Polyethyleneimine/Glucuronic acid-grafted carbon nanotubes for 5-fluorouracil delivery: adsorption optimization, pH-responsive release, and in-vitro cytotoxicity

Advances in nanocarrier engineering are central to improving chemotherapeutic performance and mitigating systemic side effects. In this study, a multifunctional platform based on oxidized single-walled carbon nanotubes (OXSWCNTs) was engineered through sequential grafting of polyethyleneimine (PEI) and conjugation with glucuronic acid (GlcA) for the efficient loading and controlled release of 5-fluorouracil (5-FU). Structural and physicochemical analyses (Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Brunauer–Emmett–Teller (BET) analysis, and Thermal gravimetry (TG)) verified successful surface construction, preserved tubular morphology, and enhanced thermal stability. The nanocomposite demonstrated an adsorption capacity (q) of 17.6 mg g−1 with a drug loading efficiency of 88% under the selected kinetic conditions (pH 4, 20 mg dosage, 90 min) at the initial drug concentration of 20 mg L−1. Adsorption kinetics were best described by the pseudo-second-order model (R2 ≥ 0.9999), while the Freundlich isotherm analysis indicated adsorption on a heterogeneous surface with multilayer coverage. Thermodynamic parameters (ΔH° = –22.6 kJ mol−1, ΔG° < 0) confirmed a spontaneous and exothermic process. In-vitro release studies revealed pronounced pH-responsiveness, with cumulative release reaching 88% at slightly acidic pH (5.6) compared to 52% at physiological pH (7.4) after 48 h. Release kinetics followed the Peppas–Sahlin model, suggesting a non-Fickian mechanism involving both diffusion and polymer relaxation. In-vitro cytotoxicity evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on human colorectal cancer cells (HT-29) showed a clear reduction in cell viability from 77% for OXSWCNT–PEI–GlcA to 60% upon 5-FU loading at 50 µg mL⁻1. These results support the suitability of OXSWCNT–PEI–GlcA as a nanocarrier with high drug-loading capacity, stable adsorption, and pH-triggered release; and further indicate its potential for controlled 5-FU delivery under tumor-relevant conditions.