Abstract:
The capability of Pluronic® F68 to stabilize human recombinant Factor VIII in solution was
assessed using zeta potential measurements. Hemophilia A is a genetic disorder in which the
body is missing Factor VIII (FVIII) from the blood coagulation cascade. The pharmaceutical
industry developed recombinant Factor VIII (rFVIII), the largest cloned molecule, as a viable
treatment option for the missing protein. The protein suffers instability in solution which
leads to aggregation, precipitation, and adsorption. Current formulations of rFVIII include
the surfactant Tween 80 as a stabilization aid. Pluronic® F68, another surfactant, has been
shown to prevent sheer in mammalian cell cultures mainly by enhancing cell resistance to
sheer stress. Pluronic® F68 may be able to increase the stability of rFVIII for prevention of
aggregation and precipitation. The stabilization of rFVIII was monitored using a zeta
potentiometer with silica as a model surface. Zeta potential was unable to register a
significant change for the initial concentrations of rFVIII used. Investigations were
performed by increasing the amount of rFVIII and testing the effect of Tween 80 on the silica
microspheres. The zeta potentiometer was not sensitive enough to register any conclusive
results as to the effectiveness of Pluronic® F68 due to interactions with Tween 80. Further
research is required to determine the effectiveness of Pluronic® F68 for rFVIII stabilization.
