ABSTRACT
A blood-brain barrier microfluidic chip platform for studying the permeability of active components in traditional Chinese medicine was developed. This model used primary human brain microvascular endothelial cells on a microfluidic chip consisting of two perpendicularly-crossing channels and a single layer porous polycarbonate membrane. The physiological shear stress in the human vasculature was also modeled in this device. Cell viability on the chip was monitored by cell staining and immunofluorescence staining. The cells spread well and the structure of an intercellular adhesion protein was satisfactory. The permeability of fluorescent tracers and three model drugs and the functional expression of P-glycoprotein (P-gp)on the blood-brain barrier were investigated. The results show that the apparent permeability coefficients (Papp) of the fluorescent tracers and three model drugs were consistent with those reported in the literature, and P-gp on the chip showed normal function, indicating that there was a complete structure and a functional BBB. The permeability of six active components of traditional Chinese medicine was investigated through this microfluidic chip and the drug concentration was determined by HPLC-MS/MS to obtain the Papp of each component. The Papp of corydaline was (4.51 ± 1.90)×10-7 cm·s-1, the Papp of tetrahydropalmatine was (9.10 ± 6.59)×10-7 cm·s-1, and the Papp of imperatorin was (9.38 ± 2.53)×10-7 cm·s-1; the concentration of isoimperatorin, baicalin and chlorogenic acid was below the limit of quantification, which suggested that isoimperatorin, baicalin and chlorogenic acid have poor permeability in this BBB chip. This blood-brain barrier microfluidic platform possesses a complete barrier function and near-physiological conditions and could be a valuable in vitro tool for drug permeability evaluation.
ABSTRACT
To investigate the stability and the conversion rules of cantharidin and cantharidic acid contained in the Mylabris aqueous solution under different conditions. The contents of cantharidin and cantharidic acid under different conditions (pH, temperature and light) were determined by HPLC-TQ-MS. The results showed that the content of cantharidin was gradually decreased with the rising of pH value, while on the contrary, the content of cantharidic acid was increased gradually; after Mylabris aqueous solution with different pH values were placed at 25, 40 ℃ and 25 ℃ respectively for lighting for 90 days, the samples were collected for analysis. The results showed the contents of cantharidin and cantharidic acid were changed greatly in the first 10 days, mainly including the decrease of cantharidic acid and increase of cantharidin when the solution was acidic, and the increase of cantharidic acid and decrease of cantharidin when the solution was alkaline. After that, the contents of the above two components basically remained stable. This study revealed that pH was the main factor to affect the contents of cantharidin and cantharidic acid, and they could be converted into each other with the changes of pH value. High temperature and light can accelerate the speed of achieving such balance. The study can provide certain reference for the quality control of the medicines using the Mylabris as raw material.