Use of vitamin B12 conjugates to deliver protein drugs by the oral route.

The treatment of patients with most peptide and protein pharmaceuticals must currently be performed by injection, with the accompanying disadvantages of patient discomfort, increased medical costs, and reduced patient compliance. It would be much easier and more acceptable if these drugs could be given by the oral route. Unfortunately, this route cannot be used with most proteins and with peptides due to both the degradation of these molecules within the intestine and their poor uptake across the intestinal wall. In this review, an uptake system is described that potentially overcomes both these problems. This system relies upon the natural uptake mechanism for vitamin B12 to cotransport peptides and proteins linked to the vitamin B12 from the intestine to the circulation. In an exciting extension to this technology, it has been found that it is also possible to transport nanoparticles, linked to the vitamin B12, into the circulation. Such nanoparticles can potentially be loaded with peptides or proteins of choice, and so protect these molecules from degradation in the intestine, while simultaneously transporting them into the circulation. These findings are an important step in realizing the possibility of delivering almost all peptides and proteins via the oral route.