Intestinal receptor targeting for peptide delivery: an expert’s personal perspective on reasons for failure and new opportunities

Abstract

The technology has been available more than 25 years that would enable the oral delivery of vaccines, proteins and peptides, thus avoiding the need for injection. To this day, injection is still the mode of delivery, yet not the main mode of choice. This review focuses on several of the potential modes for oral delivery of peptides, proteins and vaccines. Additionally, the review will provide the reader with an insight into the problems and potential solutions for several of these modes of oral delivery of peptides and proteins.

Nanoparticles for oral delivery: Design, evaluation and state-of-the-art

“…Ligands for various receptors expressed in the intestine have been used to decorate the surface of nanoparticles to achieve increased residence time and/or increased uptake. Vitamin B12 (cobalamin) functionalization of nanoparticles has been of interest for targeted delivery [47,48]. The process of oral absorption of vitamin B12 involves binding of vitamin B12 to intrinsic factor (IF) in the small intestine and receptor mediated uptake of the B12-IF complex into the intestinal epithelia [4,47,48].…”

“…Vitamin B12 (cobalamin) functionalization of nanoparticles has been of interest for targeted delivery [47,48]. The process of oral absorption of vitamin B12 involves binding of vitamin B12 to intrinsic factor (IF) in the small intestine and receptor mediated uptake of the B12-IF complex into the intestinal epithelia [4,47,48]. Receptors for the B12-IF complex are expressed on enterocytes of the duodenum, jejunum and ileum, though the majority are located in the ileum.…”

Bacterial invasion factors: Tools for crossing biological barriers and drug delivery?

“…Currently, the most effective and most common delivery of these biopharmaceuticals is the parenteral route of administration (injection and intravenous infusion). Yet, in view of its convenience and patient acceptance, oral delivery is the main mode of choice [1,2]: (i) oral systems are easy to administer (very important in situations where delivery to mass populations is required) and avoids pain and discomfort, (ii) a large variety of dosage forms can be applied and (iii) vaccines, which are delivered orally, generate mucosal immunity, e.g. against enteric pathogens [1].…”

Chemically modified peptides and proteins - critical considerations for oral delivery

“…Over the last decades, many studies have described attempts to hijack these systems for oral delivery of therapeutic peptides and proteins by conjugating the protein of interest to the natural ligands of these receptors in the hope of increasing oral absorption and this topic has been the subject of many focused reviews. 2,27,37 As the metabolic requirements for the different essential nutrients differ, so does the capacity of their transporter systems. For example, the capacity for iron uptake via transferrin complex formation is high and it is estimated that up to 100 mg of transferrin gets secreted every day from the liver into the bile which is subsequently, upon binding of iron, reabsorbed into circulation via the lymph system.…”

“…51 In contrast to the high capacity of the transferrin transporter, the capacity of the vitamin B12 absorption machinery is low (see section 4.1) and also vitamin B12 has been shown to travel to the circulation via the lymph. 37 The fate of the peptide or protein after oral absorption can differ significantly based upon which absorption pathway is being exploited. As mentioned above, the transferrin and vitamin B12 pathways lead to the lymphatic system before reaching the circulation, thus avoiding first pass metabolism in the liver.…”