The liver-targeting study of the N-galactosylated chitosan in vivo and in vitro.
In order to study the liver targeting of the N-galactosylated chitosan (GC) polymer in liver, we first conjugated the lactobionic acid with chitosan (CS) to obtain the carrier of GC with different degree of substitution of lactosyl group. Western blot was performed to detect the expression levels of the asialoglycoprotein receptors (ASGPR) in the cell lines of HepG2, SMMC-7721, and HL-7702. The protein level of ASGPR was lower in HepG2 compared to HL-7702 and SMMC-7721. Although all treated by CS, viabilities of HL-7702 and HepG2 did not experience any significant drop, while viability of SMMC-7721 decreased 15% on average from control. It was the first data about the inhibitory effect of GC on the liver cells. Fluorescein isothiocyanate (FITC) labeled GC (GC-FITC) was injected intravenously into mice at a dose of 0.02 μmol/mouse. GC-FITC showed maximum liver localization at 5 min and even detectable at 48 h after injection. Further, the accumulation of GC in liver was about 5.4-fold higher than that of CS. In conclusion, GC demonstrated its higher efficacy in drug liver targeting and thus could be a more promising drug or gene carrier in future therapies.
Institute of Materia Medica, Zhejiang Academy of Medical Sciences , Hangzhou , P. R. China.
Meihao
M
Liang
Xiaoliang
X
Zheng
Linglan
L
Tu
Zhen
Z
Ma
Zunyuan
Z
Wang
Dongmei
D
Yan
Zhengrong
Z
Shen
D061605:Administration, Intravenous; D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D004187:Disaccharides / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR
D037263:Asialoglycoprotein Receptor; D004187:Disaccharides; C005608:lactobionic acid; D048271:Chitosan
N-galactosylated chitosan; asialoglycoprotein; chitosan; liver-targeting; polymer carrier; receptor