Different zeolite systems for colon cancer therapy: monitoring of ion release, cytotoxicity and drug release behavior

Abstract

Three types of oral administrated micronized zeolites [ZSM-5, zeolite A and Faujasite NaX (ZSM-5, ZA and ZX, respectively)] were prepared as anticancer 5-fluorouracil (5-Fu) delivery systems for colon cancer treatment. They were prepared by economically widespread and cheap natural resource, kaolin, at low temperatures, using microwave advanced tool. The obtained powders were characterized by XRD, SEM/EDX and BET; meanwhile, their degradation was investigated in two gastric fluids; FaSSGF (pH 1.6) and FeSSGF (pH 5), through concentration measurement of their solution disintegrated elemental constituents of Na⁺, Al³⁺ and Si⁴⁺ ions. Also, the processes of drug release and mechanism in both solutions were investigated. Moreover, the inhibition action of 5-Fu-free and 5-Fu-conjugated zeolites on colon cancer cells (CaCo-2) was estimated. The results showed that, the prepared zeolites possessed high surface areas of 526, 250, and 578 m²/g for ZSM-5, ZA and ZX, respectively. Although, zeolite structures seemed significantly stable, their frameworks seemed more likely reactive with time. The ions and drug release for zeolites occurred in successively two stages and found to be pH dependent, where the drug and zeolite ions were significantly of higher values in the more acidic media of the gastric solution (pH 1.6) than those of the mild acidic one (pH 5). The obtained activity indicated no cytotoxic affinity for all the prepared zeolite types. Accordingly, the synthesized zeolite frameworks are proposed to be of strong potential drug delivery vehicle for the treatment of gastrointestinal cancer.

Keywords: Colon cancer; Drug delivery; Fluorouracil (5-Fu); Simulated gastric fluid; Synthetic zeolites.

Fig. 1

XRD patterns with d-spacing values of different zeolites hydrothermally heated at different temperatures and durations via microwave technique

Fig. 2

SEM micrographs and EDX analysis for ZSM-5, ZA and ZX samples

Fig. 3

a Cumulative concentration of Na⁺ (a and b), Al³⁺ (c and d) and Si⁴⁺ (e and f) ions released from ZSM-5, ZA and ZX, and b cumulative concentration fitted with h^−0.5 for Na⁺ (g and h), Al³⁺ (i and j) and Si⁴⁺ (k and l) ions released from ZSM-5, ZA and ZX after soaking in FaSSGF and FeSSGF, respectively

Fig. 4

Cumulative 5-Fu release (%) from ZSM-5, ZA and ZX in distilled FaSSGF and FeSSGF

Fig. 5

Cytotoxic effect of ZSM-5, ZA and ZX (100 µg/ml) with/without 5-FU on colon cancer cell line (CaCo-2) in comparison with pure 5-Fu using MTT assay (n = 3), data expressed as the mean value of cell cytotoxicity (% of control)

Fig. 6

Cytotoxic effect (LC50 values) of free different zeolite samples (ZSM-5, ZA and ZX) and different zeolite samples conjugated with 5-Fu against colon cancer cell line (CaCo-2) compared to 5-Fu using MTT assay (n = 3), data expressed as the mean value of cell cytotoxicity (% of control)