Design and characterization of drug delivery systems across the blood brain barrier

CHED 449

Thomas Fabre, fabret@nku.edu1, Jerome D Hogan, hoganj1@nku.edu1, Keith A. Walters, walterske@nku.edu1, Kristi L. Haik, martines@nku.edu2, Donald A. Tomalia3, and Heather A. Bullen, bullenh1@nku.edu1. (1) Department of Chemistry, Northern Kentucky University, Nunn Dr, Highland Heights, KY 41099, (2) Department of Biological Sciences, Northern Kentucky University, Nunn Dr, Highland Heights, KY 41099, (3) Dendritic NanoTechnologies, Inc, 2625 Denison Drive, Mount Pleasant, MI 48858
Dendrimers have attracted significant attention as drug delivery systems due to their highly branched properties and their ability to act as nanocontainers. This research is aimed at assessing the potential for dendrimers to serve as drug delivery vectors across the blood brain barrier (BBB), a tight seal of cells that limits drug therapy to the brain. Terminal groups on the surface of the dendrimer may be appropriately designed to allow passage through the BBB. The synthesis and characterization of biotinylated G4 and G5 poly(amidoamine) PAMAMs, as an approach to fluorescent labeled dendrimers for evaluation as drug delivery vectors across the BBB will be presented here. The high binding affinity of biotin/avidin provides a useful approach to fluorescent labeled dendrimer conjugates, using fluorescent tagged avidin markers. The biotinylated dendrimer conjugates were characterized using atomic force microscopy (AFM) attenuated total reflectance infrared spectroscopy (ATR-FTIR) and HPLC.