Traveling the Vitamin B₁₂ Pathway: Oral Delivery of Protein and Peptide Drugs

Abstract

Oral routes of administration for therapeutic peptides and proteins face two major barriers: proteolytic degradation in the stomach and an inadequate absorption mechanism for polypeptides within the intestinal lumen. As a result, peptide-based therapeutics are administered by injection, a painful process associated with lower patient compliance. The development of a means of overcoming these two major obstacles and enabling the successful delivery of peptide therapeutics by the oral route of administration has therefore been the target of extensive scientific endeavor. This Minireview focuses on oral peptide/protein delivery by the dietary uptake pathway for vitamin B(12). Recent progress in this field includes the delivery of erythropoietin, granulocyte-colony-stimulating factor, luteinizing-hormone-releasing hormone, and insulin.

Vitamin B12–Metal Conjugates for Targeted Chemotherapy and Diagnosis: Current Status and Future Prospects

“…In fact, the crystal structure of the transport protein TCII bound to vitamin B 12 (Holo-TCII) shows this group projecting out into the 1.4 nm solvent-accessible pocket around the ribose moiety (Figure 4), thus making it the most favorable site for the attachment of large moieties without affecting the recognition by TCII. [10,15] Similar features have also been observed in the crystal structure of Holo-IF, thus confirming the accessibility of the 5′-ribose site. [16] Figure 4.…”

Supramolecular nanoscale assemblies for cancer diagnosis and therapy

“…Cobalamin has a versatile uptake mechanism and is efficiently absorbed through clinically relevant ways such as oral (intestinal delivery), systemic (intravenous delivery) and topical (mucosal delivery) [131]. Vitamin B12 is involved in cellular metabolism affecting DNA synthesis and regulation in addition to fatty acid metabolism and amino acid metabolism.…”

Efficient Peroral Delivery of Insulin via Vitamin B12 Modified Trimethyl Chitosan Nanoparticles

“…Conjugation at the following sites in VB12 has been reported not to interfere with the ability of the VB12 transportation: 1) at peripheral propionamide unit on the corrin ring at ε position, 2) through the phosphate group of the α "tail", 3) to the 5'-hydroxy group (5′ -OH) of the ribose moiety, also in the α "tail" (8). The 5′-OH group of the ribose moiety of VB12 was selected as the linking site with TMC using SA as the spacer.…”

“…Application of VB12 for the delivery of pharmaceutical agents has received attention since 1970s (8). During its uptake process, VB12 firstly binds to salivary haptocorring in stomach (9,10), and subsequently binds to intrinsic factor (IF) in intestine.…”