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Reduced protein adsorption at solid interfaces by sugar excipients.

Janet R Wendorf1, Clayton J Radke, Harvey W Blanch

  • 1Department of Chemical Engineering, University of California, Berkeley, California 94720-1462, USA.

Biotechnology and Bioengineering
|September 8, 2004
PubMed
Summary

Sugar excipients significantly reduce protein adsorption to surfaces. Higher sugar concentrations and larger sugar molecules (trisaccharides) were most effective, stabilizing proteins in solution.

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Area of Science:

  • Biochemistry
  • Materials Science
  • Pharmaceutical Sciences

Background:

  • Protein adsorption at liquid-solid interfaces is crucial in biopharmaceutical formulation and medical devices.
  • Understanding factors that modulate protein adsorption is essential for preventing denaturation and aggregation.
  • Sugar excipients are commonly used in protein formulations, but their impact on adsorption needs detailed investigation.

Purpose of the Study:

  • To investigate the effect of various sugar excipients on the adsorption of model proteins (ribonuclease A, bovine serum albumin, hen egg white lysozyme) at the liquid-solid interface.
  • To determine the relationship between sugar concentration, sugar structure, and the extent of protein adsorption.
  • To elucidate the mechanism by which sugar excipients influence protein adsorption.

Main Methods:

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  • Adsorption experiments were conducted using model proteins and various sugar excipients at different concentrations.
  • Protein adsorption was quantified at the liquid-solid interface.
  • The heat of solution for amorphous saccharides was measured and correlated with protein adsorption data.

Main Results:

  • Sugar excipients demonstrably reduced the adsorption of ribonuclease A, bovine serum albumin, and hen egg white lysozyme.
  • Protein adsorption decreased proportionally with increasing sugar concentration.
  • The efficacy of sugars in reducing adsorption followed a hierarchy: trisaccharides > disaccharides > 6-carbon polyols > monosaccharides.
  • A correlation was observed between the heat of solution of amorphous saccharides and the amount of protein adsorbed.

Conclusions:

  • Sugar excipients effectively mitigate protein adsorption by stabilizing the native state of proteins in solution.
  • The size and structure of sugar molecules play a significant role in their ability to prevent protein adsorption.
  • The thermodynamic properties of sugar excipients, such as heat of solution, are linked to their protein-stabilizing capabilities, offering insights for formulation design.