PEG 400, a hydrophilic molecular probe for measuring intestinal permeability

Area of Science:

• Pharmacokinetics
• Biophysical Chemistry
• Gastroenterology

Background:

• Low-molecular-weight polyethylene glycols (PEGs) are often misclassified as lipophilic permeability probes.
• This misclassification leads to incorrect assumptions about their transport across lipid cell membranes.

Purpose of the Study:

• To investigate the relative lipophilicity of polyethylene glycols 400 and 600.
• To determine the relationship between PEG molecular size, hydrophilicity, and intestinal permeability.
• To clarify the transport and excretion mechanisms of PEGs.

Main Methods:

• Partition coefficients (Kd) of PEGs were measured in water and organic solvents of varying polarity.
• Urinary recovery of different molecular weight PEG 400 fractions was analyzed in volunteers after oral administration.
• Correlation between urinary recovery and PEG hydrophilicity was assessed.

Main Results:

• Polyethylene glycol 414 exhibited very low partition coefficient in hexane/water, indicating strong hydrophilicity.
• PEG Kd increased linearly with solvent polarity, confirming hydrophilic nature.
• Oral ingestion showed decreased urinary recovery of higher molecular weight PEGs, indicating size-limited intestinal permeability.
• Urinary recovery correlated well with hydrophilicity for intravenously administered PEGs.

Conclusions:

• Polyethylene glycols 400 and 600 are strongly hydrophilic, not lipophilic.
• PEG transport is unlikely via lipid pathways due to negligible lipid phase partitioning.
• Intestinal permeability is governed by PEG molecular size, and excretion is influenced by water solubility.