Intestinal permeability to polyethyleneglycol and sugars: a re-evaluation

Area of Science:

• Biopharmaceutics and Drug Delivery
• Physical Chemistry
• Gastroenterology

Background:

• Previous research suggested anomalous intestinal permeability for polyethylene glycols (PEGs) compared to similar molecular weight sugars.
• This led to hypotheses of multiple translocation mechanisms or a minimum molecular dimension determining penetration.
• Hydrogen-bonding capacity is a known correlate of membrane permeability and oil-water partition coefficients.

Purpose of the Study:

• To re-analyze existing intestinal permeability data for ethyleneglycol oligomers and sugars.
• To investigate the correlation between molecular hydrogen-bonding capacity and intestinal permeability.
• To determine if a single mechanism, such as passive diffusion, can explain the transport of both molecule classes.

Main Methods:

• Re-analysis of a classic dataset on human intestinal permeability.
• Calculation of hydrogen-bonding capacity for ethyleneglycol oligomers and sugars based on their functional groups.
• Correlation analysis between measured permeability and calculated hydrogen-bonding capacity.

Main Results:

• A strong correlation was demonstrated between intestinal permeability and hydrogen-bonding capacity for both polyethylene glycols and sugars.
• No discontinuity was observed between the permeability of polyethylene glycols and sugars when plotted against hydrogen-bonding capacity.
• The data support a unified model of passive diffusion across cellular membranes for all molecules studied.

Conclusions:

• Intestinal permeability of polyethylene glycols and sugars is consistent with passive diffusion driven by hydrogen-bonding capacity.
• The findings challenge the need for multiple translocation mechanisms for these molecules.
• Hydrogen-bonding capacity serves as a reliable predictor of intestinal passive diffusion.