Article (Scientific journals)
PEGylation of antibody fragments greatly increases their local residence time following delivery to the respiratory tract.
Koussoroplis, Salome Juliette; Paulissen, Geneviève; Tyteca, Donatienne et al.
2014In Journal of Controlled Release, sous presse
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Keywords :
mucoadhesion; polyethylene glycol; proteins; pulmonary drug delivery
Abstract :
[en] Inhalation aerosols offer a targeted therapy for respiratory diseases. However, the therapeutic efficacy of inhaled biopharmaceuticals is limited by the rapid clearance of macromolecules in the lungs. The aim of this research was to study the effects of the PEGylation of antibody fragments on their local residence time after administration to the respiratory tract. We demonstrate that the conjugation of a two-armed 40-kDa polyethylene glycol (PEG) chain to anti-interleukin-17A (IL-17A) F(ab')2 and anti-IL-13 Fab' greatly prolonged the presence of these fragments within the lungs of mice. The content of PEGylated antibody fragments within the lungs plateaued up to 4hours post-delivery, whereas clearance of unconjugated proteins started immediately after administration. Forty-eight hours post-delivery, F(ab')2 and Fab' content in the lungs had decreased to 10 and 14 % of the dose initially deposited, respectively. However, this value was 40 % for both PEG40-F(ab')2 and PEG40-Fab'. The prolonged pulmonary residency of the anti-IL-17A PEG40-F(ab')2 translated into an improved efficacy in reducing lung inflammation in a murine model of house dust mite-induced lung inflammation. We demonstrate that PEGylated proteins were principally retained within the lung lumen rather than the nasal cavities or lung parenchyma. In addition, we report that PEG increased pulmonary retention of antibody fragments through mucoadhesion and escape from alveolar macrophages rather than increased hydrodynamic size or improved enzymatic stability. The PEGylation of proteins might find broad application in the local delivery of therapeutic proteins to diseased airways.
Disciplines :
Cardiovascular & respiratory systems
Biochemistry, biophysics & molecular biology
Author, co-author :
Koussoroplis, Salome Juliette
Paulissen, Geneviève ;  Université de Liège - ULiège > Département de sciences fonctionnelles (DSF) > GIGA-R : Biochimie et biologie moléculaire
Tyteca, Donatienne
Goldansaz, Hadi
Todoroff, Julie
Barilly, Celine
Uyttenhove, Catherine
Van Snick, Jacques
Cataldo, Didier  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, humaines et path.
Vanbever, Rita
Language :
English
Title :
PEGylation of antibody fragments greatly increases their local residence time following delivery to the respiratory tract.
Publication date :
2014
Journal title :
Journal of Controlled Release
ISSN :
0168-3659
eISSN :
1873-4995
Publisher :
Elsevier Science, Amsterdam, Netherlands
Volume :
sous presse
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2014 Elsevier B.V. All rights reserved.
Available on ORBi :
since 26 May 2014

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