Size-dependent passage of liposome nanocarriers with preserved posttransport integrity across the middle-inner ear barriers in rats

Otol Neurotol. 2012 Jun;33(4):666-73. doi: 10.1097/MAO.0b013e318254590e.

Abstract

Objective: The goal of this study was to evaluate the impact of liposome nanocarrier size on the efficacy of its transport across the middle-inner ear barriers.

Materials and methods: The dynamic distribution of liposome nanocarriers encapsulating gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (LPS+Gd-DOTA) of sizes 95, 130, and 240 nm were observed with a 4.7 T magnetic resonance machine after transtympanic injection in Wistar rats. Histology was performed with confocal microscopy using TRITC conjugated LPS+Gd-DOTA. The integrity of the LPS+Gd-DOTA after transportation was evaluated using cryo-transmission electron microscopy (Cryo-TEM).

Results: Size-dependent transport of the LPS+Gd-DOTA across the middle-inner ear barriers was shown using magnetic resonance imaging, which indicated that the 95-nm nanocarrier showed the significantly highest transport percentage, that the 130-nm nanocarrier showed moderate transport, and that the 240 nm nanocarrier showed the lowest transport. Histologic examinations showed that the LPS+Gd-DOTA were distributed in the epithelial cells of the utricle, capillaries of the spiral ligament, and the spiral ganglion cells. LPS+Gd-DOTA remained intact in the perilymph after transportation.

Conclusion: The nanocarrier delivery strategy used in this work could be effective in the development of novel inner ear treatments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Contrast Media
  • Cryoelectron Microscopy
  • Ear, Inner / metabolism
  • Ear, Middle / metabolism
  • Heterocyclic Compounds / administration & dosage*
  • Heterocyclic Compounds / pharmacokinetics
  • Injections
  • Liposomes / metabolism
  • Magnetic Resonance Imaging
  • Male
  • Microscopy, Electron, Transmission
  • Nanocapsules / administration & dosage*
  • Nanocapsules / ultrastructure
  • Organometallic Compounds / administration & dosage*
  • Organometallic Compounds / pharmacokinetics
  • Particle Size*
  • Perilymph*
  • Rats
  • Rats, Wistar

Substances

  • Contrast Media
  • Heterocyclic Compounds
  • Liposomes
  • Nanocapsules
  • Organometallic Compounds
  • gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate