# Develop novel trans-tympanic drug delivery formulas to treat otitis media

> **NIH NIH R21** · MEDICAL COLLEGE OF WISCONSIN · 2020 · $192,500

## Abstract

The focus of this new R21 application is to develop a nanoparticle based noninvasive trans-tympanic
membrane delivery system for treating middle ear (ME) infection (otitis media, OM). OM is the most common
childhood infection and is a leading reason for pediatric office visits, new antibiotic prescriptions and surgery in
young children. US healthcare system expends over $5B annually in treating this disease. OM also has the
potential for additional serious and developmental consequences for children due to its propensity to impact
hearing. Bacterial infection, long term inflammation and over production of mucins in the ME are hallmarks of
the disease. OM is generally treated with systemic oral antimicrobial agents which, in part related to the
frequency of treatment, have become far less effective as pathogens has developed antimicrobial resistance to
these therapies. These systemic treatments also result in frequent adverse side effects including GI, cutaneous
and, at times, life-threatening events. Systemic anti-inflammatory medication, while potentially effective in
limiting some of the negative local inflammatory aspects of OM in the ME, such as mucin hyper-secretion and
hearing loss, is not generally utilized because of potential negative off-target effects. Currently, no effective
methods exist for treating chronic OM except for surgical intervention with tympanostomy tube placement
(TTP). Thus, development of more effective approaches to deliver therapeutics to the ME, especially via non-
invasive trans-tympanic membrane (TM) drug delivery, to eliminate bacterial infection and control inflammation,
while avoiding systemic exposure is of high significance. The impermeability of TM, driven by tight junctions on
the epithelial layer has strongly limited the topical delivery efficacy of therapeutics to the ME cavity. Increasing
the therapeutic flux through TM is critical for success of topical treatment. Our laboratory has developed a
novel delivery system to dramatically enhance penetration of ~100 nm positively charged nanoparticles across
the intact tympanic membrane compared to free drugs. Based on this preliminary work, we hypothesize that
cationic nanoparticles applied topically in outer-ear can effectively and rapidly translocate therapeutics
into the middle ear cavity through the TM via enhanced diffusion. Specifically, in this exploratory project
we will synthesize, characterize, and optimize single and dual-agent antibiotic and anti-inflammatory cationic
nanoparticle formulations for acute and chronic OM and test the delivery efficacy enhancements of these
formulations through the TM using ex vivo and in vivo models.

## Key facts

- **NIH application ID:** 9966877
- **Project number:** 5R21AI147607-02
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** AMIT JOSHI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $192,500
- **Award type:** 5
- **Project period:** 2019-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9966877

## Citation

> US National Institutes of Health, RePORTER application 9966877, Develop novel trans-tympanic drug delivery formulas to treat otitis media (5R21AI147607-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9966877. Licensed CC0.

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