Suppression of phagocytic cells in retinal disorders using amphiphilic poly(γ-glutamic acid) nanoparticles containing dexamethasone

Morin Ryu, Toru Nakazawa, Takami Akagi, Tatsuhide Tanaka, Ryou Watanabe, Masayuki Yasuda, Noriko Himori, Kazuichi Maruyama, Toshihide Yamashita, Toshiaki Abe, Mitsuru Akashi, Kohji Nishida

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

To investigate the potential of nanoparticles (NPs) composed of poly(γ-glutamic acid) conjugated with l-phenylalanine (γ-PGA-Phe NPs) for the treatment of retinal diseases,γ-PGA-Phe NPs (200 nm) were tested with macrophages and microglia in vitro or by intravitreal administration into normal or pathological rat eyes. The anti-inflammatory effects of the NPs containing dexamethasone (DEX-NPs) were examined using qRT-PCR in vitro by counting activated microglia and Fluorogold-labeled retinal ganglion cells in the retinas under excitotoxicity or by counting TUNEL (+) photoreceptors in the detached retinas. The NPs were taken up efficiently by cultured macrophages or microglia. At day 7, 60-80% of the diffuse signal remained in the cytoplasm of these cells. In normal rat eyes, the NPs did not accumulate in the retinas and no inflammatory cells were recruited. Conversely, under pathological conditions, the NPs were localized in activated CD11b-positive cells in the retina. DEX-NPs suppressed the expression of TNFα and MCP-1 in cultured macrophages or microglia, the activation of microglia, the loss of retinal ganglion cells (RGCs) in excitotoxic retinas, and the number of TUNEL (+) photoreceptors in detached retinas. These data suggest that γ-PGA-Phe NPs can be a powerful tool for suppressing inflammatory cells in pathological conditions in the retina.

Original languageEnglish
Pages (from-to)65-73
Number of pages9
JournalJournal of Controlled Release
Volume151
Issue number1
DOIs
Publication statusPublished - 2011 Apr 10

Keywords

  • Cytokines
  • Drug delivery
  • Microglia
  • Monocyte recruitment
  • Nanoparticles
  • Neuroprotection

ASJC Scopus subject areas

  • Pharmaceutical Science

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