Inclusion complexation of the anticancer drug pomalidomide with cyclodextrins: fast dissolution and improved...

Area of Science:

• Pharmaceutical Sciences
• Supramolecular Chemistry
• Drug Delivery

Background:

• Pomalidomide (POM), a thalidomide analogue, possesses potent anticancer and anti-angiogenic properties.
• Poor aqueous solubility of POM limits its therapeutic efficacy and formulation development.
• Cyclodextrin complexation is a strategy to enhance the solubility of poorly soluble drugs.

Purpose of the Study:

• To improve the aqueous solubility and dissolution of Pomalidomide (POM) through cyclodextrin complexation.
• To characterize the inclusion complex formed between POM and sulfobutylether-β-cyclodextrin (SBE-β-CD).
• To evaluate the impact of complexation on POM's anti-cancer activity and release kinetics.

Main Methods:

• Phase-solubility studies were conducted with nine cyclodextrin derivatives to identify the most effective one.
• Inclusion complexation between POM and SBE-β-CD was characterized using NMR, IR, CD, fluorescence spectroscopy, and XRD.
• Solid-state complexation was achieved via lyophilization, and drug release kinetics were analyzed using Korsmeyer-Peppas and Weibull models.

Main Results:

• Sulfobutylether-β-cyclodextrin (SBE-β-CD) significantly increased POM aqueous solubility.
• A 1:1 stoichiometry of POM:SBE-β-CD complex was confirmed in liquid and solid states.
• The POM-SBE-β-CD complex demonstrated fast dissolution and maintained cytotoxicity against LP-1 myeloma cells.

Conclusions:

• Complexation of Pomalidomide with SBE-β-CD effectively enhances its aqueous solubility and dissolution rate.
• The supramolecular complexation does not compromise the inherent anti-cancer activity of Pomalidomide.
• POM-SBE-β-CD inclusion complex represents a promising strategy for developing improved Pomalidomide formulations.