Cationic B-Cyclodextrin Polymers for Controlled Drug Delivery across the Blood Brain Barrier (Bbb)
Eun Seok Gil, Department of Surgery, Pennsylvania State University, 500 University Drive, Hershey, PA 17033, Tao L. Lowe, Surgery, Bioengineering, and Material Sciences & Engineering, Pennsylvania State University, 500 University Drive, Hershey, PA 17033, Jianshu Li, Department of Chemical Engineering, University of New Brunswick, Fredericton, NB, Canada, Fredericton, NB E3B 5A3, Canada, and Huining Xiao, Department of Chemical Engineering, University of New Brunswick, Fredericton, NB E3B 5A3, Canada.
The blood brain barrier (BBB), a selective protective barrier composed of a tightly packed capillary endothelial cell monolayer, prevents the passage of many substances, posing a problem for cerebral drug delivery. As drug carriers enhancing permeation characteristics to across BBB, a series of Cationic-b-Cyclodextrin polymers (CPbCDs) containing quaternary ammonium groups were designed by a one-step condensation polymerization with b-Cyclodextrin (b-CD), epichlorohydrin (EP) and choline chloride (CC). CPbCDs are examined as drug carriers across the BBB, using bovine brain microvessel endothelial cells (BBMVEC) as an in vitro BBB model. CPbCDs are not toxic to BBMVECs at concentration up to 500 µg•ml-1, and do not change the integrity of the BBMVEC monolayer including transepithelial electrical resistance, and occludin and ZO-1 tight junction expression. In addition, the charge density of CPbCDs strongly affects the permeability of CPbCDs across the BBB. These nontoxic and highly BBB permeable CPbCDs could be utilized as effective drug delivery devices for controlled release of therapeutics such as proteins and anticancer drugs to treat brain disorders.