Liposomes modified with P-aminophenyl-α-D-mannopyranoside: a carrier for targeting cerebral functional regions in mice.

ABSTRACT

Targeting of intracerebral functional regions has been limited by the inability to transport drugs across the blood-brain barrier (BBB) and by poor accumulation in these regions. To overcome these hurdles, liposomes modified with P-aminophenyl-α-d-mannopyranoside (MAN) were used as a fluorescent dye carrier through the BBB and used the specific distribution of liposomes (LIP) modified with MAN (MAN-LIP) to target various functional regions of the brain. An in vitro BBB model was established to evaluate the transendothelial ability of MAN-LIP, and liposomes uptake by C6 glioma cells was analyzed by flow cytometry and live cell imaging. Liposome targeting was evaluated using in vivo and ex vivo imaging. After MAN-LIP administration, the transendothelial ability and the delivery of fluorescent dye to the brain significantly increased. MAN-LIP concentrated in the cortex at 4 h, shifting distribution to the cerebellum and brainstem at 12 h. The fluorescence intensity in the hippocampus and pontine nuclei remained high and stable over a period of 12 h. The results demonstrate that MAN-LIP is able to enhance cellular uptake in vitro and also promotes penetration through the BBB and accumulation in the brain with a distinct spatio-temporal pattern.