Document Detail


Ex vivo study of bevacizumab transport through porcine nasal mucosa.
MedLine Citation:
PMID:  22120685     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Géraldine Samson; Alicia García de la Calera; Sophie Dupuis-Girod; Frédéric Faure; Evelyne Decullier; Gilles Paintaud; Céline Vignault; Jean-Yves Scoazec; Christine Pivot; Henri Plauchu; Fabrice Pirot
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Publication Detail:
Type:  Journal Article     Date:  2011-11-18
Journal Detail:
Title:  European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V     Volume:  80     ISSN:  1873-3441     ISO Abbreviation:  Eur J Pharm Biopharm     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-06     Completed Date:  2012-05-22     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  9109778     Medline TA:  Eur J Pharm Biopharm     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  465-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
Affiliation:
Pôle Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon, France. geraldine.samson@chu-lyon.fr
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MeSH Terms
Descriptor/Qualifier:
Administration, Intranasal
Angiogenesis Inhibitors / administration & dosage,  pharmacokinetics*,  toxicity
Animals
Antibodies, Monoclonal, Humanized / administration & dosage,  pharmacokinetics*,  toxicity
Biological Availability
Biological Transport
Diffusion
Enzyme-Linked Immunosorbent Assay
Nasal Mucosa / drug effects,  metabolism*
Permeability
Swine
Telangiectasia, Hereditary Hemorrhagic / drug therapy
Chemical
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Antibodies, Monoclonal, Humanized; 2S9ZZM9Q9V/bevacizumab

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