Calcified Phospholipid Complex of Glycyrrhizic Acid for an Enhanced Oral Absorption

Glycyrrhizic acid (GA) exhibits an extremely low oral bioavailability. Herein, a calcium-ion-bridged phospholipid complex strategy was developed. The calcified phospholipid complex (GA-Ca-PC) was constructed via strong electrostatic/coordination interactions between calcium ions, carboxyl groups (from GA), and phosphate groups (from soybean lecithin), as confirmed by Fourier transform infrared (FT-IR) spectroscopy. Calcium ion bridges improved the stability of GA phospholipid complexes in the intestinal tract. Molecular dynamics simulations revealed the complex GA-Ca_1.0-PC with a molar ratio of Ca²⁺ and GA at 1:1 could extensively interact with the membrane. Moreover, the single-pass intestinal perfusion studies indicated the substantially higher membrane permeability of GA-Ca_1.0-PC in the small intestines compared with the conventional phospholipid complexes (GA-PC) and GA molecules. GA-Ca_1.0-PC system showed 4.08-fold and 22.75-fold higher oral bioavailability compared with GA-PC and GA, respectively. Therefore, GA-Ca_1.0-PC significantly ameliorated the progression of liver fibrosis. Collectively, calcium-ion bridging was demonstrated to be an effective strategy to stabilize phospholipid complexes which could improve the oral absorption efficacy of triterpenoid saponins.