Chitosan-polygalacturonic acid-double-layered liposomes for oleanolic acid delivery: In vitro semi-dynamic digestion, improved cell uptake and liver protection.

Oleanolic acid (OA) is a terpenoid compound with anti-inflammatory and antioxidant effects, while its low stability and bioavailability limit the wide application. In this study, OA was incorporated into liposomes (OA-LIP), chitosan (CHI) coated liposomes (CHI-OA-LIP), and CHI-polygalacturonic acid (PGA)-double-layered (PGA-CHI-OA-LIP). The in vitro semi-dynamic digestion, cell absorption and pre-protective function for the liver-injured mouse of liposomes were evaluated. Compared to OA-LIP (91.96 ± 0.45 %), the polysaccharides double-layered OA-LIP, PGA-CHI-OA-LIP (99.84 ± 0.22 %), significantly improved the encapsulation efficiency of OA and exhibited higher stability during storage at room temperature and at 4 °C. In the in vitro semi-dynamic digestion and Caco-2 cell model, compared to free OA (6.22 ± 1.17 %, 6.56 ± 2.35 μg/mL), PGA-CHI-OA-LIP increased the bioavailability and cell absorption rate to 45.78 ± 0.71 % and 27.62 ± 1.69 μg/mL, respectively. Furthermore, it can improve the antioxidant capacity of Caco-2 cells, up-regulate the level of transportable terpene-related genes. In the mouse liver injury model, PGA-CHI-OA-LIP effectively reduced the activities of AST (aspartate aminotransferase) and ALT (alanine aminotransferase), decreased inflammatory factors, and thus effectively alleviated the infiltration and necrosis of liver cells. This study provided a promising avenue to improve the bioavailability of sensitive functional molecules and to develop versatile formula to repair liver damage.