Enhancement of gastrointestinal absorption of isoliquiritigenin by nanostructured lipid carrier

•Isoliquiritigenin-loaded nanostructured lipid carrier (ISL-NLC) could enhance oral absorption of ISL.•The absorption percent of ISL in the stomach for 2 h was less than 10%.•The intestinal absorption process of ISL was first-order process with passive diffusion mechanism.•The main absorptive segment of ISL was colon.

Isoliquiritigenin (ISL) has various pharmacological effects. Our previous studies demonstrated that the oral bioavailability of ISL was low and the concentration-time profiles of ISL exhibited double peaks after oral administration in rat, but the underlying mechanisms remained unknown. The objective of this study was to clarify the gastrointestinal (GI) absorptive characteristics of ISL using in situ intestinal perfusion model as well as explain double peaks phenomenon after oral administration and to evaluate the potential of using nanostructured lipid carrier (NLC) as an oral delivery carrier for poorly water soluble drugs. The results showed that the absorption percent in the stomach for 2 h was less than 10%, the absorption process of intestine was first-order process with passive diffusion mechanism, and the main absorptive segment was colon. Isoliquiritigenin-loaded nanostructured lipid carrier (ISL-NLC) could enhance oral absorption of ISL. The reason for the Double Peak Phenomenon following oral administration in ISL plasma concentrations versus time profiles is Variability of Absorption within different regions of the gut, very low absorption from the stomach, jejunum, duodenum and ileum compared with the absorption from the colon. A pharmacokinetic study was conducted in rats after a single dose oral administration of ISL at 20 mg/kg in the form of either ISL-NLC or isoliquiritigenin solution (ISL-Sol). The AUC (0∼∞) values were 5.43 ± 0.67 μg h mL−1 and 29.60 ± 2.88 μg h mL−1 after administration of the ISL-Sol and ISL-NLC, respectively. The relative bioavailability of ISL-NLC to isoliquiritigenin was 545%. Our studies provide evidence that NLC are valuable as an oral delivery carrier to enhance the absorption of a poorly water soluble drug, ISL.

Graphical abstractConstruct isoliquiritigenin-loaded nanostructured lipid carriers (ISL-NLC) that could significantly enhance the bioavailability of isoliquiritigenin and increase gastrointestinal absorption of isoliquiritigenin.Figure optionsDownload full-size imageDownload as PowerPoint slide