Effects of arginine on photostability and thermal stability of IgG1 monoclonal antibodies

This study demonstrates that arginine is a highly effective solvent additive which significantly reduces the light induced aggregation of four IgG1 type monoclonal antibodies (named as IMC-1A, IMC-1B, IMC-1C and IMC-1D) as measured by size exclusion chromatography. All experiments were performed in...

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Bibliographic Details
Published inCurrent pharmaceutical biotechnology Vol. 10; no. 8; p. 761
Main Authors Maity, Haripada, O'Dell, Courtney, Srivastava, Arvind, Goldstein, Joel
Format Journal Article
LanguageEnglish
Published Netherlands 01.12.2009
Subjects
Antibodies, Monoclonal - chemistry
Arginine - pharmacology
Buffers
Calorimetry, Differential Scanning
Chromatography, Gel
Chromatography, High Pressure Liquid
Drug Stability
Immunoglobulin G - chemistry
Light
Photochemical Processes
Protein Folding
Protein Stability
Solubility
Spectrometry, Fluorescence
Temperature
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Summary:This study demonstrates that arginine is a highly effective solvent additive which significantly reduces the light induced aggregation of four IgG1 type monoclonal antibodies (named as IMC-1A, IMC-1B, IMC-1C and IMC-1D) as measured by size exclusion chromatography. All experiments were performed in a phosphate buffer system containing either sodium chloride or arginine hydrochloride. The protein samples were exposed to light in a photo chamber according to ICH (International Conference on Harmonization) guidelines. Thermal unfolding transition temperature (T(m)) of IMC-1A as determined by differential scanning calorimetry (DSC) was significantly decreased ( approximately 3.3 degrees C) in the presence of arginine hydrochloride as compared to in sodium chloride. However, a noticeable increase in thermal stability was observed for IMC-1B, IMC-1C and IMC-1D in the presence of arginine hydrochloride. The photostability of all these molecules was significantly enhanced by arginine hydrochloride and both a direct and inverse correlation was observed between conformational stability and photostability. To our knowledge, this paper for the first time, demonstrates that arginine hydrochloride considerably reduces the light induced aggregation of monoclonal antibodies. Arginine hydrochloride is also known to increase protein solubility and its ability to extensively reduce light induced aggregation makes it a potential solvent additive for the formulation development of therapeutic proteins.
ISSN:1873-4316
DOI:10.2174/138920109789978711