The blood-brain barrier (BBB) impermeability and selectivity
prevent the transport of many therapeutic molecules into the
brain, making ineffective their use for treatment of neurological
diseases.1 Pituitary adenylate cyclase-activating polypeptide
(PACAP) is a neuroprotective peptide proposed for treatment of
central nervous system (CNS) diseases.2 However, its clinical use
is limited by the efflux component of peptide transport system-6
(PTS-6), which reduces its brain uptake3, and also for its low
stability in human plasma, rapid degradation and peripheral
actions.4 Nanocarrier-mediated method is a non-invasive strategy
to explore for brain drug delivery; among them, liposomes are
attractive tools that can be easily modified to improve their delivery.
5 We developed liposomes loaded with PACAP and functionalized
on the surface with gH625 peptide, a membrane-perturbing
domain in glycoprotein H of Herpes simplex virus 1. gH625
can traverse the membrane bilayer and deliver several cargoes
across cell membranes in vitro6 and crosses the BBB in vivo.7We
evaluated the efficiency of gH625-liposomes to deliver PACAP
to the brain in Swiss CD1 mice after intravenous administration
using light sheet fluorescence microscopy. Our results show that
gH625-liposomes ameliorate both PACAP reaching and crossing
the BBB, increasing the number of neuronal cells labeled with
PACAP. These data suggest that gH625-liposomes represent a
promising strategy to deliver therapeutic agents to CNS for the
treatment of neurological diseases but also to provide an effective
imaging and/or diagnostic tool for the brain
