pH sensitive thiolated cationic hydrogel for oral insulin delivery

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Drug Delivery Systems

Background:

• Oral delivery of insulin faces challenges due to enzymatic degradation and poor absorption in the gastrointestinal tract.
• Developing effective carriers for oral insulin delivery is crucial for improving diabetes management.
• pH-sensitive polymers offer potential for targeted drug release in specific gastrointestinal environments.

Purpose of the Study:

• To synthesize and characterize pH-sensitive thiolated Polydimethylaminoethylmethacrylate (PDCPA) for oral insulin delivery.
• To evaluate the physicochemical properties, mucoadhesion, and permeability of PDCPA.
• To assess the in vivo efficacy of insulin-loaded PDCPA in diabetic rats.

Main Methods:

• PDCPA synthesized via carbodiimide chemistry, crosslinking Polymethacrylic acid with thiolated Polydimethylaminoethylmethacrylate (PDCys).
• Physicochemical characterization included IR and NMR spectroscopy, particle size analysis (284 nm), zeta potential (37.3 mV), texture analysis for mucoadhesion, and transepithelial electrical resistance measurements.
• In vivo efficacy evaluated by administering insulin-loaded PDCPA to male diabetic rats and monitoring blood glucose reduction.

Main Results:

• PDCPA confirmed by IR and NMR spectroscopy.
• PDCPA exhibited favorable characteristics: particle size of 284 nm, zeta potential of 37.3 mV, enhanced mucoadhesion compared to the parent polymer, and a >50% reduction in transepithelial electrical resistance.
• Permeation studies indicated improved permeability of PDCPA over the parent polymer.
• In vivo studies showed a 19% blood glucose reduction in diabetic rats treated with insulin-loaded PDCPA.

Conclusions:

• Synthesized PDCPA is a promising pH-sensitive material for oral insulin delivery.
• PDCPA demonstrates enhanced mucoadhesion and permeability, facilitating improved insulin absorption.
• In vivo results confirm the potential of insulin-loaded PDCPA for effective blood glucose management in diabetic models.