Absorption of Polyethylene Glycol (PEG) Polymers: The Effect of PEG Size on Permeability

Polyethylene glycol (PEG) polymers are large amphiphilic molecules that are highly hydrated in solution. To explore the permeability properties of different sized PEG polymers across epithelial membranes in vivo, we examined the absorption of fluorescently labeled PEG conjugates sized 0.55-20kDa fro...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2009-08, Vol.98 (8), p.2847-2856
Main Authors: Gursahani, Hema, Riggs-Sauthier, Jennifer, Pfeiffer, Juergen, Lechuga-Ballesteros, David, Fishburn, C. Simone
Format: Article
Language:English
Subjects:
absorption
Absorption - drug effects
Absorption - physiology
Animals
Biological and medical sciences
delivery/permeability
diffusion/transport
Dose-Response Relationship, Drug
epithelial
General pharmacology
Male
Medical sciences
Particle Size
passive
pegylation
permeability
Permeability - drug effects
pharamcokinetics
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Polyethylene Glycols - chemistry
Polyethylene Glycols - metabolism
Polyethylene Glycols - pharmacology
polymers
Polymers - chemistry
Polymers - metabolism
Rats
Rats, Sprague-Dawley
Respiratory Mucosa - drug effects
Respiratory Mucosa - metabolism
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Summary:Polyethylene glycol (PEG) polymers are large amphiphilic molecules that are highly hydrated in solution. To explore the permeability properties of different sized PEG polymers across epithelial membranes in vivo, we examined the absorption of fluorescently labeled PEG conjugates sized 0.55-20kDa from the lung, since this system provides a reservoir that limits rapid diffusion of molecules away from the site of delivery and enables permeability over longer times to be examined. Following intratracheal delivery in rats, the PEG polymers underwent absorption with first-order kinetics described by single exponential decay curves. PEG size produced a marked influence on the rate of uptake from the lung, with half-lives ranging from 2.4 to 13h, although above a size of 5kDa, no further change in rate was observed. PEG size likewise affected retention in alveolar macrophages and in lung tissue; whereas smaller PEG sizes (5kDa) remained in lung cells and tissue for up to 7 days. These data demonstrate that PEG polymers can be absorbed across epithelial membranes and that PEG size plays a dominant role in controlling the rate and mechanism of absorption.
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.21635