Determination of binding affinity for chenodeoxycholate in equilibrium with sulfobutylether-β-cyclodextrin.

Area of Science:

• Supramolecular Chemistry
• Physical Chemistry
• Pharmaceutical Sciences

Background:

• Chenodeoxycholate (CDC) is a bile acid with potential pharmaceutical applications.
• Sulfobutylether-β-cyclodextrin (SBE-β-CD) is a frequently used pharmaceutical excipient for drug solubilization.
• Understanding the binding interactions between CDC and SBE-β-CD is crucial for developing effective drug formulations.

Purpose of the Study:

• To investigate the relationship between monomeric and total chenodeoxycholate (CDC) concentrations in solutions containing sulfobutylether-β-cyclodextrin (SBE-β-CD).
• To quantify the binding affinity between CDC and SBE-β-CD using a defined binding model.
• To elucidate the stoichiometry of the inclusion complex formed between CDC and SBE-β-CD.

Main Methods:

• Kinetic dialysis technique utilizing radiolabeled chenodeoxycholate (CDC).
• Analysis of CDC solutions with varying concentrations of SBE-β-CD (1 mM and 5 mM).
• Application of a binding model with binding constants (K₁ and K₂) and least-squares fitting for curve optimization.

Main Results:

• A clear relationship was established between monomeric and total CDC concentrations.
• High binding affinity (K₁) and negligible affinity (K₂) indicate the formation of 1:1 inclusion complexes.
• Analysis suggests that 1:2 inclusion complex formation and SBE-β-CD self-association are unlikely under the studied conditions.

Conclusions:

• The study confirms the formation of 1:1 inclusion complexes between CDC and SBE-β-CD.
• The binding affinity was successfully quantified and interpreted.
• This research provides a foundational understanding for further investigations into CDC self-association and binding interactions with cyclodextrins.