Peptide gH625 enters into neuron and astrocyte cell lines and crosses the blood–brain barrier in rats

Abstract

Peptide gH625, derived from glycoprotein H of herpes simplex virus type 1, can enter cells efficiently and deliver a cargo. Nanoparticles armed with gH625 are able to cross an in vitro model of the blood–brain barrier (BBB). In the present study, in vitro experiments were performed to investigate whether gH625 can enter and accumulate in neuron and astrocyte cell lines. The ability of gH625 to cross the BBB in vivo was also evaluated. gH625 was administered in vivo to rats and its presence in the liver and in the brain was detected. Within 3.5 hours of intravenous administration, gH625 can be found beyond the BBB in proximity to cell neurites. gH625 has no toxic effects in vivo, since it does not affect the maximal oxidative capacity of the brain or the mitochondrial respiration rate. Our data suggest that gH625, with its ability to cross the BBB, represents a novel nanocarrier system for drug delivery to the central nervous system. These results open up new possibilities for direct delivery of drugs into patients in the field of theranostics and might address the treatment of several human diseases.

Activity of Chitosan and Its Derivatives against Leishmania major and Leishmania mexicana In Vitro

“…The degree of correlation between pixels in the red and green channels was assessed by using the Colocalization Colormap plugin in the ImageJ software. This plugin enables quantitative visualization of colocalization by calculating the normalized mean deviation product (nMDP) in a color nMDP scale (from Ϫ1 to 1): negative indexes (cold colors) refer to no colocalization, while indexes of more than 0 (hot colors) display colocalization and higher numbers refer to greater colocalization (73,74).…”

Enhanced uptake of gH625 by blood brain barrier compared to liver in vivo: characterization of the mechanism by an in vitro model and implications for delivery

“…To evaluate the effect of concentration on the systemic delivery of NBD-gH625, a fluorescence microscopy analysis was performed as previously reported 24 .…”

“…In a previous work, gH625 was shown to be able to cross the BBB in vivo 24 . Uptake was not linked to alterations of cell viability or maximal mitochondrial oxidative capacity, suggesting that gH625 could potentially be used as a brain delivery system for macromolecules 24 .…”

“…In a previous work, gH625 was shown to be able to cross the BBB in vivo 24 . Uptake was not linked to alterations of cell viability or maximal mitochondrial oxidative capacity, suggesting that gH625 could potentially be used as a brain delivery system for macromolecules 24 . In general a high accumulation in the target tissue results in an improved therapeutic effect, while a large amount of drug distributed to non-target organs may cause unwanted toxicity and/or side effects.…”

“…Recently, the peptide gH625, belonging to this class of membranotropic sequences, showed remarkable vector properties, efficiently delivering a range of cargoes 15 . gH625 is essentially internalized by a non endocytic mechanism avoiding endosomal entrapment 16 – 23 and is also shown to be able to cross the BBB in vitro and in vivo 16 , 24 . The peculiar ability of crossing physical barriers is probably correlated to the amino acid residues which seem to be central for the interaction and destabilization of the target lipid membranes; moreover, it is able to assume an amphipathic α-helical structure in membranes which is key to favouring the binding of proteins to membranes 25 .…”