Evaluation of porous networks of poly(2-hydroxyethyl methacrylate) as interfacial drug delivery devices

Abstract

Long-term implantable drug delivery devices are desirable to achieve rapid and reliable delivery of bioactive substances to the body. The limitation of most implantable devices is the resulting chronic inflammatory response and fibrous encapsulation of the implant, which prevents effective drug delivery for prolonged periods. One method of overcoming this problem is the addition of an intermediary that could prevent capsule formation. Biocompatible materials with interconnected pore structures greater than 8–10 μm have been shown to support the ingrowth and maintenance of vascularized tissue. In this investigation, we evaluate the efficacy of using porous hydrogel sponges for the tissue interface in an implantable drug delivery device. Porous networks of poly(2-hydroxyethyl methacrylate) (PHEMA) were synthesized using a thermally initiated free-radical solution polymerization. To characterize the microstructure of the PHEMA networks, scanning electron microscopy and mercury porosimetry were used. By altering the solvent fraction in the reaction mixture, PHEMA sponges were synthesized with interconnected pores ranging in size from from 6 to 15 μm with porosities of 55% to 87%. Following the in vitro evaluation, sponges were attached to the distal end of a 20-gauge catheter tubing, and implanted subcutaneously and intraperitoneally. After 5 months implantation, insulin was infused into the devices from external pumps and rapid insulin absorption was observed in conjunction with dramatic lowering of blood glucose levels. From histological evaluation of explanted devices, we observed highly vascularized tissue surrounding the mesenteric implants. These results indicate that it may be possible to use PHEMA sponges for a tissue intermediary for long-term implantable drug delivery devices.