title: Application of PHYCON 6600 to achieve sustained release of an antitumor drug (carmofur).
abstract: This study attempted to develop sustained release implantable dosage forms based on PHYCON 6600, a new silicone gel. The solid gel is prepared at ambient temperature by polymerization of two basic components (PHYCON A and PHYCON B solutions) for about 1 h. The application we explored was the use of implantable PHYCON-drug composites in tumor therapy. Carmofur (1-hexylcarbamoyl-5-fluorouracil, HCFU) was chosen as a practical antitumor drug. Using an in vitro dissolution test, near zero-order release rate was observed over a period of about 35 days. The amount of drug released by the 'burst phenomenon' was found to be less than the HCFU toxic dose. In vivo studies of antitumor activity were carried out by measuring the lifespan of lymphoma-inoculated mice (ILS). The increase in lifespan (38.5%) following intraperitoneal administration of the PHYCON formulations was similar to that (36.4%) following injection of the drug alone for 5 days. Our results suggest that the injectable and implantable sustained release formulations of the antitumor drug in PHYCON might be suitable for tumor chemotherapy.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Imasaka
authors.forename: H
authors.initials: H
authors.lastname: Ueda
authors.forename: T
authors.initials: T
authors.lastname: Azuma
authors.forename: T
authors.initials: T
authors.lastname: Nagai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations; D004343:Drug Implants; D005079:Excipients; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020034:Silicone Gels; D012828:Silicones
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004343:Drug Implants; D005079:Excipients; C069501:Phycon 6600; D020034:Silicone Gels; D012828:Silicones; C017367:carmofur; D005472:Fluorouracil