Figure 599: General configuration of nanoparticles
conjugated for treatment of Alzheimer’s Disease. NPs can be loaded with
a variety of AD therapeutics, such as anti-amyloid-beta antibodies,
acetylcholinesterase (AChE) inhibitors, antioxidants, and proteosomes to
degrade hyperphosphorylated tau. Different materials can be utilized for
the shell of NPs. The NPs are also functionalized so that they can be
transported from the blood lumen into the brain parenchyma.
Polymeric nanoparticles (NPs) Polymeric nanoparticles are
particles of small size that have gained attention in recent years for
their applications as drug delivery systems. Drug compounds can either
be encapsulated inside the polymeric nanoparticles or adsorbed onto the
polymeric core. The relatively small size of polymeric NPs make them an
attractive choice, especially in regards to BBB permeability. Recent
research has been focused on developing biodegradable polymer
nanoparticles. This formulation offers advantages such as the
degradation of the polymer shell to release the drug compounds
encapsulated within the core into the biological environment. Polymeric
nanoparticles (NPs) have exhibited considerable potential for drug
delivery, particularly in the context of therapeutic interventions for
Alzheimer’s disease (AD). The aforementioned materials possess notable
attributes such as elevated biocompatibility, augmented
biodegradability, and regulated release
characteristics100. Numerous investigations have
examined the utilization of polymeric nanoparticles (NPs) as a means of
delivering therapeutic agents, including curcumin, amyloid-beta
generation inhibitors, and BACE 1 antisense genes, for the treatment of
Alzheimer’s disease (AD).
Curcumin, a compound renowned for its notable antioxidant and
anti-inflammatory properties, has been incorporated into chitosan-coated
polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) with the
objective of enhancing its solubility and
stability101,102. The aforementioned nanoparticle
formulations exhibited superior biocompatibility, regulated drug
release, and diminished cytotoxicity compared to unbound curcumin. In
vivo experiments involving curcumin-loaded nanoparticles (NPs) have
demonstrated enhanced delivery efficiency and improved distribution
within the brain. This has resulted in a reduction in oxidative stress
levels and the emergence of potential therapeutic advantages for
Alzheimer’s disease (AD) 101,102.
As an alternative methodology, the research team devised neuron
tau-targeting biomimetic nanoparticles (NPs) by encapsulating
poly(lactic-co-glycolic acid) (PLGA) NPs with red blood cell (RBC)
membranes, followed by functionalization with tau-PET
tracers103. The aforementioned nanoparticle (NP)
entities have demonstrated notable efficacy in traversing the
blood-brain barrier (BBB) and exhibit a strong affinity for
hyperphosphorylated tau. Consequently, this interaction leads to a
decrease in levels of phosphorylated tau and subsequent neuronal cell
death, as observed in both controlled laboratory settings (in vitro) and
living organisms (in vivo). Administration of nanoparticles (NPs) to
transgenic mouse models of Alzheimer’s disease (AD) resulted in notable
amelioration of memory deficits and alleviation of AD-related
symptoms103.
In addition, the utilization of nanoparticles (NPs) encapsulating an
amyloid-beta generation inhibitor known as S1, along with curcumin, and
conjugated with brain-targeting peptides, resulted in significant
reductions in cytokine production, restoration of antioxidant activity,
and a decrease in oxidative stress levels in mouse models of Alzheimer’s
disease (AD)104. The aforementioned nucleotide
polymorphisms (NPs) have exhibited promising capabilities in
ameliorating the progression of Alzheimer’s disease (AD) through precise
modulation of distinct molecular pathways.
In addition, a comprehensive delivery system encompassing genetic
material and peptides encapsulated within PEGylated dendrigraft
poly-L-lysine nanoparticles was developed105. The
primary objective of this system was to downregulate BACE BACE 1, an
essential enzyme implicated in the generation of amyloid-beta plaques.
The successful delivery of the BACE 1 antisense gene and tau-related
fibril inhibitor peptide by nanoparticle carriers (NPs) resulted in a
notable decrease in BACE 1 positive signals and a reduction in p-tau
positive signals in mice with Alzheimer’s disease (AD).
These studies underscore the considerable promise of polymeric
nanoparticles (NPs) in their capacity to serve as efficacious vehicles
for drug delivery in the context of AD therapy. Polymeric nanoparticles
(NPs) exhibit great potential in the realm of Alzheimer’s disease (AD)
therapy because of their ability to enhance the delivery and targeting
of therapeutic agents. Nevertheless, it is imperative to conduct
additional investigations and rigorous clinical trials to
comprehensively evaluate the safety and effectiveness of these
interventions before their widespread adoption.