Ultrasound-enhanced bevacizumab release from echogenic liposomes for inhibition of atheroma progression |
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Authors: | Melvin E Klegerman Ali K Naji Kevin J Haworth Yuejiao Zou Eva Golunski Tao Peng |
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Institution: | 1. Department of Internal Medicine, Division of Cardiovascular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA,;2. Department of Internal Medicine, Division of Cardiovascular Diseases, University of Cincinnati, Cincinnati, OH, USA, and;3. Biomedical Engineering Program, University of Cincinnati, Cincinnati, OH, USA |
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Abstract: | Context: Bevacizumab (BEV) is a monoclonal antibody to vascular endothelial growth factor (VEGF) that ameliorates atheroma progression by inhibiting neovascularization.Objective: We aimed to determine whether BEV release from echogenic liposomes (BEV-ELIP) could be enhanced by color Doppler ultrasound (US) and whether the released BEV inhibits VEGF expression by endothelial cells in vitro.Materials and methods: BEV-ELIP samples were subjected to 6?MHz color Doppler ultrasound (MI?=?0.4) for 5?min. We assessed release of BEV with a direct ELISA and with fluoresceinated BEV (FITC-BEV) loaded into ELIP by the same method. Human umbilical vein endothelial cell (HUVEC) cultures were stimulated to express VEGF by 10?nM phorbol-12-myristate 13-acetate (PMA). Cell-associated VEGF levels were determined using a cell-based ELISA.Results: Overall, US caused an additional 100?µg of BEV to be released or exposed per BEV-ELIP aliquot within 60?min BEV-ELIP treated with US inhibited VEGF expression by 90% relative to non-treated controls and by 70% relative to BEV-ELIP without US. Also, US-treated BEV-ELIP inhibited HUVEC proliferation by 64% relative to untreated controls and by 45% relative to BEV-ELIP without US.Discussion and conclusion: We have demonstrated that BEV-ELIP retains its VEGF-binding activity in a liposomal formulation and that clinical Doppler US can significantly increase that activity, both by releasing free BEV and by enhancing the surface exposure of the immunoreactive antibody. |
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Keywords: | Controlled release/delivery in vitro models nanotechnology therapeutic antibodies |
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