What they found
TL;DR (qwen3.6:35b): This systematic review evaluates biochemical and biomechanical strategies to enhance round window membrane permeability for delivering drugs, including gene therapy vectors, to the inner ear. While numerous methods show promise in animal models, further research is needed to translate these approaches into clinical practice.
Sensorineural hearing loss is a major public health concern, yet its treatment remains limited by the anatomical complexity and biological barriers protecting the cochlea. Among these, the round window membrane (RWM) constitutes a key interface for local drug delivery to the inner ear. However, passive diffusion via intratympanic injection is often insufficient, particularly for hydrophilic, large, or negatively charged molecules such as gene therapy vectors. This systematic review aimed to evaluate biomechanical and biochemical strategies to enhance RWM permeability for more efficient and targeted drug delivery to the inner ear, including direct permeability modulation of the RWM properties or indirect enhancement mechanisms increasing drug delivery without altering intrinsic membrane permeability. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a comprehensive literature search was conducted using the Scopus, MEDLINE/PubMed, Cochrane, and CINAHL electronic databases. In vivo studies and clinical trials involving biochemical or biomechanical strategies to enhance RWM permeability were included. Risk of bias was assessed using the SYRCLE (Systematic Review Center for Laboratory Animal Experimentation) tool. Out of 1776 screened articles, 89 met the inclusion criteria. Four biochemical approaches and three biomechanical strategies were identified, respectively: (1) hydrogels, thermogels, and emulsions, (2) nanosystems, (3) microsystems, and (4) permeabilizers, and (1’) sonoporation, (2’) acoustic stimulation, and (3’) magnetic systems. Most studies reported improved drug delivery to the inner ear or therapeutic efficacy. While earlier research focused on hydrogels, thermogels, emulsions, permeabilizers, and acoustic stimulation for small molecules such as corticoids and antioxidants, recent studies increasingly explore nanosystems, microsystems, sonoporation, and magnetic methods to facilitate the delivery of larger agents, in
How this applies to our program
Improving drug delivery across the round window membrane is critical for effectively targeting hair cells with genetic therapies or protective agents relevant to STRC/DFNB16-related hearing loss. This review identifies specific nanosystems and sonoporation techniques that could facilitate the intracellular delivery of therapeutic molecules to the cochlea.
Key numbers
- 89 studies met the inclusion criteria out of 1776 screened articles
- Four biochemical approaches were identified, including hydrogels and nanosystems
- Three biomechanical strategies were identified, including sonoporation and magnetic systems
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