David Collins

Sustained in vivo activity of recombinant human granulocyte colony stimulating factor (rHG-CSF) incorporated into hyaluronan

Abstract Recombinant human granulocyte colony stimulating factor (rHG-CSF), was incorporated into viscous solutions of hyaluronan (HA) for subcutaneous injection into hamsters. Incorporation of rHG-CSF into HA caused no apparent aggregation or degradation of the protein after storage for up to 6 weeks at either 4°C or 37°C. Subcutaneous (s.c.) injection of rHG-CSF alone caused an elevation of white blood cells (WBC) which peaked at 24 h and returned to baseline 48 h after injection. By contrast, s.c. injection of rHG-CSF formulated in 2% (w/v) HA (rHG-CSF/2% HA) yielded elevated WBC at 4–5 days after injection. rHG-CSF/2% HA exhibited prolonged elevation of plasma rHG-CSF levels for up to 4 days after s.c. injection as compared to rHG-CSF alone. Both the molecular weight and concentration of HA affected the viscosity and release of rHG-CSF after injection. At equal viscosity, incorporation of rHG-CSF into higher M r HA exhibited a more prolonged WBC elevation than rHG-CSF incorporated into lower M r HA; at equal M r , 2% (w/v) and 4% (w/v) solutions of HA exhibited more prolonged elevation of WBC than did 1% (w/v) HA. However, no significant difference in release was noted between the 2% (w/v) and 4% HA (w/v) formulations. These results are discussed in relation to the non-ideal colloid osmotic properties of HA.