The present study provides new insight into the design ofliposomes for brain targeting. Liposomes functionalized withanti-transferrin receptor antibody and anti-A antibody are inter-nalized by porcine brain capillary endothelial cells and are capableof reaching the brain of animal models if the anti-transferrinreceptor antibody is coupled to the liposome surface throughstreptavidin–biotin complex. Our system is stable and functionalfor at least 2 months. We are only beginning to understand how dif-ferent conditions affect the conjugation of antibodies to liposomesand their transport through the BBB. We cannot determine yet if theanti-A antibody is involved in the liposome uptake and transportthrough the barrier but our results appear to point in that direction.Liposomes modified with antibodies promise to have a broad appli-cation in the treatment of diseases of the central nervous system.Future studies will allow the optimization of liposomes for drugdelivery to the brain and accordingly it will be an asset to reconcilethe results obtained so far in different laboratories.