IOVS Journal of Bacteriology
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(Investigative Ophthalmology and Visual Science. 2007;48:2030-2036.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-0853
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Nanoparticles Sustain Expression of Flt Intraceptors in the Cornea and Inhibit Injury-Induced Corneal Angiogenesis

Pooja D. Jani,1,2 Nirbhai Singh,1,2 Crystal Jenkins,1 Swita Raghava,3 Yun Mo,3 Shivan Amin,1 Uday B. Kompella,3 and Balamurali K. Ambati1

1From the Department of Ophthalmology, Medical College of Georgia, Augusta, Georgia; and the 3Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska.

PURPOSE. To determine whether long-term expression of intraceptors can be achieved using plasmid albumin nanoparticles and whether nanoparticles can inhibit and cause regression of murine corneal neovascularization induced by mechanical–chemical trauma.

METHODS. Albumin nanoparticles encapsulating pCMV.Flt23K were developed as a lyophilized product that is easily redispersed in an aqueous medium. Nanoparticles were injected into the corneas of uninjured BALB/c mice and observed for toxicity for 3 weeks. Entry of nanoparticles into corneal cells was demonstrated through transmission electron microscopy and confocal imaging. Naked pCMV.Flt23K, nanoparticles encapsulating pCMV.Flt23K, or empty pCMV nanoparticles were injected into uninjured mouse corneas. These corneas were subjected to mechanical alkali trauma 3 weeks after injection.

RESULTS. Nanoparticles were nontoxic to the cornea and entered into corneal keratocyte cytoplasm. They persisted for at least 4 weeks in the cornea, expressed effective intraceptor levels for at least 5 weeks, and reduced corneal neovascularization by approximately 40% (P = 0.035) at 5 weeks after administration.

CONCLUSIONS. Albumin nanoparticles are not toxic to the cornea and can express intraceptors for extended periods that are effective in suppressing injury-induced corneal neovascularization.






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Copyright © 2007 by the Association for Research in Vision and Ophthalmology