Thermodyn amic study on the interaction of excipients and protein
- VernacularTitle:热力学研究辅料与蛋白药物之间的相互作用
- Author:
Wenjuan WANG
;
Bingquan WANG
;
Jun HAN
- Publication Type:Journal Article
- Keywords:
protein formulation;
IgG1 monoclonal antibody;
thermal stability;
excipient;
amino acid;
specific interaction
- From:
Chinese Journal of Biochemical Pharmaceutics
2015;37(7):5-9
- CountryChina
- Language:Chinese
-
Abstract:
Objective To determine the effects of different excipients ( amino acids, carbohydrates and nonionic surfactants) on thermal stability of the IgG1 monoclonal antibody, and to examine the interactions between the excipients and the protein.Methods Differential scanning calorimetry ( DSC) was used to study thermal stability of the protein in different solutions and got information on the solubility of the unfolded forms of the protein.Isothermal titration calorimetry ( ITC) was used to examine the binding interactions between the excipients and the protein.ResuIts Negatively charged amino acids could significantly reduce the denaturation temperature (Tm) of IgG1( Tm >9 ℃), and other excipients didn’t have a major effect ( Tm <1℃).Excipients shared different impacts on thermal stability of the IgG1 monoclonal antibody under different pH, and negatively charged amino acids result in a much lower Tm at pH 5 than at pH 7.The ITC binding isotherms of different excipients (including polysorbate 20 and 80) and IgG1 were almost straight lines, while there was strong binding interaction between polysorbate 20 or 80 and Human Serum Albumin (HSA).ConcIusion The results suggest that there is no binding interaction between these studied excipients and the IgG1 monoclonal antibody; instead electrostatic interactions seem to play a leading role between the excipients and the IgG1 monoclonal antibody.
