TY - JOUR
T1 - Targeted delivery of atorvastatin via asialoglycoprotein receptor (ASGPR)
AU - Zhang, Youxi
AU - Zhang, Xinfu
AU - Zeng, Chunxi
AU - Li, Bin
AU - Zhang, Chengxiang
AU - Li, Wenqing
AU - Hou, Xucheng
AU - Dong, Yizhou
N1 - Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/6/1
Y1 - 2019/6/1
N2 - Targeted drug delivery platforms can increase the concentration of drugs in specific cell populations, reduce adverse effects, and hence improve the therapeutic effect of drugs. Herein, we designed two conjugates by installing the targeting ligand GalNAc (N-acetylgalactosamine)onto atorvastatin (AT). Compared to the parent drug, these two conjugates, termed G2-AT and G2-K-AT, showed increased hepatic cellular uptake. Moreover, both conjugates were able to release atorvastatin, and consequently showed dramatic inhibition of β-hydroxy-β-methylglutaryl-CoA (HMG-CoA)reductase and increased LDL receptors on cell surface.
AB - Targeted drug delivery platforms can increase the concentration of drugs in specific cell populations, reduce adverse effects, and hence improve the therapeutic effect of drugs. Herein, we designed two conjugates by installing the targeting ligand GalNAc (N-acetylgalactosamine)onto atorvastatin (AT). Compared to the parent drug, these two conjugates, termed G2-AT and G2-K-AT, showed increased hepatic cellular uptake. Moreover, both conjugates were able to release atorvastatin, and consequently showed dramatic inhibition of β-hydroxy-β-methylglutaryl-CoA (HMG-CoA)reductase and increased LDL receptors on cell surface.
KW - Asialoglycoprotein receptor
KW - Atorvastatin
KW - Ligand conjugates
KW - N-Acetylgalactosamine
KW - Targeted delivery
UR - https://www.scopus.com/pages/publications/85064240947
U2 - 10.1016/j.bmc.2019.04.019
DO - 10.1016/j.bmc.2019.04.019
M3 - Article
C2 - 31005367
AN - SCOPUS:85064240947
SN - 0968-0896
VL - 27
SP - 2187
EP - 2191
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 11
ER -