Curcumin-loaded PLGA-PEG nanoparticles conjugated with B6 peptide for potential use in Alzheimer’s disease

Abstract

Alzheimer’s disease is a neurodegenerative disorder mainly characterized by β-amyloid deposit and tau hyperphosphorylation with no curative treatments. Curcumin (Cur) has been proved to have potential use in Alzheimer’s disease with its anti-amyloid, anti-inflammatory, and anti-oxidant properties, etc. However, its hydrophobicity and low bioavailability hinder its application. In this paper, we designed a novel brain-target nanoparticle, poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-PEG) conjugated with B6 peptide and was loaded with Cur (PLGA-PEG-B6/Cur) and administered it into HT22 cells and APP/PS1 Al transgenic mice. The in vitro assays including dynamic light scattering (DLS), flow cytometry (FCM), red blood cell (RBC) lysis, and thromboelastography (TEG) analysis indicated that this nanoparticle could narrow the diameter of Cur, increase its cellular uptake and possess good blood compatibility. The results from Morris water maze proved that PLGA-PEG-B6/Cur could tremendously improve the spatial learning and memory capability of APP/PS1 mice, compared with native Cur. The ex vivo assays including Bielschowsky silver staining, immunostaining, and western blotting demonstrated that PLGA-PEG-B6/Cur could reduce hippocampal β-amyloid formation and deposit and tau hyperphosphorylation. Thus, we suggested that PLGA-PEG-B6/Cur nanoparticles would be of potential and promising use for the treatment of Alzheimer’s disease.

<p>Curcumin-loaded nanoparticles: a novel therapeutic strategy in treatment of central nervous system disorders</p>

“…Overall, this study offered PLGA nanoparticles as a promising tool for the delivery of drugs in treatment of AD. 45 Fan et al 48 also prepared curcumin-loaded PLGA-PEG nanoparticles conjugated with B6 peptide (PLGA-PEG-B6/Cur). The in vitro assays including dynamic light scattering (DLS), flow cytometry (FCM), red blood cell (RBC) lysis, and thromboelastographic (TEG) analysis showed good bio-safety and high bioavailability of PLGA-PEG-B6/Cur.…”

“…In conclusion, the results of the current study illustrated that PLGA-PEG-B6/Cur might be considered as a promising therapeutic strategy for the treatment of AD in the future. 48…”

Curcumin-loaded chitosan–bovine serum albumin nanoparticles potentially enhanced Aβ 42 phagocytosis and modulated macrophage polarization in Alzheimer’s disease

“…This demonstrated that the green fluorescence emitted by free curcumin inside the cells was very weak, which indicated that most of the free curcumin was not taken up by the macrophage cell line, RAW 264.7. As NPs might have promising potential for highly efficient intracellular drug delivery [ 41 , 42 ], it was observed that curcumin-loaded CS-BSA NPs showed increased fluorescence intensity when compared with cells treated with free curcumin, suggesting that CS-BSA NPs could improve the cellular uptake of curcumin. Herein, this observation indicated that CS-BSA NPs could effectively promote drug accumulation within the cells.…”

27-Hydroxycholesterol contributes to cognitive deficits in APP/PS1 transgenic mice through microbiota dysbiosis and intestinal barrier dysfunction

“…A part of the fixed brain as well as the distal ileum and proximal colon tissues were embedded in paraffin, cut into 5 μm sections, stained with hematoxylin and eosin (HE), and examined by light microscopy (n = 6/group). The Aβ load in the brains was assessed using Bielschowsky silver stain (BSS), which was performed according to the previously published protocols [27]. A portion of intestinal (distal ileum specimens and proximal colon) tissue was processed for ultrastructural examination.…”

“…As one of the major side chains and enzymatic origin oxysterols found in the human circulation, 27-hydroxycholesterol (27-OHC) is ubiquitously produced by the mitochondrial enzyme CYP27A1 [13]. 27-OHC has been suggested to be involved in the pathogenesis of gastrointestinal and neurodegenerative diseases [14] due to its strong pro-inflammatory properties and ability to act as an endogenous selective estrogen receptor modulator (SERM). It is able to act as ligands for different isoforms of the estrogen receptor (ER) [15].…”