Functionalized curcumin/ginsenoside Rb1 dual-loaded liposomes: Targeting the blood-brain barrier and improving pathological features associated in APP/PS-1 mice

The brain is a crucial organ in the body, shielded from external substances by the blood-brain barrier (BBB). However, this barrier also impedes the treatment of numerous brain diseases, including Alzheimer's disease (AD). Therefore, Mannose (MAN)-modified co-loaded Curcumin (CUR) and ginsenoside Rb1 (Rb1) liposomes were prepared to address the above situation. Glucose transporter 1 (GLUT 1) is a transmembrane glycoprotein overexpressed on the BBB. MAN is specifically recognized and efficiently transported by GULT1. In addition, the neuroprotective compounds CUR and Rb1 are co-loaded into liposomes, which can penetrate the blood-brain barrier (BBB) and potentially be used to treat AD. MAN-CUR/Rb1 liposomes were prepared using a thin film hydration method combined with an ammonium sulfate gradient. The resulting liposomes had a round shape and a diameter of 110 nm and showed good stability. Results from cellular uptake experiments, in vitro BBB models, and in vivo imaging in mice confirmed that MAN-CUR/Rb1 liposomes not only crossed the BBB but also accumulate in N2a cells/bEnd.3 cells. Furthermore, in vivo animal experiments showed that MAN-CUR/Rb1 liposomes improved AD-related pathological features, inhibited oxidative stress and neuroinflammation, and enhanced learning and cognition in APP/PS-1 mice. Based on these findings, MAN-CUR/Rb1 liposomes hold promise as a potential treatment for AD.