Abstract
We have developed a novel sustained-release system for protein drugs using silicone. The silicone formulation is an injectable dosage form, and designed to maintain the protein drug effects for months by sustained-release. Since the silicone formulation can be prepared without heating nor organic solvents, various protein drugs, which are generally unstable, can be applied to the silicone formulation. The purposes of the study are (1) to investigate the drug release from the silicone formulation in vivo, and (2) to improve the release profiles. In this study, interferon (IFN) was used as an example of the protein drugs. The IFN silicone formulation was prepared and investigated IFN release profiles in vitro for 30 days. The IFN silicone formulation released IFN through this period in a first-order profile. When the IFN silicone formulations were administered into nude mice which bore human renal cell carcinoma, the IFN silicone formulation significantly inhibited the growth of the tumor. From these results, it is found that IFN was released from silicone without loss of its bioactivity. For these experiments, matrix type IFN silicone formulation was used, and its release profile was first-order as above mentioned. In order to achieve zero-order release, a covered-rod type IFN silicone formulation has been developed. We found that the covered-rod silicone formulation released IFN in a zero-order profile for 60 days in vitro. In addition, it maintained serum IFN concentration for 30 days in nude mice. The half life of the serum IFN concentration after the administration of the IFN covered-rod formulation was about 158 hrs, which was 26 folds longer than that of IFN aqueous solution. From these results, the silicone formulation is thought to be especially effective for the treatment of chronic diseases and for preventive treatment of high risk patients.
