Cellular evaluation of insulin transmucosal delivery

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Cell Biology

Background:

• Poly(methacrylic acid)-graft-poly(ethylene glycol) (P(MAA-g-EG)) microparticles are explored for oral protein delivery.
• Investigating microparticle characteristics is crucial for optimizing drug transport.

Purpose of the Study:

• To evaluate how PEG molecular weight and microparticle size affect intestinal epithelial integrity and insulin permeability.
• To understand the impact of P(MAA-g-EG) microparticles on Caco-2 cell monolayers.

Main Methods:

• Utilized human intestinal epithelial Caco-2 cell monolayers.
• Monitored transepithelial electrical resistance (TEER) to assess cell monolayer integrity.
• Measured insulin permeability across the cell layers.
• Tested P(MAA-g-EG) microparticles with PEG molecular weights of 400 and 1000.
• Evaluated microparticle sizes ranging from 25-90 µm, 90-150 µm, and 150-212 µm.

Main Results:

• P(MAA-g-EG) microparticles reduced TEER by 50%, indicating temporary disruption of the cell monolayer.
• Cell monolayer integrity recovered within 3 hours after microparticle removal.
• No significant changes in TEER were observed with varying PEG molecular weights (400 vs. 1000).
• Smaller microparticle sizes and shorter PEG chains correlated with higher insulin permeability.
• Insulin-loaded microparticles demonstrably enhanced insulin transport.

Conclusions:

• P(MAA-g-EG) microparticles can temporarily affect intestinal epithelial integrity.
• Microparticle size and PEG chain length are key factors influencing insulin permeability.
• These findings support the potential of P(MAA-g-EG) microparticles for enhancing oral insulin delivery.