For the transferrin receptor-mediated
transcytosis, we have demonstrated that there are a
large number of transferrin receptors on the
surface of intestinal epithelial cells. Using
cultured epithelial cell lines, i.e., MDCK and
Caco-2, we have shown that transferrin can be used
as a carrier for transepithelial transport of other
proteins and peptides. We also have found that
certain non-toxic agents such as Brefeldin A can
further enhance this transcytotic process.
Currently, we are exploiting this receptor-mediated
transport mechanism for the oral delivery of
insulin as transferrin conjugates for the treatment
of diabetes in animal models.
Wan J, Taub ME, Shah D and Shen WC: Brefeldin A
enhances receptor-mediated transcytosis of
transferrin in filter-grown Madin-Darby canine
kidney cells. J Biol Chem 267:13446-13450, 1992.
Shah D and Shen WC: The establishment of
polarity and enhanced transcytosis of transferrin
receptors in enterocyte-like caco-2 cells. J Drug
Targeting 2:93-99, 1994.
Shah D and Shen WC, Transepithelial delivery of
an insulin-transferrin conjugate in enterocyte-like
Caco-2 cells. J Pharm Sci, 85:1306-1311, 1996.
Wang J, Shen D and Shen WC: Oral delivery of an
insulin-transferrin conjugate in
streptozotocin-treated CF/1 mice. Pharm Res
14:(abstract in press), 1997.
Transferrin Receptor (TfR)-mediated Transcytosis