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.