Alginate sulfonamide hydrogel beads for 5-fluorouracil delivery: antitumor activity, cytotoxicity assessment, and theoretical investigation

This study focused on grafting a new monomer (E)-N-(4-(3-(4-bromophenyl) acryloyl) phenyl)-4-methyl benzene sulfonamide (Br-PS) onto sodium alginate (Alg) using a free radical polymerization method. The optimal parameters for the grafting polymerization reaction were investigated, including initiator and monomer concentrations, polymerization reaction duration, and temperature. Additionally, the conversion, graft, and solid content percentages were calculated. The resulting novel poly (Br-PS)-g-Alg was thoroughly analyzed using Fourier-transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H NMR), and scanning electron microscopy (SEM). Moreover, poly (Br-PS)-g-Alg was tested for cytotoxicity and selectivity values on lung cancer cell line (A549), breast cancer cell line (MDA-MB-231), and a normal cell line (MDCK) using the neutral red uptake test. Poly (Br-PS)-g-Alg demonstrated more inhibitory impact (IC50 = 33.37 and 40.9 μg/mL) and high selectivity (selectivity index = 4.83 and 3.94) on the A549 and MDA-MB-231 cell lines, respectively. Furthermore, uniform beads of creative poly (Br-PS)-g-Alg were fabricated, and their swelling rate in various media was studied. These beads could potentially serve as drug carriers for 5-fluorouracil (5-FU). Release experiments in simulated gastric (SGF) and intestinal fluids (SIF) showed a slower 5-FU release pattern in SGF compared to SIF. The proposed structures of poly (Br-PS)-g-Alg were theoretically verified using density functional theory with DFT/B3LYP/6–31(G) basis set, revealing distinct interactions due to the presence of different functional groups. The findings of this study could significantly impact the development of new drug delivery systems. [Display omitted] •Free radical polymerization of sodium alginate with sulphonamide chalcone (Br-PS) and spectral investigation.•Elucidation of different interactions between alginate and Br-PS monomer utilized DFT/B3LYP/6–31(G)basis set.•Anti-proliferative activity of alginate and the synthesized polymer using A549, MDA-MB-231 tumor cells•Drug release of 5-flurouracil on the Ca+2 alginate beads at different Ph and physical interaction between them.