Synthesis and characterization of a porous poly(hydroxyethylmethacrylate- co-ethylene glycol dimethacrylate)-based hydrogel device for the implantable delivery of insulin

摘要

Poly(hydroxyethylmethacrylate-co-ethylene glycol dimethacrylate) [poly(HEMA-co-EGDMA)]-based hydrogel devices were synthesized by a free-radical polymerization reaction with 2-hydroxyethylmethacrylate as the monomer, different concentrations of ethylene glycol dimethacrylate (EGDMA) as the crosslinking agent, and ammonium persulfate/N,N,N',N'-tetra-methyl ethylenediamine as the free-radical initiator. The porosity of the poly(HEMA-co-EGDMA) hydrogels was controlled with water as the porogen. The Fourier transform infrared spectrum of poly(HEMA-co-EGDMA) showed absorption bands associated with -C=O stretching at 1714 cm ~(-1), C-O-C stretching vibrations at 1152 cm ~(-1), and a broad band at 3500-3800 cm ~(-1) corresponding to -OH stretching. Atomic force microscopy studies showed that the hydrogel containing 67% water had pores in the range of 3500-9000 nm, whereas the hydrogel containing 7% water did not show measurable pores. The hydrogel synthesized with 1% EGDMA showed 50% thallium-201 release within the first 30 min and about 80% release within 60 min. In vitro insulin-release studies suggested that the hydrogel with 27% water showed sustained release up to 120 min, whereas the hydrogels with 47 and 67% water showed that nearly all of the insulin was released within 60 min. Hydrogel devices synthesized with 27% water and filled with insulin particles showed sustained release for up to 8 days, whereas the hydrogels synthesized with 47 and 67% water released insulin completely within 3 days of administration. Animal studies suggested that the hydrogel devices synthesized with 27% water and filled with insulin-loaded particles (120 IU) were able to control blood glucose levels for up to 5 days after implantation.