Mono-Dendronized β-Cyclodextrin Derivatives as Multitasking Containers for Curcumin. Impacting Its Solubility,...

Area of Science:

• Supramolecular Chemistry
• Materials Science
• Medicinal Chemistry

Background:

• Curcumin (CUR) exhibits limited aqueous solubility and bioavailability.
• Beta-cyclodextrin (βCD) is a known host molecule for improving drug solubility.
• Dendronized βCD derivatives offer potential for enhanced host-guest complexation.

Purpose of the Study:

• To investigate the use of mono-dendronized βCD derivatives as containers for curcumin.
• To evaluate the impact of dendron size on curcumin's aqueous solubility and tautomerism.
• To optimize the formation of curcumin-βCD inclusion complexes.

Main Methods:

• Synthesis and characterization of βCD-1G, βCD-2G, and βCD-3G derivatives.
• Density Functional Theory (DFT) calculations for gas-phase geometry optimization.
• Phase solubility studies to assess curcumin solubilization.
• Comparison of coprecipitation and lyophilization for inclusion complex formation.

Main Results:

• All dendronized βCD derivatives showed improved solubility for CUR compared to native βCD.
• DFT confirmed dendrons did not obstruct CUR entry into the βCD cavity.
• Coprecipitation was more efficient than lyophilization for forming inclusion complexes.
• βCD-2G complexation preferentially stabilized the antioxidant-active diketo tautomer of CUR.

Conclusions:

• Mono-dendronized βCD derivatives are effective carriers for enhancing curcumin solubility and stability.
• The generation of the dendron influences the preorganization and complexation of curcumin.
• The βCD-2G derivative is particularly promising for delivering curcumin in its biologically active diketo tautomeric form.