title: Ex vivo study of bevacizumab transport through porcine nasal mucosa.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Pôle Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon, France. geraldine.samson@chu-lyon.fr
authors: Géraldine
authors: G
authors: Samson
authors: Alicia
authors: A
authors: García de la Calera
authors: Sophie
authors: S
authors: Dupuis-Girod
authors: Frédéric
authors: F
authors: Faure
authors: Evelyne
authors: E
authors: Decullier
authors: Gilles
authors: G
authors: Paintaud
authors: Céline
authors: C
authors: Vignault
authors: Jean-Yves
authors: JY
authors: Scoazec
authors: Christine
authors: C
authors: Pivot
authors: Henri
authors: H
authors: Plauchu
authors: Fabrice
authors: F
authors: Pirot
mesh_terms: D000281:Administration, Intranasal; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D000068258:Bevacizumab; D001682:Biological Availability; D001692:Biological Transport; D004058:Diffusion; D004797:Enzyme-Linked Immunosorbent Assay; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism*; D010539:Permeability; D013552:Swine; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000188:drug therapy
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab