期刊
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
卷 102, 期 1, 页码 150-159出版社
WILEY
DOI: 10.1002/jbm.a.34680
关键词
nanoparticles; pullulan; pH-sensitive; hepatic targeting; anti-cancer
资金
- National Natural Science Foundation of China [50973071, 21174090]
pH-sensitive pullulan-doxorubicin (DOX) conjugates were synthesized by attaching DOX onto pullulan derivate through hydrazone bond that was stable under neutral environment but readily cleaved under mildly acidic condition. By changing the feed ratio of DOX to the pullulan derivate, conjugates with drug-loading content up to 30 wt % were obtained. In aqueous solution, the conjugates spontaneously formed uniform core-shell structured nanoparticles with DOX as core and pullulan as shell. The diameters of the nanoparticles ranged from 50 to 110 nm according to the drug-loading content. In vitro releasing experiments showed that more than 75% DOX released within 2 h at pH 5.0, while less than 15% DOX released after 12 h at pH 7.4. This pH-responsive manner of DOX release might assist the quick diffusion of DOX from the acidic endosome/lysosome and the intracellular transfer into the nucleus. Pullulan on the nanoparticles surface provided the nanoparticles with active targeting property to hepatic cells through specific interaction with asialoglycoprotein receptors on the membrane of hepatic cells, without the necessity of introducing any extra ligand. These pullulan-DOX conjugate nanoparticles were expected to be promising drug delivery system for liver targeting antitumor chemotherapy. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 150-159, 2014.
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