Mechanistic Understanding of Protein- Silicone Oil Interactions

Purpose: To investigate interactions between protein and silicone
oil so that we can provide some mechanistic understanding of
protein aggregation in silicone oil lubricated syringes and its prevention
by formulation additives such as Polysorbate 80 and
Poloxamer 188.
Methods: Interfacial tension values of silicone oil/water interface
of abatacept solutions with and without formulation
additives were obtained under equilibrium conditions using
Attension Theta optical tensiometer. Their adsorption and
desorption profiles were measured using Quartz Crystal
Microbalancing with Dissipation monitoring (QCM-D). The
degree of aggregation of abatacept was assessed based on
size exclusion measurement.
Results: Adsorption of abatacept at the oil/water interface was
shown. Polysorbat 80 was more effective than Poloxamer 188
in preventing abatacept adsorption. Moreover, it was noted that
some of the adsorbed abatacept molecules were not desorbed
readily upon buffer rinse. Finally, no homogeneous aggregation
was observed at room temperature and a slight increase of
aggregation was only observed for samples measured at 40°C
which can be prevented using Polysorbate 80.
Conclusions: Interfacial adsorption of proteins is the key step
and maybe responsible for the phenomenon of soluble-protein
loss when contacting silicone oil and the irreversible adsorption
of protein may be associated with protein denaturation/
aggregation.