INTERFERON-CONTAINING CONTROLLED-RELEASE POLYMERS FOR LOCALIZED CEREBRAL IMMUNOTHERAPY

Controlled-release ethylene-vinyl acetate copolymers (EVAc), which wer e used previously for the in vivo intracerebral delivery of chemothera peutics, were evaluated as a possible route of localized intracerebral delivery of interferon (IFN). Natural mouse IFN-alpha/beta (Mu-IFN-al pha/beta) was incorporated into polymers at 5% or 10% by weight with 2 x 10(4) U or 4 x 10(4) U, respectively. in vitro and in vivo studies of the release of Mu-IFN-alpha/beta from EVAc polymers showed the rele ased IFN to be biologically active, as determined by the inhibition as say of viral cytopathic effect (CPE), Evaluation of the in vitro kinet ics of release showed that most of the IFN activity was released in th e first 4 days, with the rest being released thereafter. The in vivo k inetic release of Mu-IFN-alpha/beta from intracerebrally implanted pol ymers showed that most of the IFN activity was released within 24 h af ter polymer implantation in the hemisphere ipsilateral to the polymer, This IFN activity gradually decreased over the next 72 h, with a sign ificant linear trend (p < 0.0001). The hemisphere contralateral to the implanted polymer showed no significant levels of IFN activity throug hout the 4 days of evaluation. By contrast, blood levels of IFN increa sed from day 1 to day 4, showing a significant linear trend (p = 0.012 5), with IFN levels on day 4 being significantly higher (p < 0.05) tha n on day 1 after polymer implant. This study demonstrates the feasibil ity of intracranial controlled local delivery of IFN using a polymer d elivery device.