Hydrolytically unstable poly(phosphazene) PPHOS matrices with 50% ethy
l glycinato/50% p-methylphenoxy substitution were investigated as vehi
cles for the controlled release of macromolecules. Specifically, the e
ffects of matrix pH environment and macromolecule loading were studied
. C-14-labeled inulin was incorporated into matrices by a solvent cast
ing technique at 1, 10 and 40% loadings (w/w). Degradation and release
studies were performed at 37 degrees C at pH 2.0, 7.4 and 10.0. The P
PHOS polymer degraded relatively slowly in neutral and basic solutions
(pH 7.0 and pH 10.0). In contrast, significantly (p < 0.01) higher le
vels of degradation were seen in acidic solutions (pH 2.0) after 35 da
ys. The presence of the hydrophilic macromolecule inulin in the polyme
r matrix resulted in increased degradation of PPHOS with time. Inulin
release, like polymer degradation, was highest at pH 2.0 followed by p
H 10.0 and 7.4. Inulin release appeared to be dependent on polymer deg
radation and inulin diffusion. High inulin loading increased the level
s of initial drug burst release and resulted in higher levels of ultim
ate drug release as measured at 25 days. Environmental scanning electr
on microscopy (ESEM) demonstrated smooth surfaces on matrices without
drug, rough and granular surfaces on matrices loaded with inulin befor
e release, and surfaces possessing micropores and macropores after inu
lin loading and release. PPHOS polymers can predictably release macrom
olecules such as inulin. Release can be modulated through changes in p
H environment and drug loading.