Self-association of cyclodextrins and cyclodextrin complexes in aqueous solutions

Area of Science:

• Supramolecular Chemistry
• Pharmaceutical Sciences

Background:

• Cyclodextrins (CDs) are oligosaccharides forming self-assembled structures in aqueous solutions.
• These structures include transient clusters, nanoparticles, and microparticles with varying critical aggregation concentrations (cac).

Purpose of the Study:

• To investigate the critical aggregation concentration (cac) of various cyclodextrins (CDs) in aqueous solutions.
• To understand the impact of factors like chemical modifications, chaotropic agents, and drug complexation on CD aggregation and its implications for pharmaceutical applications.

Main Methods:

• Estimation of critical aggregation concentration (cac) for native cyclodextrins (αCD, βCD, γCD) and a modified cyclodextrin (HPβCD) in aqueous media.
• Analysis of the influence of chaotropic agents and drug/CD complex formation on cac values.

Main Results:

• Native CDs (αCD, βCD, γCD) exhibit low cac values (25, 8, 9 mg/ml).
• HPβCD shows a significantly higher cac (118 mg/ml).
• Chaotropic agents increase cac, while drug complexation can either increase or decrease it.

Conclusions:

• Transient CD aggregates, though often overlooked, significantly impact CD physiochemical properties and pharmaceutical utility.
• Understanding cac and aggregation behavior is crucial for optimizing drug solubilization and delivery, particularly through mucosal membranes via drug/CD complex nanoparticles.