title: Magnetic targeted delivery of dexamethasone acetate across the round window membrane in guinea pigs.
abstract: OBJECTIVE
  Magnetically susceptible PLGA nanoparticles will effectively target the round window membrane (RWM) for delivery of dexamethasone-acetate (Dex-Ac) to the scala tympani.
  
  
  BACKGROUND
  Targeted delivery of therapeutics to specific tissues can be accomplished using different targeting mechanisms. One technology includes iron oxide nanoparticles, susceptible to external magnetic fields. If a nanocomposite composed of biocompatible polymer (PLGA), magnetite, and Dex-Ac can be pulled into and across the mammalian RWM, drug delivery can be enhanced.
  
  
  METHODS
  In vitro targeting and release kinetics of PLGA-magnetite-Dex-Ac nanoparticles first were measured using a RWM model. Next, these optimized nanocomposites were targeted to the RWM by filling the niche in anesthetized guinea pigs. A permanent magnet was placed opposite the RWM for 1 hour. Cochlear soft tissues, perilymph, and RWM were harvested after euthanasia and steroid levels were measured using HPLC.
  
  
  RESULTS
  Membrane transport, in vitro, proved optimal targeting using a lower particle magnetite concentration (1 versus 5 or 10 mg/ml). In vivo targeted PLGA-magnetite-Dex-Ac particles had an average size of 482.8 ± 158 nm (DLS) and an average zeta potential -19.9 ± 3.3 mV. In 1 hour, there was significantly increased cochlear targeted delivery of Dex or Dex-Ac, compared with diffusion alone.
  
  
  CONCLUSIONS
  Superparamagnetic PLGA-magnetite-Dex-Ac nanoparticles under an external magnetic field (0.26 mT) for 1 hour significantly increased Dex-Ac delivery to the inner ear. The RWM was not completely permeated and also became loaded with nanocomposites, indicating that delivery to the cochlea would continue for weeks by PLGA degradation and passive diffusion.
authors.affiliation: Hough Ear Institute, Oklahoma City, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Du
authors.forename: Kejian
authors.initials: K
authors.lastname: Chen
authors.forename: Satish
authors.initials: S
authors.lastname: Kuriyavar
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kopke
authors.forename: Brian P
authors.initials: BP
authors.lastname: Grady
authors.forename: David H
authors.initials: DH
authors.lastname: Bourne
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Dormer
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000008:administration & dosage*; D004333:Drug Administration Routes; D016503:Drug Delivery Systems; D005260:Female; D006168:Guinea Pigs; D058185:Magnetite Nanoparticles; D008297:Male; D012405:Round Window, Ear / Q000187:drug effects* / Q000378:metabolism
chemical_list: D058185:Magnetite Nanoparticles; D003907:Dexamethasone