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

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.