Extra virgin olive oil-based phospholipid complex/self-microemulsion enhances oral absorption of salvianolic acid B through inhibition of catechol-O-methyltransferase-mediated metabolism

被引：7

作者：

Wang, Yutong ^{[1
]}

Huang, Jinyu ^{[1
]}

Wang, Zilin ^{[1
]}

Wang, Xitong ^{[1
]}

Liu, Heng ^{[1
]}

Li, Xiangwei ^{[1
]}

Qiao, Hongzhi ^{[1
]}

Wang, Lingchong ^{[1
]}

Chen, Jing ^{[1
]}

Chen, Xiao ^{[2
]}

Li, Junsong ^{[1
]}

机构：

[1] Nanjing Univ Chinese Med, Sch Pharm, 138 Xianlin Ave, Nanjing 210023, Peoples R China

[2] China Pharmaceut Univ, Sch Biopharm, 639 Longmian Rd, Nanjing 211198, Peoples R China

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2022年 / 611卷

基金：

美国国家科学基金会; 中国国家自然科学基金;

关键词：

Self-microemulsion; Phospholipid complex; Salvianolic acid B; Catechol-O-methyltransferase; Extra virgin olive oil; Bioavailability; DRUG-DELIVERY SYSTEM; BIOAVAILABILITY; PERMEABILITY; COMT; PHARMACOKINETICS; MILTIORRHIZA; SODIUM;

D O I：

10.1016/j.ijpharm.2021.121330

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The oral bioavailability of many phenolic acid drugs is severely limited due to the high hydrophilicity and extensive first-pass effect induced by catechol-O-methyltransferase (COMT) metabolism. The present study investigated the inhibitory activity of the pharmaceutical excipients of extra virgin olive oil (EVOO) against COMT and evaluated the potential of a self-microemulsion loaded with a phospholipid complex containing EVOO for oral absorption enhancement of salvianolic acid B (SAB), a model phenolic acid. In vitro COMT assay showed that EVOO could effectively inhibit enzyme activity in the rat liver cytosol. Next, the SAB phospholipid complex/ self-microemulsion containing EVOO (named SP-SME1) was prepared and characterized (particle size, 243.60 +/- 6.96 nm and zeta potential, -23.67 +/--1.36 mV). The phospholipid complex/self-microemulsion containing ethyl oleate (EO) (named SP-SME2) was taken as the control group. Compared with free SAB, the apparent permeability coefficient (P-app value) of the two SP-SMEs significantly increased (12.0-fold and 10.90-fold). Pharmacokinetic study demonstrated that the AUC(0-infinity) value of SAB for the SP-SME1 group significantly increased by 4.72 and 2.82 times compared to those for free SAB (p < 0.001) and SP-SME2 (p < 0.01), respectively. Moreover, the AUC(0-infinity) value of monomethyl-SAB (metabolite of SAB, MMS) for the SP-SME1 group decreased by 0.83 times compared to that for SP-SME2. In conclusion, the EVOO-based phospholipid complex/ self-microemulsion greatly enhanced the oral absorption of SAB, which was mainly attributed to the inhibition of COMT activity induced by EVOO.

引用

页数：11