title: A novel chitosan-hydrogel-based nanoparticle delivery system for local inner ear application.
abstract: OBJECTIVE
  A chitosan-hydrogel-based nanoparticle (nanohydrogel) delivery system can be used to deliver therapeutic biomaterials across the round window membrane (RWM) into the inner ear in a mouse model.
  
  
  BACKGROUND
  Delivering therapies to the inner ear has always been a challenge for the otolaryngologist. Advances in biomedical nanotechnology, increased understanding of the RWM diffusion properties, and discovery of novel therapeutic targets and agents, have all sparked interest in the controlled local delivery of drugs and biomaterials to the inner ear using nanoparticles (NPs).
  
  
  METHODS
  Fluorescently-labeled liposomal NPs were constructed and loaded into a chitosan-based hydrogel to form a nanohydrogel, and in vitro studies were performed to evaluate its properties and release kinetics. Furthermore, the nanohydrogel was applied to the RWM of mice, and perilymph and morphologic analysis were performed to assess the NP delivery and distribution within the inner ear.
  
  
  RESULTS
  NPs with an average diameter of 160 nm were obtained. In vitro experiments showed that liposomal NPs can persist under physiologic conditions for at least two weeks without significant degradation and that the nanohydrogel can carry and release these NPs in a controlled and sustained manner. In vivo findings demonstrated that the nanohydrogel can deliver intact nanoparticles into the perilymphatic system and reach cellular structures in the scala media of the inner ear of our mouse model.
  
  
  CONCLUSIONS
  Our study suggests that the nanohydrogel system has great potential to deliver therapeutics in a controlled and sustained manner from the middle ear to the inner ear without altering inner ear structures.
authors.affiliation: *Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; †Department of Neuroscience, Baylor College of Medicine, Houston, Texas; and ‡Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.
authors.forename: Shayanne A
authors.initials: SA
authors.lastname: Lajud
authors.forename: Danish A
authors.initials: DA
authors.lastname: Nagda
authors.forename: Peter
authors.initials: P
authors.lastname: Qiao
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Alyssa
authors.initials: A
authors.lastname: Civantos
authors.forename: Rende
authors.initials: R
authors.lastname: Gu
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Cheng
authors.forename: Andrew
authors.initials: A
authors.lastname: Tsourkas
authors.forename: Bert W
authors.initials: BW
authors.lastname: O'Malley
authors.forename: Daqing
authors.initials: D
authors.lastname: Li
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D048271:Chitosan / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D007758:Ear, Inner / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage*; D010498:Perilymph / Q000187:drug effects* / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D048271:Chitosan