The Delivery Challenge in Neurodegenerative Disorders: The Nanoparticles Role in Alzheimer’s Disease Therapeutics and Diagnostics

Abstract

Alzheimer’s disease (AD) is one of the main causes of disability and dependency among elderly people. AD is a neurodegenerative disorder characterized by a progressive and irreversible cognitive impairment, whose etiology is unclear because of the complex molecular mechanisms involved in its pathophysiology. A global view of the AD pathophysiology is described in order to understand the need for an effective treatment and why nanoparticles (NPs) could be an important weapon against neurodegenerative diseases by solving the general problem of poor delivery into the central nervous system (CNS) for many drugs. Drug delivery into the CNS is one of the most challenging objectives in pharmaceutical design, due to the limited access to the CNS imposed by the blood-brain barrier (BBB). The purpose of this review is to present a comprehensive overview of the use of NPs as delivery systems for therapeutic and diagnostic purposes in models of AD.

Overcoming the Blood–Brain Barrier. Challenges and Tricks for CNS Drug Delivery

“…However, non-targeted liposomes will not effectively pass a healthy BBB, but with surface modification, for example, adding polymers, polysaccharides, peptides or antibodies, the characteristics and targets of LPs can be specified. Furthermore PEGylation is used to prevent liposomes from being eliminated by the immune system and improve biodistribution [87]. As for transporter-mediated crossing of the BBB, transferrin was added to the surface of LPs, to deliver gene therapy in Parkinson's disease animal models [88].…”

“…Cationic LPs are ideal for delivering drugs and genetic material due to their positively charged surface, which facilitates interaction with the cell membrane and enhances uptake. Their advantage is also their disandvantage: due to the cationic properties, peripheral tissues and serum proteins bind and block them from being able to pass the BBB [87]. Song and coworkers have constructed an ApoE-containing high density lipoprotein (HDL) inspired nanocarrier [89], which is BBB permeable [90] and has high Aβ-binding affinity [91], for the treatment of Alzheimer's disease (AD).…”

“…Dendrimers (DDs) are macromolecules composed of three layers of polymers: 1) a central core; 2) branches, which are attached to the core and determine the generation of the DD (i.e., equals the number of layers the branches consist of. For example, a DD with three layers of branches is indicated as a G3 DD), and 3) the terminal functional groups, which create the surface of the nanoparticle [87]. The surface can be specialized for its function.…”

“…Magnetic NPs (MNP) are nanoparticles with a metal core (mostly iron-oxide) that has an unpaired electron, therefore, has magnetic property. Iron is the most popular core material due to its low toxicity and easy elimination through the endogenous iron metabolic pathway and is usually used in oxide form because it is a more stable state [87]. Multiple coating is used to enhance drug delivery, such as polysaccharides (dextrin), polyethylene-glycol (PEG), phospholipids, peptides, for protection of the metal core from the body, improve pharmacokinetics, lower toxicity [107].…”

Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil

“…The use of nanocarriers as a promising tool to overcome the limitations of the intranasal route has been gaining interest over recent decades. Nanotechnology-based drug delivery systems (polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, microemulsions, nanoemulsions, and liposomes) are characterized by their nanoscale size range, which can be appropriate to transport drugs to the brain and enhance the therapeutic performance of active agents used in the treatment of neurodegenerative disorders [ 15 , 18 ].…”