Journal
COLLOIDS AND SURFACES B-BIOINTERFACES
Volume 147, Issue -, Pages 459-466Publisher
ELSEVIER
DOI: 10.1016/j.colsurfb.2016.08.037
Keywords
Glycyrrhizic acid; Liposome; Lipid bilayer; Membrane permeability; Drug delivery; Nuclear magnetic resonance; Molecular dynamics
Funding
- Russian Foundation for Basic Research [15-04-02538, 15-29-05792]
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Glycyrrhizic acid (GA) is a triterpene glycoside extracted from licorice root. Due to its amphiphilicity GA is capable of forming complexes with a variety of hydrophobic molecules, substantially increasing their solubility. GA can enhance the therapeutic effects of various drugs. It was hypothesized that the increased bioavailability of the drug by GA is not only due to increased solubility, but also to enhancement of drug permeability through cell membranes. In this study the interaction of GA with POPC liposomes and model DOPC, POPC and DPPC bilayers was investigated by NMR with addition of shift reagents and MD simulations. This work helps to better understand the mechanism of enhanced drug bioavailability in the presence of GA. NMR and MD reveal that GA does penetrate into the lipid bilayer. NMR shows that GA changes the mobility of lipids. GA is predominantly located in the outer half-layer of the liposome and that the middle of the hydrophobic tails is the preferred location. GA freely passes through the bilayer surface to the inner part bringing a few water molecules. Also both approaches indicate pore formation in the presence of GA. The GA interaction with membranes is an additional aspect of the biological activity of GA-based drug delivery systems. (C) 2016 Elsevier B.V. All rights reserved.
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