Intratympanic injections of emulsion-like dispersions to augment cinnarizine amount in a healthy rabbit inner ear model

Nanomedicine (Lond). 2024;19(21-22):1717-1741. doi: 10.1080/17435889.2024.2373042. Epub 2024 Jul 23.

Abstract

Aim: To investigate eutectic liquid-based emulsion-like dispersions for intratympanic injections to augment cinnarizine permeability across round window membrane in a healthy rabbit inner ear model.Methods: Two-tier systematic optimization was used to get the injection formula. The drug concentrations in perilymph and plasma were analyzed via. Ultra-performance liquid chromatography-tandem mass spectrometry method after 30-, 60-, 90- and 120-min post intratympanic injection time points in rabbits.Results: A shear-thinning behavior, immediate drug release (∼98.80%, 10 min) and higher cell viability (>97.86%, 24 h) were observed in dispersions. The cinnarizine level of 8168.57 ± 1236.79 ng/ml was observed in perilymph at 30 min post intratympanic injection in rabbits.Conclusion: The emulsion-like dispersions can augment drug permeability through round window membrane.

Keywords: Artificial neural network; central composite design; cinnarizine; emulsion-like dispersions; healthy rabbit inner ear model.

Plain language summary

[Box: see text].

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cinnarizine* / administration & dosage
  • Cinnarizine* / chemistry
  • Cinnarizine* / pharmacokinetics
  • Drug Liberation
  • Ear, Inner / drug effects
  • Ear, Inner / metabolism
  • Emulsions* / chemistry
  • Humans
  • Injection, Intratympanic
  • Perilymph / metabolism
  • Permeability / drug effects
  • Rabbits
  • Round Window, Ear / drug effects
  • Round Window, Ear / metabolism

Substances

  • Emulsions
  • Cinnarizine