Lipid nanoparticles-encapsulated brain-derived neurotrophic factor mRNA delivered through the round window niche in the cochleae of guinea pigs

Exp Brain Res. 2021 Feb;239(2):425-433. doi: 10.1007/s00221-020-05970-0. Epub 2020 Nov 19.

Abstract

The treatment of sensorineural hearing loss (SNHL) may be achieved via the application of a cochlear implant (CI) that allows the electrical stimulation of spiral ganglion neurons (SGNs). Nevertheless, the efficacy of CIs is limited by the degeneration of SGNs following SNHL. Although the application of exogenous neurotrophic factors has been reported to decrease SGN degeneration, non-invasive targeted drug delivery systems are required to achieve effective results. In this study, an SS-cleavable proton-activated lipid-like material [ssPalm; a neutral lipid nanoparticle (LNP)], was loaded with mRNA, and the efficacy of this material as a delivery system was investigated. Our results showed that LNPssPalm carrying brain-derived neurotrophic factor (BDNF) mRNA was suitable for the treatment of inner ear diseases, preventing the degeneration of SGNs. In conclusion, this modern nanotechnology-based bioconjugation system, LNPssPalm, is a potential non-invasive targeted therapy allowing the delivering biomaterials to specific structures within the inner ear for the treatment of SHNL.

Keywords: BDNF; Inner ear; Nanomedicine; Sensorineural hearing loss; Spiral ganglion neurons.

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor* / genetics
  • Cochlea
  • Guinea Pigs
  • Lipids
  • Nanoparticles*
  • RNA, Messenger

Substances

  • Brain-Derived Neurotrophic Factor
  • Lipids
  • RNA, Messenger