title: Low molecular weight silicones particularly facilitate human serum albumin denaturation.
abstract: There is a market trend towards the administration of therapeutic proteins using sterilized, pre-filled glass syringes lubricated with silicone oil. It has been widely reported that initially clear solutions of proteins can become turbid during transport and storage, with unclear outcomes with respect to bioefficacy. While the basic processes of interactions of proteins with hydrophobic entities, leading to denaturation and aggregation, are increasingly well understood, the apparently random occurrence of such processes in syringes is not. To better understand the parameters that may be responsible for this change, we report the systematic examination of a series of factors that can affect the behavior of the protein human serum albumin (HSA) when in contact with silicone oil in water. Fluorescence spectroscopy showed that greater mixing times and greater concentrations of silicones (polydimethylsiloxane (PDMS)), especially lower molecular weight hydrophobic silicones like octamethyltetracyclosiloxane (D4), were associated with increased protein denaturation. The turbidity of HSA solutions, due to the formation both of silicone oil-in-water (O/W) emulsions and protein aggregates, was also facilitated by the presence of D4. A series of mixtures of silicone oils, all of which exhibited a viscosity of 1000 cSt but which were comprised of different silicone constituents, clearly showed a correlation between the presence of lower molecular silicones and enhanced solution turbidity. While the addition of a non-ionic silicone-polyether surfactant led to greater turbidity by increasing the number of stabilized oil droplets, it was not accompanied by protein denaturation. These results are consistent with HSA denaturation and subsequent aggregation as a consequence of contact particularly with low molecular weight, hydrophobic silicones that are more mobile, leading to more efficient protein/silicone contact.
authors: School of Biomedical Engineering, McMaster University, 1280 Main St. West, Hamilton, ON, Canada L8S 4M1.
authors: Lamees M
authors: LM
authors: Nayef
authors: School of Biomedical Engineering, McMaster University, 1280 Main St. West, Hamilton, ON, Canada L8S 4M1.
authors: Madiha F
authors: MF
authors: Khan
authors: School of Biomedical Engineering, McMaster University, 1280 Main St. West, Hamilton, ON, Canada L8S 4M1; Department of Chemistry and Chemical Biology, McMaster University, 1280 Main St. West, Hamilton, ON, Canada L8S 4M1. Electronic address: mabrook@mcmaster.ca.
authors: Michael A
authors: MA
authors: Brook
mesh_terms: D004655:Emulsions; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D054327:Lubricants / Q000737:chemistry*; D008970:Molecular Weight; D066329:Protein Aggregates; D011489:Protein Denaturation; D012709:Serum Albumin / Q000737:chemistry*; D012827:Silicone Oils / Q000737:chemistry*; D013594:Syringes; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D004655:Emulsions; D054327:Lubricants; D066329:Protein Aggregates; D012709:Serum Albumin; D012827:Silicone Oils; D014867:Water
keywords: Protein aggregation; Protein denaturation; Silicone oil; Syringe lubricants