The incorporation and release of glucose oxidase and interleukin 2 from a bead formed macroporous hydrophilic polymer matrix

Abstract

Freeze-thaw photopolymerization at low temperature of a mixed solution of 2-hydroxyethyl methacrylate (HEMA), ethylene glycol dimethacrylate (EDM), and either glucose oxidase (GOx) or interleukin 2 (IL-2) around frozen ice crystals has been used to generate a bead-formed macroporous hydrophilic matrix with potential for immobilization and sustained release. The mean equilibrium acetate buffer content (EBC) of unloaded p-HEMA beads at room temperature and controlled humidity was ≈72%. The incorporation of GOx into beads significantly increased the EBC to ≈76%. The release of GOx was characterized by a short initial burst release which declined rapidly until by day 14 no further biologically active enzyme release could be detected. Bead size had no significant effect on the total mean cumulative release of GOx at room temperature. Since only ≈ 4% of the original therapeutic load of GOx was released over 14 days a substantial proportion of biologically active enzyme had become associated with the hydrogel matrix surface generating a bead formed immobilised enzyme system. Total cumulative release profiles for IL-2 were almost linear and maintained for at least 16 days. In absolute terms, the proportion of the original theoretical incorporated load subsequently released over this period was low. However, such a low level sustained release of IL-2 may lend itself therapeutically to a reduction in unwanted non-specific systemic activity.

Osmotic-Driven Release Kinetics of Bioactive Therapeutic Proteins from a Biodegradable Elastomer are Linear, Constant, Similar, and Adjustable

“…It was shown that severe toxicity can be induced by the prolonged high doses of systemic IL-2 (28). Previous attempts on localized IL-2 delivery include the use of dextran gels (29), liposomes (30,31), PLGA microspheres (32,33), and HEMA films (34). These studies showed that VEGF and IL-2 can be released for a 1-to 3-week period, but these delivery methods suffered from the rapid initial burst release, low total fraction released, nonlinear release, and rapid protein denaturation within the first week of release.…”

Therapeutic efficacy of IL‐2‐loaded hydrogels in a mouse tumor model

“…Several delivery systems for IL‐2 have been used, both liposomal formulations and polymer‐based release systems7–17 (for review, see ref. 18), but control over the release rate of IL‐2 has been difficult to achieve.…”