Preclinical development and ocular biodistribution of gemini-DNA nanoparticles after intravitreal and topical administration: towards non-invasive glaucoma gene therapy
| Autor: | Marianna Foldvari, J. Torin Huzil, Michael A. Beazely, Samih Alqawlaq, Marina V. Ivanova, Jeremy M Sivak, John G. Flanagan |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Intraocular pressure medicine.medical_specialty Biodistribution genetic structures Administration Topical Biomedical Engineering Nerve fiber layer Pharmaceutical Science Medicine (miscellaneous) Glaucoma Bioengineering Gene delivery Eye Retinal ganglion chemistry.chemical_compound Mice Ophthalmology medicine Animals General Materials Science Retina business.industry Gene Transfer Techniques Retinal Genetic Therapy medicine.disease eye diseases Mice Inbred C57BL medicine.anatomical_structure chemistry Molecular Medicine Nanoparticles sense organs business |
| Zdroj: | Nanomedicine : nanotechnology, biology, and medicine. 10(8) |
| ISSN: | 1549-9642 |
| Popis: | 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. From the Clinical Editor 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. |
| Databáze: | OpenAIRE |
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