Enzymatically cross-linked arabinoxylan microspheres as oral insulin delivery system

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Nanotechnology

Background:

• Oral delivery of protein therapeutics like insulin is challenging due to degradation in the gastrointestinal (GI) tract.
• Arabinoxylans (AX), a type of polysaccharide, offer potential for developing novel drug delivery systems.
• Enzymatic cross-linking presents a method for creating stable microspheres for therapeutic applications.

Purpose of the Study:

• To develop and characterize arabinoxylans (AX) microspheres for oral insulin delivery.
• To investigate the interaction between ferulic acid-derived phenoxy radicals and insulin during microsphere formation.
• To evaluate the in vitro release profile, insulin structural stability, and in vivo efficacy of the AX microspheres as an oral insulin carrier.

Main Methods:

• Preparation of AX microspheres by enzymatic oxidation of ferulic acid, with in situ insulin entrapment.
• Characterization of microspheres using FT-IR spectroscopy and scanning electron microscopy.
• In vitro release studies to assess insulin retention in the upper GI tract.
• Circular dichroism (CD) spectroscopy to evaluate insulin secondary structure stability.
• In vivo studies on a murine model to assess hypoglycemic effects and bioavailability.

Main Results:

• AX microspheres were successfully prepared with a spherical shape and an average diameter of 320 μm.
• Enzymatic oxidation did not lead to covalent interaction between ferulic acid radicals and insulin.
• Microspheres minimized insulin loss in the upper GI tract, retaining ~75% of insulin.
• Insulin's secondary structure remained stable, irrespective of the insulin/AX mass ratio.
• Significant hypoglycemic effects and improved insulin bioavailability were observed in vivo.

Conclusions:

• Enzymatically cross-linked AX microspheres are a promising carrier for oral insulin delivery.
• The developed microspheres protect insulin from degradation and enhance its bioavailability.
• This approach offers a viable strategy for developing effective oral protein-based therapeutics.