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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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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.
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.
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).
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.
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