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L. Zhang, J. Xu, R. Xu, C. Roberts; Targeted Delivery of Multifunctional Microbubbles for Anti-VEGF Therapy of Neovascular Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2010;51(13):521.
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To investigate the technical feasibility of using biodegradable multifunctional microbubbles for targeted delivery of anti-VEGF therapy for the treatment of age-related macular degeneration.
Biodegradable poly (lactic-co-glycolic acid) (PLGA) microbubbles are fabricated by a modified double emulsion process. The microbubble surface morphology, size distribution, and surface charge are evaluated by scanning electron microscope, dynamic light scattering, and zeta potential, respectively.Anti-VEGF antibodies (e.g., bevacizumab and ranibizumab) are conjugated with microbubbles by activating carboxyl functional groups using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). The conjugation efficiency is evaluated by sandwich enzyme-linked immunosorbent assay (ELISA) test.After conjugation, the microbubbles are labeled by a fluorescence dye (Alexa Red 680). The antibody binding affinity and stability of multifunctional microbubbles are evaluated using a monoclonal antihuman IgG1 antibody.
Scanning electron Microscopic images of microbubbles are captured. The size distribution of microbubbles is 1.011±0.232um. The surface charge of microbubbles is -7.83±0.82mV. The conjugation efficiencies of anti-VEGF antibodies are characterized. Multifunctional microbubbles can be visualized and quantitatively characterized by fluorescence and ultrasound imaging modalities simultaneously.
Multifunctional microbubbles conjugated with anti-VEGF antibodies can bind with antihuman IgG1 antibody and be detected by fluorescence and ultrasound imaging simultaneously. Our results demonstrate the technical potential for image-guided delivery of anti-VEGF therapy in neovascular age-related macular degeneration.
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