Effects of dilution and prolonged storage with preservative in a polyethylene container on Bevacizumab (Avastin™) for topical delivery as a nasal spray in anti-hereditary hemorrhagic telangiectasia and related therapies.
| Autor: | Kaja S; Vision Research Center and Department of Ophthalmology, University of Missouri - Kansas City, School of Medicine, Kansas City, MO 64108, USA., Hilgenberg JD, Everett E, Olitsky SE, Gossage J, Koulen P |
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| Jazyk: | angličtina |
| Zdroj: | Human antibodies [Hum Antibodies] 2011; Vol. 20 (3-4), pp. 95-101. |
| DOI: | 10.3233/HAB-2011-0244 |
| Abstrakt: | 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. |
| Databáze: | MEDLINE |
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