Bioactive chitosan sulfonamide hydrogels and nanohydrogels: design, synthesis and characterization

Abstract

Chitosan is a versatile polysaccharide that can be modified to enhance its properties for diverse biomedical applications. Sulfonamide derivatives can be utilized in the development of drugs and bioactive compounds. In this study, chitosan was modified with diphenyl sulfone 3,3'-disulfonyl chloride to produce hydrogel Cs-DPS -I, along with its analogs nanohydrogel NCs-DPS-III. Furthermore, in the presence of glutaraldehyde, hydrogel Cs-DPS-G-II, and its corresponding nanohydroge l NCs-DPS-G-IV were synthesized through Schiff-base formation. The chemical structure, composition, and morphology of the hydrogels and nanohydrogels were evidenced by different techniques. The swelling behavior of the hydrogels and nanohydrogels was studied under various pH values (3.0, 7.0 and10.0) and temperatures (25, 40, 60 and 80 °C). Furthermore, the loading efficiency, capacity and release of 5-fluorouracil (5-FU) onto the hydrogels and nanohydrogels were assessed. Among the tested hydrogels, Cs-DPS-I displayed the most promising results in terms of drug-loading efficiency and capacity for 5-FU that reached 83.8% and 172.8 mg/g, respectively. The prepared hydrogel Cs-DPS-I-Alg exhibited the highest drug-release rate at pH 1.2, which reached 85.54%. In addition, the antimicrobial efficacy of newly synthesized hydrogels and nanohydrogels was evaluated against a range of Gram-positive bacteria, Gram-negative bacteria, and selected fungi. The hydrogel Cs-DPS-G-II demonstrated superior inhibitory activity toward the examined bacterial strains, including Staphylococcus aureus (22), Bacillus subtilis (21), Escherichia coli (16) and proteus (19). Also, it exhibited the most significant effect against the tested fungi, Aspergillus (22) and Candida (24). These findings demonstrated that modifying chitosan with diphenyl sulfone 3,3`-disulfonyl chloride enhances its biologic potency.

Graphical abstract