Surface functional modification of self-assembled insulin nanospheres for improving intestinal absorption

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Nanotechnology

Background:

• Therapeutic proteins like insulin face poor oral absorption due to the gastrointestinal tract's harsh environment.
• Existing delivery methods struggle to protect proteins from degradation and ensure efficient uptake.
• Self-assembly offers a promising approach for creating protein-based nanocarriers.

Purpose of the Study:

• To develop a free-carrier oral delivery system for insulin using self-assembled nanospheres.
• To enhance insulin's oral absorption efficiency and bioavailability.
• To protect insulin from degradation in the gastrointestinal tract.

Main Methods:

• Insulin was self-assembled into nanospheres (INS) via thermal induced phase separation.
• INS were surface-modified with ɛ-poly-L-lysine (EPL) to form a protective core-shell structure (INS@EPL).
• Particle characterization, in vitro dissolution studies, cell permeability assays (Caco-2), and in vivo hypoglycemic effect studies in diabetic rats were performed.

Main Results:

• Uniform spherical nanoparticles (150-300 nm) of INS and INS@EPL were successfully fabricated with retained biological potency.
• INS@EPL demonstrated improved insulin release profiles at intestinal pH and enhanced paracellular permeability in Caco-2 cells.
• Enteral administration of INS@EPL showed significantly more potent and prolonged hypoglycemic effects in diabetic rats compared to INS.

Conclusions:

• Surface functional modification of self-assembled insulin nanospheres with a shell-crosslinked polycationic peptide (EPL) is a viable strategy for oral protein delivery.
• The INS@EPL system effectively protects insulin and enhances its absorption, leading to improved therapeutic outcomes.
• This approach holds promise for the oral delivery of therapeutic proteins, overcoming current bioavailability challenges.