The Inclusion of a Matrix Metalloproteinase-9 Responsive Sequence in Self-assembled Peptide-based Brain-Targeting Nanoparticles Improves the Efficiency of Nanoparticles Crossing the Blood-Brain Barrier at Elevated MMP-9 Levels

This study investigated whether the inclusion of a matrix metalloproteinase-9 (MMP-9) responsive sequence in self-assembled peptide-based brain-targeting nanoparticles (NPs) would enhance blood-brain barrier (BBB) penetration when MMP-9 levels are elevated both brain and blood circulation. Brain-targeting peptides were conjugated at N-terminus to MMP-9-responsive peptides, these lipid moiety (cholesteryl chloroformate or palmitic acid). Two constructs did not have peptides. NPs characterised for size, charge, critical micelle concentration, toxicity, compatibility, neural cell uptake, release profiles, vitro BBB permeability simulating normal levels. The MMP-9-sensitive sequences improve model drug presence active from compared distilled water. 19F NMR studies suggested burial inside making them inaccessible MMP-9. Only cholesterol-GGGCKAPETALC (responsive MMP-9) showed <5% haemolysis, <1 pg/mL IL-1β 500 μg/mL THP1 cells, with 70.75 ± 5.78% crossing 24 h In conclusion, higher transport across ligand was