Noninvasive Ocular Drug Delivery System of Dexamethasone Sodium Phosphate in the Treatment of Experimental Uveitis Rabbit

J Ocul Pharmacol Ther. 2017 Dec;33(10):753-762. doi: 10.1089/jop.2017.0053. Epub 2017 Oct 12.

Abstract

Purpose: To investigate the efficacy and safety of dexamethasone sodium phosphate administered through Visulex system (DSP-Visulex) in treating experimental uveitis.

Methods: Uveitis was induced in rabbits by subcutaneous injections of complete Freund's adjuvant and an intravitreal injection of H37RA antigen. After induction, the animals of the control group received no treatment and the others received various treatment regimens of DSP-Visulex. Each regimen was different in DSP strength (4%, 8%, and 15%), application time, or treatment frequency. Efficacy and safety of DSP-Visulex were evaluated by ophthalmic observations and histopathological examinations for ocular inflammations and pathology.

Results: The control group exhibited panuveitis with significant inflammation in the vitreous, choroid, and retina, but less in the conjunctiva, cornea, and anterior chamber. The uveitis occurred within 24 h after induction and persisted throughout the study in the control group. All treatments showed some reduction in inflammation in the vitreous, choroid, and retina. The higher dose regimens generally showed more rapid and higher degree of resolution than the lower dose regimens. The posterior eye tissues of the 15% and 8% DSP-Visulex appeared normal with minimal or no inflammation, whereas the untreated eye and the 4% DSP-Visulex eyes showed minimal response.

Conclusions: All DSP-Visulex regimens suppressed the signs of inflammation and were well tolerated over the course of a 29-day study. The 8% and 15% DSP-Visulex treatment regimens were safe and efficacious for anterior, intermediate, and posterior uveitis. On the other hand, the 4% DSP-Visulex regimen may only be considered for anterior and intermediate uveitis.

Keywords: dexamethasone; experimental uveitis; noninvasive; ocular drug delivery; topical treatment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / pathology
  • Dexamethasone / administration & dosage
  • Dexamethasone / analogs & derivatives*
  • Dexamethasone / toxicity
  • Disease Models, Animal*
  • Drug Delivery Systems*
  • Glucocorticoids / administration & dosage*
  • Glucocorticoids / toxicity
  • Panuveitis / drug therapy*
  • Panuveitis / pathology
  • Rabbits

Substances

  • Glucocorticoids
  • dexamethasone 21-phosphate
  • Dexamethasone