A fruitful area of future research will be to determine if there are any systems that can target drug delivery to the brain and also enable the use of recombinant protein therapeutics for this purpose. Novel developments emerging in the field of polymer science and nanotechnology provide an option by which the obstacles of limited brain entry can be surmounted (Kingsley et al., 2006). Although several different polymeric materials have been explored for localised delivery to the brain, these have been unsuccessful due to a variety of factors such as inflammatory responses to implants and their invasiveness. Despite this setback, nanomedicines such as polyethylene glycol-coated liposomes carrying chemotherapeutic drugs for systemic release have been successfully developed and allowed for clinical use, raising the possibility that similar methods for delivery to the brain can be developed in the near future. Other examples of nanomaterials include nanoparticles, polymeric micelles and nanogels (Vinogradov et al., 2004; Kabanov and Gendelman, 2007; Begley, 2004). All have potential as drug delivery systems targeting the brain.A number of recent studies involving polymeric micelles and drug nanosuspensions are of particular relevance to this review. Using brain microvessel endothelial cells Miller et al. (1997) showed that micelles of Pluronic copolymers can affect drug transport by inhibition of P-gp and redirection of vesicular transport (Miller et al., 1997). Subsequently, the same research group found that Pluronic P85 unimers increase accumulation of a P-gp dependent drug in Caco-2 and bovine brain microvessel endothelial cell monolayers by inhibiting P-gp efflux (Batrakova et al., 1998, 2003; Kabanov and Gendelman, 2007). Furthermore, Pluronic P85 inhibited substrate efflux via MRP1 and MRP2 (Miller et al., 1999). Spitzenberger et al. (2007) explored the effects of Pluronic P85, antiretroviral therapy (AZT, 3TC and nelfinavir) or both on a severe combined immunodeficiency animal model of HIVE. This model of HIVE involved inoculating mice with human monocyte-derived macrophages infected with HIV-1 (Spitzenberger et al., 2007). The authors found that Pluronic P85, as well as both the drugs and P85 combined, showed the most significant decrease in percentage of HIV-1 infected monocyte-derived macrophages (8–22% of control) which was superior to the antiretroviral drug group alone (38% of control). This study not only demonstrates that Pluronic P85 increases the penetration of antiretrovirals drugs into the brain but also that block copolymers may have antiretroviral effects, particularly in cells such as macrophages which serve as a viral reservoir in the CNS (Spitzenberger et al., 2007). A recent study has also shown that Pluronic P85 effectively inhibits the interaction of P-gp with the PIs, nelfinavir and saquinavir and that other transporters (including MRP) may also be inhibited by Pluronic P85 (Shaik et al., 2008).Drug nanosuspensions refer to drug particles that are often stabilised by non-ionic PEG-containing surfactants or with mixtures of lipids. This technology is highly advantageous, in the sense that it has a high-drug loading capacity, it is relatively simple to use and can be applied to many drugs. One application of this technology was in studies that used indinavir nanosuspensions for cell-mediated delivery to the CNS. The concept of cell-mediated delivery of nanocarriers to the CNS when loaded with a drug is based upon leukocyte recruitment during an inflammatory response to a pathogen. In particular the process of migration, phagocytosis and exocytosis of inflammatory cells such as macrophages, neutrophils and T cells (Kabanov and Gendelman, 2007). Indinavir nanosuspensions were internalised into bone marrow derived macrophage lysosymes and subsequently the drug was released into the extracellular environment. Thus, these experiments found that indinavir nanosuspension-laden bone marrow derived macrophages were able to carry and release the drug in tissue (Dou et al., 2007). Furthermore, a study in which indinavir nanosuspension bone marrow derived macrophages were administered to HIV-1-challenged mice demonstrated reduced numbers of HIV-infected cells in plasma, lymph nodes, spleen, liver and lungs. The impressive result from this study demonstrates the potential of cell-mediated delivery of nanocarriers to the brain in diseases such as HIV (Kabanov and Gendelman, 2007).It would therefore be advantageous if in vivo models could be used to validate novel methods of drug delivery to the brain and if genomic and proteomic techniques can be used to identify new blood–brain and blood–CSF barrier transporters. This could possibly be done if a greater emphasis is placed on the molecular interaction between different transport systems in the BBB, the toxicity induced by drug delivery technologies and molecular imaging of the brain and vasculature (Neuwelt et al., 2008).