May 2008
Volume 49, Issue 13
ARVO Annual Meeting Abstract  |   May 2008
Nanoparticle Drug Delivery for Treatment of Retinal Neovascularisation
Author Affiliations & Notes
  • R. A. Wassel
    Charlesson LLC, Oklahoma City, Oklahoma
  • D. Chen
    Charlesson LLC, Oklahoma City, Oklahoma
  • Y. Hu
    Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
  • J.-X. Ma
    Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
  • Footnotes
    Commercial Relationships  R.A. Wassel, None; D. Chen, None; Y. Hu, None; J. Ma, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 4804. doi:
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      R. A. Wassel, D. Chen, Y. Hu, J.-X. Ma; Nanoparticle Drug Delivery for Treatment of Retinal Neovascularisation. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4804. doi:

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

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Purpose: : CLT-003, a novel thalidomide analog, has been shown to have a transitory inhibitory effect on angiogenesis and vascular leakage when injected into the vitreous humor. The goal of this study is to develop a sustained release formulation that can deliver the drug for several months, reducing the need for frequent injections.

Methods: : Primary bovine retinal capillary endothelial cells and pericytes were treated with varying doses of CLT-003 and CLT-003 nanoparticles and subjected to MTT assays to determine the effect on cell viability. Brown Norway rats were given an intraperitoneal injection of streptozotocin to induce diabetes, and blood glucose levels were monitored weekly for two weeks. Multiple groups of diabetic and non-diabetic rats received an intravitreal injection of 2 µg to 50 µg CLT-003 in one eye, and the vehicle alone in the contralateral eye as a control. ERGs were recorded prior to the injection and 2 days before the animals were killed. At 2, 4 and 6 weeks post-injection, the effect on retinal vascular leakage was measured using FITC-albumin as the tracer and the protein levels of several inflammatory and angiogenic proteins were quantified with Elisa.

Results: : At micromolar concentration, CLT-003 nanoparticles have potent and dose-dependent effects on reducing endothelial cell viability without producing detectable adverse effects in pericyte cells at the same concentrations used. In contrast to the transient inhibitory effect on endothelial cells of CLT-003 alone, the CLT-003 nanoparticles generated sustained release of CLT-003 in vitro for 2 weeks and showed prolonged inhibitor effects on endothelial cell growth. An intravitreal injection of CLT-003 induced significant but transient reduction of retinal vascular leakage but did not cause any detectable toxicities as shown by ERG and histology examinations. Evaluation of the prolonged effect of CLT-003 on retinal vascular leakage in STZ-diabetic rats is underway.

Conclusions: : CLT-003 nanoparticle can mediate sustained release of CLT-003 and prolong its effects. The results suggest that CLT-003 nanoparticle may be a suitable therapeutic option for patients with diabetic retinopathy, diabetic macular edema, and age-related macular degeneration.

Keywords: neovascularization • drug toxicity/drug effects • diabetic retinopathy 

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