Alpha- and Beta-Cyclodextrin Inclusion Complexes with 5-Fluorouracil: Characterization and Cytotoxic Activity
Cristina Di Donato1, Margherita Lavorgna2, Roberto Fattorusso3
1Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, via Antonio Vivaldi 43, 81100 Caserta, Italy. cristina.didonato@unina2.it.
Molecules (Basel, Switzerland)
|December 6, 2016
Summary
Cyclodextrin complexation enhances the bioavailability and solubility of 5-fluorouracil, a chemotherapy drug. These complexes show improved cytotoxic activity against various cancer cell lines, suggesting potential for better cancer treatment formulations.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Medicinal Chemistry
Background:
- Cyclodextrins are natural macrocyclic oligosaccharides that form inclusion complexes, modifying guest molecule properties.
- 5-fluorouracil (5-FU) is a pyrimidine analogue used in chemotherapy for colon, liver, and stomach cancers, but its bioavailability and solubility can be limiting.
- Improving 5-FU's physicochemical and pharmaceutical properties is crucial for enhancing its therapeutic efficacy.
Purpose of the Study:
- To improve the bioavailability and solubility of 5-fluorouracil (5-FU) by complexing it with alpha- and beta-cyclodextrins.
- To characterize the solid-state and solution properties of the 5-FU/cyclodextrin inclusion complexes.
- To evaluate the impact of cyclodextrin complexation on the cytotoxic activity of 5-FU against various cancer cell lines.
Main Methods:
- Solid-state inclusion complexes prepared by kneading method.
- Characterization using Fourier transform-infrared (FT-IR) spectroscopy and X-ray powder diffractometry.
- Solution studies included Job plot method for stoichiometry, UV-VIS titration for binding constants at different pHs, and MTT assay for cytotoxic activity against MCF-7, Hep G2, Caco-2, and A-549 cell lines.
Main Results:
- Both alpha- and beta-cyclodextrin inclusion complexes were successfully prepared and characterized.
- 1:1 stoichiometry was confirmed for all complexes, with binding constants determined at various pHs.
- Complexation significantly enhanced the cytotoxic activity of 5-FU. Beta-cyclodextrin complex showed highest activity against MCF-7 (IC50 = 31 µM at 72h), while alpha-cyclodextrin complex was most potent against A-549 (IC50 = 73 µM at 72h).
Conclusions:
- Cyclodextrin complexation offers a viable strategy to improve the solubility and bioavailability of 5-fluorouracil.
- The enhanced cytotoxic activity of the inclusion complexes suggests their potential for improved therapeutic efficacy in cancer treatment.
- These findings support the use of 5-FU/cyclodextrin inclusion complexes in pharmaceutical formulations for more effective cancer chemotherapy.
