Studies on the non-covalent complexes between oleanolic acid and cyclodextrins using electrospray ionization tandem...

Area of Science:

• Supramolecular Chemistry
• Analytical Chemistry
• Pharmaceutical Sciences

Background:

• Oleanolic acid (OA) is a natural anti-inflammatory compound.
• Cyclodextrins (CDs) are widely used to improve drug solubility and bioavailability.
• Understanding non-covalent complex formation is crucial for drug delivery applications.

Purpose of the Study:

• To investigate the formation and stability of non-covalent inclusion complexes between oleanolic acid (OA) and alpha-, beta-, and gamma-cyclodextrins (CDs).
• To establish a correlation between solution-phase complexation and gas-phase behavior using ESI-MS(n).
• To evaluate the potential of ESI-MS(n) as a tool for assessing non-covalent complex stability.

Main Methods:

• Solubility studies to assess complex formation in solution.
• Electrospray ionization tandem mass spectrometry (ESI-MS(n)) for gas-phase analysis.
• Molecular modeling calculations to support experimental findings.

Main Results:

• A direct correlation was observed between solution association constants and gas-phase complex stability as measured by ESI-MS(n).
• Stable 1:1 inclusion complexes were formed with all three CDs, with beta- and gamma-CDs also forming 2:1 complexes.
• Multi-component complexes (e.g., alpha-CD-OA-beta-CD) were identified, suggesting sandwich-type complexation by beta- and gamma-CDs.
• Gas-phase stability order was determined as alpha-CD-OA < beta-CD-OA < gamma-CD-OA.

Conclusions:

• ESI-MS(n) is a reliable method for evaluating solution-phase non-covalent complexes.
• Beta- and gamma-cyclodextrins can form complex inclusion structures with oleanolic acid, including sandwich-type complexes.
• The study provides insights into the supramolecular interactions relevant for enhancing the delivery of oleanolic acid.