Norcantharidin-associated galactosylated chitosan nanoparticles for hepatocyte-targeted delivery.
In this study a new chitosan (CS) derivative, galactosylated chitosan (GC), was synthesized and used to prepare norcantharidin-associated GC nanoparticles (NCTD-GC NPs) by taking advantage of the ionic cross-linkage between the molecules of the anti-hepatocarcinoma medicine NCTD and of the GC as carrier. NCTD-GC NPs were obtained with average particle size of 118.68 +/- 3.37 nm, entrapment efficiency of 57.92 +/- 0.40%, and drug-loading amount of 10.38 +/- 0.06%. Several important factors influencing the entrapment efficiency, drug-loading amount, and particle size of NCTD-GC NPs were studied. The characteristics of sustained and pH-sensitive release of NCTD from NCTD-GC NPs in vitro were studied. In addition, in vitro cellular uptake and cytotoxicity of nanoparticles to hepatoma cell lines SMMC-7721 and HepG2 were also investigated. In vitro, and compared to CS-based NCTD-CS NPs, NCTD-GC NPs demonstrated satisfactory compatibility with hepatoma cells and strong cytotoxicity against hepatocellular carcinoma cells. In vivo antitumor activity of NCTD-GC NPs was evaluated in mice bearing H22 liver tumors. NCTD-GC NPs displayed tumor inhibition effect in mice, better than either the free NCTD or the NCTD-CS NPs. As a hepatocyte-targeting carrier, GC NPs are potentially promising for clinical applications.


BACKGROUND
In this paper, a galactosylated chitosan (GC), was synthesized and norcantharidin (NCTD)-associated galactosylated chitosan nanoparticles (NCTDGC NPs) were generated by coupling NCTD--an anti-hepatocarcinoma drug--and GC as carrier. Compared to chitosan nanoparticles, NCTD-GC-NPs demonstrated satisfactory compatibility with hepatoma cells and strong cytotoxicity against the cells.
Wang
Qin
Q
Department of Pharmaceutics, School of Pharmacy, Soochow University, Suzhou, China.
Zhang
Liang
L
Hu
Wei
W
Hu
Zhan-Hong
ZH
Bei
Yong-Yan
YY
Xu
Jing-Yu
JY
Wang
Wen-Juan
WJ
Zhang
Xue-Nong
XN
Zhang
Qiang
Q
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000188:drug therapy*; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D005690:Galactose / Q000737:chemistry*; D008113:Liver Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D004337:Drug Carriers; C069741:norcantharidin; D048271:Chitosan; D005690:Galactose