生物黏附辅料对葛根总黄酮类化合物在Caco-2细胞模型中转运的影响

目的:葛根总黄酮（PTF）可治疗心脑血管疾病,但膜通透性差,口服生物利用度低。一些辅料如卡波姆、壳聚糖和羟丙基甲基纤维素可以提高口服生物利用度。传统的体外评价技术,包括大鼠肠灌流和细胞模型,不能评价PTF整体的吸收机制。方法:本研究评价辅料的黏附性及对PTF在Caco-2细胞单层模型中转运的影响。采用cDNA微阵列测定PTF和PTF+辅料给药后的Caco-2细胞的基因表达变化,从基因水平揭示辅料对PTF整体吸收的影响机制。结果:体外黏附和Caco-2细胞转运实验表明,与单独PTF相比,加入辅料后对胃黏膜具有更高的黏附性,且在Caco-2细胞模型中的转运效率更高。PTF与辅料的相互作用显著改变了某些基因的表达,可能影响PTF的吸收效率。结论:不同的生物黏附聚合物能提高PTF的肠道吸收,可能与ATP结合盒(ABC)和溶质载体转运体(SLC)的表达基因有关。

Effect of bioadhesive excipients on absorption of total flavonids from Puerariae Lobatae Radix transporting across Caco-2 cell monolayer

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.