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Enhancing Round Window Membrane Permeability for Inner Ear Drug Delivery: A Systematic Review.

Agathe Bedoux1,2, Pauline Ropero3, Yohan Bouleau4

  • 1Univ. Bordeaux, INSERM, BioTis, U1026, Bordeaux, France.

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Summary
This summary is machine-generated.

This review explores methods to improve drug delivery to the inner ear for sensorineural hearing loss. New biomechanical and biochemical strategies show promise for enhanced treatment efficacy.

Keywords:
biochemical strategiesbiomechanical strategiesgene therapy vectorsinner ear drug deliveryround window membranesensorineural hearing loss

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Area of Science:

  • Otorhinolaryngology
  • Biomedical Engineering
  • Pharmacology

Background:

  • Sensorineural hearing loss is a significant public health issue with limited treatment options.
  • The cochlea's complex anatomy and biological barriers, particularly the round window membrane (RWM), hinder effective drug delivery.
  • Intratympanic injection's passive diffusion is often inadequate for large or hydrophilic molecules like gene therapy vectors.

Purpose of the Study:

  • To systematically review biomechanical and biochemical strategies for enhancing RWM permeability.
  • To evaluate methods for improving drug delivery efficiency and targeting to the inner ear.
  • To identify strategies that modulate RWM properties or indirectly enhance drug delivery.

Main Methods:

  • Conducted a systematic literature search following PRISMA guidelines across Scopus, MEDLINE/PubMed, Cochrane, and CINAHL.
  • Included *in vivo* studies and clinical trials investigating biochemical or biomechanical RWM enhancement strategies.
  • Assessed risk of bias using the SYRCLE tool; 89 articles met inclusion criteria from 1776 screened.

Main Results:

  • Identified four biochemical approaches (hydrogels, nanosystems, microsystems, permeabilizers) and three biomechanical strategies (sonoporation, acoustic stimulation, magnetic systems).
  • Most reviewed strategies demonstrated improved inner ear drug delivery or therapeutic outcomes.
  • Recent research increasingly focuses on advanced methods like nanosystems and sonoporation for larger molecules, including gene therapy.

Conclusions:

  • Various biochemical and biomechanical strategies effectively enhance RWM permeability for inner ear drug delivery in preclinical models.
  • A shift towards advanced delivery systems is observed, targeting larger molecules like gene therapy vectors.
  • Further research is crucial for the clinical translation of these promising drug delivery methods.