Effects of dilution and prolonged storage with preservative in a polyethylene container on Bevacizumab (AvastinTM) for topical delivery as a nasal spray in anti-hereditary hemorrhagic telangiectasia and related therapies

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 AvastinTM (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 AvastinTM 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 AvastinTM 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 AvastinTM and allow the consideration of novel AvastinTM formulations, including its use in a metered-dose nasal spray for the treatment of HHT and other applications.