3 research outputs found
gH625-liposomes as tool for pituitary adenylate cyclase-activating polypeptide brain delivery
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
LDLR-mediated targeting and productive uptake of siRNA-peptide ligand conjugates in vitro and in vivo
siRNAs have become one of the most promising therapeutic agents because of their specificity and their potential to modulate the expression of gene-related diseases. Any gene of interest can be potentially up or down-regulated, making RNA-based technology the healthcare breakthrough of our era. However, the functional and specific delivery of siRNAs into tissues of interest and into the cytosol of target cells remains highly challenging, mainly due to the lack of efficient and selective delivery systems. Among the variety of carriers for siRNA delivery, peptides have become essential candidates because of their high selectivity, stability and conjugation versatility. Here, we describe the development of molecules encompassing siRNAs against SOD1 , conjugated to peptides that target the LDLR, and their biological evaluation both in vitro and in vivo . Abstract Figure GRAPHICAL ABSTRAC
LDLR-mediated targeting and productive uptake of siRNA-peptide ligand conjugates in vitro and in vivo
siRNAs have become one of the most promising therapeutic agents because of their specificity and their potential to modulate the expression of gene-related diseases. Any gene of interest can be potentially up or down-regulated, making RNA-based technology the healthcare breakthrough of our era. However, the functional and specific delivery of siRNAs into tissues of interest and into the cytosol of target cells remains highly challenging, mainly due to the lack of efficient and selective delivery systems. Among the variety of carriers for siRNA delivery, peptides have become essential candidates because of their high selectivity, stability and conjugation versatility. Here, we describe the development of molecules encompassing siRNAs against SOD1 , conjugated to peptides that target the LDLR, and their biological evaluation both in vitro and in vivo . Abstract Figure GRAPHICAL ABSTRAC