Carboxyalkylchitosan-based hydrogels with “imine clip”: Enhanced stability and amino acids-induced disassembly under physiological conditions

Stimuli-Responsive Dual Cross-Linked N-Carboxyethylchitosan Hydrogels with Tunable Dissolution Rate

“…This can be related to the contribution of non-covalent interactions to the stabilization of the supramolecular structure of MbSA-cross-linked hydrogels. As we have recently shown [ 17 ], gelation in CEC-salicylimine solution due to non-covalent interactions only was observed already at SA/CEC molar ratio of 1:10. The difference in the evolution of mechanical spectra of CEC hydrogels cross-linked with MbSA ( Figure 1 b) and GA ( Figure S1 , Supplementary Information) confirms the completeness of the hydrogel formation via chemical cross-linking with GA within 30 min in contrast to the increase in strength of the MbSA cross-linked hydrogel within several days.…”

“…A comparison of the rheological properties of chitosan and CEC hydrogels formed after the addition of aromatic monoaldehyde (salicylaldehyde—SA) and dialdehyde (MbSA) to polymer solutions revealed the following features ( Figure 1 and Table S1 , Supplementary Information): (i) MbSA, as a cross-linker capable of forming bis-Schiff bases with primary amino groups of CEC, yields hydrogels with the same storage modulus as can be obtained with SA at a five-fold higher CHO/NH 2 molar ratio ( Figure 1 a, taking into account that 1 mole of MbSA contains 2 moles of CHO groups); (ii) hydrogels formed after the addition of both SA and MbSA in weakly alkaline media (CEC-based hydrogels) were remarkably stronger than hydrogels formed in weakly acidic media (chitosan-based hydrogels) at the same CHO/NH 2 molar ratio ( Figure 1 a); (iii) the storage moduli of CEC/MbSA hydrogels slowly increased within several days as it was earlier observed for salicylimines of CEC and chitosan [ 8 , 17 ] ( Figure 1 b).…”

“…In comparison with the earlier reported cross-linking of glycol chitosan with benzaldehyde-capped PEO-PPO-PEO [ 16 ], MbSA yields hydrogels at a lower molar fraction of cross-linker that correlates with the higher stability of an imine bond formed by aromatic aldehydes with a hydroxyl group in the ortho-position (‘imine clip’). The formation of an ‘imine clip’ between salicylaldehyde and CEC was proved earlier using FT-IR and 13 C-NMR spectroscopy [ 17 ], so the same chemistry can be assumed for cross-linking with MbSA. Despite the low MbSA content in the hydrogels and significant overlapping of MbSA and CEC absorption bands in FT-IR spectra, notable changes were detected in the region of primary and secondary amine absorption (815–910 cm −1 ).…”

“…However, due to chitosan’s solubility in acidic media only, the fabrication of chitosan-based dynamic supramolecular assemblies under physiological pH is not feasible. To overcome this limitation, hydrogels of water-soluble chitosan derivatives have been proposed based on glycol chitosan and benzaldehyde-capped PEO-PPO-PEO [ 16 ], and carboxyalkyl chitosans with salicylaldehyde [ 17 ], vanillin [ 18 ], dibenzaldehyde-terminated poly(ethylene glycol) [ 19 ], and dextran-graft-aniline tetramer-graft-4-formylbenzoic acid [ 20 ]. It was also demonstrated that higher stability of benzoic imine bond at physiological pH resulted in a higher storage modulus of the hydrogels of salicylimines of carboxyalkylchitosans in comparison with chitosan-based hydrogels [ 17 ].…”

“…Since gelation in solutions of Schiff bases of chitosan and its derivatives with aromatic monoaldehydes occurs via non-covalent hydrophobic interactions and hydrogen bonding [ 8 , 14 , 17 , 25 ], we expected that chemical cross-linking via the formation of bis-Schiff bases would yield stronger hydrogels with preserved stimuli-responsive behavior at lower CHO/NH 2 molar ratios.…”