Development of Nanoparticle Antibiotic Adjuvant for the Treatment of Chronic Suppurative Otitis Media
Royal National Institute for Deaf People
Stanford University
We request support to investigate the use of functionalized gold nanoclusters as an adjuvant therapy for chronic suppurative otitis media (CSOM). CSOM is characterized by a chronically discharging infected middle ear that is most frequently caused by Pseudomonas aeruginosa (PA) and Staphylococcus aureus and is a leading cause of permanent hearing loss. In CSOM, PA exists in bacterial communities known as biofilms. Fluoroquinolone eardrops are the primary method of treatment; however, this treatment is ineffective in fully eradicating the infection because of the inability of fluoroquinolones to target a subpopulation of metabolically inactive bacteria known as persister cells within the biofilms. Persister cells repopulate the biofilm niche after therapy discontinuation, causing relapse of CSOM. The result is multiple rounds of surgery and a lifelong struggle with CSOM. There is a large unmet need to develop new medical therapies aimed at persister cells in biofilms of CSOM. Our lab recently created a novel PA CSOM animal model with bioluminescent strains of PA and validated it as mimicking human disease in chronicity, fluoroquinolone therapy recalcitrance, and hair cell death (hearing loss). We have created an anionic hydrophilically functionalized gold nanocluster covalently conjugated with cell penetrating peptide (AuNC@CPP) as an adjuvant for fluoroquinolones. Co-administration of the AuNC@CPP with ofloxacin completely eliminates persister cells in both stationary phase and biofilms of PA in vitro. The proposed work will develop the first adjuvant therapy that specifically targets recalcitrant CSOM and lays the foundation for future research of this treatment in other chronic biofilm infections.
5.1 Pharmaceuticals