Controlled macromolecule release from poly(phosphazene) matrices

Abstract

Hydrolytically unstable poly(phosphazene) PPHOS matrices with 50% ethyl glycinato/50% p-methylphenoxy substitution were investigated as vehicles for the controlled release of macromolecules. Specifically, the effects of matrix pH environment and macromolecule loading were studied. 14C-labeled inulin was incorporated into matrices by a solvent casting technique at 1, 10 and 40% loadings (w/w). Degradation and release studies were performed at 37°C at pH 2.0, 7.4 and 10.0. The PPHOS polymer degraded relatively slowly in neutral and basic solutions (pH 7.0 and pH 10.0). In contrast, significantly ( p < 0.01) higher levels of degradation were seen in acidic solutions (pH 2.0) after 35 days. The presence of the hydrophilic macromolecule inulin in the polymer matrix resulted in increased degradation of PPHOS with time. Inulin release, like polymer degradation, was highest at pH 2.0 followed by pH 10.0 and 7.4. Inulin release appeared to be dependent on polymer degradation and inulin diffusion. High inulin loading increased the levels of initial drug burst release and resulted in higher levels of ultimate drug release as measured at 25 days. Environmental scanning electron microscopy (ESEM) demonstrated smooth surfaces on matrices without drug, rough and granular surfaces on matrices loaded with inulin before release, and surfaces possessing micropores and macropores after inulin loading and release. PPHOS polymers can predictably release macromolecules such as inulin. Release can be modulated through changes in pH environment and drug loading.