Ex vivo study of bevacizumab transport through porcine nasal mucosa

Introduction: Hereditary hemorrhagic telangiectasia (HI-IT) 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. Material and methods: Transmucosal absorption of bevacizumab was examined by using nasal mucosa specimens mounted onto static vertical diffusion cells then treated with bevacizumab solution (25 mg mL(-1), 500 mu g) for 2.5 h. Bevacizumab concentrations were measured by enzyme-linked immunosorbent assays. Mucosal integrity was examined by histological examination of treated mucosa. Results: Transmucosal transport of bevacizumab followed a Fickian diffusion process (permeability coefficient: [0.63 +/- 22] x 10(-6) cm s(-1); and steady-state flux: 56.4 +/- 19.6 mu g cm(-2) h(-1)). Total recovery of bevacizumab throughout the 2.5 h experiment was 83% of the initial dose distributed (i) at the mucosal surface (263 +/- 73 mu g: similar to 53%) and (ii) into (95 +/- 14 mu g; similar to 19%) and through (56 +/- 26 mu g; similar to 11%) the mucosa. There was no evidence of any noticeable histological effects, confirming the harmlessness of nasal bevacizumab delivery. Conclusion: 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. (C) 2011 Elsevier B.V. All rights reserved.