The challenges of oral peptide delivery

For oral peptide therapeutics to be effective, formulations must:

• prevent peptide degradation in the gastro-intestinal tract
• promote peptide permeability

Peptides need to be lipophilized to be incorporated in lipid excipients

Most peptides are hydrophilic and therefore cannot be incorporated in lipid-based formulations. They need to be lipidized (i.e. increase their LogP).

Hydrophobic ion pairing (HIP) is a strategy to increase the lipophilicity of peptides. Using three model peptides, a marked increase in LogP was obtained, demonstrating that HIP-peptides were lipophilic.

Self emulsifying drug delivery system (SEDDS): a simple and efficient solution

• consists of a mixture of oils, surfactants and solvents designed to solubilize the drug throughout the digestion process
• offers an effective protection of HIP-peptide from enzyme degradation and glutathione reduction
• permeates through the intestinal mucus
• enables high HIP-peptide payload

Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC): a promising solution

• Lipid-based nanocarriers are expected to increase peptide delivery to the enterocyte, due to their nanosize which favours intracellular transport.
• SLN are composed of lipids in solid state at room and body temperature, usually long chain triglycerides or partial glyceride, fatty acids, waxes,etc.
• NLC contain both solid and liquid lipid at room and body temperature. The liquid lipids act as crystallization inhibitors of the solid lipid.

• The nanoparticles were shown to be able to cross the mucus and the enterocyte in in vitro models.