Synthesis, cytotoxicity, and phase-solubility study of cyclodextrin click clusters

Area of Science:

• Supramolecular Chemistry
• Pharmaceutical Excipients
• Drug Delivery Systems

Background:

• Conventional cyclodextrins (CDs) are widely used as pharmaceutical excipients but have limitations in solubility and drug complexation.
• Novel CD derivatives are needed to overcome these restrictions and improve drug formulation efficacy.
• Cyclodextrin click clusters (CCCs) represent a new class of CD-based excipients synthesized via click chemistry.

Purpose of the Study:

• To synthesize and characterize novel cyclodextrin click clusters (CCCs) as potential pharmaceutical excipients.
• To evaluate the water solubility, cytotoxicity, and drug-solubilizing capabilities of the synthesized CCCs.
• To compare the properties of CCCs with conventional cyclodextrin derivatives.

Main Methods:

• Synthesis of three CCCs: HT-β-CD, HT-β-CD(OMe)2, and ST-β-CD, using copper(I)-catalyzed azide-alkyne cycloaddition.
• Assessment of water solubility using water turbidity testing.
• Evaluation of cytotoxicity via MTT cell viability assay on HeLa cells.
• Determination of drug-solubilizing effect using a phase-solubility study with prednisolone.

Main Results:

• The synthesized CCCs exhibited at least 20 times higher water solubility compared to native β-cyclodextrin.
• CCCs demonstrated low cytotoxicity, with HT-β-CD(OMe)2 and ST-β-CD showing no cytotoxicity at tested concentrations (∼5 mM).
• Phase-solubility studies indicated that CCCs effectively increased the solubility of prednisolone in a concentration-dependent manner.

Conclusions:

• Cyclodextrin click clusters (CCCs) are viable alternatives to conventional cyclodextrin derivatives.
• CCCs offer superior water solubility and reduced cytotoxicity, making them promising excipients for pharmaceutical applications.
• The enhanced properties of CCCs can help overcome limitations associated with traditional cyclodextrin chemistry in drug formulation.