Localized heat application as a strategy for enhanced oral peptide absorption - A proof-of-concept study

Area of Science:

• Biomedical Engineering
• Drug Delivery
• Gastrointestinal Physiology

Background:

• Oral peptide delivery faces significant challenges due to poor gastrointestinal absorption.
• Chemical permeation enhancers (PEs) are widely used, but physical methods are emerging.
• Improving macromolecule bioavailability via oral administration is a key pharmaceutical goal.

Purpose of the Study:

• To investigate localized mild heat as a physical permeation enhancer for oral drug delivery.
• To evaluate the efficacy of mild heat alone and in combination with sodium caprate (C10).
• To explore the impact of heat on gastrointestinal cell permeability and tight junction integrity.

Main Methods:

• Utilized Caco-2 cell monolayers to model the gastrointestinal mucosa.
• Applied localized mild heat (≤42°C) and sodium caprate (C10).
• Measured changes in cell permeability, transepithelial electrical resistance, and tight junction protein expression/organization.
• Conducted in vitro and ex vivo permeability assessments.

Main Results:

• Mild heat moderately increased cell monolayer permeability and reduced electrical resistance without significant cytotoxicity.
• Heat exposure induced reorganization of tight junction proteins, suggesting a phosphorylation-dependent mechanism.
• The combination of mild heat and C10 demonstrated an additive effect on increasing permeability.
• No significant alteration in tight junction protein expression was observed.

Conclusions:

• Mild heat serves as a viable physical permeation enhancer for oral drug delivery.
• Combining mild heat with chemical PEs like C10 can synergistically improve macromolecule absorption.
• This approach offers a promising strategy to enhance the oral bioavailability of peptides and other large molecules.