Preclinical evaluation of topically-administered PEGylated Fab’ lung toxicity

Freches, D.; Rocks, Natacha; Patil, H. P.; Perin, Fabienne; Van Snick, J.; Vanbever, R.; Cataldo, Didier

doi:10.1016/j.ijpx.2019.100019

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Preclinical evaluation of topically-administered PEGylated Fab’ lung toxicity

Freches, D.; Rocks, Natacha; Patil, H. P. et al.

2019 • In International Journal of Pharmaceutics: X, 1

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/259264

DOI
10.1016/j.ijpx.2019.100019

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Keywords :

Alveolar macrophages; Lung toxicity; Monoclonal antibodies; PEGylation; Pulmonary drug delivery; Article; J774A1 cell line

Abstract :

[en] PEGylation is a promising approach to increase the residence time of antibody fragments in the lungs and sustain their therapeutic effects. However, concerns arise as to the potential pulmonary toxicity of antibody fragments conjugated to high molecular weight (HMW) polyethylene glycol (PEG), notably after repeated administrations, and the possibility of PEG accumulation in the lungs. The purpose of this proof-of-concept study is to give insights about the safety of lung administration of a Fab’ anti-IL17A antibody fragment conjugated to two-armed 40 kDa PEG (PEG40). The presence of the PEG40 moiety inside alveolar macrophages remained stable for at least 24 h after intratracheal administration of PEG40-Fab’ to mice. PEG40 was then progressively cleared from alveolar macrophages. Incubation of PEG40 alone with macrophages in vitro did not significantly harm macrophages and did not affect phagocytosis or the production of inflammatory markers. After acute or chronic administration of PEG40-Fab’ to mice, no signs of significant pulmonary toxicity or inflammatory cell accumulation were observed. A vacuolization of alveolar macrophages not associated with any inflammation was noticed when PEG40, PEG40-Fab’, or unPEGylated Fab’ were administered. To conclude this preliminary proof of concept study, acute or repeated pulmonary administrations of PEGylated Fab’ appear safe in rodents. © 2019 The Authors

Disciplines :

Pharmacy, pharmacology & toxicology

Author, co-author :

Freches, D.; Advanced Drug Delivery & Biomaterials, Louvain Drug Research Institute, Université catholique de Louvain (UCLouvain), Brussels, Belgium

Rocks, Natacha ; Université de Liège - ULiège > Département de pharmacie > Pharmacie galénique

Patil, H. P.; Advanced Drug Delivery & Biomaterials, Louvain Drug Research Institute, Université catholique de Louvain (UCLouvain), Brussels, Belgium

Perin, Fabienne ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques

Van Snick, J.; Ludwig Cancer Research Ltd, Brussels Branch, Avenue Hippocrate 74, UCLouvain, 7459, Brussels, B-1200, Belgium

Vanbever, R.; Advanced Drug Delivery & Biomaterials, Louvain Drug Research Institute, Université catholique de Louvain (UCLouvain), Brussels, Belgium

Cataldo, Didier ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement

Language :

English

Title :

Preclinical evaluation of topically-administered PEGylated Fab’ lung toxicity

Publication date :

2019

Journal title :

International Journal of Pharmaceutics: X

eISSN :

2590-1567

Publisher :

Elsevier B.V.

Volume :

Peer reviewed :

Peer Reviewed verified by ORBi

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since 26 April 2021

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