Conclusion
In summary, we designed a hydrogel formulation (100µM[AgNPs-PVP]-18%[P407]), which achieved complete eradication of the two most common bacterial OM pathogens, i.e.,S. pneumoniae and NTHi in vitro without causing cytotoxicity. The AgNPs-PVP was synthesized via a chemical reduction reaction using NaBH4 as the reducing agent and PVP as the stabilizer. The as-synthesized AgNPs-PVP demonstrated a narrow size distribution (~10 nm), which led to their effective eradication of the bacterial OM pathogens at MIC values of 6.25 µM (~1.04 µg/mL) for S. pneumoniae and 12.5 µM (~2.13 µg/mL) for NTHi. To realize the local and sustained delivery of the AgNPs-PVP, a hydrogel with reverse thermal gelation properties was formulated, promising a delivery system with ease of administration through (perforated) tympanic membranes and sustained presence in the auditory bullae. Gelation temperature of the final hydrogel formulation, 100µM[AgNPs-PVP]-18%[P407], was measured to be 24.06 ± 1.28 °C using linear oscillatory shear rheology. The antimicrobials released from 100µM[AgNPs-PVP]-18%[P407] eradicated the two aforementioned OM pathogens without triggering cytotoxicity. This was the first time that AgNPs were used against OM pathogens, and the hydrogel formulation thus points to an effective and biocompatible solution to treat OM while circumventing the health concerns associated with systemic antibiotic exposure.