June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Comparison of the toxicity of different drug delivery nanoparticles in RPE and photoreceptor cells
Author Affiliations & Notes
  • Yueran Yan
    Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • Haijiang Lin
    Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • Hidetaka Matsumoto
    Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • Peggy Bouzika
    Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • Joan Miller
    Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • Demetrios Vavvas
    Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA
  • Footnotes
    Commercial Relationships Yueran Yan, None; Haijiang Lin, None; Hidetaka Matsumoto, None; Peggy Bouzika, None; Joan Miller, Massachusetts Eye and Ear Infirmary (P), Novartis (I), Alcon (C), KalVista Pharmaceuticals (C); Demetrios Vavvas, MEEI (P), Kala pharmaceuticals (C), Roche (C), Genentech (C)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 1940. doi:
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      Yueran Yan, Haijiang Lin, Hidetaka Matsumoto, Peggy Bouzika, Joan Miller, Demetrios Vavvas; Comparison of the toxicity of different drug delivery nanoparticles in RPE and photoreceptor cells. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1940.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Multiple nanoparticles made of synthetic materials have been widely used as drug delivery systems. However, their toxicity to the retina is still not clear. In this study, three different kinds of nanoparticles made of poly lactic-co-glycolic acid (PLGA), polycaprolactone (PCL) and PEGylated polymer (PEG-P) were studied and their toxic effects in RPE cells and photoreceptors were determined in vitro and in vivo.

Methods: PLGA, PCL, and PEG-P nanoparticles were prepared by an oil-in-water (O/W) emulsion/solvent evaporation method. ARPE19 cells were treated with different concentrations of each of the three nanoparticles. The toxicity observed in each case was determined at different time points by MTT (Sigma Aldrich), LDH (Promega), ATP (Promega) and TUNEL (Millipore) assays. For the in vivo study, PEG-P nanoparticles were injected into C57BL/6 mouse eyes intravitreally and sub-retinally. Eyes were enucleated at day 3 or 7. TUNEL staining was used to evaluate photoreceptor cell death. Photoreceptor cell loss was evaluated by measuring the thickness of outer nuclear layer (ONL). Microglias in ONL were quantified in retinal whole mount immunolabeled with Iba-1 antibody. RPE degeneration was also assessed in RPE whole mount immunolabeled with ZO-1 antibody.

Results: Our experiments showed that there was almost no toxicity of PEG-P nanoparticles in ARPE19 cells. Most importantly, no toxicity was observed when exposing the cells to a high PEG-P concentration (200ug/ml) for up to 1 week. PLGA nanoparticles showed greater toxicity than their counterparts. At 24 hours, PLGA caused more than 20% cell death at a concentration of 25ug/ml and 50% cell death at 200ug/ml. These results were confirmed with different cell death assays. The toxic effect of these nanoparticles in the RPE cells and the photoreceptors was also determined in vivo.

Conclusions: PLGA, PCL, and PEG-P nanoparticles show different toxicity profiles. PEG-P has the least toxicity in the RPE cells and photoreceptors.

Keywords: 608 nanomedicine • 607 nanotechnology • 688 retina  
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