Development of PEGDMA: MAA based hydrogel microparticles for oral insulin delivery.

An oral insulin delivery system based on copolymers of poly(ethylene glycol) dimethacrylate and methacrylic acid was developed and its functional activity was tested in non-obese diabetic rats. Poly(ethylene glycol) dimethacrylates (PEGDMA) were synthesized by esterification reaction of different molecular weight poly(ethylene glycol) with methacrylic acid (MAA) in presence of acid catalyst. PEG dimethacrylates of molecular weight ranging from 400 to 4000 and methacrylic acid were further copolymerized by suspension polymerization to obtain pH sensitive hydrogel microparticles. The diameter of poly(PEGDMA:MAA) microparticles increased with increasing the molecular weight of the poly(ethylene glycol) dimethacrylate used for respective microparticle synthesis. Insulin was loaded into the hydrogel microparticles by partitioning from concentrated insulin solution. In vitro release studies of insulin loaded microparticles were performed by simulating the condition of gastrointestinal tract, which showed the minimal insulin leakage (18-25%) at acidic pH (2.5) and significantly higher release at basic pH (7.4). Animal studies were carried out to investigate the abilities of the insulin loaded hydrogel microparticles to influence the blood glucose levels of the diabetic rats. In studies with diabetic rats, the blood glucose level reduced for animals that received the insulin loaded hydrogel microparticles and the effect lasted for 8-10h. It was also observed, two capsules per day of poly(PEGDMA4000:MAA) hydrogel microparticles containing 80 I.U./kg of insulin dose were sufficient to control the blood glucose level of fed diabetic rats between 100 and 300 mg/dl.