Sustained-release of urease from a poloxamer gel matrix

With the increase of extremely specific polypeptide drugs arising from advances in recombinant DNA techniques, there exists a need with which to optimally deliver these genetically engineered drugs. This results from the normally short circulating half-life of these macromolecules. A well characterized model enzyme, urease, was formulated in a 20, 30, and 35% w/w poloxamer 407 gel matrix and the release profile determined in a membraneless diffusion system (Area = 11.4 cm2) in vitro at 37 degrees C over 8 hours. Polymer release into a pH = 7.0 phosphate buffer receptor phase due to matrix erosion was constant throughout 8 hours and ranged from 1.07% +/- 0.04 cm-2 hr-1 to 0.48% +/- 0.02 cm-2 hr-1 for the 20% w/w and 35% w/w poloxamer gel matrices, respectively. The predominant mechanism governing release of protein from the semisolid, poloxamer 407 gel matrix in vitro was matrix erosion with the cumulative urease released ranging from 89.5% +/- 3.5 after 7 hours (20% w/w, n = 3) to 46.6% +/- 0.3 following 8 hours of released (35% w/w, n = 3), respectively. The percent relative biological activity of the enzyme [(Act.poly/Act.cont)*100] remaining was determined following incubation in a 14% w/w concentration of poloxamer 407 for 8 hours at 4, 22, and 37 degrees C. The percent relative enzyme activity remaining following incubation in the 14% w/w poloxamer 407 solution after 8 hours was not significantly different (p greater than 0.05) between samples incubated at 4 degrees C (94.2% +/- 2.4) and 37 degrees C (89.7% +/- 1.7). Hydrodynamic properties of dilute urease and poloxamer 407 solutions were assessed using viscometry.(ABSTRACT TRUNCATED AT 250 WORDS)