BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia and severe, recurrent epistaxis is a common clinical phenotype associated with HHT. An intranasal treatment regime of diluted Avastin™ (Bevacizumab; recombinant humanized anti-vascular epithelial growth factor immunoglobin G1) using apulsatile nasal irrigator has proven efficacious in clinical practice. However, concerns regarding the stability of Avastin™ following dilution and prolonged storage in standard containers used for drug delivery, such as polyethylene bottles, have so far prevented a more widespread clinical use. Compatibility with the preservative benzalkonium chloride was also unknown. OBJECTIVE: This study aimed at determining, whether dilution, prolonged refrigerated storage and the presence of the preservative benzalkonium chloride - as required for novel Avastin™ formulations - affected the biochemical and electrochemical properties of the drug. METHODS: We performed a detailed biochemical and electrochemical analysis of Avastin™, including native and sodium dodecyl sulfate polyacrylamide gel electrophoresis, enzyme-linked immunosorbent assay and isoelectric focusing. RESULTS: We did not detect any evidence of degeneration or aggregation following dilution and prolonged, refrigerated storage or from the presence of benzalkonium chloride. All biochemical and electrochemical properties of Avastin™ after dilution and prolonged, refrigerated storage were undistinguishable from control. CONCLUSIONS: Our data provide important insight into the stability of Avastin™ and allow the consideration of novel Avastin™ formulations, including its use in a metered-dose nasal spray for the treatment of HHT and other applications.
BACKGROUND:Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia and severe, recurrent epistaxis is a common clinical phenotype associated with HHT. An intranasal treatment regime of diluted Avastin™ (Bevacizumab; recombinant humanized anti-vascular epithelial growth factor immunoglobin G1) using apulsatile nasal irrigator has proven efficacious in clinical practice. However, concerns regarding the stability of Avastin™ following dilution and prolonged storage in standard containers used for drug delivery, such as polyethylene bottles, have so far prevented a more widespread clinical use. Compatibility with the preservative benzalkonium chloride was also unknown. OBJECTIVE: This study aimed at determining, whether dilution, prolonged refrigerated storage and the presence of the preservative benzalkonium chloride - as required for novel Avastin™ formulations - affected the biochemical and electrochemical properties of the drug. METHODS: We performed a detailed biochemical and electrochemical analysis of Avastin™, including native and sodium dodecyl sulfatepolyacrylamide gel electrophoresis, enzyme-linked immunosorbent assay and isoelectric focusing. RESULTS: We did not detect any evidence of degeneration or aggregation following dilution and prolonged, refrigerated storage or from the presence of benzalkonium chloride. All biochemical and electrochemical properties of Avastin™ after dilution and prolonged, refrigerated storage were undistinguishable from control. CONCLUSIONS: Our data provide important insight into the stability of Avastin™ and allow the consideration of novel Avastin™ formulations, including its use in a metered-dose nasal spray for the treatment of HHT and other applications.
Authors: Lu Liu; David A Ammar; Lindsey A Ross; Naresh Mandava; Malik Y Kahook; John F Carpenter Journal: Invest Ophthalmol Vis Sci Date: 2011-02-22 Impact factor: 4.799
Authors: Blessing C Ilochonwu; Marko Mihajlovic; Roel F Maas-Bakker; Charis Rousou; Miao Tang; Mei Chen; Wim E Hennink; Tina Vermonden Journal: Biomacromolecules Date: 2022-06-23 Impact factor: 6.978