Stimulation of triglyceride-rich lipoprotein secretion by polysorbate 80: in vitro and in vivo correlation using Caco-2 cells and a cannulated rat intestinal lymphatic model.
OBJECTIVE
To assess the effects of polysorbates 80 and 60 on intestinal lipoprotein processing in vitro, using Caco-2 cells, and to compare the results with those obtained using an in vivo intestinal lymphatic cannulated rat model.


METHODS
Caco-2 monolayers were used to monitor changes in lipoprotein secretion following exposure to excipients. In vivo data was obtained by monitoring intestinal lymphatic triglyceride levels following intraduodenal administration of the excipient to an anesthetised mesenteric lymph cannulated rat.


RESULTS
Caco-2 cells digested the polysorbate 80 to liberate oleic acid, which was used by the cells to enhance basolateral secretion of triglyceride-rich lipoproteins including chylomicrons. This response was not seen with polysorbate 60. Polysorbate 80 elicited a similar response in vivo in the rat model, stimulating enhanced triglyceride secretion in mesenteric lymph. Inhibition of lipoprotein secretion by Cremophor EL in Caco-2 cells was reversed by co-administration with polysorbate 80.


CONCLUSIONS
Polysorbate 80 promoted chylomicron secretion in Caco-2 cells and counteracted the inhibitory effects of other surfactants. These properties, in tandem with its P-gp inhibitory activity, make polysorbate 80 an ideal excipient for lymphotrophic vehicles. The ability to predict the in vivo response to Polysorbate 80 implies that the Caco-2 model is useful for studying absorption mechanisms from oral lipid-based formulations.
Seeballuck
Fergal
F
Department of Pharmaceutics and Pharmaceutical Technology, University of Dublin, Trinity College, Dublin 2, Ireland.
Lawless
Emma
E
Ashford
Marianne B
MB
O'Driscoll
Caitriona M
CM
D000818:Animals; D018938:Caco-2 Cells; D002404:Catheterization; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D042601:Lymphatic Vessels / Q000378:metabolism*; D008297:Male; D008643:Mesentery; D008954:Models, Biological; D011136:Polysorbates / Q000008:administration & dosage* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000378:metabolism*
D005227:Fatty Acids; D008074:Lipoproteins; D011136:Polysorbates; D014280:Triglycerides