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High drug loading pH‐sensitive pullulan‐DOX conjugate nanoparticles for hepatic targeting
Author(s) -
Li Huanan,
Bian Shaoquan,
Huang Yihang,
Liang Jie,
Fan Yujiang,
Zhang Xingdong
Publication year - 2014
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.34680
Subject(s) - pullulan , conjugate , asialoglycoprotein receptor , drug delivery , nanoparticle , doxorubicin , materials science , biophysics , drug carrier , combinatorial chemistry , chemistry , nuclear chemistry , in vitro , biochemistry , nanotechnology , polysaccharide , chemotherapy , hepatocyte , medicine , mathematical analysis , mathematics , surgery , biology
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. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 150–159, 2014.