Supramolecular Hydrogel Formation Based on Inclusion Complexation Between Poly(ethylene glycol)-Modified Chitosan and α-Cyclodextrin

Supramolecular hydrogels have been prepared on the basis of polymer inclusion complex (PIC) formation between poly(ethylene glycol) (PEG)‐modified chitosans and α‐cyclodextrin (α‐CD). A series of PEG‐modified chitosans were synthesized by coupling reactions between chitosan and monocarboxylated PEG using water‐soluble carbodiimide (EDC) as coupling agent. With simple mixing, the resultant supramolecular assembly of the polymers and α‐CD molecules led to hydrogel formation in aqueous media. The supramolecular structure of the PIC hydrogels was confirmed by differential scanning calorimetry (DSC), X‐ray diffraction, and 13C cross‐polarized/magic‐angle spinning (CP/MAS) NMR characterization. The PEG side‐chains on the chitosan backbones were found to form inclusion complexes (ICs) with α‐CD molecules, resulting in the formation of channel‐type crystalline micro‐domains. The IC domains play an important role in holding together hydrated chitosan chains as physical junctions. The gelation property was affected by several factors including the PEG content in the polymers, the solution concentration, the mixing ratio of host and guest molecules, temperature, pH, etc. All the hydrogels in acidic conditions exhibited thermo‐reversible gel‐sol transitions under appropriate conditions of mixing ratio and PEG content in the mixing process. The transitions were induced by supramolecular association and dissociation. These supramolecular hydrogels were found to have phase‐separated structures that consist of hydrophobic crystalline PIC domains, which were formed by the host‐guest interaction between α‐CD and PEG, and hydrated chitosan matrices below the pKa. The formation of inclusion complexes between α‐cyclodextrin and PEG‐modified chitosan leads to the formation of hydrogels that can undergo thermo‐reversible supramolecular dissociation.