Many therapeutic drugs are excluded from entering the brain, due to their lack of transport through the blood-brain-barrier (BBB). The development of new strategies for enhancing drug delivery to the brain is of great importance in diagnostics and therapeutics of central nervous diseases. To overcome this problem, we have developed a viral fusion peptide (gH625)derived from the glycoprotein gH of Herpes simplex type 1, possessing several advantages including high cell translocation potency, absence of toxicity of peptide itself and the feasibility as an efficient carrier for delivering therapeutics. Therefore, it was hypothesized that brain delivery of nanoparticles conjugated with gH625 should be efficiently enhanced. gH625 was functionalized to the surface of fluorescent aminated polystyrene nanoparticles (NPs) via a covalent binding procedure and NPuptake mechanism and permeation across in vitroBBB model were studied. At early incubation time, the uptake of NPs with gH625 by brain endothelial cells was greater than that of the NPs without the peptide and their intracellular motion was mainly characterized by a random walk behavior. Most importantly, gH625peptide decreased NP intracellular accumulation as large aggregates and enhanced the NPBBB crossing. In summary, our results establish that the surface functionalization with gH625 may change NP fate by providing a good strategy for the design of promising carriers to deliver drugs across the BBB for the treatment of brain diseases.

Shuttle-mediated nanoparticle delivery to the blood-brain barrier.

GALDIERO, Massimiliano;
2013

Abstract

Many therapeutic drugs are excluded from entering the brain, due to their lack of transport through the blood-brain-barrier (BBB). The development of new strategies for enhancing drug delivery to the brain is of great importance in diagnostics and therapeutics of central nervous diseases. To overcome this problem, we have developed a viral fusion peptide (gH625)derived from the glycoprotein gH of Herpes simplex type 1, possessing several advantages including high cell translocation potency, absence of toxicity of peptide itself and the feasibility as an efficient carrier for delivering therapeutics. Therefore, it was hypothesized that brain delivery of nanoparticles conjugated with gH625 should be efficiently enhanced. gH625 was functionalized to the surface of fluorescent aminated polystyrene nanoparticles (NPs) via a covalent binding procedure and NPuptake mechanism and permeation across in vitroBBB model were studied. At early incubation time, the uptake of NPs with gH625 by brain endothelial cells was greater than that of the NPs without the peptide and their intracellular motion was mainly characterized by a random walk behavior. Most importantly, gH625peptide decreased NP intracellular accumulation as large aggregates and enhanced the NPBBB crossing. In summary, our results establish that the surface functionalization with gH625 may change NP fate by providing a good strategy for the design of promising carriers to deliver drugs across the BBB for the treatment of brain diseases.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11591/184020
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