Improving oral bioavailability of water-insoluble idebenone with bioadhesive liposomes

Abstract

The clinical application of water-insoluble idebenone (IDB) is significantly suffering from the poor aqueous solubility in the gastrointestinal (GI) fluids and limited oral bioavailability. Herein, we designed an IDB-loaded bioadhesive liposome based on poly (maleic anhydride-alt-1-octadecene) (PMO) (termed as IBL) to improve the intestinal absorption and oral bioavailability. IBL was nanometer-sized particles with a Z-average diameter of 95.12 nm and IDB exhibited as amorphous or molecular state in the IBL formulation. At 2 h of oral administration, the tissue concentration of IDB in the duodenum, jejunum, and ileum in the IBL treated group was notably improved 2.69-, 3.21- and 3.44- fold over counterpart liposomal formulation of IDB (LI). Moreover, in the IBL treated group, the oral bioavailability of IDB was obviously enhanced 3.79-fold than that in free drug suspension and 2.33-fold when compared to counterpart LI treatment. Therefore, the bioadhesive liposome represents a feasible and elegant strategy to improve the oral absorption of water-insoluble IDB.