Synthesis and Characterization of Methoxy-Exfoliated Montmorillonite Nanosheets as Potential Carriers of 5-Fluorouracil Drug with Enhanced Loading, Release, and Cytotoxicity Properties

• Published in: Molecules (Basel, Switzerland) Vol. 28; no. 15; p. 5895
• Main Authors: Alqahtani, Mashael D, Bin Jumah, May N, Al-Hashimi, Abdulrahman, Allam, Ahmed A, Abukhadra, Mostafa R, Bellucci, Stefano
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.08.2023; MDPI
• Subjects: 5-fluorouracil; Adsorption; Bentonite; Chemicals; Chemotherapy; Clay; Colorectal cancer; Comparative analysis; Cytotoxicity; Drug dosages; Ethylenediaminetetraacetic acid; exfoliation; Fluorouracil; Investigations; loading; Methanol; Montmorillonite; Product enhancement; Ultrasonic imaging; Egypt; 5-fluorouracil; methanol; bentonite; loading; exfoliation; cytotoxicity
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28155895

Natural bentonite clay (BE) underwent modification steps that involved the exfoliation of its layers into separated nanosheets (EXBE) and further functionalization of these sheets with methanol, forming methoxy-exfoliated bentonite (Mth/EXBE). The synthetically modified products were investigated as enhanced carriers of 5-fluorouracil as compared to raw bentonite. The modification process strongly induced loading properties that increased to 214.4 mg/g (EXBE) and 282.6 mg/g (Mth/EXBE) instead of 124.9 mg/g for bentonite. The loading behaviors were illustrated based on the kinetic (pseudo-first-order model), classic isotherm (Langmuir model), and advanced isotherm modeling (monolayer model of one energy). The Mth/EBE carrier displays significantly higher loading site density (95.9 mg/g) as compared to EXBE (66.2 mg/g) and BE (44.9 mg/g). The loading numbers of 5-Fu in each site of BE, EXBE, and Mth/EXBE (>1) reflect the vertical orientation of these loaded ions involving multi-molecular processes. The loading processes that occurred appeared to be controlled by complex physical and weak chemical mechanisms, considering both Gaussian energy (<8 KJ/mol) as well as loading energy (<40 KJ/mol). The releasing patterns of EXBE and Mth/EXBE exhibit prolonged and continuous properties up to 100 h, with Mth/EXBE displaying much faster behaviors. Based on the release kinetic modeling, the release reactions exhibit non-Fickian transport release properties, validating cooperative diffusion and erosion release mechanisms. The cytotoxicity of 5-Fu is also significantly enhanced by these carriers: 5-Fu/BE (8.6% cell viability), 5-Fu/EXBE (2.21% cell viability), and 5-Fu/Mth/EXBE (0.73% cell viability).