The Influences of Dynamic Transport of GLUT1 on the Distribution of Mannosylated Liposomes in Transient Ischemia Reperfusion Mice Brain

It has been reported that p-aminophenyl-alpha-D-mannopyranoside modified liposomes (MAN-LIP) had specific affinity with glucose transporter 1 (GLUT1), which could facilitate the entry of carriers into healthy mice brain. Here, we report the use of MAN-LIP to targeting delivery to transient ischemic mice brain and discuss the dynamic relationship between the accumulation of MAN-LIP in ischemic regions and GLUT1 involved in the transport process. In vitro, oxygen glucose deprived/reoxygenation (OGD/R), simulating cerebral transient ischemia, dynamically up-regulated GLUT1 expression in C6 glioma cells and enhanced its internalized capacity, which influenced the transport of MAN-LIP. In this mechanism, OGD/R led to a linear decrease of MAN-LIP transport across the blood brain barrier (BBB) by bEND. 3 cells in vitro (2.1 fold, 1.8 fold and 1.4 fold at OGD/R 4 h, 12 h, and 24 h, compared with normal condition, respectively) and result to a converse-V shape increase of MAN-LIP transport by C6 glioma cells (1.5 fold, 2.1 fold and 1.8 fold compared with normal at OGD/R 4 h, 12 h and 24 h, respectively). In vivo time-dependent optical imaging showed that MAN-LIP could have a higher accumulation (linear enhancement) in ischemia/reperfusion region (I/R) compared with LIP, which was consistent with the dynamic expression of GLUT1 ex vivo. Overall, the changed role of GLUT1 in the various tissues could have impact on the entry of MAN-LIP into the brain and its accumulation in the affected regions, which should be taken into account when we designed drug delivery system targeting to cerebral ischemic stroke.