The purpose of this project is to establish a commercially viable, in vitro disease model for the blood-brain barrier in AIDS dementia complex (ADC) and system for testing anti-HIV drugs in vitro. This model will be useful for examining the penetration of HIV antiviral drugs through the infected and uninfected blood-brain barrier and for testing the efficacy of candidate drugs on HIV in infected brain endothelium. These studies can be expanded to investigations of drug permeation to the CNS in general and are not limited to the delivery of anti-retroviral agents. The in vitro model employs brain microvascular endothelial cells cultured in hollow fiber capillaries surrounded by astroglia to induce a tri- dimensional barrier with flow through the vessel lumen. Culture medium is pumped through the luminal and abluminal spaces separately allowing measurement of molecular traffic across the barrier. This dynamic in vitro blood-brain barrier model (DIV-BBB) reproduces the physiology of the BBB in vivo including specific ion and molecular transport systems not available in other in vitro models.
Establish a scientific validation of a system (equipment, cells, techniques) that can be used to test candidate drugs on contract for their ability to penetrate the human blood-brain barrier and to have efficacy against HIV in vivo. The product will be both the test system itself and the service of testing compounds for pharmaceutical companies.
