SBIR-STTR Award

The barrier to diffusion and transport of substances from the blood into the brain is denoted the blood-brain barrier. The blood-brain barrier severely limits delivery to the brain of drugs that could be beneficial for treatment of central nervous system (CNS) diseases. Current methods for testing drug access to the brain are time consuming, imprecise, expensive, and wasteful of laboratory animals.It is planned to develop an in vitro model of the blood-brain barrier. It will be accomplished by developing methods to effectively co-culture the cells that form the blood-brain barrier, endothelial cells and astrocytes, in such a way as to simulate the environment of the brain and induce the barrier characteristics inherent to the capillaries there. The model will consist of a cellular monolayer connected by tight junctions on a permeable membrane or filter so that the barrier and transport properties can be completely characterized. The criteria for barrier formation will be based primarily on immunological characterization, -electrical resistance measurements, and transport studies. The in vitro model will allow researchers to readily assay the ability of drugs to cross the blood-brain barrier and will become a standard method for screening potential CNS therapeutics.

Anticipated Results:
The development of an in vitro model for the blood-brain barrier will permit rapid and routine screening of drug delivery to the CNS. It will expedite the development of new drugs and the modification of existing drugs to make them useful therapeutics for CNS diseases. The likely benefits will be more rapid development of new drugs for brain tumors, Alzheimer's disease, AIDS dementia, and psychiatric disorders.National Institute Of General Medical Sciences (NIGMS)

In the coming years, the treatment of neurological disorders will be largely dependent on the development of new therapeutic agents and the modification of compounds already in existence. The blood-brain barrier keeps most drugs out of the brain and severely limits their usefulness. Pharmaceutical companies will, therefore, need to screen many compounds for their entry into the brain and will also have to consider strategies designed toovercome the blood-brain barrier. Currently, compounds are screened by injecting them into large numbers of animals and either observing behavioral effects or removing brains and measuring uptake. These procedures are indirect and cumbersome and also raise important animal welfare concerns. A cell culture model of the bloodbrain barrier would both facilitate rapid screening for compounds able to enter the brain and would also allow the systematic use of cell and molecular biological techniques to develop drug delivery systems.In this research, a technique for growing brain endothelial cells such that they form, in cell culture, an equivalent of the blood-brain barrier will be developed, as well as a set of experiments that will enable this model system to be used routinely by groups interested in nervous system therapeutics. Ways in which this model system can be utilized to explore novel modes of drug delivery to the brain will also be described.Awardee's statement of the potential commercial applications of the research:The product described in this project constitutes a cell culture system with characteristics of the blood-brain barrier. It can be used by pharmaceutical companies to rapidly screen compounds for entry into the brain and to develop drug delivery systems for the brain.National Institute of General Medical Sciences (NIGMS)