KSEF R&D Excellence: Cell-Specific Drug Delivery Into the Brain

Drug delivery into the central nervous system (CNS) is a difficult and challenging task. The blood-brain barrier, which exists at the level of brain microvascular endothelial cells and astrocytes, is impermeable to many drugs. In addition, there are several cell types within the CNS (such as, neurons, astrocytes, microglial cells and endothelial cells), which are Involved to a different degree (or not at all) in specific brain pathology. For example, HIV can replicate in astrocytes, microglial cells, and endothelial cells, but not in neurons. Therefore, it is of critical therapeutic significance to deliver anti-HIV drugs specifically into the cell types that are involved in the disease process. Such a strategy would lead to two important therapeutic objectives: a) to obtain high concentrations of anti-HIV drugs within the cell types where HIV replicates and b) to prevent the harmful effects of anti-HIV drugs towards the cell types that are not actively involved in HIV replication. The main aim of the present proposal is to develop a novel technology for the cell-specific delivery of anti-HIV drugs. We propose to achieve this goal by using antibody-modified liposomes, so called immunoliposomes. Briefly, anti-HIV drugs will be incorporated into liposomes, which are lipid soluble and can easily cross the blood-brain barrier. In addition, the liposomes will be conjugated with specific antibodies to target individual cell types. For example, we will use anti-GFAP antibody to target astrocytes and anti-Mac-1 antibody to target microglial cells. We believe that such a strategy would allow us to markedly improve the efficacy of anti-HIV drugs. It also should be pointed out that similar strategies of drug delivery could be used to treat other brain diseases, including stroke or brain tumors. Therefore, the proposed research will have a most positive outcome in treatment and management of several serious brain disorders.