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A. Khalili, D. Paull, J. S. Ellis, S. Dhingra, P. T. Khaw, S. Brocchini; Prolonged Local Ocular Delivery of an Antibody. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5992.
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To determine the release profile and physicochemical properties of a protein-based ocular delivery device.
Bevacizumab (Avastin, Genentech) was fabricated into an implantable solid form. The in vitro release profile of antibody was measured (UV spectrophotometry and surface plasmon resonance) using a flow rig (volume of 200 µl; flow rate of 2 µl/min). The released-antibody was characterized by size exclusion chromatography (SEC), gel electrophoresis, surface plasmon resonance (SPR), dynamic light scattering, and biological assays.
The active antibody (measured by SPR) was released from our ocular delivery device over a period of approximately 120 hours (within the therapeutic range) and 150 hours for the total antibody (measured by UV spectrophotometry). No shift in the SEC peak of eluted Avastin (76 minutes) was observed. Higher molecular weight species were not observed by SEC or gel electrophoresis, which suggests that there was no significant aggregation. Biological assays also confirmed that activity of Avastin was still preserved after formulation into the ocular delivery device.
Using Avastin as a model, we are developing a slow release device to allow for the prolonged, local delivery of an antibody.
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