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 4h, shifting distribution to the cerebellum and brainstem at 12h. The fluorescence intensity in the hippocampus and pontine nuclei remained high and stable over a period of 12h. 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.