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. Author manuscript; available in PMC: 2025 Sep 1.
Published in final edited form as: Adv Healthc Mater. 2024 May 21;13(22):e2400457. doi: 10.1002/adhm.202400457

Figure 5. The in vivo application, treatment efficacy, pharmacokinetics, and biocompatibility of the hydrogel formulations.

Figure 5.

a A scheme showing the injection of the hydrogel formulation through the outer ear canal, for non-invasive and local delivery of antibiotics across intact tympanic membrane (TM) for treatment of acute otitis media (AOM).

b The study timeline for the in vivo chinchilla AOM model.

c The percentage of chinchilla ears with non-zero colony-forming unit (CFU) counts of non-typeable Haemophilus Influenzae (NTHi) in the middle ear fluid (MEF) before (i.e., Day 0) and after receiving the treatment of [P407 + cip] (n = 4), [P407 + cip + 3CPE(SDS)] (n = 4), and [P407 + cip + 2% ML] (n = 6), or no treatment (n = 4). Statistical analysis was performed using two-way ANOVA with Dunnett’s test vs. [untreated] for day 7, ns = non-significant, ** p < 0.01.

d The CFU count of NTHi in the MEF extracted from the same animals as in [c]. The Log10 CFU value of zero was represented as one instead of - ∞ for illustration purposes; data are median and interquartile range.

e The concentration of ciprofloxacin in the middle ear fluid extracted from the same animals as in [c]. Data are mean ± Standard Error of Mean (SEM).

f Representative images showing sectioned TM from NTHi-infected and healthy chinchillas after 7 days of treatment, with hematoxylin & eosin (H&E) staining, black arrow indicates regions of infiltrating leukocytes. The average thickness for a healthy untreated TM was measured to be 12 ± 3 μm (n = 1). The average thickness for infected TM was measured to be 49 ± 46 μm, 42 ± 21 μm, 101 ± 70 μm, and 36 ± 10 μm, after receiving no treatment or treatment with [P407 + cip], [P407 + cip + 3CPE(SDS)], and [P407 + cip + 2% ML], respectively (n = 3 for [P407 + cip], n = 4 for all other groups), scale bar = 200 μm.

g Representative images showing section TM from NTHi-infected and healthy chinchillas after 7 days of treatment, with Gram staining, black arrow indicates clusters of bacteria, ME: middle ear, OE: outer ear, scale bar = 200 μm.