Portal de Periódicos da CAPES

Ex vivo study of bevacizumab transport through porcine nasal mucosa

2011; Elsevier BV; Volume: 80; Issue: 2 Linguagem: Inglês

10.1016/j.ejpb.2011.11.004

1873-3441

Géraldine Samson, Alicia García de la Calera, Sophie Dupuis‐Girod, Frédéric Faure, Évelyne Decullier, Gilles Paintaud, Céline Vignault, Jean‐Yves Scoazec, C. Pivot, Henri Plauchu, Fabrice Pirot,

Coagulation, Bradykinin, Polyphosphates, and Angioedema

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 (25 mg mL(-1), 500 μg) 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(-6) cm s(-1); and steady-state flux: 56.4 ± 19.6 μg cm(-2)h(-1)). Total recovery of bevacizumab throughout the 2.5h experiment was 83% of the initial dose distributed (i) at the mucosal surface (263 ± 73 μg; ∼53%) and (ii) into (95 ± 14 μg; ∼19%) and through (56 ± 26 μg; ∼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.