Improving the absorption of earthworm fibrinolytic enzymes with mucosal enhancers

Abstract

Earthworm fibrinolytic enzymes (EFEs), an ideal drug for cardiovascular diseases, have a very low oral bioavailability. In order to improve the absorption of EFEs, six different enhancers were selected to increase the intestinal absorption of EFEs. In vitro (Caco-2 monolayers) and in vivo (mice) experiments were carried out to find the optimum concentration and action time of these enhancers for EFE absorption. We found that EFEs could be transported into blood across intestinal endothelial membrane after administration via intragastric administration with low bioavailability. These results obtained from in vitro experiments were similar to those in vivo. Moreover, menthol and glucose showed absorption enhancement properties with a relatively low cytotoxicity.

Keywords::

• Earthworm fibrinolytic enzymes
• absorption enhancer
• tight junction
• Caco-2 cells
• bioavailability
• paracellular transport

Acknowledgements

We thank Jinghua Zhang and Pengcheng Li for their suggestions in the discussion.

Declaration of interest

This work was supported by the National Science Grant of P.R. China (No. 30871858) and the program of Jiangsu province (BE200830155).