Silicone oil induced aggregation of proteins.
Prior to delivery to the patient, protein pharmaceuticals often come in contact with a variety of surfaces (e.g., syringes and stoppers), which are treated to facilitate processing or to inhibit protein binding. One such coating, silicone oil, has previously been implicated in the induction of protein aggregation. We have investigated the propensity of model proteins to aggregate when silicone oil is present in solution and find significant induction of aggregation in four proteins of various molecular weights and isoelectric points in the presence of 0.5% oil. The ability of silicone oil to induce conformational changes that might be responsible for this aggregation was also examined by a combination of circular dichroism (CD) and derivative UV spectroscopy. Neither method produces evidence of large conformational changes or alterations in thermal stability although in a limited number of cases some small changes suggest the possibility of minor structural alterations. The most probable explanation for silicone oil induced aggregation is that the oil has direct effects on intermolecular interactions responsible for protein association through interaction with protein surfaces or indirectly through effects on the solvent.
Jones
Latoya S
LS
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047-3729, USA.
Kaufmann
Allyn
A
Middaugh
C Russell
CR
D002942:Circular Dichroism; D003208:Concanavalin A / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008970:Molecular Weight; D009113:Muramidase / Q000737:chemistry; D009391:Nephelometry and Turbidimetry; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D012259:Ribonuclease, Pancreatic / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D012827:Silicone Oils / Q000737:chemistry*; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet
D011506:Proteins; D012827:Silicone Oils; D012996:Solutions; D003208:Concanavalin A; D012710:Serum Albumin, Bovine; D012259:Ribonuclease, Pancreatic; D009113:Muramidase