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.
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.
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DOI：
10.3233/hab-2011-0244
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Koulen P
中科院分区：
文献类型：
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作者：
Kaja S;Hilgenberg JD;Everett E;Olitsky SE;Gossage J;Koulen P
遗传性出血性毛细血管扩张症（HHT）是一种常染色体显性遗传的血管发育不良，严重的，复发性鼻出血是一种常见的临床表型与HHT。使用脉动鼻冲洗器的稀释的Avastin™（贝伐单抗;重组人源化抗血管上皮生长因子免疫球蛋白G1）的鼻内治疗方案已在临床实践中被证明是有效的。然而，关于Avastin™在用于药物递送的标准容器如聚乙烯瓶中稀释和长期储存后的稳定性的担忧迄今为止阻碍了更广泛的临床应用。与防腐剂苯扎氯铵的相容性也是未知的。我们对Avastin™进行了详细的生化和电化学分析，在稀释和长期冷藏后未检测到任何变性或聚集的证据。我们的数据为Avastin™的稳定性提供了重要的见解，并允许考虑新的Avastin™制剂，包括其在用于治疗HHT的定量鼻喷雾剂和其他应用中的用途。
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 a pulsatile 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. We performed a detailed biochemical and electrochemical analysis of Avastin™ and did not detect any evidence of degeneration or aggregation following dilution and prolonged, refrigerated storage. 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.