Systemic therapeutic peptide delivery via gastrointestinal tract

NextGenRnD® Solution No. 12

Current state-of-the-art

The problem

The efficiency of gastrointestinal (GI) delivery for larger molecules like peptides using current methods is either low or very low and the reports are frequently controversial. To deliver large hydrophilic peptide active pharmaceutical ingredient (API) into systemic circulation three events must happen. First, API molecules should be internalized by human gut epithelial (enterocytes) and/or lamina propria cells. Second, enterocytes and/or lamina propria cells should release the APIs into the lamina propria interstitial tissue, i.e., interstitium. Third, after release, API molecules should enter the systemic circulation either via blood or lymphatic capillaries.

The third event is simple as gut lamina propria is well-vascularized interstitial space and contains both blood capillaries as well as lymphatic capillaries, which can uptake large molecules (up to 100 nanometers or ~200 kDa), including peptides, by different mechanisms. It is the first and the second event that pose the major challenge for the delivery of therapeutic peptides.

The solution

We propose novel and safe delivery system for a novel class of peptide pre-pro-drugs using cGMP standards. The driver of our delivery system provides the natural and safe delivery of pre-pro-API using ultra-efficient pathways that were shaped by evolution, whereas the pre-pro-API is tuned for internalization, release, and uptake. Pre-pro-API peptide concept represents the novel class of peptide drug utilizing cellular machinery for the proper delivery of API to the systemic circulation in unmodified form. This leads to a synergistic effect that should result in substantial lowering of therapeutic peptide API doses.

In this Solution, NextGenRnD reveals the gastrointestinal delivery system that can: (i) deliver hydrophilic therapeutic peptide APIs not exceeding 100 amino acid residues into systemic circulation; (ii) enhance absorption and delivery of peptides without loss of biological activity; (iii) be manufactured in quantities up to kilograms of API per year; (iv) substantially reduce the required API quantity needed for achieving therapeutic effect; and (v) be safely used in humans.

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