July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Therapeutic Effect of Ophthalmic Formulation containing Nilvadipine Nanoparticles on Retinal Dysfunction in Rats Injected with Streptozotocin
Author Affiliations & Notes
  • Noriaki Nagai
    Faculty of Pharmacy, Kindai University, Osaka, Japan, Japan
  • Saori Deguchi
    Faculty of Pharmacy, Kindai University, Osaka, Japan, Japan
  • Miyu Ishii
    Faculty of Pharmacy, Kindai University, Osaka, Japan, Japan
  • Yuya Fukuoka
    Faculty of Pharmacy, Kindai University, Osaka, Japan, Japan
  • Hiroko Otake
    Faculty of Pharmacy, Kindai University, Osaka, Japan, Japan
  • Yosuke Nakazawa
    Faculty of Pharmacy, Keio University, Tokyo, Japan
  • Footnotes
    Commercial Relationships   Noriaki Nagai, None; Saori Deguchi, None; Miyu Ishii, None; Yuya Fukuoka, None; Hiroko Otake, None; Yosuke Nakazawa, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5289. doi:
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    • Get Citation

      Noriaki Nagai, Saori Deguchi, Miyu Ishii, Yuya Fukuoka, Hiroko Otake, Yosuke Nakazawa; Therapeutic Effect of Ophthalmic Formulation containing Nilvadipine Nanoparticles on Retinal Dysfunction in Rats Injected with Streptozotocin. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5289.

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

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Abstract

Purpose : Retinopathy leads to irreparable vision loss via capillary closure and areas of nonperfusion, although, the current instillation systems do not allow a sufficient amounts of drugs to treat retinopathy to reach the posterior segment. In this study, we designed the dispersions containing nilvadipine nanoparticles (NILnano), and evaluated the therapeutic effect in retinal dysfunction.

Methods : NILnano ophthalmic formulation were prepared by using wet bead mill method and various additives (2-hydroxypropyl-β-cyclodextrin, benzalkonium chloride, D-mannitol, and methylcellulose). The retinal dysfunction was caused by intraperitoneally injecting streptozotocin to rats (100 mg/kg×2; STZ rat). Changes in retinal function were evaluated by electroretinogram (ERG) and immunological method, respectively.

Results : The NIL microparticles were crushed with a bead mill, which reduced the mean particle size from 16 mm to 77 nm. Additionally, no aggregation or precipitation of NIL nanoparticles was observed for NILnano (mean particle size of NILnano 2 weeks after preparation was 82 nm). Retinal dysfunction was observable 2 weeks after rats received intraperitoneal injections of streptozotocin (100 mg/kg×2, consecutive days, STZ rat), and the changes in retinal function were evaluated by ERG and immunological methods. the levels of a-wave, b-wave and oscillatory potentials amplitude in rats decreased 2 weeks after the injection of streptozotocin. In addition, the increases in the inner plexiform layer as well as the outer- and inner-nuclear layer (neural layer) were observed in the retinas of STZ rats. The distance between cells in the neural layer in normal and STZ rats were 71.0 ± 3.57 mm and 130.6 ± 5.46 mm, respectively, and that the enhanced retinal thickening caused the decrease in ERG. The instillation of NILnano allowed the topical supplement of nilvadipine into the retina, and NILnano (2 times/day) prevented the retinal disorders caused by the injection of excessive streptozotocin.

Conclusions : The retinal dysfunctions in rats injected with streptozotocin are attenuated by instillation of NILnano ophthalmic formulation. These findings provide significant information that can be used to design further studies aimed at therapeutic treatment of retinopathy.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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