| Enhancing Doxorubicin Permeability Across The Blood Brain Barrier By Cationic Beta-Cyclodextrin Polymers | ||
| Eun Seok Gil, Department of Surgery, Pennsylvania State University, 500 University Drive, Hershey, PA 17033, Tao L. Lowe, Departments of Surgery, Bioengineering, and Materials Science and 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 and State Key Lab of Pulp & Paper Eng, South China University of Tech., Fredericton, NB E3B 5A3, Canada This study describes novel cationic beta-cyclodextrin polymers (CPbCDs) containing quaternary ammonium groups as drug delivery carriers across the blood brain barrier (BBB). Our previous work demonstrated the effect of charge density of CPbCDs on the endothelial toxicity, the tight junction integrity and permeability of CPbCDs toward an in vitro model BBB using bovine brain microvessel endothelial cell (BBMVEC) monolayer. In current work, we have studied the effect of CPbCDs on the permeability of doxorubicin (Doxo) across the BBB, and the cell death effect of CPbCD/Doxo complexes on U87 tumor cells. CPbCDs not only were one time more permeable than 4 kD dextran control, but also enhanced Doxo permeability by a factor of 2.3 across the BBMVEC monolayer. Furthermore, CPbCD containing more quaternary ammonium groups showed less cholesterol extraction from BBMVECs. CPbCD/Doxo complexes showed less cytotoxicity to BBMVECs than free Doxo after 4 h exposure, whereas CPbCD/Doxo complexes killed U87 tumor cells as effectively as free Doxo after 60 hr exposure. Future works on the in vivo biodistribution of CPbCDs and Doxo and the in vivo biological activity of CPbCD/Doxo complexes to brain cancer are underway. Extended Abstract Status: Not Uploaded | ||