Polyol-induced increases in thermal stability of antibodies by DSC

Polyol-induced increases in thermal stability of antibodies

Learn how differential scanning calorimetry can be used to assess the effects of polyol excipients on antibodies. DSC was used to monitor polyol-induced increases in thermal stability across seven monoclonal antibodies. The increases in thermal stability were measured as a function of polyol concentration and orientation of hydroxyl groups. It was found that increases in thermal stability were linear with respect to alcohol concentration.

Introduction

Aggregation of proteins has been an intense area of study largely due to the growth of the biotechnology industry. As protein therapeutics are developed, aggregation must be monitored and reduced as it can potentially cause immunogenicity¹ as well as a possible decrease in activity.^2,3 One of the ways aggregation is controlled is through the use of osmolytes as excipients.⁴ Many excipients have been shown to induce stability through preferential exclusion. A particular subclass of these molecules includes polyols and carbohydrates.^5,6 Polyols are typically added to protein formulations in order to increase tonicity and improve stability.

The addition of polyol osmolytes has been shown to prevent aggregation, retain activity, inhibit chemical degradation, enhance the refolding of proteins,⁷ and increase the thermal stability of proteins.^4-6,8-11 It has been shown that the more hydroxyl groups on the carbon chain of the polyol, the greater the thermodynamic stability that can be induced. This has been attributed to an entropic effect where the polyol is excluded from the surface of the protein. The polyol has a greater impact on the water-peptide interactions than it does on the interactions with the nonpolar groups that are exposed when the protein is denatured.¹²