# A novel nanodialysis platform for inner ear detoxification

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $486,930

## Abstract

Despite being the first-line therapy for many types of cancer, Cisplatin can alter the course of
chemotherapy through ototoxicity as well as decrease a patient's quality of life. Cisplatin-induced ototoxicity
represents an important challenge to patient care because of the lack of effective treatment.
 Based on extensive studies in our laboratory, the Principle Investigator (PI) has developed a stable, safe,
regulated, and controllable hydrogel-based delivery system of drugs, biomaterials, or nanoparticles to the inner
ear from the middle ear. The application is performed simply by applying a hydrogel on the round window
membrane (RWM) with a flexible otoscope in the outpatient setting. This platform also has the advantage of an
enzymatic “off-switch,” which allows for controlled degradation of the hydrogel and rapid cessation of payload
delivery to the inner ear.
 Magnetic nanoparticles (NPs) composed of superparamagnetic iron oxide (SPIO) have been widely used
for many biomedical applications. These SPIO NPs (SPIONs) are typically encased in biocompatible coatings,
such as polymers or lipids, which increase retention time of the particle within the organism and allow for
surface functionalization. The resulting “MultiFunctional NanoParticles (MFNPs)” can be conjugated to a
multitude of targeting ligands (forming targeted (t)MFNPs) to sequester any number of identified toxins.
 The proposed study is to develop an inner ear nanodialysis detoxification platform for drug-induced
ototoxicity. Synthesized glutathione-conjugated tMFNPs (G-tMFNPs) are capable of binding with cisplatin.
During the detoxification process, G-tMFNPs will be noninvasively delivered to the inner ear through the RWM
by a chitosan glycerophosphate (CGP) hydrogel system. With a rotatory magnetic device (RMD), these G-
tMFNP will then be distributed from the base to the apex of the entire cochlea consequently sequestering
cisplatin in the perilymph and endolymph. Once cisplatin has entered the inner ear, G-tMFNAs will bind to
cisplatin and form G-tMFNP-cisplatin complexes; The G-tMFNP-cisplatin complexes will be safely removed
from the inner ear by RMD and external magnet application. Furthermore, this proposed system is modular
and easily modifiable; therefore, it can be used for the elimination of a variety of ototoxic agents. The proposed
study will be evaluated in an animal model with cisplatin-induced ototoxicity in clinical settings.
 The PI believes that the proposed inner ear nanodialysis system, to our knowledge, is the first system that
serves as a platform for detoxification in cisplatin-induced ototoxicity. If this innovative system proves effective
and safe, it will represent a major breakthrough in the prevention and treatment of drug-induced ototoxicity,
where a noninvasive inner ear dialysis system is desperately needed.

## Key facts

- **NIH application ID:** 10440322
- **Project number:** 5R01DC017144-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Daqing Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $486,930
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440322

## Citation

> US National Institutes of Health, RePORTER application 10440322, A novel nanodialysis platform for inner ear detoxification (5R01DC017144-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10440322. Licensed CC0.

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