Doxorubicin Loaded Polyphosphate Glass Microspheres for Transarterial Chemoembolization

Abstract

Polyphosphate glass microspheres (PGM) are currently under development for application in transarterial chemoembolization (TACE), the standard of care treatment for intermediate stage hepatocellular carcinoma. PGMs are radiopaque, hemostatic, and resorbable. This thesis investigates the compatibility of doxorubicin (DOX), a chemotherapeutic, with this PGM system.

A process was developed to synthesize PGMs that were efficiently loaded with DOX, spherical in nature, and in the clinically relevant size range. DOX release and PGM degradation were assessed as a function of elution media pH, PGM composition, and %DOX loading. In vitro cytocompatibility of PGM degradation products and the pharmacological activity of released DOX were also evaluated.

Composition, therapeutic loading, and pH minimally affected PGM degradation. DOX release was mediated by eluant pH, and was highly linear while appearing to retain its pharmacological activity. However, PGM degradation products were also found to be cytotoxic. Overall, this PGM system shows promise as a TACE device.