Abstract

The delivery of anticancer drugs to the brain is profoundly limited by blood-brain barrier (BBB)The purpose of this work is to develop a new carrier for doxorubicin to overcome the BBB. Polyamidoamine (PAMAM) dendrimer, a novel nanoscopic high-branching polymer, was exploited as an efficient carrier of doxorubicin. The MTT assay showed that PAMAM (generation 3) had little cytotoxicity in brain capillary endothelial cells (BCECs). The results of fluorescence intensity assay and fluorescent microscopy showed that the cellular uptake of  PAMAM/doxorubicin complex was much higher than that of free doxorubicin and exhibited concentration and time dependent manners. The action of PAMAM in increasing the cellular uptake of doxorubicin was stronger than that of verapamil, a P-glycoprotein (P-gp) inhibitor. In body distribution study, the brain uptake of doxorubicin in PAMAM/doxorubicin group increased dramatically (about 6-fold) compared to that in free doxorubicin group. These data suggest that the novel PAMAM/drug complex is a simple but efficient system, which showed great capability to cross the BBB. PAMAM dendrimer could be used as an effective carrier to deliver anticancer drugs to the brain.

Key words: PAMAM, doxorubicin, blood-brain barrier, p-glycoprotein.