Supramolecular Hydrogel Based on Pseudopolyrotaxane Aggregation for Bacterial Microenvironment‐Responsive Antibiotic Delivery

Due to the extensive use of antibiotics, the variety and number of drug-resistant pathogens have increased dramatically and have become a major global health problem. This imposes significant demands on the rational and effective use of antibiotics. To this end, a supramolecular hydrogel based on pseudopolyrotaxanes aggregation is proposed for antibiotic delivery. Supramolecular cross-linking strategies allow hydrogels to be obtained under mild conditions that facilitate the encapsulation of antibiotics. The presence of pH-sensitive imine bonds allows for the reversible detachment of PEG residues from the PEGylated hyaluronic acid backbone in an acidic environment, which leads to reversible changes in hydrogel crosslink density and thus controls antibiotic release behavior. Antimicrobial assessments indicated that the hydrogel exhibited good antimicrobial efficiency against both Gram-positive and negative bacteria, while responding to the bacterial microenvironment and enabling a burst release of antibiotics in severe infections. The proposed hydrogel also has excellent biocompatibility and thus possesses great potential for biomedical applications.