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

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. An 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 (Papp value) of the two SP-SMEs significantly increased (12.0-fold and 10.90-fold). A pharmacokinetic study demonstrated that the AUC0-∞ value of SAB for the SP-SME1 group significantly increased by 4.72 and 2.82 times compared to that for free SAB (p