Oral Delivery of Peptides Using a Core-Shell Silica Construct

3/17/2021 11:50 - 12:25

We have designed a nanoparticle construct for oral delivery of peptides and other macromolecules based on a core-shell principle.  A peptide candidate is combined with the excipients, L-arginine and zinc chloride, to produce a nm core, over which silica is coated.  The basis of the technology is that the excipients provide stability to the peptide and can also act as intestinal permeation enhancers when co-released in the small intestine close to the epithelium. It is therefore designed to promote epithelial uptake of the released peptide and not the nanoparticle.  Silica is used because it is biocompatible and dissolves at the small intestinal pH but not gastric pH.  Proof-of-concept studies in rodents using insulin and exenatide show that the process is not damaging to these peptides and, in the case of insulin, significant plasma glucose lowering was achieved in rats following duodenal instillations. The synthetic process is a simple four step one, which can be scaled. Next steps will examine the concept when the peptide-entrapped nanoparticles are gavaged to rats and then as a solid dose formulation in a large animal model.

David Brayden, Full Professor (Advanced Drug Delivery), University College Dublin