Formation and Characterization of Cisplatin-Loaded Poly(benzyl 1-glutamate) Microspheres for Chemoembolization

Chemoembolization using microspheres of 100- to 200-µm is a useful way to treat primary and secondary hepatic tumors. In a search for a better embolic material, we described in detail the preparation and characterization of a poly(benzyl 1-glutamate) (PBLG) microspheres containing cisplatin (CDDP). We determined the optimal experimental conditions to produce spherical free-flowing microspheres that were able to release drug content (44% [w/w] CDDP) in a sustained manner. We found that solvent viscosity played a key role in determining the resulting microsphere characteristics. Microscopic studies showed that increasing the polymer concentration (to 10% [w/v]) and the viscosity of the organic phase produced microspheres with uniform drug distribution. Increasing polymer concentration also markedly improved drug incorporation efficiency. In vitro release studies revealed that the release of CDDP was a function of drug loading; microspheres with a higher amount of entrapped CDDP had a slower release rate. This observation and the fact that CDDP/ PBLG microspheres did not show “burst effect” at higher loading is ascribed to the formation of uniformly distributed drug crystal networks within the polymer matrix. The favorable properties of the CDDP/PBLG system warrants its further evaluation on experimental animal models for the treatment of hepatic tumors.