Low temperature incorporation of bovine serum albumin into a bead formed macroporous hydrophilic polymer matrix with potential for sustained release

Abstract

A process of freeze-thaw polymerization involving the low temperature photopolymerization of a mixed solution of monomers and bovine serum albumin around frozen ice crystals has been used to generate a bead formed macroporous hydrophilic matrix with potential for sustained release. Beads over the size range 100-3000 microns were fabricated with surface and internal pores of between 0.7-2.6 microns whose diameter could be controlled by manipulation of the monomers to solvent ratio. Increasing both the proportion of monomers in the monomer solution and the percentage of BSA incorporated reduced the EWC of beads. The BSA release profile was characterized by an initial burst followed by a lower but sustained release lasting up to 1 month. The total cumulative release of BSA and the proportion of the incorporated BSA load subsequently released were both reduced in physiological saline compared with distilled water but enhanced by freeze drying, mild agitation and incubation at 37 degrees C.

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

“…On the other hand, ultrastructural examination of GOx loaded beads fabricated in the present study using freeze-thaw photopolymerization [14] confirmed that the initial burst release profile (Fig. 1) was not a function of the excessive outer-surface deposition of GOx during fabrication (Fig.…”

“…The largest proportion of beads separated in the S00-1000,um size range and the mean total bead yield expressed as a percentage of the total weight of monomers used was 76.8 ± 3.8% (n = 10). The mean equilibrium buffer (sodium acetate/sodium chloride buffer, pH 7.4) content (EBC) of unloaded p-HEMA beads, expressed as a percentage of the weight of buffer within a bead sample at room temperature and controlled humidity [16] was 71.7 ± 0.92% (n = 15) compared with an EWC value for unloaded p-HEMA beads of 60.0±0.15% (n = 15), [14] (see Fig. 3).…”

“…Macroporous beads containing either IL-2 or glucose oxidase were prepared by a novel freeze-thaw photopolymerization process [14]. Briefly, this involved the rapid mixing of a stable solution of the macromolecule in buffer with the photoinitiator uranyl nitrate and constituent monomers of the hydrophilic matrix using a monomer to solvent ratio of 50:50 and a buffer to ethylene glycol ratio of 4 : 1.…”

“…Clearly, the immobilization of the GOx on the surface of the macropores further enhanced the extent of matrix hydration facilitated by acetate induced network swelling. How this occurs is difficult to ascertain, especially since the incorporation of increasing concentrations of BSA have been shown to significantly and progressively reduce the EWC of p-HEMA beads [14].…”

“…Photopolymerization generates a bead-formed matrix at low temperature which can be harvested, washed, and stored. The effects physicochemical parameters and the fabrication process have on the release of macromolecules from the matrix have been described previously [14,15].…”