Formation of Supramolecular Gels from Host–Guest Interactions between PEGylated Chitosan andα‐Cyclodextrin

Abstract Chitosan‐based hydrogels are prepared via the formation of polypseudorotaxanes (PPR), by selectively threading α ‐cyclodextrin ( α ‐CD) macrocycles onto polymeric chains, which, through the formation of microcrystalline domains, act as junction points for the network. Specifically, host–guest inclusion complexes are formed between α ‐CD and PEGylated chitosan (PEG‐Ch), resulting in the formation of supramolecular gels. PEG‐grafted chitosan is obtained with a reaction yield of 79.8%, a high degree of grafting (50.9% GW) and water solubility (≈16 mg mL −1 ), as assessed by turbidimetry. A range of compositions for mixtures of PEG‐Ch solutions (0.2–0.8% w/w) and α ‐CD solutions (2−12% w/w, or 0.04–0.2% mol) are studied. Regardless of PEG content, gels are not formed at low α ‐CD concentrations (<4%). Dynamic rheology measurements reveal stiff gels (G’ above 15k) and a narrow linear viscoelastic region, reflecting their brittleness. The highest elastic modulus is obtained for a hydrogel composition of 0.4% PEG‐Ch and 6% α ‐CD. Steady‐state measurements, cycling between low and high shear rates, confirm the thixotropic nature of the gels, demonstrating their capacity to fully recover their mechanical properties after being exposed to high stress, making them good candidates to use as in‐situ gel‐forming materials for drug delivery to topical or parenteral sites.