title: Potentiation of 5-fluorouracil encapsulated in zeolites as drug delivery systems for in vitro models of colorectal carcinoma.
abstract: The studies of potentiation of 5-fluorouracil (5-FU), a traditional drug used in the treatment of several cancers, including colorectal (CRC), were carried out with zeolites Faujasite in the sodium form, with different particle sizes (NaY, 700nm and nanoNaY, 150nm) and Linde type L in the potassium form (LTL) with a particle size of 80nm. 5-FU was loaded into zeolites by liquid-phase adsorption. Characterization by spectroscopic techniques (FTIR, (1)H NMR and (13)C and (27)Al solid-state MAS NMR), chemical analysis, thermal analysis (TGA), nitrogen adsorption isotherms and scanning electron microscopy (SEM), demonstrated the successful loading of 5-FU into the zeolite hosts. In vitro drug release studies (PBS buffer pH 7.4, 37°C) revealed the release of 80-90% of 5-FU in the first 10min. To ascertain the drug release kinetics, the release profiles were fitted to zero-order, first-order, Higuchi, Hixson-Crowell, Korsmeyer-Peppas and Weibull kinetic models. The in vitro dissolution from the drug delivery systems (DDS) was explained by the Weibull model. The DDS efficacy was evaluated using two human colorectal carcinoma cell lines, HCT-15 and RKO. Unloaded zeolites presented no toxicity to both cancer cells, while all DDS allowed an important potentiation of the 5-FU effect on the cell viability. Immunofluorescence studies provided evidence for zeolite-cell internalization.
authors.affiliation: Centre of Chemistry, Chemistry Department, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
authors.forename: Natália
authors.initials: N
authors.lastname: Vilaça
authors.forename: Ricardo
authors.initials: R
authors.lastname: Amorim
authors.forename: Ana F
authors.initials: AF
authors.lastname: Machado
authors.forename: Pier
authors.initials: P
authors.lastname: Parpot
authors.forename: Manuel F R
authors.initials: MF
authors.lastname: Pereira
authors.forename: Mariana
authors.initials: M
authors.lastname: Sardo
authors.forename: João
authors.initials: J
authors.lastname: Rocha
authors.forename: António M
authors.initials: AM
authors.lastname: Fonseca
authors.forename: Isabel C
authors.initials: IC
authors.lastname: Neves
authors.forename: Fátima
authors.initials: F
authors.lastname: Baltazar
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008856:Microscopy, Fluorescence; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D017550:Spectroscopy, Fourier Transform Infrared; D017641:Zeolites
chemical_list: D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D053769:Nanocapsules; C539489:faujasite; D017641:Zeolites; D005472:Fluorouracil
keywords: 5-Fluorouracil (5-FU); Cytotoxicity; Drug delivery; Encapsulation; Potentiation; Zeolites