Nanomedicine: Nanotechnology, Biology and Medicine
Volume 4, Issue 4 , Pages 340-349, December 2008

Ocular nanoparticle toxicity and transfection of the retina and retinal pigment epithelium

  • Tarl W. Prow, PhD

      Affiliations

    • The Wilmer Ophthalmological Institute, The Johns Hopkins University, Baltimore, Maryland
    • ,
  • Imran Bhutto, MD, PhD

      Affiliations

    • The Wilmer Ophthalmological Institute, The Johns Hopkins University, Baltimore, Maryland
    • ,
  • Sahng Y. Kim, MD

      Affiliations

    • The Wilmer Ophthalmological Institute, The Johns Hopkins University, Baltimore, Maryland
    • ,
  • Rhonda Grebe, BS

      Affiliations

    • The Wilmer Ophthalmological Institute, The Johns Hopkins University, Baltimore, Maryland
    • ,
  • Carol Merges, MS

      Affiliations

    • The Wilmer Ophthalmological Institute, The Johns Hopkins University, Baltimore, Maryland
    • ,
  • D. Scott McLeod

      Affiliations

    • The Wilmer Ophthalmological Institute, The Johns Hopkins University, Baltimore, Maryland
    • ,
  • Koichi Uno, MD, PhD

      Affiliations

    • The Wilmer Ophthalmological Institute, The Johns Hopkins University, Baltimore, Maryland
    • ,
  • Mohamed Mennon, MD

      Affiliations

    • The Wilmer Ophthalmological Institute, The Johns Hopkins University, Baltimore, Maryland
    • ,
  • Li Rodriguez, PhD

      Affiliations

    • Food and Drug Administration, Rockville, Maryland
    • ,
  • Kam Leong, PhD

      Affiliations

    • Duke University, Durham, North Carolina, USA
    • ,
  • Gerard A. Lutty, PhD

      Affiliations

    • The Wilmer Ophthalmological Institute, The Johns Hopkins University, Baltimore, Maryland
    • Corresponding Author InformationCorresponding author. Wilmer Ophthalmological Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287-9115, USA.

Received 3 August 2007; received in revised form 19 February 2008; accepted 6 June 2008. published online 22 July 2008.

Abstract 

Chitosan, PCEP (poly{[(cholesteryl oxocarbonylamido ethyl) methyl bis(ethylene) ammonium iodide] ethyl phosphate}), and magnetic nanoparticles (MNPs) were evaluated for the safe delivery of genes in the eye. Rabbits were injected with nanoparticles either intravitreally (IV) or subretinally (SR) and sacrificed 7 days later. Eyes were grossly evaluated for retinal pigment epithelium abnormalities, retinal degeneration, and inflammation. All eyes were cryopreserved and sectioned for analysis of toxicity and expression of either enhanced green or red fluorescent proteins. All of the nanoparticles were able to transfect cells in vitro and in vivo. IV chitosan showed inflammation in 12/13 eyes, whereas IV PCEP and IV MNPs were not inflammatory and did not induce retinal pathology. SR PCEP was nontoxic in the majority of cases but yielded poor transfection, whereas SR MNPs were nontoxic and yielded good transfection. Therefore, we conclude that the best nanoparticle evaluated in vivo was the least toxic nanoparticle tested, the MNP.

Key words: Chitosan, Magnetic nanoparticle, Gene delivery, Retina, Toxicity

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 This work was supported by the National Eye Institute grant R03EY013744 (G.L.), R01EY09357 (G.L.), EY01765 (Wilmer), the Johns Hopkins Hematology Training grant T32HL007525 (T.P.), the Altsheler Durell Foundation (G.L.), and unrestricted funds from a Research to Prevent Blindness grant (Wilmer).

PII: S1549-9634(08)00086-5

doi:10.1016/j.nano.2008.06.003

Nanomedicine: Nanotechnology, Biology and Medicine
Volume 4, Issue 4 , Pages 340-349, December 2008

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