Precise delivery of obeticholic acid
10.1016/j.apsb.2020.09.004
- Author:
Guofeng JI
1
;
Lushun MA
1
;
Haochen YAO
2
;
Sheng MA
2
;
Xinghui SI
2
;
Yalin WANG
2
;
Xin BAO
2
;
Lili MA
2
;
Fangfang CHEN
1
;
Chong MA
1
;
Leaf HUANG
3
;
Xuedong FANG
1
;
Wantong SONG
2
Author Information
1. Department of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
2. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
3. Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
- Publication Type:Journal Article
- Keywords:
ALT, alanine aminotransferase;
AST, aspartate aminotransferase;
BUN, blood urea nitrogen;
CDCA, chenodeoxycholic acid;
Cr, creatinine;
FXR, farnesoid X receptor;
Farnesoid X receptor;
H&E, hematoxylin and eosin;
HCC, hepatocellular carcinoma;
HPLC, high-performance liquid chromatography;
HSCs, hepatic stellate cells;
IFN-γ, interferon-γ;
IVIS, in vivo imaging system;
LSECs, liver sinusoidal endothelial cells;
Liver cancer;
Liver sinusoidal endothelial cells;
NE, nanoemulsion;
NKT cells, natural killer T cells;
Nanoemulsion;
OCA, obeticholic acid;
Obeticholic acid;
PBC, primary biliary cholangitis;
TACE, transarterial chemoembolisation;
TSR, tumor suppression rate
- From:
Acta Pharmaceutica Sinica B
2020;10(11):2171-2182
- CountryChina
- Language:English
-
Abstract:
Primary bile acids were reported to augment secretion of chemokine (C‒X‒C motif) ligand 16 (CXCL16) from liver sinusoidal endothelial cells (LSECs) and trigger natural killer T (NKT) cell-based immunotherapy for liver cancer. However, abundant expression of receptors for primary bile acids across the gastrointestinal tract overwhelms the possibility of using agonists against these receptors for liver cancer control. Taking advantage of the intrinsic property of LSECs in capturing circulating nanoparticles in the circulation, we proposed a strategy using nanoemulsion-loaded obeticholic acid (OCA), a clinically approved selective farnesoid X receptor (FXR) agonist, for precisely manipulating LSECs for triggering NKT cell-mediated liver cancer immunotherapy. The OCA-nanoemulsion (OCA-NE) was prepared
