The potential of chitosan in enhancing peptide and protein absorption across the TR146 cell culture model-an in vitro model of the buccal epithelium.
OBJECTIVE
To investigate the potential of chitosan (CS) to enhance buccal peptide and protein absorption, the TR146 cell culture model, a model of the buccal epithelium, was used.


METHODS
The sensitivity of TR146 cells to several CS solutions (different salts with different MW) was investigated by using the MTS/ PMS assay. Permeability studies were performed to determine the enhancing effect of CS glutamate (1, 20, 40, 60, and 100 microg/mL) on the permeability of 3H-mannitol and fluorescein isothiocyanate labeled dextrans (FD) with various MW (4.4-19.5 kD) across the cell culture model.


RESULTS
Sensitivity of TR146 cells to CS solutions depended on the concentration, the pH, and the type of CS salt. CS glutamate solutions (pH 6.0) were found to be the least harmful. CS glutamate was able to increase the permeability of model substances with MW up to 9.5 kD across the cell model. An enhancing effect was found for CS concentrations of 20 microg/mL and higher, correlating with a decrease in TEER values. The 20 microg/mL CS concentration had a negligible effect on the enzyme activity of the cells as determined by the MTS/PMS assay.


CONCLUSIONS
CS glutamate is effective in enhancing the transport of macromolecules across the buccal TR146 cell culture model. Therefore. it might be a promising vehicle for peptide and protein buccal administration.
Portero
Ana
A
Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, Spain.
Remuñán-López
Carmen
C
Nielsen
Hanne Mørck
HM
D000042:Absorption; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002686:Chitin / Q000031:analogs & derivatives / Q000494:pharmacology*; D048271:Chitosan; D005079:Excipients; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D018698:Glutamic Acid / Q000494:pharmacology; D006801:Humans; D008353:Mannitol / Q000378:metabolism; D008970:Molecular Weight; D009061:Mouth Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D010539:Permeability; D011506:Proteins / Q000378:metabolism*; D013268:Stimulation, Chemical
D005079:Excipients; D005456:Fluorescent Dyes; D010455:Peptides; D011506:Proteins; D002686:Chitin; D018698:Glutamic Acid; D008353:Mannitol; D048271:Chitosan; D016650:Fluorescein-5-isothiocyanate