Oral insulin delivery by epithelium microenvironment-adaptive nanoparticles

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery

Background:

• Oral protein drug delivery faces challenges due to the need for nanoparticles to navigate intestinal barriers.
• Existing nanoplatforms often require a fixed set of surface properties, limiting their adaptability.
• A need exists for nanocarriers with tunable surface characteristics for effective in vivo drug delivery.

Purpose of the Study:

• To develop a novel, adaptable nanoplatform for oral protein delivery.
• To engineer nanoparticles that can transition from hydrophilic to hydrophobic surfaces in response to the jejunal microenvironment.
• To evaluate the efficacy of this nanoplatform for oral insulin delivery.

Main Methods:

• Synthesized a biodegradable copolymer (PLGA-Hyd-PEG) with pH-sensitive hydrazone bonds.
• Fabricated pH-sensitive core-shell nanoparticles encapsulating insulin.
• Tested nanoparticle mucus penetration, cellular uptake, and in vivo pharmacodynamics in rats.
• Administered nanoparticles orally via enteric-coated capsules.

Main Results:

• PLGA-Hyd-PEG nanoparticles demonstrated stability in jejunal fluid and rapid mucus penetration.
• Nanoparticles underwent surface transformation from hydrophilic to hydrophobic at pH ~5.5, enhancing cellular internalization.
• Intrajejunal administration led to significant blood glucose reduction in rats.
• Oral administration of encapsulated nanoparticles in capsules reduced blood glucose by 35% for 10 hours in diabetic rats.

Conclusions:

• The developed nanoplatform exhibits adaptive surface properties for improved oral drug delivery.
• This strategy offers a new approach to overcoming biological barriers for oral protein therapeutics.
• The PLGA-Hyd-PEG nanocarrier system shows promise for efficient oral insulin delivery.