Pharmacokinetic and safety evaluation of a transscleral sustained unoprostone release device in monkey eyes

Nobuhiro Nagai, Shinji Yamada, Junichi Kawasaki, Eri Koyanagi, Saaya Saijo, Hirokazu Kaji, Matsuhiko Nishizawa, Toru Nakazawa, Toshiaki Abe

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


PURPOSE. We evaluate the ocular tissue distribution and retinal toxicity of unoprostone (UNO) during 12 months, after transscleral sustained-UNO administration using a drug delivery device in monkey eyes. METHODS. The device consisted of a reservoir, controlled-release cover, and a drug formulation of photopolymerized polyethylene glycol dimethacrylate. Six mg UNO was loaded into the device (length, 17 mm; width, 4.4 mm; height, 1 mm). The concentrations of M1, a primary metabolite of UNO, in the retina, choroid, vitreous, lens, aqueous humor, iris, ciliary body, and plasma were determined by liquid chromatography-tandem mass spectrometry at 3, 6, and 12 months after implantation. Retinal toxicity was evaluated by electroretinography (ERG), optical coherence tomography (OCT), and IOP at preimplantation, and at 6, 9, and 12 months after implantation. Focal ERGs were performed at 9 and 12 months after implantation. RESULTS. M1 was detected in the choroid and retina with maximum peaks of 243.2 and 8.41 ng/g at 6 months, respectively. M1 in the ciliary body and iris was detected with maximum peaks of 7.66 and 10.4 ng/g at 6 and 12 months, respectively. Less than 1 ng/mL or ng/g of M1 was detected in the aqueous humor, vitreous, and lens. No changes were observed in retinal function as assessed by ERG, IOP, or macula thickness and retinal histology by OCT examinations during the 12-month period. No differences in focal ERG amplitudes, especially in the macula, were observed. CONCLUSIONS. The device provided intraocular sustained delivery of UNO for 12 months without producing severe retinal toxicity.

Original languageEnglish
Pages (from-to)644-652
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Issue number2
Publication statusPublished - 2018 Feb


  • Drug delivery system
  • Polyethylene glycol dimethacrylate
  • Retina
  • Unoprostone

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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