Dextran-Coated Iron Oxide Nanoparticles Loaded with 5-Fluorouracil for Drug-Delivery Applications

Abstract

This study aims to design and test different formulations composed of dextran-coated iron oxide nanoparticles (IONPs) loaded with 5-Fluorouracil (5-FU) with varying nanoparticle:drug ratios on colorectal cancer cells. The stable suspension of IONPs s was synthesized by the adapted co-precipitation method. The stable suspension of IONPs was mixed with a solution of dextran and 5-FU solubilized in a saline solution. The final suspensions with optimized ratios of IONP:5-FU in the final suspension were 0.5:1, 1:1, and 1.5:1. The information on the morphology and size distribution of the IONPs suspension and IONP loads with 5-FU was obtained using scanning electron microscopy (SEM). The presence of 5-FU and dextran on the surface of the IONPs was highlighted by energy-dispersive X-ray spectroscopy (EDS) studies. The determination of the surface charge of the nanoparticles in the final suspensions of IONP:5-FU was achieved by measuring the zeta potential (ζ). The hydrodynamic diameter of the resulting suspensions of IONP:5-FU was determined by dynamic light scattering (DLS). A cytocompatibility analysis was performed using Caco-2 (human epithelial colorectal adenocarcinoma) cells. In this research, our goal was to find a relationship between the formulation ratio of nanoparticles and drug, and the cellular response after exposure, as a strategy to increase the efficacy of this drug-delivery system. The nanoparticle uptake and antitumor activity, including modulation of oxidative stress, apoptosis, and proliferation biomarkers, were analyzed. The present study showed that the nanoformulation with the ratio IONP:5-FU 1.5:1 had the highest anti-tumor efficiency. Moreover, decreased MCM-2 expression in Caco-2 cells exposed to dextran-coated iron oxide nanoparticles loaded with 5-FU was demonstrated for the first time.

Dual ionotropic crosslinked biopolymer magnetic nanocomposites as 5‐Fluorouracil nanocarrier for potential colorectal cancer treatment

“…An obvious inconsistent 5FU release of Cs‐Alg 5FU NCs compared to Cs‐Alg/IO 5FU NCs was observed after 24 h at pH 4.2 which caused the protonation of ‐NH 2 groups of Cs and ‐COOH groups of Alg weaken the interaction between Alg and Cs in acidic medium resulted unstable formulation with burst release of 5FU 69 . The drug release consistency of Cs‐Alg/IO 5FU NCs in both pH conditions may contributed by the continuous magnetic field and negative surface charge of Fe 3 O 4 NPs, which also increases stability, 70,71 as supported by the zeta potential results. The significant difference of final drug released in pH 4.2 between both NCs contributed by the presence of Fe 3 O 4 NPs which act as co‐crosslinking agent that forms more interaction and compressed network between biopolymers and 5FU 72 .…”