The physical, transport, and metabolic barriers presented by the cerebral microvessel endothelium, the blood- brain barrier (BBB), protect the brain from damage from toxic substances and ensure the delivery of nutrients required for the functioning of the brain thus creating a stable neuronal microenvironment. However, the BBB poses a challenge to many CNS-acting drugs, including drugs active against human African trypanosomiasis (HAT), which must cross the BBB to reach their target. HAT or more commonly called African sleeping sickness, is a major public health problem in sub-Saharan Africa. It is fatal if untreated. Classified as one of the most neglected tropical diseases, research into developing successful treatments for the illness with reduced side-effects is of utmost importance. The disease has two stages - a haemolymphatic stage after the bite of an infected tsetse fly, followed by a central nervous system (CNS) stage where the parasite penetrates the brain, causing death if left untreated. Pentamidine is a less toxic blood stage drug, which research has shown has a limited ability to cross the BBB due to its removal by efflux transporters (Journal of Pharmacology and Experimental Therapeutics, 329(2009), 967-971). Eflornithine is a second stage drug used clinically but, surprisingly, was found not to cross the healthy murine BBB well (Journal of Neurochemistry, 107(2008), 1136-1146). The overall aim of the project is to use nanocarriers to inhibit the efflux transporters expressed at the BBB that extrude the anti- HAT drug, pentamidine, and increase its delivery into the brain. A secondary aim is to understand the transport of eflornithine across the BBB. Methods that will be utilized range from small angle neutron scattering through to in vitro cell culture assays (hCMEC/D3) and in situ brain perfusion techniques.