# Innovative therapy for diseases of the middle ear

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $335,396

## Abstract

ABSTRACT
Treatment for chronic otitis media often involves breaching the integrity of the tympanic membrane (TM). This
can include tympanotomy and/or tympanostomy tube insertion, which provide aeration and allow the penetration
of topical medications through the membrane. Local drug treatment has been found to be highly effective in
treating otitis. However, in children, breaching the membrane requires general anesthesia. Moreover, any
treatment involving surgery is expensive and in parts of the world is not practical, leading to hearing loss and
deaths due to otitis media in many developing countries. To enhance medical treatment of middle ear disorders,
we used sequential selection of phage-display peptide libraries to identify rare, novel peptides that cross the
tympanic membrane via an active process while transporting cargo. Bacteriophage bearing one of these peptides
enters the middle ear at 106-7 times the rate of an untargeted phage. The peptides also cross the membrane
independent of phage. We have optimized delivery by extension of peptide length, identified amino acid
sequence, motifs linked to rapid transit, demonstrated transit across the human tympanic membrane and
obtained important evidence regarding the mechanism of transport. However, a number of barriers exist to
translation into clinical usage. Longer-term safety and efficacy of trans-TM peptides transport needs to be
evaluated. A practical method for long-term delivery should be developed. Application of peptide-mediated
transport to large drug packages should be explored. The transport mechanism should be better understood.
Whether there are more efficient peptides for transport across the human TM, than those discovered in animal
models, should be determined. Finally, delivery of medications across the human TM should be confirmed. The
proposed research will further develop an entirely novel paradigm for the treatment of middle ear diseases.
Transtympanic drug delivery would achieve higher middle ear drug levels and avoid side- or off-target effects,
when compared to systemic medications. This methodology will have widespread applications for the treatment
of otitis media and other middle ear conditions.

## Key facts

- **NIH application ID:** 10116359
- **Project number:** 5R01DC012595-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Allen F. Ryan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $335,396
- **Award type:** 5
- **Project period:** 2012-07-01 → 2024-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116359

## Citation

> US National Institutes of Health, RePORTER application 10116359, Innovative therapy for diseases of the middle ear (5R01DC012595-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10116359. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*