September 1993
Volume 34, Issue 10
Free
Articles  |   September 1993
Evaluation of retinal toxicity and liposome encapsulation of the anti-CMV drug 2'-nor-cyclic GMP.
Author Affiliations
  • S Shakiba
    Department of Ophthalmology, University of California, San Diego, La Jolla 92093-0946.
  • K K Assil
    Department of Ophthalmology, University of California, San Diego, La Jolla 92093-0946.
  • A D Listhaus
    Department of Ophthalmology, University of California, San Diego, La Jolla 92093-0946.
  • D Munguia
    Department of Ophthalmology, University of California, San Diego, La Jolla 92093-0946.
  • M Flores-Aguilar
    Department of Ophthalmology, University of California, San Diego, La Jolla 92093-0946.
  • C Vuong
    Department of Ophthalmology, University of California, San Diego, La Jolla 92093-0946.
  • C A Wiley
    Department of Ophthalmology, University of California, San Diego, La Jolla 92093-0946.
  • R L Tolman
    Department of Ophthalmology, University of California, San Diego, La Jolla 92093-0946.
  • J D Karkas
    Department of Ophthalmology, University of California, San Diego, La Jolla 92093-0946.
  • G Bergeron-Lynn
    Department of Ophthalmology, University of California, San Diego, La Jolla 92093-0946.
Investigative Ophthalmology & Visual Science September 1993, Vol.34, 2903-2910. doi:
  • Views
  • PDF
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      S Shakiba, K K Assil, A D Listhaus, D Munguia, M Flores-Aguilar, C Vuong, C A Wiley, R L Tolman, J D Karkas, G Bergeron-Lynn; Evaluation of retinal toxicity and liposome encapsulation of the anti-CMV drug 2'-nor-cyclic GMP.. Invest. Ophthalmol. Vis. Sci. 1993;34(10):2903-2910.

      Download citation file:


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

      ×
  • Supplements
Abstract

PURPOSE: Human cytomegalovirus (HCMV) is an important pathogen in the immunocompromised patient. CMV retinitis is a leading cause of blindness in patients with AIDS. Ganciclovir and foscarnet are currently the treatments being used for this retinitis, but they both have major toxicities when used systemically. Intravitreal therapy with ganciclovir has been used in some patients who cannot tolerate systemic treatment. The major problem with this modality is the necessity for administration of between 1 and 3 intravitreal injections per eye per week. 2'-nor-cyclic GMP is a nucleotide analog, a cyclic phosphate derivative of ganciclovir. Neutral salts of the compound are extremely water soluble, and the charged phosphate group at neutral pH make it an ideal candidate for encapsulation into a multivesicular liposome system. METHODS: The authors evaluated the retinal toxicity of the diethanolammonium salt 2'-nor-cyclic GMP by using electroretinographic, morphologic, and ophthalmoscopic techniques after intravitreal injections in rabbit eye. RESULTS: The intraocular therapeutic index for 2'-nor-cyclic GMP is 20. At the 10 micrograms dose, electroretinogram, ophthalmoscopic examination, and both light and electron microscopy revealed no abnormalities. Toxicity was evident at 50 micrograms and higher doses with ERG changes (loss of amplitude) and retinal pathology that varied from vacuolization of the retinal pigment epithelium and loss of height of the outer photoreceptor segment to loss of the entire outer retina. In addition, an in vitro drug release half-life of 1,000 hours (more than 75 times that of ganciclovir) was found for 2'-nor-cyclic GMP in liposome, which may be able to be exploited in the therapy of patients with CMV retinitis unable to tolerate toxic systemic therapy. CONCLUSION: The anti-CMV drug, 2'-nor-cyclic GMP, may be promising for intravitreal injection, particularly if encapsulated into liposomes.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×