title: Dual effects of Tween 80 on protein stability.
abstract: In this paper, we used IL-2 mutein as a model protein and evaluated the effect of Tween 80, a non-ionic surfactant. In summary, we found that the dual effects of Tween 80 on the stability of IL-2SA, such as that shaking-induced aggregation of IL-2 mutein was significantly inhibited in the presence of Tween 80. However, this surfactant adversely affected the stability of IL-2 mutein in solution during storage in terms of both oxidation and aggregation. These adverse effects are strongly temperature and formulation-dependent. Data particularly showed that IL-2 mutein in solution forms soluble aggregates to a different degree in different formulations during storage at 40 degrees C for 2 months. Aggregation was barely detectable during storage at 5 degrees C for 22 months. Addition of 0.1% Tween 80 significantly increased the rate of IL-2 mutein aggregation during storage. The IL-2 mutein aggregates are linked by both disulfide and non-disulfide bonds and their relative contribution is temperature-dependent. IL-2 mutein can be oxidized also to a different degree in different formulations during storage and the oxidation rate is strongly temperature-dependent with an activation energy between 21 and 25 kcal/mol. Addition of 0.1% Tween 80 not only increased the rate of oxidation in general but also altered the temperature-dependency of IL-2 mutein oxidation.
authors: Pfizer Inc., Global Biologics, 700 Chesterfield Parkway West, Chesterfield, MO 63017, USA. wei.2.wang@pfizer.com
authors: Wei
authors: W
authors: Wang
authors: Y John
authors: YJ
authors: Wang
authors: D Q
authors: DQ
authors: Wang
mesh_terms: D004356:Drug Storage; D005998:Glycine / Q000737:chemistry; D006639:Histidine / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007376:Interleukin-2 / Q000737:chemistry / Q000235:genetics; D008353:Mannitol / Q000737:chemistry; D009154:Mutation; D009391:Nephelometry and Turbidimetry; D010084:Oxidation-Reduction; D010592:Pharmaceutic Aids / Q000737:chemistry*; D011136:Polysorbates / Q000737:chemistry*; D011489:Protein Denaturation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry; D013314:Stress, Mechanical; D013395:Sucrose / Q000737:chemistry; D013696:Temperature
chemical_list: D007376:Interleukin-2; D010592:Pharmaceutic Aids; D011136:Polysorbates; D011506:Proteins; D011994:Recombinant Proteins; D008353:Mannitol; D006639:Histidine; D013395:Sucrose; D005998:Glycine