Topical treatment of eosinophilic otitis media and sinusitis using lysozyme-polysaccharide conjugates

Eosinophilic otitis media and sinusitis are intractable disorders characterized by eosinophilic inflammation associated with bronchial asthma, which can be considered as a unified airway disease rather than as disorders with localized eosinophilic inflammation. The production of eosinophilic mucin and emergence of antibiotic-resistant bacteria at the site of inflammation are factors that make it difficult to treat eosinophilic otitis media and sinusitis. Therefore, development of a new topical agent with adequate antibacterial activity against the antibiotic-resistant bacteria and adequate efficacy for removing the viscous mucin is being sought. Therefore, we focused on lysozyme, which has already been used as a medical preparation, with its anti-inflammatory effects and antibacterial activity against some Gram-positive bacteria. In this study, we developed lysozyme-polysaccharide conjugates using the Maillard reaction to improve the aforementioned activities and examined the antibacterial activity against antibiotic-resistant bacteria and the inner ear toxicity of lysozyme-polysaccharide conjugates, for potential development of a cleaning agent for the middle ear. Testing of the antibacterial activity of lysozyme-chitosan conjugate showed antibacterial activities against MRSA and P. aeruginosa. In addition, the inner ear toxicity study in Guinea pigs revealed no obvious inner ear toxicity. Therefore lysozyme-chitosan conjugate are useful as a topical therapeutic agent (cleaning agent) and their clinical application is expected in the future.