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Leilei Zhang, Cynthia J. Roberts, Alan D. Letson, Ronald X. Xu; Comparison Of Avastin And Lucentis Conjugated Microbubbles For Targeted Delivery In Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(14):447.
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To investigate the characteristics of Avastin and Lucentis conjugated multifunctional microbubbles for potential use in the targeted delivery of anti-VEGF therapy for age-related macular degeneration.
Multifunctional biodegradable poly (lactic-co-glycolic acid) (PLGA) microbubbles were fabricated by a modified double emulsion process. Two fluorescence dyes, Texas red and indocyanine green (ICG), were encapsulated into microbubbles, respectively. After lyophilization, the multifunctional microbubbles provide both fluorescence contrast and ultrasound contrast. The microbubble morphology, size distribution, surface charge, and contrast intensity curve based on concentration were characterized by scanning electron microscope, dynamic light scattering, zeta potential, multi-spectral fluorescence and ultrasound, respectively. The anti-VEGF drugs, Avastin and Lucentis, were conjugated to microbubbles by activating carboxyl functional groups. The conjugation efficiency was characterized by sandwich enzyme-linked immunosorbent assay (ELISA) test. The targeted delivery was verified by conjugated multifunctional microbubbles binding with anti-human IgG1 antibody.
The size distribution of microbubbles was 1.011±0.232um. The surface charge of microbubbles was -7.83±0.82mV. There was a linear relationship between fluorescence intensity, ultrasound intensity and microbubbles concentration. The conjugation efficiency of Avastin was higher than Lucentis (70.22%±5.04% vs 46.43%±13.02% for 1.25mg/ml microbubble concentration).
Avastin and Lucentis conjugated microbubbles have the potential to be used for targeted delivery in age-related macular degeneration. Although the conjugation efficiency of Avastin is higher than Lucentis, it should also be considered that the molecular weight of Lucentis is smaller compared to Avastin.
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