Improving the absorption of earthworm fibrinolytic enzymes with mucosal enhancers.
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.
Yu
Qinghua
Q
Key Lab of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, Jiangsu, China.
Li
Pengcheng
P
Yang
Qian
Q
D000818:Animals; D001682:Biological Availability; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004492:Edetic Acid / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D010450:Endopeptidases / Q000493:pharmacokinetics*; D000431:Ethanol / Q000494:pharmacology / Q000633:toxicity; D005453:Fluorescence; D005947:Glucose / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D008610:Menthol / Q000494:pharmacology / Q000633:toxicity; D051379:Mice; D009835:Oligochaeta / Q000201:enzymology*; D010539:Permeability / Q000187:drug effects; D020358:Sodium Cholate / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D012967:Sodium Dodecyl Sulfate / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity
D008610:Menthol; D012967:Sodium Dodecyl Sulfate; D000431:Ethanol; D004492:Edetic Acid; D010450:Endopeptidases; D005947:Glucose; D020358:Sodium Cholate