Physiological and Pathological Factors Affecting Drug Delivery to the Brain by Nanoparticles

Abstract

The prevalence of neurological/neurodegenerative diseases, such as Alzheimer's disease is known to be increasing due to an aging population and is anticipated to further grow in the decades ahead. The treatment of brain diseases is challenging partly due to the inaccessibility of therapeutic agents to the brain. An increasingly important observation is that the physiology of the brain alters during many brain diseases, and aging adds even more to the complexity of the disease. There is a notion that the permeability of the blood–brain barrier (BBB) increases with aging or disease, however, the body has a defense mechanism that still retains the separation of the brain from harmful chemicals in the blood. This makes drug delivery to the diseased brain, even more challenging and complex task. Here, the physiological changes to the diseased brain and aged brain are covered in the context of drug delivery to the brain using nanoparticles. Also, recent and novel approaches are discussed for the delivery of therapeutic agents to the diseased brain using nanoparticle based or magnetic resonance imaging guided systems. Furthermore, the complement activation, toxicity, and immunogenicity of brain targeting nanoparticles as well as novel in vitro BBB models are discussed.

“Drug‐Carrier” Synergy Therapy for Amyloid‐β Clearance and Inhibition of Tau Phosphorylation via Biomimetic Lipid Nanocomposite Assembly

“…However, the higher density of ligand could not only decrease the binding ability of nanoparticles to receptors due to steric hindrances caused by too closely adjacent ligands, but also possibly enhance nonspecific interactions in vivo. [ 31 ] Therefore, an optimal ligand density is required to promote sufficient BBB crossing. To optimize the efficiency of BBB penetration, preparations with different α Ang ligand densities of 1%, 5%, 10%, and 15% (corresponding lipids were denoted as 1% APLN/MB, 5% APLN/MB, 10% APLN/MB, and 15% APLN/MB, respectively) were prepared.…”

“…Transmembrane resistance (TEER) of the cell monolayer was measured every day to indicate the formation of hCMEC/D3 monolayers. When TEER value reached 50 Ω cm −2 and remained stable (Figure S5, Supporting Information), [ 31 ] various C6‐loading preparations were added in the upper chamber. To evaluate BBB permeability and cellular internalization, fluorescence images of BV‐2 cells on the lower chamber were visualized under inverted fluorescence microscope.…”

Specific anti‐glioma targeted‐delivery strategy of engineered small extracellular vesicles dual‐functionalised by Angiopep‐2 and TAT peptides

“…The main challenge in treating glioma is BBB permeation and delivery of anticancer drug at the therapeutic dose to the tumour (Islam et al., 2021; Pardridge, 2007). Nonspecific cytotoxicity, poor biocompatibility and low delivery efficiency have been reported in the traditional nano‐delivery systems (Thomas et al., 2003).…”

Structure‐Based Varieties of Polymeric Nanocarriers and Influences of Their Physicochemical Properties on Drug Delivery Profiles

“…[ 14 ] Delivery to central nervous system faces challenges posed by blood‐brain barrier (BBB). [ 15 , 16 , 17 , 18 ] A recent study showed, only about 1% of nanocarriers can accumulate with high permeability and retention in xenografted tumors; this low rate is possibly due to multiple physiological barriers. [ 19 , 20 ] These challenges indicate that the nanocarriers must be substantially improved.…”