gH625-nanosystems transported across BBB

BBB plays a critical role in the brain protection against toxic and infectious agents, but also creates an obstacle for effective systemic drug delivery to the CNS. The high impermeability and selectivity preclude the transport of many therapeutic molecules to the CNS, many drugs for neurological disorders do not achieve effective concentration within the brain tissue following intravenous or oral administration. Enhancement of doses or extended administration of drugs, to avoid this problem, often significantly increase systemic toxicity risks. During the last decade, drug delivery into the brain has been extensively investigated and two therapeutic strategies have been developed: invasive and noninvasive techniques.[1] In particular, with the advent of nanomedicine, nanosystems have been proposed as noninvasive methods to cross the BBB and deliver drugs to CNS.[2] Many of these carriers can be transported across in vitro and in vivo BBB models by endocytosis and/or transcytosis.[3] Different CPPs have been used to functionalize nanosystems to increase the cellular uptake. Moreover several studies demonstrated that the peptide gH625 directly translocates across the membrane bilayer and transports into the cytosol several cargoes. Its mechanism of internalization involves the endocytic pathway only partially; it facilitates the escape from endocytic vesicles; and does not show any toxicity. The aim was to evaluate if gH625 can be used to develop efficient nanosystems to deliver therapeutic agents to the brain.