Dual Phase‐Conversion Strategy Reinforced Otitis Media Therapy Using Metastable Iron Sulfide‐Loaded Thermosensitive Hydrogel

Abstract Otitis media (OM) is a common bacterial disease in otolaryngology, which has a high incidence rate and seriously affects people's health and quality of life. The abuse of antibiotics is a severe public health problem worldwide, contributing to the emergence of multidrug‐resistant bacteria and vestibular/cochlear damage, leading to sensorineural hearing loss. In this study, PLGA‐PEG‐PLGA thermosensitive hydrogel (PPPTH) is employed as a drug delivery carrier to deliver metastable cystine‐denoted iron sulfides compounds (Cys‐nFeS) to treat Staphylococcus aureus (S. aureus) ‐induced OM by topical injection through the eardrum. The combination of Cys‐nFeS and PPPTH (Cys‐nFeS/PPPTH) prevents Cys‐nFeS from rapidly oxidizing and constantly releasing Cys‐nFeS, fulfilling the goal of continuous therapy. The destructive effect of Cys‐nFeS/PPPTH on bacteria and bacterial biofilms in vitro and in vivo is evaluated. The results show that Cys‐nFeS/PPPTH has good antibacterial and biofilm destruction effects, low cytotoxicity, and excellent anti‐inflammatory effects. Moreover, it is found that Cys‐nFeS/PPPTH can repair S. aureus ‐induced hearing loss in OM. This study demonstrates the promising potential of Cys‐nFeS/PPPTH for middle ear delivery and antibacterial treatment.