PEGylation prolongs the pulmonary retention of an anti-IL-17A Fab’ antibody fragment after pulmonary delivery in three different species
| Autor: | Danielle Freches, Rita Vanbever, Catherine Uyttenhove, Maria Machado Franco, Sam Philip Heywood, Harshad P. Patil |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.drug_class Pharmaceutical Science 02 engineering and technology Polyethylene glycol Monoclonal antibody Polyethylene Glycols Rats Sprague-Dawley Immunoglobulin Fab Fragments Mice 03 medical and health sciences chemistry.chemical_compound Drug Delivery Systems Species Specificity PEG ratio medicine Animals Respiratory system Lung IC50 Autoantibodies Dose-Response Relationship Drug biology Interleukin-17 Fast protein liquid chromatography 021001 nanoscience & nanotechnology Molecular biology Rats 030104 developmental biology chemistry NIH 3T3 Cells PEGylation biology.protein Female Rabbits Antibody 0210 nano-technology |
| Zdroj: | International Journal of Pharmaceutics. 521:120-129 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2017.02.021 |
| Popis: | The PEGylation of antibody fragments has been shown to greatly prolong their residence time in the lungs in mice. The purpose of this research was to confirm the effect of PEGylation in higher animal species, that is, the rat and the rabbit. An anti-IL-17A Fab' antibody fragment was conjugated to a two-armed 40kDa polyethylene glycol (PEG) via site-selective thiol PEGylation. PEGylation did not significantly alter the binding activity of the Fab' fragment but it largely enhanced its inhibitory potency. PEGylation increased the residence time of the Fab' in the lungs of mice, rats and rabbits. Following intratracheal administration, the unconjugated Fab' was cleared from the lungs within 24h while large quantities of the PEGylated Fab' remained present up to 48h. No significant differences in clearance were noted between the three animal species although there was a tendency of longer residence time in higher species. PEGylation represents a promising approach to sustain the presence of antibody fragments in the lungs and to enhance their therapeutic efficacy in respiratory diseases. |
| Databáze: | OpenAIRE |
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