INTRODUCTION

IgG antibodies have been engineered in receptor binding sites for therapeutic applications as treatment of cancer and autoimmune diseases.  While changes in amino acid sequence to the overall structure are minimal, dramatic differences in solution viscosity is observed especially at high concentrations which are required for subcutaneous delivery.  The viscosity of various antibody solutions can vary from 2 centi Poise (cP) to 90 cP at 125 mg/ml.  This has a substantial impact on biotechnological manufacturing processes and drug administration.  We have systematically measured rheological properties of antibody solutions as a function of ionic strength and Hofmeister series.

EXPERIMENTAL

Anton Paar US300 rheometer was used for rotational rheometry to determine shear rate dependence on viscosity.  The shear rate ranged between 0.5 to 5000 1/sec.  The antibody concentration was above 125mg/ml in various buffer conditions. 

RESULTS

Solution viscosity is measured for 125mg/ml antibody solution in 30mM histidine at pH 6.0 (Figure 1).  At this concentration, the solution behaves as a Newtonian fluid.  As salt is added to the antibody solution, the viscosity is reduced.  It is more effectively reduced for chaotropes than kosmotropes.

Figure 1.  Impact of salts on solution viscosity of 125mg/ml antibody solution in 30mM histidine buffer at pH 6.0.  Various salts of sodium are added to the antibody solution.   

CONCLUSION

Solution viscosity was reduced by the addition of salts.  Solution viscosity is more effectively reduced with chaotropes than with kosmotropes.  We hypothesize electrostatic interaction plays a role in breaking self-association of antibody solution at high concentrations. 

ACKNOWLEDGEMENTS

We acknowledge Drs. Tom Patapoff and Tom Scherer for helpful discussions. 

REFERENCE

1.     Liu J.; Nguyen M.D.H.; Andya J.D.; Shire S.J. J. Pharm. Sci. 2005, 94, 1928.