期刊
CARBOHYDRATE POLYMERS
卷 98, 期 1, 页码 181-188出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2013.05.077
关键词
Hyaluronic acid; PEGylation; Reduction/pH dual-sensitivity; Doxorubicin; Nanoparticle; Targeted drug delivery
资金
- National Natural Science Foundation of China [50773062, 50603020]
- Natural Science Basic Research Plan in Shaanxi Province of China [SJ08-ZT12, 2011K13-01-09]
- Fundamental Research Funds for the Central Universities [xjj20100115, xjj2012146]
To minimize the side effect of chemotherapy, a novel reduction/pH dual-sensitive drug nanocarrier, based on PEGylated dithiodipropionate dihydrazide (TPH)-modified hyaluronic acid (PEG-SS-HA copolymer), was developed for targeted delivery of doxorubicin (DOX) to hepatocellular carcinoma. The copolymer was synthesized by reductive amination via Schiffs base formation between TPH-modified HA and galactosamine-conjugated poly(ethylene glycol) aldehyde/methoxy poly(ethylene glycol) aldehyde. Conjugation of DOX to PEG-SS-HA copolymer was accomplished through the hydrazone linkage formed between DOX and PEG-SS-HA, and confirmed by FTIR and H-1 NMR spectra. The polymer-DOX conjugate could self-assemble into spherical nanoparticles (similar to 150 nm), as indicated by TEM and DLS. In vitro release studies showed that the DOX-loaded nanoparticles could release DOX rapidly under the intracellular levels of pH and glutathiose. Cellular uptake experiments demonstrated that the nanoparticles could be efficiently internalized by HepG2 cells. These results indicate that the PEG-SS-HA copolymer holds great potential for targeted intracellular delivery of DOX. (C) 2013 Elsevier Ltd. All rights reserved.
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