April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Comparison of Long-Acting Bevacizumab Formulations in the Treatment of Choroidal Neovascularization in a Rat Model
Author Affiliations & Notes
  • C. K. Pan
    Ophthalmology,
    University of Colorado, Aurora, Colorado
  • C. Durairaj
    Pharmaceutical Sciences,
    University of Colorado, Aurora, Colorado
  • U. B. Kompella
    Pharmaceutical Sciences & Ophthalmology,
    University of Colorado, Aurora, Colorado
  • O. Agwu
    School of Medicine, Case Western Reserve University, Cleveland, Ohio
  • S. C. Oliver
    Ophthalmology,
    University of Colorado, Aurora, Colorado
  • H. Quiroz-Mercado
    Denver Health Medical Center, Denver, Colorado
  • N. Mandava
    Ophthalmology,
    University of Colorado, Aurora, Colorado
  • J. Olson
    Ophthalmology,
    University of Colorado, Aurora, Colorado
  • Footnotes
    Commercial Relationships  C.K. Pan, None; C. Durairaj, None; U.B. Kompella, None; O. Agwu, None; S.C. Oliver, None; H. Quiroz-Mercado, None; N. Mandava, None; J. Olson, None.
  • Footnotes
    Support  NIH EY017045 (UBK through Emory University)
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2457. doi:https://doi.org/
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      C. K. Pan, C. Durairaj, U. B. Kompella, O. Agwu, S. C. Oliver, H. Quiroz-Mercado, N. Mandava, J. Olson; Comparison of Long-Acting Bevacizumab Formulations in the Treatment of Choroidal Neovascularization in a Rat Model. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2457. doi: https://doi.org/.

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

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Abstract

Purpose: : To compare the reduction from control in the size of experimentally-induced choroidal neovascularization (CNV) in rat eyes treated with bevacizumab, poly(ethylene-glycol) (PEG)-bevacizumab conjugate, and poly(lactic-co-glycolic acid) (PLGA)-encapsulated bevacizumab.

Methods: : A carboxyl-group-terminated PEG was pegylated to bevacizumab by carbodiimide-mediated conjugation in the molar ratio of 1:1. Bevacizumab-loaded nanoparticles were prepared by a solid-in-oil-in-water (S/O/W) encapsulation method using PLGA polymer. 48 eyes from 24 rats were divided equally into 4 groups. In each group, 3 eyes were assigned to a treatment subgroup, each receiving a different injection - control, bevacizumab, PEG-bevacizumab conjugate, and PLGA-encapsulated bevacizumab. In all groups, laser photocoagulation was used to rupture Bruch’s membrane. In group 1, laser was followed by injection, which was then followed by harvesting the rats to assess the CNV area. All three steps were separated by a 2 week interval. In groups 2, 3, and 4, injection preceded laser photocoagulation by a variable interval and all rats were harvested 2 weeks post-laser treatment. In group 2, laser and injection were separated by 2 weeks. In group 3, laser followed injection by 4 weeks. In group 4, laser followed injection by 6 weeks. The CNV area was measured for each subgroup and compared against its control. Pair-wise comparisons were conducted to assess for statistically significant differences between subgroups.

Results: : In group 3, the PEG-bevacizumab and PLGA-encapsulated bevacizumab treatment subgroups showed a 9.0% (p = 0.384) and 20.3% (p = 0.077) reduction in CNV area versus control while there was no reduction in CNV area in the bevacizumab-alone subgroup. However, this was not found to be statistically significant. All treatment subgroups in schedule groups 1, 2, and 4, showed statistically significant reduction of CNV area versus control (p < 0.05).

Conclusions: : The reduction in CNV area in all treatment subgroups, with the exception of those in group 3, suggests successful formulation of PEG-bevacizumab conjugate and PLGA-encapsulated bevacizumab while retaining the active anti-angiogenic properties. Further studies with various doses and longer intervals between injection and laser are needed to evaluate the long-acting efficacy of these formulations.

Keywords: choroid: neovascularization • vascular endothelial growth factor • retinal neovascularization 
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