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.