Protection against Neurodegeneration in the Hippocampus Using Sialic Acid- and 5-HT-Moduline-Conjugated Lipopolymer Nanoparticles
Journal
ACS Biomaterials Science and Engineering
Journal Volume
5
Journal Issue
3
Pages
1311-1320
Date Issued
2019
Author(s)
Abstract
Significant involvement of oxidative stress in the brain can develop Alzheimer's disease (AD); however, a great number of clinical trials explains the limited success of antioxidant therapy in dealing with this neurodegenerative disease. Here, we established a lipopolymer system of poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) incorporated with phosphatidic acid (PA) and modified with sialic acid (SA) and 5-hydroxytryptamine-moduline (5HTM) to improve quercetin (QU) activity against oxidative stress induced by amyloid-£] (A£]) deposits. Morphological studies revealed a uniform exterior of QU-SA-5HTM-PA-PLGA NPs with a spherical structure and enhanced aggregation with inclusion of PA in the formulation. A better brain-targeted delivery of the lipopolymeric NPs was verified from the high blood-brain barrier (BBB) permeability of QU through strong interactions of surface SA and 5HTM with O-linked N-acetylglucosamine and 5-HT1B receptors, respectively. Immunofluorescence staining images also supported QU-SA-5HTM-PA-PLGA NPs to traverse the microvessels of AD rat brain. Western blot analysis showed that QU-loaded PA-PLGA NPs suppressed caspase-3 expression. The ability of the nanocarriers to recognize A£] fibrils was demonstrated from the reduced senile plaque formation and the attenuated acetylcholinesterase and malondialdehyde activity in the hippocampus. Hence, the medication of QU-SA-5HTM-PA-PLGA NPs can facilitate the BBB penetration and prevent A£] accumulation, lipid peroxidation, and neuronal apoptosis for the AD management. ? 2019 American Chemical Society.
Subjects
5-HT-moduline
lipopolymer
phosphatidic acid
poly(lactide- co-glycolide)
sialic acid
SDGs
Other Subjects
Carboxylic acids; Cell death; Disease control; Electrophoresis; Nanoparticles; Oxidative stress; 5-HT-moduline; Lipo-polymer; Phosphatidic acids; Poly lactide-co-glycolide; Sialic acids; Neurodegenerative diseases; acetylcholinesterase; amyloid beta protein; caspase 3; leucylserylalanylleucine; malonaldehyde; n acetylglucosamine; phosphatidic acid; polyglactin; quercetin; serotonin; serotonin 1B receptor; sialic acid; Alzheimer disease; animal experiment; animal model; animal tissue; antioxidant activity; Article; blood brain barrier; controlled study; drug delivery system; drug formulation; drug penetration; electric resistance; hippocampus; human; human cell; immunofluorescence test; lipid peroxidation; male; membrane permeability; microvasculature; nerve degeneration; neuroapoptosis; neuroprotection; nonhuman; oxidative stress; particle size; priority journal; protein expression; rat; senile plaque; Western blotting; zeta potential
Type
journal article