A NEW STRATEGY TO DELIVER PACAP TO THE BRAIN

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuroprotective peptide, but its brain uptake is limited by the blood-brain barrier (BBB) component, such as peptide transport system-6 (PTS-6) [1]. The liposomes represent an attractive tool to deliver molecules across the BBB; they can be easily modified on surface to improve their delivery. The peptide gH625, a membrane-perturbing domain in glycoprotein H of Herpes Simplex virus 1, has been extensively used for vector-mediated strategies that enable passage of several cargoes across cell membranes in vitro [2] and crosses the BBB [3]. We evaluated the efficiency of liposomes functionalized with gH625 to deliver PACAP to the brain of Swiss CD1 mice after intravenous injection using light sheet fluorescence microscopy. gH625 liposomes improves both PACAP reaching and crossing the BBB, with a higher number of PACAP labeled neuronal cells. This study suggests a promising strategy to deliver PACAP to CNS for brain diseases treatment.