Liver targeting of compound liposomes mediated by glycyrrhetinic acid derivative receptor and its effect on hepatic stellate cells.
10.19540/j.cnki.cjcmm.20230605.301
- Author:
Xiu-Li WANG
1
;
Hui-da GUAN
1
;
Shu-Xian QU
1
;
Bo-Wen XUE
2
;
Geng LI
3
;
Xing-Yu LIU
4
;
Li-Sha CHEN
4
;
Heng GU
5
Author Information
1. Beijing University of Chinese Medicine Beijing 102488, China.
2. Southwest University Chongqing 400715, China.
3. Chinese Medicine Regulatory Scientific Research Center of NMPA,China Academy of Chinese Medical Sciences Beijing 100700, China.
4. Technical Center Beijing Workstation, Shanghai Tobacco Group Co., Ltd. Beijing 101121, China.
5. Kunming Hospital of Traditional Chinese Medicine Kunming 650011, China.
- Publication Type:Journal Article
- Keywords:
3-succinate-30-stearyl glycyrrhetinic acid ester;
compound liposome;
hepatic stellate cell;
liver targeting
- MeSH:
Humans;
Liposomes;
Hepatic Stellate Cells;
Glycyrrhetinic Acid/pharmacology*;
Liver;
Liver Cirrhosis/genetics*;
Collagen/pharmacology*
- From:
China Journal of Chinese Materia Medica
2023;48(19):5195-5204
- CountryChina
- Language:Chinese
-
Abstract:
The 3-succinate-30-stearyl glycyrrhetinic acid(18-GA-Suc) was inserted into glycyrrhetinic acid(GA)-tanshinone Ⅱ_A(TSN)-salvianolic acid B(Sal B) liposome(GTS-lip) to prepare liver targeting compound liposome(Suc-GTS-lip) mediated by GA receptors. Next, pharmacokinetics and tissue distribution of Suc-GTS-lip and GTS-lip were compared by UPLC, and in vivo imaging tracking of Suc-GTS-lip was conducted. The authors investigated the effect of Suc-GTS-lip on the proliferation inhibition of hepatic stellate cells(HSC) and explored their molecular mechanism of improving liver fibrosis. Pharmacokinetic results showed that the AUC_(Sal B) decreased from(636.06±27.73) μg·h·mL~(-1) to(550.39±12.34) μg·h·mL~(-1), and the AUC_(TSN) decreased from(1.08±0.72) μg·h·mL~(-1) to(0.65±0.04) μg·h·mL~(-1), but the AUC_(GA) increased from(43.64±3.10) μg·h·mL~(-1) to(96.21±3.75) μg·h·mL~(-1). The results of tissue distribution showed that the AUC_(Sal B) and C_(max) of Sal B in the liver of the Suc-GTS-lip group were 10.21 and 4.44 times those of the GTS-lip group, respectively. The liver targeting efficiency of Sal B, TSN, and GA in the Suc-GTS-lip group was 40.66%, 3.06%, and 22.08%, respectively. In vivo imaging studies showed that the modified liposomes tended to accumulate in the liver. MTT results showed that Suc-GTS-lip could significantly inhibit the proliferation of HSC, and RT-PCR results showed that the expression of MMP-1 was significantly increased in all groups, but that of TIMP-1 and TIMP-2 was significantly decreased. The mRNA expressions of collagen-I and collagen-Ⅲ were significantly decreased in all groups. The experimental results showed that Suc-GTS-lip had liver targeting, and it could inhibit the proliferation of HSC and induce their apoptosis, which provided the experimental basis for the targeted treatment of liver fibrosis by Suc-GTS-lip.
