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.