PEGylated insulin loaded complexation hydrogels for protected oral delivery

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Protein Chemistry

Background:

• Existing oral protein delivery systems struggle to protect proteins from proteolytic degradation.
• pH-sensitive carriers often lack sufficient mucoadhesion for effective intestinal release.
• Poly(ethylene glycol) (PEG) chains offer potential for mucoadhesion and drug protection.

Purpose of the Study:

• To develop and evaluate pH-sensitive poly(methacrylic acid-grafted ethylene glycol) (P(MAA-g-EG)) gels as carriers for oral protein delivery.
• To enhance protein stability and intestinal absorption using PEGylation of insulin.
• To investigate the role of PEG graft density in carrier loading and release mechanisms.

Main Methods:

• Synthesis and characterization of P(MAA-g-EG) gels.
• Conjugation of PEG to insulin (LysB29) to create PEGylated insulin (PI).
• In vitro studies using Caco-2/HT-29-MTX co-cultures to assess cellular transport and transepithelial resistance.
• In vivo studies in Sprague-Dawley rats to measure insulin absorption and bioavailability.

Main Results:

• P(MAA-g-EG) gels demonstrated pH-sensitive, H-bonded interactions with PEGylated insulin, facilitating controlled release.
• PEGylation of insulin improved its stability against proteolytic degradation and enhanced mucoadhesion.
• In vitro and in vivo studies confirmed improved cellular transport and bioavailability of PEGylated insulin delivered via the P(MAA-g-EG) system.
• PEG graft density influenced the carrier's loading and release kinetics.

Conclusions:

• P(MAA-g-EG) gels represent a promising platform for oral protein delivery, offering enhanced protection and absorption.
• PEGylation of insulin is an effective strategy to improve its stability and mucoadhesive properties for oral administration.
• This novel system holds potential for improved therapeutic outcomes in protein-based treatments, such as diabetes management.