Evidence map›Paper›PMID 40848758›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2025

Round window membrane extracellular vesicles facilitate inner ear drug delivery.

S Holdsclaw, D Silkstone, F Moazzam, H Jeanneret, N Tehsin, E Norris, E Talic, K Popowski, G Cruse, K Cheng and 1 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

S HoldsclawDepartment of Biological Sciences, North Carolina State University, Raleigh, NC, USA; Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC, USA.
D SilkstoneDepartment of Biomedical Engineering, North Carolina State University, Raleigh, NC, USA; Department of Biomedical Engineering, Duke University, Durham, NC, USA.
F MoazzamDepartment of Biomedical Engineering, North Carolina State University, Raleigh, NC, USA.
H JeanneretDepartment of Biomedical Engineering, North Carolina State University, Raleigh, NC, USA; Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC, USA.
N TehsinDepartment of Biological Sciences, North Carolina State University, Raleigh, NC, USA.
E NorrisDepartment of Biological Sciences, North Carolina State University, Raleigh, NC, USA.
E TalicDepartment of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC, USA.
K PopowskiDepartment of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC, USA.
G CruseDepartment of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC, USA.
K ChengDepartment of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC, USA; Department of Biomedical Engineering, Columbia University, New York, NY, USA.
A MoattiDepartment of Biomedical Engineering, North Carolina State University, Raleigh, NC, USA; Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: amoatti@pitt.edu.

Funding

Enhanced intratympanic delivery of therapeutics to treat and prevent hearing loss using nanovesicles in the porcine modelR00DC019960 · NIDCD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Adele Moatti · 2024 to 2026
$747k
Enhanced intratympanic delivery of therapeutics to treat and prevent hearing loss using nanovesicles in the porcine modelK99DC019960 · NIDCD · NORTH CAROLINA STATE UNIVERSITY RALEIGH · PI MOATTI, ADELE · 2022 to 2023
$205k
NIDCD NIH HHS K99 DC019960NIDCD NIH HHS R00 DC019960
6 · The paper itself

Abstract

Hearing loss affects over 430 million people worldwide, yet effective treatments remain limited, in part due to challenges of inner ear drug delivery, a process that is risky, unreliable, and inefficient. Addressing this challenge calls for delivery approaches that ensure therapies reach the inner ear safely and effectively. Intratympanic (IT) injection, which delivers drugs directly into the middle ear, is currently the safest method for preserving cochlear integrity. However, its efficiency is limited by the round window membrane (RWM), a barrier with tight junctions that restricts therapy-related substance passage into the inner ear. We propose that extracellular vesicles (EVs) released by RWM cells could serve as a novel vehicle for drug delivery, as their membrane features and intravesicular components may facilitate IT transport. Importantly, EVs are also expected to elicit minimal immune responses, addressing a key safety concern for inner ear therapies. We isolated and characterized EVs derived from RWM cells, including sequencing and Ingenuity Pathway Analysis to predict drug delivery pathways and immune-related functions. To establish translational relevance, we investigated their uptake in vitro and assessed passage across the RWM ex vivo and in vivo, demonstrating that dexamethasone-loaded EVs effectively crossed the membrane in a porcine model. We further demonstrated functional delivery potential by showing enhanced cytoplasmic retention of brain-derived neurotrophic factor (BDNF) and improved adeno-associated virus (AAV)-mediated transduction in vitro.

Indexed as

DexamethasoneDrug Delivery SystemsExtracellular VesiclesRound Window, EarAnimalsEar, InnerHumansSwineDexamethasoneExtracellular vesiclesInner ear drug deliveryIntratympanicRound window membrane

Identifiers

PMID40848758
PMCPMC12836284

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.