GH625-liposomes As Tool for Pituitary Adenylate Cyclase-activating Polypeptide Brain Delivery

Overview

Journal Sci Rep

Specialty Science

Date 2019 Jun 26

PMID 31235716

Citations 14

Authors

Giuseppina Iachetta

Annarita Falanga

Yves Molino

Maxime Masse

Francoise Jabes

Yasmine Mechioukhi

Vincenza Laforgia

Michel Khrestchatisky

Stefania Galdiero

Salvatore Valiante

Affiliations

Soon will be listed here.

Abstract

The blood-brain barrier (BBB) regulates the traffic of molecules into the central nervous system (CNS) and also limits the drug delivery. Due to their flexible properties, liposomes are an attractive tool to deliver drugs across the BBB. We previously characterized gH625, a peptide derived from Herpes simplex virus 1. The present study investigates the efficiency of liposomes functionalized on their surface with gH625 to promote the brain uptake of neuroprotective peptide PACAP (pituitary adenylate cyclase-activating polypeptide). Using a rat in vitro BBB model, we showed that the liposomes preparations were non-toxic for the endothelial cells, as assessed by analysis of tight junction protein ZO1 organization and barrier integrity. Next, we found that gH625 improves the transfer of liposomes across endothelial cell monolayers, resulting in both low cellular uptake and increased transport of PACAP. Finally, in vivo results demonstrated that gH625 ameliorates the efficiency of liposomes to deliver PACAP to the mouse brain after intravenous administration. gH625-liposomes improve both PACAP reaching and crossing the BBB, as showed by the higher number of brain cells labelled with PACAP. gH625-liposomes represent a promising strategy to deliver therapeutic agents to CNS and to provide an effective imaging and diagnostic tool for the brain.

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