Release of taxol from poly(epsilon-caprolactone) pastes: Effect of water-soluble additives

We have developed a taxol-loaded polymeric surgical paste for application at tumor resection sites. The paste vehicle is based on poly(epsilon-caprolactone) (PCL), a low melting, biodegradable, biocompatible polymer containing dispersed water-soluble additives. Following gentle heating to between 44-56 degrees C, the paste can be applied in the molten state from a syringe to tumor resection sites. Taxol/additives were co-precipitated, pulverized and incorporated into molten low molecular weight PCL. The taxol/additive/PCL composite was characterized using swelling in water, drug release into phosphate buffered saline (pH 7.4) at 37 degrees C and scanning electron microscopic studies on samples suspended in water. In vivo drug release and anti-angiogenic activity of the composites were evaluated using the chick chorioallantoic membrane (CAM) assay. In addition, in vivo efficacy was investigated using a subcutaneous tumor in mice. The in vitro release of taxol from PCL was increased by the addition of water-soluble agents. Taxol released from the matrix inhibited angiogenesis in the CAM model and caused a mean tumor regression of about 63% in a mice tumor model.