Application of new silicone gel to sustained release dosage form of antitumor drug.

Abstract

The object of this study was to develop a sustained release implantable dosage form of a new silicone gel (PHYCON 6600R) which undergoes addition polymerization to produce a solid gel at ordinary temperature. Implantable PHYCON-drug composites were studied as a means of tumor therapy using 3',5'-diesters of 5-fluoro-2'-deoxyuridine (FUdR-Cn) as a model for antitumor drugs. Using an in vitro dissolution test, we found that the release characteristics of drugs from these preparations could be controlled by the addition of powdered L-alanine. In vivo studies of antitumor activity were carried out, using preparations containing the dodecyl ester (FUdR-C12) by measuring the lifespan of lymphoma-inoculated mice. Antitumor activity, reflected in increased lifespan, was shown to be greater following intraperitoneal administration of the PHYCON formulations (drug and L-alanine) than following injections of the drug alone. Our results suggest that sustained release implantable formulations of antitumor drugs in PHYCON might be suitable for tumor chemotherapy.