Influence of intestinal colloidal structures and self-assembly on lipidbased formulations for enhancing peptide drug bioavailability

Therapeutics based on peptides show promise in the treatment of conditions such as diabetes, cancer, and
irritable bowel syndrome. Their big size and hydrophilic nature, however, make it difficult to achieve the best
oral bioavailability because of the intestinal epithelium's low permeability. To improve bioavailability,
different methods have been looked into, such as endocytic routes, microneedles, co-releasing transient
"permeability enhancer" fatty acid-based molecules, and combining PE molecules with lipid-based
excipients in pharmaceutical dosage forms. In the small intestine, fatty acid formulation and intestinal fluids
produce colloidal and solubilizing structures, which aid drug absorption. The intestinal medium and
formulation constituents interact intricately due to structural changes caused by dilution, digesting, and
absorption. The unpredictability of lipid-based permeability-enhanced administration reduces disease
treatment efficacy. To address these challenges, a comprehensive approach using small-angle X-ray and
neutron scattering, and molecular dynamics simulations is proposed. This integrated framework aims to
provide a detailed understanding of colloidal structures formed by the permeation enhancers, as well as
taurocholate, and phospholipids, the major components of intestinal fluids. This knowledge will enable the
tailored design of oral drug delivery systems for peptide drugs, addressing individual variabilities and
increasing bioavailability.