TY - JOUR
T1 - Interferon-containing controlled-release polymers for localized cerebral immunotherapy
AU - Wiranowska, Marzenna
AU - Ransohoff, Joseph
AU - Weingart, Jon D.
AU - Phelps, Christopher
AU - Phuphanich, Surasak
AU - Brem, Henry
PY - 1998/6
Y1 - 1998/6
N2 - Controlled-release ethylene-vinyl acetate copolymers (EVAc), which were used previously for the in vivo intracerebral delivery of chemotherapeutics, were evaluated as a possible route of localized intracerebral delivery of interferon (IFN). Natural mouse IFN-α/β (Mu-IFN-α/β) was incorporated into polymers at 5% or 10% by weight with 2 x 104 U or 4 x 104 U, respectively. In vitro and in vivo studies of the release of Mu-IFN-α/β from EVAc polymers showed the released IFN to be biologically active, as determined by the inhibition assay of viral cytopathic effect (CPE). Evaluation of the in vitro kinetics of release showed that most of the IFN activity was released in the first 4 days, with the rest being released thereafter. The in vivo kinetic release of Mu-IFN-α/β from intracerebrally implanted polymers showed that most of the IFN activity was released within 24 h after polymer implantation in the hemisphere ipsilateral to the polymer. This IFN activity gradually decreased over the next 72 h, with a significant linear trend (p < 0.0001). The hemisphere contralateral to the implanted polymer showed no significant levels of IFN activity throughout the 4 days of evaluation. By contrast, blood levels of IFN increased from day 1 to day 4, showing a significant linear trend (p = 0.0125), with IFN levels on day 4 being significantly higher (p < 0.05) than on day 1 after polymer implant. This study demonstrates the feasibility of intracranial controlled local delivery of IFN using a polymer delivery device.
AB - Controlled-release ethylene-vinyl acetate copolymers (EVAc), which were used previously for the in vivo intracerebral delivery of chemotherapeutics, were evaluated as a possible route of localized intracerebral delivery of interferon (IFN). Natural mouse IFN-α/β (Mu-IFN-α/β) was incorporated into polymers at 5% or 10% by weight with 2 x 104 U or 4 x 104 U, respectively. In vitro and in vivo studies of the release of Mu-IFN-α/β from EVAc polymers showed the released IFN to be biologically active, as determined by the inhibition assay of viral cytopathic effect (CPE). Evaluation of the in vitro kinetics of release showed that most of the IFN activity was released in the first 4 days, with the rest being released thereafter. The in vivo kinetic release of Mu-IFN-α/β from intracerebrally implanted polymers showed that most of the IFN activity was released within 24 h after polymer implantation in the hemisphere ipsilateral to the polymer. This IFN activity gradually decreased over the next 72 h, with a significant linear trend (p < 0.0001). The hemisphere contralateral to the implanted polymer showed no significant levels of IFN activity throughout the 4 days of evaluation. By contrast, blood levels of IFN increased from day 1 to day 4, showing a significant linear trend (p = 0.0125), with IFN levels on day 4 being significantly higher (p < 0.05) than on day 1 after polymer implant. This study demonstrates the feasibility of intracranial controlled local delivery of IFN using a polymer delivery device.
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U2 - 10.1089/jir.1998.18.377
DO - 10.1089/jir.1998.18.377
M3 - Article
C2 - 9660244
AN - SCOPUS:0031831258
SN - 1079-9907
VL - 18
SP - 377
EP - 385
JO - Journal of Interferon and Cytokine Research
JF - Journal of Interferon and Cytokine Research
IS - 6
ER -