The long-term objective of the proposed career plan is to build on the strengths of The University of Akron as a renowned polymer research facility to develop an internationally recognized biomaterials program. Extending previous research experience on producing bioactive polymeric materials, the PI will establish a research program developing new materials for targeted and controlled drug release and for tissue engineering. The objective of the proposed research is to develop a targeted drug delivery system, which would transport bioactive compounds directly to the desired site of administration, thereby reducing side effects and increasing patient compliance. Adverse drug events and lack of patient compliance are responsible for up to 25% of hospital admissions, costing the health care system over $136 billion annually. The unique drug delivery system proposed will combine bioinert poly(ethylene oxide) stars with targeting ligands (OX26) and drugs (venlafaxine) to achieve site-directed drug delivery. The monoclonal antibody OX26 targets transferrin receptors in brain capillary endothelial cells, thus allowing the construct to cross the blood-brain barrier. Venlafaxine, an antidepressant, will then be released in the brain. Long PEO arms, either underivatized or with OX26 ligand, will shield the venlafaxine from metabolism prior to crossing the blood-brain barrier.
The proposed research is interdisciplinary, combining polymer design, synthesis, and characterization with biochemistry and biological testing. A new method has been developed for the synthesis of star polymers, starting from symmetric homo-bifunctional groups and a dendrimer core, which allows selective addition of polymer arms containing either ligands or drugs. An in vitro model of the blood-brain barrier involving cocultures of capillary endothelial cells with astrocytes will be employed to examine the efficacy of the targeted drug delivery system.
The intent is to completely integrate research activities with educational activities by including graduate students, undergraduates, high school students and high school teachers in the research group. Bringing together graduate and undergraduate students from varied disciplines to work on the research project will give them teamwork experience in preparation for their careers, whether in academia or industry. Communication skills are enhanced as students present their work both orally and in written reports. Undergraduates working on research projects participate in inquiry-based learning and gain skills required for life-long learning. Outreach to the local high schools will stimulate high school faculty with cutting edge research and provide mentoring opportunities for talented high school students, perhaps lighting the spark for a future scientist or engineer.
The unique targeted drug delivery system proposed will open new therapeutic opportunities. The combination of shielding drugs from metabolism while directing them to the desired site of administration creates a powerful new tool in the fight against disease. Involving students in the research will provide mentoring opportunities, increasing student retention and serving as a forum for inquiry-based learning.
