ABSTRACT
Objective: Pueraria total flavonids (PTF) can treat cardiovascular and cerebrovascular diseases, but it has poor membrane permeability and oral bioavailability. Some excipients, such as carbomer, chitosan, and hydroxypropyl methylcellulose, can improve the oral bioavailability. Traditional in vitro evaluation techniques, including the rat intestinal perfusion and cell line models, cannot evaluate PTF absorption and holistic transporters. Methods: This study evaluated excipients’ adhesiveness and effect on PTF transport across Caco-2 cell monolayer. cDNA microarrays identified gene expression changes in Caco-2 cells exposed to PTF and PTF with excipients, and revealed the mechanism underlying the effect of excipients on PTF absorption. Results: In vitro adhesion and transport experiments across Caco-2 showed that excipients had higher adhesiveness to gastric mucosa and transport efficiency across Caco-2 cells than PTF alone. The interaction of PTF with excipients significantly changed the expression of some genes, which might influence the absorption rate of PTF. Conclusion: Different bioadhesive polymers can improve intestinal absorption of PTF, which was related to some genes affiliated to the ATP-binding cassette (ABC) and solute carrier transporter (SLC) to some extent.
ABSTRACT
Objective To study the absorption mechanism of the antihypertensive peptide,Val-Leu-Pro-Pro-Val(VLPVP) in Caco-2 cell model. Method Caco-2 cell model was used in vitro to investigate the effects of time,pH,drug concentration,enhancers and inhibitors on the absorption of VLPVP. VLPVP concentration was measured by HPLC. Results The transport rate of VLPVP reached the maximal level at pH7.4,and was positively correlated to transport time and drug concentration. The peptide transporter inhibitors(Gly-Pro,arphamenine A) ,the endocytosis inhibitor(phenyl arsenoxide) didn’t influence the transport of VLPVP,while the paracellular transport enhancer(sodium deoxycholate) ,the inhibitor of multi-drug resistant protein(MK-571) and the energy inhibitor(sodium azide) enhanced it from apical to basolateral side significantly,but the latter two didn’t influence the transport from basolateral to apical side. Conclusion Paracellular diffusion was suggested to have been the main mechanism for the absorption of intact VLPVP and MRP2 had strong eflux effect on the transepithelial transport of VLPVP.