Thermosensitive Injectable Dual Drug-Loaded Chitosan-Based Hydrogels for Treating Bacterial Endometritis

Endometritis, a prevalent obstetric condition primarily caused by <i>Escherichia coli</i> (<i>E. coli)</i> and <i>Staphylococcus aureus</i> (<i>S. aureus</i>), significantly threatens the reproductive performance of female animals. In this study, thermosensitive injectable chitosan (CS)/β-glycerophosphate (β-GP) hydrogels loaded with berberine (BBR) and carvacrol (CAR) were prepared for endometritis treatment. <i>In vitro</i>, BBR/CAR-CS/β-GP hydrogels exhibited rapid gelation within 5 min at 37 °C, excellent injectability, and more than 90% degradation within 30 days under enzymatic action. The dual drug-loaded system also exhibited controlled release of BBR and CAR and demonstrated the antimicrobial activity against <i>E. coli</i> and <i>S. aureus</i>. <i>In vivo</i>, uterine injection of BBR/CAR-CS/β-GP hydrogels alleviated infection-induced injuries and reduced the bacterial load in infected uterine tissues. In summary, these findings highlight the potential of BBR/CAR-CS/β-GP hydrogels as innovative carriers for drug delivery targeting endometritis.