Weak antibody-cyclodextrin interactions determined by quartz crystal microbalance and dynamic/static light scattering

Area of Science:

• Biochemistry
• Physical Chemistry
• Pharmaceutical Sciences

Background:

• Antibody stabilization against stress is crucial for biopharmaceutical formulations.
• Hydroxypropyl β-cyclodextrin (HPβCD) is a potential excipient for antibody stabilization.
• Two hypotheses for HPβCD's mechanism: surface activity vs. specific protein interactions.

Purpose of the Study:

• To investigate the mechanism of antibody stabilization by HPβCD.
• To determine if HPβCD interacts directly with monoclonal antibodies.
• To differentiate between surface activity and specific interactions as the stabilizing mechanism.

Main Methods:

• Quartz Crystal Microbalance (QCM) to study protein adsorption.
• Static and Dynamic Light Scattering to analyze protein-protein interactions.
• Investigated IgG antibodies in native and unfolded states.

Main Results:

• HPβCD reduced IgG antibody adsorption onto surfaces in both folded and unfolded states.
• Light scattering data showed increased repulsive forces between protein molecules with increasing HPβCD concentration.
• These findings suggest HPβCD interacts with antibodies, reducing hydrophobicity and altering intermolecular forces.

Conclusions:

• HPβCD's stabilizing effect on IgG antibodies is likely due to direct interactions with the protein.
• The mechanism is not attributed to HPβCD's surface activity.
• Direct cyclodextrin-protein interactions modulate antibody behavior and enhance stability.