title: Preclinical development and ocular biodistribution of gemini-DNA nanoparticles after intravitreal and topical administration: towards non-invasive glaucoma gene therapy.
abstract: Gene therapy could offer improvement in the treatment of glaucoma compared to the current standard of lowering intraocular pressure. We have developed and characterized non-viral gemini surfactant-phospholipid nanoparticles (GL-NPs) for intravitreal and topical administration. Optimized GL-NPs (size range 150-180 nm) were biocompatible with rat retinal ganglion (RGC-5) cells with >95% viability by PrestoBlue™ assay. GL-NPs carrying Cy5-labeled plasmid DNA demonstrated distinct trafficking behavior and biodisposition within the eye in vivo after intravitreal or topical application with respect to pathways of movement and physicochemical stability. After intravitreal injection in mice, GL-NPs localized within the nerve fiber layer of the retina, whereas after topical application, GL-NPs were located in several anterior chamber tissues, including the limbus, iris and conjunctiva. GL-NPs were thermodynamically stable in the vitreous and tear fluid and were trafficked as single, non-aggregated particles after both types of administration.
  
  
  BACKGROUND
  In this paper, the development and characterization of non-viral gemini surfactant-phospholipid nanoparticles is reported with the goal of establishing a gene delivery system that addresses glaucoma in a non-invasive fashion. The authors found that after topical application, the concentration of these nanoparticles was higher in anterior chamber-related components of the eye, whereas intra-vitreal administration resulted in accumulation in the retinal nerve fibre layer.
authors.affiliation: School of Pharmacy, University of Waterloo, Waterloo, ON, Canada.
authors.forename: Samih
authors.initials: S
authors.lastname: Alqawlaq
authors.affiliation: Ophthalmology and Vision Science, University of Toronto, Toronto, ON, Canada; University Health Network, Division of Visual Science, Toronto Western Research Institute, Toronto Western Hospital, Toronto, ON, Canada.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Sivak
authors.affiliation: School of Pharmacy, University of Waterloo, Waterloo, ON, Canada.
authors.forename: J Torin
authors.initials: JT
authors.lastname: Huzil
authors.affiliation: School of Pharmacy, University of Waterloo, Waterloo, ON, Canada.
authors.forename: Marina V
authors.initials: MV
authors.lastname: Ivanova
authors.affiliation: School of Optometry, University of Waterloo, Waterloo, ON, Canada; Ophthalmology and Vision Science, University of Toronto, Toronto, ON, Canada; University Health Network, Division of Visual Science, Toronto Western Research Institute, Toronto Western Hospital, Toronto, ON, Canada.
authors.forename: John G
authors.initials: JG
authors.lastname: Flanagan
authors.affiliation: School of Pharmacy, University of Waterloo, Waterloo, ON, Canada.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Beazely
authors.affiliation: School of Pharmacy, University of Waterloo, Waterloo, ON, Canada. Electronic address: foldvari@uwaterloo.ca.
authors.forename: Marianna
authors.initials: M
authors.lastname: Foldvari
mesh_terms: D000287:Administration, Topical; D000818:Animals; D005123:Eye / Q000378:metabolism*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005901:Glaucoma / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*
keywords: gene delivery; glaucoma; nanoparticles; non-viral; ocular administration; preclinical; retina; topical