Kinetics of bile salt binding to liposomes revealed by carboxyfluorescein release and mathematical modeling

Abstract

We propose a mathematical model for the release of carboxyfluorescein from liposomes whose membrane permeability is modified by the binding of different bile salts to the leaflets of the lipid bilayer. We find that the permeability of the liposomal bilayer depends on the difference in the concentrations of bile salt in the inner and outer leaflets and is only minimally influenced by the total concentration of bile salt in the bilayer. Deoxycholate and cholate are found to behave similarly in enhancing permeability for limited times, whereas the novel bile salt, 12-monoketocholate, flips from the outer to inner leaflet slowly, thereby enhancing membrane permeability for a prolonged time.

Keywords::

• Liposomes
• bile salts

Acknowledgment

P.H. and A.R. thank the School of Pharmacy at the University of Otago in Dunedin for its kind hospitality during our stay.

Declaration of interest

This work has been supported by the grant “Collaborative Research: Predicting the Release Kinetics of Matrix Tablets” (DMS 1016214 to P.H. and DMS 1016136 to A.R.) of the National Science Foundation of the United States of America. The authors report no conflicts of interest.

ERRATUM

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