titration. The hydrodynamic diameter of the HPGs ranged from 5-10 nm and the addition of COOH groups decreased the zeta potential of the, polymers. HPG-C-8/10-MePEG(6.5)-COOH113 bound up to 10% w/w cisplatin, whereas HPG-C-8/10-MePEG(6.5)-COOH348 bound up to 20% w/w drug with 100% efficiency. Drug was released from HPG-C-8/10-MePEG(6.5)-COOH348 over 7 days at the same rate, regardless of the pH. Cisplatin release from HPG-C-8/10-MePEG(6.5)-COOH348 was significantly slower than HPG-C-8/10-MePEG(6.5)-COOH113 at pH 6 and 7.4, but similar at pH 4.5. Release of cisplatin into artificial urine was considerably faster than into buffer. Carboxylated HPGs demonstrated good biocompatibility, and drug-loaded HPGs effectively inhibited proliferation of KU-7-luc bladder cancer cells.
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