title: Trans-meningeal drug delivery to optic nerve ganglion cell axons using a nanoparticle drug delivery system.
abstract: The purpose of this study was to investigate if neuroprotective drugs can cross the optic nerve sheath in vitro. Four optic nerves were used for this study. Two porcine nerves were harvested at the time of euthanasia and two human nerves were obtained at the time of therapeutic globe enucleation. The optic nerve sheaths were dissected and placed as a membrane in a two chamber diffusion cell to test meningeal penetration by both brimonidine alone and brimonidine encapsulated in nanoparticle (NP-brimonidine). Brimonidine concentration was assayed by UV-vis spectrometer measurement of absorbance at 389 nm. Increasing concentration of brimonidine on the receiver side of the chamber was measured in both the brimonidine alone and the brimonidine encapsulated experiments. The human data were fitted with a two parameter exponential regression analysis (brimonidine alone donor r(2) = 0.87 and receiver r(2) = 0.80, NP-brimonidine donor r(2) = 0.79 and receiver r(2) = 0.84). Time constant (τ) was 10.2 h (donor) and 13.1 h (receiver) in the brimonidine study, and 24.0 h (donor) and 15.9 h (receiver) in the NP-brimonidine study. Encapsulated brimonidine had a longer time to reach equilibrium. Passage of brimonidine through the optic nerve sheath was demonstrated in the experiments. Increase in time constants when comparing the NP-brimonidine with the brimonidine curves in the human studiesindicates that diffusion is delayed by the initial parameter of drug being loaded in NP. Direct treatment of injured optic nerve axons may be possible by trans-meningeal drug diffusion.
authors.affiliation: Vanderbilt Eye Institute, 2311 Pierce Avenue, Nashville, TN 37232-8808, USA. Electronic address: karen.e.schmitt@vanderbilt.edu.
authors.forename: Karen
authors.initials: K
authors.lastname: Grove
authors.affiliation: Chemistry Department, 7619 Stevenson Center, Vanderbilt University, Nashville, TN 37232, USA. Electronic address: julnmeyer@gmail.com.
authors.forename: Julia
authors.initials: J
authors.lastname: Dobish
authors.affiliation: Chemistry Department, 7619 Stevenson Center, Vanderbilt University, Nashville, TN 37232, USA. Electronic address: eva.m.harth@vanderbilt.edu.
authors.forename: Eva
authors.initials: E
authors.lastname: Harth
authors.affiliation: Biomedical Engineering, 5824 Stevenson Center, Vanderbilt University, Nashville, TN 37232, USA. Electronic address: martha.e.ingram@gmail.com.
authors.forename: Martha-Conley
authors.initials: MC
authors.lastname: Ingram
authors.affiliation: Biomedical Engineering, 5824 Stevenson Center, Vanderbilt University, Nashville, TN 37232, USA. Electronic address: bob.galloway@vanderbilt.edu.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Galloway
authors.affiliation: Vanderbilt Eye Institute, 2311 Pierce Avenue, Nashville, TN 37232-8808, USA. Electronic address: louise.mawn@vanderbilt.edu.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Mawn
mesh_terms: D000818:Animals; D001369:Axons; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D009900:Optic Nerve / Q000187:drug effects* / Q000473:pathology; D009901:Optic Nerve Diseases / Q000188:drug therapy* / Q000473:pathology
chemical_list: D018696:Neuroprotective Agents
keywords: brimonidine; diffusion; drug delivery; human; nanoparticle; neuroprotection; optic nerve; porcine