Conformal immunomodulatory hydrogels for the treatment of otitis media

• Published in: Journal of nanobiotechnology 2024-10, Vol.22 (1), p.619-17, Article 619
• Main Authors: Jin, Yuefan, Shang, Yueyi, Wu, Cuiping, Chen, Zhengnong, Shi, Haibo, Wang, Hui, Li, Linpeng, Yin, Shankai
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibacterial agents; Antibiotic-resistant therapy; Biofilms - drug effects; Conformal hydrogels; Diagnosis; Dosage and administration; Drug resistance in microorganisms; Drug therapy; Ear, Middle; Fluid-regulated strategy; Gels (Pharmacy); Health aspects; Hydrogels - chemistry; Immunomodulating Agents - chemistry; Immunomodulating Agents - pharmacology; Immunomodulating Agents - therapeutic use; Innate immune response; Male; Ofloxacin - pharmacology; Ofloxacin - therapeutic use; Otitis media; Otitis Media - drug therapy; Otitis media treatment; Patient outcomes; Prevention; Rats; Rats, Sprague-Dawley; Tympanic Membrane - drug effects
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-024-02908-4

Otitis media (OM), a condition stemming from the proliferation of various bacteria within the tympanic cavity (TC), is commonly addressed through the administration of ofloxacin (OFL), a fluoroquinolone antibiotic. Nevertheless, the escalating issue of antibiotic resistance and the challenge of drug leakage underscore the exploration of an alternative, more effective treatment modality in clinical practice. Here, we introduce a simple and easily implementable fluid-regulated strategy aimed at delivering immunomodulatory hydrogels into the TC, ensuring conformal contact with the irregular anatomical surfaces of the middle ear cavity to more effectively eliminate bacteria and treat OM. This innovative strategy exhibits expedited therapeutic process of antibiotic-resistant, acute and chronic OM rats, and significant reductions in the severity of tympanic membrane (TM) inflammation, residual bacteria within the TC (0.12 *10 CFU), and the thickness of TM/TC mucosa (17.63/32.43 μm), as compared to conventional OFL treatment (3.6, 0.76 *10 CFU, 48.70/151.26 μm). The broad-spectrum antibacterial and antibiofilm properties of this strategy against a spectrum of OM pathogens are demonstrated. The strategy is validated to bolster the host's innate immune response through the stimulation of antibacterial protein synthesis, macrophage proliferation and activation, thereby accelerating bacterial eradication and inflammation resolution within the TC. This facile, cost-effective and in vivo degradable technology exhibits promising prospects for future clinical implementation.