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H. Kim, R.J. D'Amato, R.J. Lutz, P. Yuan, J. Baffi, J.D. Wolfe, G. Byrnes, M.R. Robinson, K.G. Csaky; A Subconjunctival Implant for Delivery of Cytochalasin E in a Model of Choroidal Neovascularization: A Pilot Study . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4429.
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Purpose: Cytochalasin E (Cyto E), an epoxide containing a fungal-derived metabolite, exhibits antiangiogenic activity in vitro and in vivo. The goal of this study was to evaluate the in vitro release rates and efficacy of a Cyto E subconjunctival implant in a rat model of choroidal neovascularization (CNV). Methods: Implants were fabricated using a compressed 2 mm diameter Cyto E pellet coated with uncured 10 % (w/v) polyvinylalcohol, a non-reactive biocompatable polymer. In vitro release rates were determined by placing the implants in PBS and measuring the drug concentrations over time by HPLC every 24-72 hours, each time replacing the PBS to simulate sink conditions. Implants were inserted into the subconjunctival space of Brown Norway rats at the same time that an adenoviral vector expressing vascular endothelial growth factor 165 (Ad-VEGF 165) was injected into the subretinal space to stimulate CNV production. The animals were sacrificed at 2 and 3 weeks post-implantation and the eyes were evaluated for the presence of CNV using a FITC-dextran perfusion / flat mount quantitation method. Results: The in vitro release rates showed an initial Cyto E release of 9.8 ± 3.0 ug/day over the initial 4 days followed by a relatively constant release of 4.7 ± 0.8 ug/day between days 5 and 28. Six rats received subconjunctival Cyto E implant and six rats received a sham implant (no drug). Clinically, the implants appeared to be well tolerated and no implant extrusions were noted. No significant quantifiable CNV was not present at 2 weeks in either the Cyto E or sham implant group. However, at 3 weeks, 1/3 eyes with a Cyto E implant showed measurable CNV whereas; 3/3 eyes with a sham implant showed CNV. Conclusions: Sustained-release Cyto E subconjunctival implants can be fabricated for delivery of drug into the posterior pole with relatively steady release over the time course of the CNV model (3 weeks). The rat eyes receiving Cyto E implants showed less production of CNV at 3 weeks compared with the sham group. Efficacy studies are ongoing to further evaluate the potential of Cyto E to treat CNV.
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