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Effect of polyols on the conformational stability and biological activity of a model protein lysozyme

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Abstract

The purpose of this study was to investigate the stabilizing action of polyols against various protein degradation mechanisms (eg, aggregation, deamidation, oxidation), using a model protein lysozyme. Differential scanning calorimeter (DSC) was used to measure the thermodynamic parameters, mid point transition temperature and calorimetric enthalpy, in order to evaluate conformational stability. Enzyme activity assay was used to corroborate the DSC results. Mannitol, sucrose, lactose, glycerol, and propylene glycol were used as polyols to stabilize lysozyme against aggregation, deamidation, and oxidation. Mannitol was found to stabilize lysozyme against aggregation, sucrose against deamidation both at neutral pH and at acidic pH, and lactose against oxidation. Stabilizers that provided greater conformational stability of lysozyme against various degradation mechanisms also protected specific enzyme activity to a greater extent. It was concluded that DSC and bioassay could be valuable tools for screening stabilizers in protein formulations.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, 58105, Fargo, ND

    Somnath Singh & Jagdish Singh

  2. Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University Medical Center, Omaha, NE

    Somnath Singh

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  1. Somnath Singh
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  2. Jagdish Singh
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Singh, S., Singh, J. Effect of polyols on the conformational stability and biological activity of a model protein lysozyme. AAPS PharmSciTech 4, 42 (2003). https://doi.org/10.1208/pt040342

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  • DOI: https://doi.org/10.1208/pt040342

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