RELEASE OF TAXOL FROM POLY(EPSILON-CAPROLACTONE) PASTES - EFFECT OF WATER-SOLUBLE ADDITIVES

We have developed a taxol-loaded polymeric surgical paste for applicat ion at tumor resection sites. The paste vehicle is based on poly(epsil on-caprolactone) (PCL), a low melting, biodegradable, biocompatible po lymer containing dispersed water-soluble additives. Following gentle h eating to between 44-56 degrees C, the paste can be applied in the mol ten state from a syringe to tumor resection sites. Taxol/additives wer e co-precipitated, pulverized and incorporated into molten low molecul ar weight PCL. The taxol/additive/PCL composite was characterized usin g swelling in water, drug release into phosphate buffered saline (pH 7 .4) at 37 degrees C and scanning electron microscopic studies on sampl es suspended in water. In vivo drug release and anti-angiogenic activi ty of the composites were evaluated using the chick chorioallantoic me mbrane (CAM) assay. In addition, in vivo efficacy was investigated usi ng a subcutaneous tumor in mice. The in vitro release of taxol from PC L was increased by the addition of water-soluble agents. Taxol release d from the matrix inhibited angiogenesis in the CAM model and caused a mean tumor regression of about 63% in a mice tumor model.