Ex vivo study of bevacizumab transport through porcine nasal mucosa

• Published in: European journal of pharmaceutics and biopharmaceutics 2012-02, Vol.80 (2), p.465-469
• Main Authors: Samson, Géraldine, García de la Calera, Alicia, Dupuis-Girod, Sophie, Faure, Frédéric, Decullier, Evelyne, Paintaud, Gilles, Vignault, Céline, Scoazec, Jean-Yves, Pivot, Christine, Plauchu, Henri, Pirot, Fabrice
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - pharmacokinetics; Angiogenesis Inhibitors - toxicity; Animals; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - pharmacokinetics; Antibodies, Monoclonal, Humanized - toxicity; Bevacizumab; Biological and medical sciences; Biological Availability; Biological Transport; Diffusion; Enzyme-Linked Immunosorbent Assay; General pharmacology; Hereditary hemorrhagic telangectasia; Medical sciences; Monoclonal antibody; Nasal Mucosa - drug effects; Nasal Mucosa - metabolism; Permeability; Pharmaceutical technology. Pharmaceutical industry; Pharmacokinetics; Pharmacology. Drug treatments; Swine; Telangiectasia, Hereditary Hemorrhagic - drug therapy; Transmucosal transport
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2011.11.004

Bevacizumab recovery throughout 2.5h experiment in nasal cavity porcine mucosa mounted onto static vertical diffusion cells. Transmucosal absorption of bevacizumab as a function of time. Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder associated with abnormal angiogenesis and disabling epistaxis, for which bevacizumab is reported to be a new therapeutic option. In the present study, bevacizumab transport in porcine nasal mucosa was investigated to determine antibody bioavailability. Transmucosal absorption of bevacizumab was examined by using nasal mucosa specimens mounted onto static vertical diffusion cells then treated with bevacizumab solution (25mgmL−1, 500μg) for 2.5h. Bevacizumab concentrations were measured by enzyme-linked immunosorbent assays. Mucosal integrity was examined by histological examination of treated mucosa. Transmucosal transport of bevacizumab followed a Fickian diffusion process (permeability coefficient: [0.63±22]×10−6cms−1; and steady-state flux: 56.4±19.6μgcm−2h−1). Total recovery of bevacizumab throughout the 2.5h experiment was 83% of the initial dose distributed (i) at the mucosal surface (263±73μg; ∼53%) and (ii) into (95±14μg; ∼19%) and through (56±26μg; ∼11%) the mucosa. There was no evidence of any noticeable histological effects, confirming the harmlessness of nasal bevacizumab delivery. In the present study, absorption of bevacizumab into nasal mucosa was demonstrated, providing new fundamentals that are mandatory for further clinical trials in HHT patients.