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Updated: Sep 10, 2025
09:34
Canalostomy As a Surgical Approach to Local Drug Delivery into the Inner Ears of Adult and Neonatal Mice
Published on: May 25, 2018
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Round window membrane extracellular vesicles facilitate inner ear drug delivery
S Holdsclaw1, D Silkstone2, H Jeanneret3
1Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA; Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC, USA.
Summary
Extracellular vesicles (EVs) from the round window membrane show potential for improved inner ear drug delivery. These EVs enhance therapeutic transport across the round window membrane, offering a safer and more effective treatment for hearing loss.
Area of Science:
- Biomedical Engineering
- Otolaryngology
- Drug Delivery Systems
Background:
- Hearing loss affects over 400 million people globally, with current treatments limited by inefficient inner ear drug delivery.
- Intratympanic (IT) injection is the safest method but faces challenges due to the round window membrane's (RWM) restrictive nature.
- Extracellular vesicles (EVs) from RWM cells offer a promising alternative for enhanced drug delivery due to their inherent properties and low immunogenicity.
Purpose of the Study:
- To explore the release and characteristics of RWM-derived EVs for inner ear drug delivery.
- To evaluate the efficiency of RWM-EVs in transporting therapeutic agents across the RWM.
- To assess the potential of RWM-EVs for delivering drugs and gene therapy vectors in preclinical models.
Main Methods:
- Characterization of RWM cell-derived EVs and their release pathways (clathrin-mediated endocytosis, Golgi-ER transport, gap junction trafficking).
- Comparative evaluation of RWM-EV, mesenchymal stem cell (MSC)-EV, and liposome uptake and passage efficiency in porcine RWM cells.
- In-vivo assessment of dexamethasone-loaded RWM-EV passage after IT delivery in pigs.
- Investigation of brain-derived neurotrophic factor (BDNF) and adeno-associated virus (AAV) loaded EV uptake and transduction in HEK293T and RWM cells.
Main Results:
- RWM-derived EVs demonstrate efficient uptake and passage across porcine RWM cells, outperforming MSC-EVs and liposomes in certain aspects.
- In-vivo studies confirmed the passage of dexamethasone-loaded RWM-EVs following IT administration in pigs.
- EVs loaded with BDNF and AAVs showed successful uptake and transduction capabilities in target cells, indicating potential for gene therapy applications.
Conclusions:
- RWM-derived EVs represent a novel and effective platform for improving intratympanic drug and gene therapy delivery.
- This approach overcomes the limitations of the RWM barrier, offering a safer and more efficient route for treating inner ear disorders.
- Further development of RWM-EV-based therapies holds significant promise for advancing the clinical treatment of hearing loss and other cochlear conditions.
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