Dual-modified nanoparticles overcome sequential absorption barriers for oral insulin delivery

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery

Background:

• Oral insulin delivery faces significant challenges due to gastrointestinal barriers, including transepithelial transport obstacles.
• These barriers impede insulin absorption, limiting the efficacy of oral insulin formulations.

Purpose of the Study:

• To construct a functional nanoparticle (PG-FAPEP) for sequential overcoming of intestinal absorption barriers.
• To enhance oral insulin delivery and improve bioavailability using a dual-surface-modified nanoparticle system.

Main Methods:

• Dual surface modification of nanoparticles (PG-FAPEP) with folate and a charge-convertible tripeptide.
• Investigating nanoparticle interaction with enterocytes, including folate receptor-mediated endocytosis, lysosomal escape via the proton sponge effect, and PHT1-mediated exocytosis.

Main Results:

• PG-FAPEP nanoparticles efficiently traversed the intestinal epithelium.
• Achieved a high oral insulin bioavailability of 14.3% and a sustained hypoglycemic effect in vivo.
• Demonstrated successful overcoming of apical and basolateral absorption barriers.

Conclusions:

• The dual-modification strategy effectively addresses multiple absorption barriers for oral macromolecule delivery.
• PG-FAPEP nanoparticles show significant potential for improving oral insulin bioavailability and therapeutic outcomes.
• This approach offers a promising pathway for the oral delivery of large molecules.