Pharmacologic Effect of Recombinant Human IFN-alpha, Continuously Released from a Matrix Prepared from a Polyglycerol Ester of Fatty Acids, on 2',5'-Oligoadenylate Synthetase Activity in Murine Liver

The objective of this study was to assess the pharmacologic effect of continuously released recombinant human interferon-alpha (rHuIFN-alpha) in the liver, the target organ of chronic hepatitis B and C, using 2',5'-oligoadenylate synthetase (2',5'-OAS) activity as an indicator of an antiviral state. A cylindrical matrix prepared from tetraglycerol dipalmitate (TGDP), a polyglycerol ester of fatty acids (PGEF), released rHuIFN-alpha in a pseudo-zero-order manner for about 1 week after implantation into mice, without any major loss of rHuIFN alpha biologic activity during the release period. To evaluate the pharmacologic effect of the rHuIFN-alpha continuously released from this type of matrix, we established a murine test system. Bolus injections of rHuIFN-alpha solution at three doses increased 2',5'-OAS activities in murine liver extract and serum in a dose-dependent manner, indicating that this system is suitable for evaluating rHuIFN-alpha activity. After subcutaneous insertion of TGDP-matrix implants ...