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.

Drug resistance reversed by silencing LIM domain-containing protein 1 expression in colorectal carcinoma

“…5-FU and its analogs are widely used as first-line chemotherapeutic agents for patients with advanced CRC and these chemotherapeutics are known to function through various mechanisms (11,12). It has been suggested that upregulated LIMD1 gene expression may be the major mechanism underlying acquired 5-FU resistance in CRC (13). In the context of the agents applied in the present study, the modulation of MRP1 expression was found to clearly sensitize the MDR CRC phenotype to chemotherapy.…”

Natural Polymer/Inorganic Material Based Hybrid Scaffolds for Skin Wound Healing

“…160 Vilaça et al have proved that drug loaded zeolite can be engulfed by colorectal cancer (CRC) cell lines (Fig.14). 166 Our group has conducted numerous studies to evaluate the versatility of zeolites in biomedical field. We prepared several biocomposites like gelatin/zeolite, pectin/zeolite, and gelatin/hyaluronic acid/zeolite scaffolds.…”

<I>In Vitro</I> and <I>In Vivo</I> Evaluation of Pectin/Copper Exchanged Faujasite Composite Membranes

“…The supercage is linked to several 12 membered rings with diameter of 0.74 nm. 47 The negative lattice charge of faujasite is balanced by positively charged copper ions which are entrapped within pores of zeolite. 48 It has been reported that copper ions are effective in causing in vitro bacterial inactivation by binding to the microbial DNA, preventing bacterial replication, 49 thus improving the antibacterial property of faujasites.…”