Lipid nanoparticles
Lipid nanoparticles are often composed of single-layer or multiple-layers of phospholipids. Furthermore, the amphipathic nature of lipid nanoparticles allows them to offer unique drug-encapsulation capabilities. Hydrophilic drug compounds can be embedded within the lipid nanoparticles’ aqueous compartments, while hydrophobic drug compounds can be encapsulated with their membranes. The biological similarity of lipid nanoparticles and cellular membranes allow lipid nanoparticles to penetrate and accumulate in biological tissue with enhanced efficacy, compared to other nanoparticle counterparts. Additionally, their ability to prevent the loaded drug compound from degradation make them an attractive choice to employ for therapeutic applications. Specifically, lipid nanoparticles, including liposomes as a prominent example, have shown considerable promise as efficacious vehicles for the targeted administration of therapeutic agents in the context of Alzheimer’s disease (AD) intervention106. Numerous studies have been conducted to examine the utilization of lipid nanoparticles as a vehicle for administering therapeutic agents and impeding pivotal pathological mechanisms, such as tau aggregation, linked to Alzheimer’s disease (AD)107,108.
Ross et al. developed a novel approach for creating liposomes with multiple functions107. These liposomes were specifically designed to encapsulate curcumin, which is a bioactive compound with potential therapeutic applications. Additionally, liposomes were modified with nerve growth factor (NGF), cardiolipin (CL), and wheat germ agglutinin (WGA) to enhance their functionality. Curcumin is widely recognized for its notable attributes in the mitigation of inflammation and inhibition of tau phosphorylation107,109. The neurotrophic factor known as NGF mitigates neuronal apoptosis, thereby potentially promoting neuronal survival. In contrast, CL enhances the affinity of liposomes towards neurons in close proximity to amyloid-beta accumulations. The facilitation of blood-brain barrier (BBB) penetration is a notable effect of WGA compounds. The synthesized liposomes significantly downregulated the expression of phosphorylated p38 proteins, phosphorylated tau protein levels, and phosphorylated c-Jun N-terminal kinase. Furthermore, the liposomes demonstrated excellent efficacy in improving BBB penetration, decreasing amyloid-β accumulation, stimulating axonogenesis, and preventing neurodegeneration.
Thus, in vitro investigations have demonstrated a notable decrease in the accumulation of amyloid-beta and tau proteins, thereby indicating potential therapeutic implications for Alzheimer’s disease (AD).
Vakilinezhad et al. undertook the task of formulated solid lipid nanoparticles (SLNs) specifically engineered to encapsulate nicotinamide, an inhibitor of histone deacetylase (HDAC)106. The rationale behind this design was to investigate the potential of nicotinamide-loaded SLNs to mitigate tau hyperphosphorylation, a pathological process associated with cognitive impairment. We hypothesized that the delivery of nicotinamide via SLNs could enhance its therapeutic efficacy in improving cognitive function. Researchers have successfully enhanced brain delivery, mitigated neurotoxicity, and enhanced cognitive outcomes in animal models of Alzheimer’s disease (AD) by modifying solid lipid nanoparticles (SLNs) with polysorbate 80, phosphatidylserine (PS), or phosphatidic acid (PA).In vitro studies confirmed the biocompatibility of the phosphatidyl-serine and phosphatidic acid functionalized nicotinamide-loaded SLNs. Biodistribution studies showed that the synthesized SLNs improved brain delivery of nicotinamide across the BBB. Furthermore, Morris water maze tests and memory examinations supported that the synthesized SLNs enhanced cognition, cultivated normal neuronal cell functionalities, and inhibited tau hyperphosphorylation. The utilization of PS-SLNs demonstrated notable efficacy in impeding the progression of Alzheimer’s disease (AD) through the reduction of tau hyperphosphorylation.
Song et al. formulated lipoprotein-based nanoparticles that were strategically functionalized with ApoE3110. The primary objective of this innovative approach was to augment the permeability of the blood-brain barrier (BBB) and subsequently ameliorate memory impairments in mice with Alzheimer’s disease (AD). Nanoparticles exhibit a propensity for binding to amyloid-beta, thereby facilitating its degradation through the concerted efforts of microglia and astroglia. Additionally, they play a crucial role in promoting hepatic elimination of amyloid-beta, thereby mitigating amyloid deposition and alleviating neurological alterations. Detailed studies indicated that the synthesized nanostructures could travel across the BBB, stimulate amyloid-β and tau degradation, facilitate microgliosis, and restore memory capabilities in AD mouse models.. Thus, the nanoparticles under investigation exhibit promising attributes that render them viable candidates for safe and biocompatible therapeutic interventions110.
Hu et al. employed the technique of encapsulating tannic acid within liposomal nanoparticles to impede the process of tau aggregation111. The interaction between tannic acid and tau peptides impedes the folding process of the latter, thereby inhibiting the formation of intricate conformations and subsequently mitigating the aggregation of tau fibrils. The ability of tannic acid liposomes to traverse the blood-brain barrier (BBB) implies their prospective utility as therapeutic interventions for Alzheimer’s disease (AD)111.
In the realm of Alzheimer’s disease (AD) therapy, Lipid nanoparticles have emerged as a promising avenue for targeted drug delivery and inhibitors of tau aggregation in AD therapy. The aforementioned studies underscore the potential of these nanoparticles in impeding crucial pathological mechanisms and fostering cognitive enhancement in AD models.