Vitamin B12-mediated uptake of erythropoietin and granulocyte colony stimulating factor in vitro and in vivo

Proteins are normally very poorly absorbed from the intestine as the intestinal epithelial cells act as a barrier to the uptake of all but the smallest of molecules. We have used the natural uptake mechanism for Vitamin B-12 (VB12) to increase the absorption of proteins from the gut. VB12 was conjugated to two recombinant human therapeutic proteins, granulocyte colony stimulating factor (G-CSF) and erythropoietin (EPO). In an in vitro model of VB12 uptake, high levels of VB12-G-CSF conjugates were shown to be transported across the epithelial cell monolayer when compared to free G-CSF. In in vivo experiments in rats, both VB12-EPO and VB12-G-CSF conjugates were transported into the circulation from the gut lumen. Uptake was sufficient to generate a therapeutic response in animals receiving VB12-G-CSF, but not in those administered G-CSF alone. These preliminary findings have important implications in the oral delivery of peptide and protein pharmaceuticals. Copyright (C) 1996 Elsevier Science B.V.