INTRODUCTION: 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. 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 μg) for 2.5h. 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]× 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. 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.
INTRODUCTION: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. 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 μg) for 2.5h. 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]× 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. CONCLUSION: In the present study, absorption of bevacizumab into nasal mucosa was demonstrated, providing new fundamentals that are mandatory for further clinical trials in HHTpatients.