title: Alpha- and Beta-Cyclodextrin Inclusion Complexes with 5-Fluorouracil: Characterization and Cytotoxic Activity Evaluation.
abstract: Cyclodextrins are natural macrocyclic oligosaccharides able to form inclusion complexes with a wide variety of guests, affecting their physicochemical and pharmaceutical properties. In order to obtain an improvement of the bioavailability and solubility of 5-fluorouracil, a pyrimidine analogue used as chemotherapeutic agent in the treatment of the colon, liver, and stomac cancers, the drug was complexed with alpha- and beta-cyclodextrin. The inclusion complexes were prepared in the solid state by kneading method and characterized by Fourier transform-infrared (FT-IR) spectroscopy and X-ray powder diffractometry. In solution, the 1:1 stoichiometry for all the inclusion complexes was established by the Job plot method and the binding constants were determined at different pHs by UV-VIS titration. Furthermore, the cytotoxic activity of 5-fluorouracil and its complexation products were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on MCF-7 (breast cancer cell line), Hep G2 (hepatocyte carcinoma cell line), Caco-2 (colon adenocarcinoma cell line), and A-549 (alveolar basal epithelial carcinoma cell line). The results showed that both inclusion complexes increased the 5-fluorouracil capability of inhibiting cell growth. In particular, 5-fluorouracil complexed with beta-cyclodextrin had the highest cytotoxic activity on MCF-7; with alpha-cyclodextrin the highest cytotoxic activity was observed on A-549. The IC50values were equal to 31 and 73 µM at 72 h, respectively. Our results underline the possibility of using these inclusion complexes in pharmaceutical formulations for improving 5-fluorouracil therapeutic efficacy.
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, via Antonio Vivaldi 43, 81100 Caserta, Italy. cristina.didonato@unina2.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Di Donato
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, via Antonio Vivaldi 43, 81100 Caserta, Italy. margherita.lavorgna@unina2.it.
authors.forename: Margherita
authors.initials: M
authors.lastname: Lavorgna
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, via Antonio Vivaldi 43, 81100 Caserta, Italy. roberto.fattorusso@unina2.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Fattorusso
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, via Antonio Vivaldi 43, 81100 Caserta, Italy. carla.isernia@unina2.it.
authors.forename: Carla
authors.initials: C
authors.lastname: Isernia
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, via Antonio Vivaldi 43, 81100 Caserta, Italy. marina.isidori@unina2.it.
authors.forename: Marina
authors.initials: M
authors.lastname: Isidori
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, via Antonio Vivaldi 43, 81100 Caserta, Italy. gaetano.malgieri@unina2.it.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Malgieri
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, via Antonio Vivaldi 43, 81100 Caserta, Italy. concetta.piscitelli@unina2.it.
authors.forename: Concetta
authors.initials: C
authors.lastname: Piscitelli
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, via Antonio Vivaldi 43, 81100 Caserta, Italy. chiara.russo@unina2.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Russo
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, via Antonio Vivaldi 43, 81100 Caserta, Italy. luigi.russo2@unina2.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Russo
authors.affiliation: Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, via Antonio Vivaldi 43, 81100 Caserta, Italy. rosa.iacovino@unina2.it.
authors.forename: Rosa
authors.initials: R
authors.lastname: Iacovino
mesh_terms: D018938:Caco-2 Cells; D005472:Fluorouracil / Q000737:chemistry / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D009369:Neoplasms / Q000188:drug therapy*; D047391:alpha-Cyclodextrins / Q000737:chemistry / Q000494:pharmacology; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000494:pharmacology
chemical_list: D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins; D005472:Fluorouracil
keywords: 5-fluorouracil; cyclodextrin; cytotoxicity; inclusion complex