June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Therapeutic effect of stealth-type polymeric nanoparticles with encapsulated cyclosporine A on experimental autoimmune uveoretinitis
Author Affiliations & Notes
  • Tsutomu Sakai
    Ophthalmology, Jikei Univ School of Medicine, Setagaya-ku, Japan
  • Kana Kuroyanagi
    Ophthalmology, Jikei Univ School of Medicine, Setagaya-ku, Japan
  • Tsutomu Ishihara
    Chemical biology and applied chemistry, Nihon university college of engineering, Kooriyama, Japan
  • Kiichiro Okano
    Ophthalmology, Jikei Univ School of Medicine, Setagaya-ku, Japan
  • Hiroshi Tsuneoka
    Ophthalmology, Jikei Univ School of Medicine, Setagaya-ku, Japan
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 5067. doi:
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      Tsutomu Sakai, Kana Kuroyanagi, Tsutomu Ishihara, Kiichiro Okano, Hiroshi Tsuneoka; Therapeutic effect of stealth-type polymeric nanoparticles with encapsulated cyclosporine A on experimental autoimmune uveoretinitis. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5067.

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

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Abstract

Purpose: The therapeutic effects of cyclosporine A encapsulated in biocompatible and biodegradable blended nanoparticles of poly (lactic acid) (PLA) homopolymers and PEG-block-PLA copolymers (stealth nanocyclosporine) were examined in an experimental autoimmune uveoretinitis (EAU) model in Lewis rats.

Methods: EAU was induced by S-antigen peptide in Lewis rats. Accumulation of systemically administered Cy7-labeled stealth nanoparticles in inflamed eyes of rats with EAU was assessed using in vivo fluorescence imaging. And the therapeutic effect of stealth nanocyclosporine or saline on EAU was examined. The eyes were obtained 7 days after the treatment and the histological score was determined. using pathological findings. The expression of inflammatory cytokines including IL-6, IL-17, and VEGF was determined immunohistochemically.

Results: Cy7-stealth nanoparticles accumulated in inflamed eyes of rats with EAU and remained in situ for a 3-day period. Systemically administered stealth nanocyclosporine reduced the clinical scores of rats with EAU within 1 day and maintained the effect for 2 weeks. This treatment also decreased the histological scores and the expression of inflammatory cytokines in the retina of EAU.

Conclusions: The strong therapeutic benefit on EAU obtained with the stealth nanocyclosporine may have been due to prolonged blood circulation and targeting to the inflamed uvea and retina, in addition to sustained release in situ.

Keywords: 489 cyclosporine • 503 drug toxicity/drug effects • 746 uveitis-clinical/animal model  
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