Recent Uses of Lipid Nanoparticles, Cell-Penetrating and Bioactive Peptides for the Development of Brain-Targeted Nanomedicines against Neurodegenerative Disorders

Abstract

The lack of effective treatments for neurodegenerative diseases (NDs) is an important current concern. Lipid nanoparticles can deliver innovative combinations of active molecules to target the various mechanisms of neurodegeneration. A significant challenge in delivering drugs to the brain for ND treatment is associated with the blood–brain barrier, which limits the effectiveness of conventional drug administration. Current strategies utilizing lipid nanoparticles and cell-penetrating peptides, characterized by various uptake mechanisms, have the potential to extend the residence time and bioavailability of encapsulated drugs. Additionally, bioactive molecules with neurotropic or neuroprotective properties can be delivered to potentially mediate the ND targeting pathways, e.g., neurotrophin deficiency, impaired lipid metabolism, mitochondrial dysfunction, endoplasmic reticulum stress, accumulation of misfolded proteins or peptide fragments, toxic protein aggregates, oxidative stress damage, and neuroinflammation. This review discusses recent advancements in lipid nanoparticles and CPPs in view of the integration of these two approaches into nanomedicine development and dual-targeted nanoparticulate systems for brain delivery in neurodegenerative disorders.

Cell-Penetrating Peptides-Mediated Therapeutic Agents Delivery into the Central Nervous System

“…101,102 (2) CPP-nucleic acid conjugates can be encapsulated in nanoparticles, such as liposomes or polymeric nanoparticles, which can protect them from nuclease degradation and improve their stability. 103,104 (3) Co-administration of nuclease inhibitors, such as heparin or polyvinyl sulfate, can help protect CPP-nucleic acid conjugates from nuclease degradation. 105 (4) Conjugation of CPPs with polyethylene glycol (PEG) can increase their stability and circulation time, as well as reduce their susceptibility to nuclease degradation.…”

“…To address this issue, researchers have developed several strategies to protect CPP-nucleic acid conjugates from nuclease degradation: (1) Nucleic acids can be chemically modified to enhance their stability and resistance to nuclease degradation. Common modifications include the use of phosphorothioate linkages, 2′-O-methyl, 2′-O-methoxyethyl, or locked nucleic acid (LNA) residues. , (2) CPP-nucleic acid conjugates can be encapsulated in nanoparticles, such as liposomes or polymeric nanoparticles, which can protect them from nuclease degradation and improve their stability. , (3) Co-administration of nuclease inhibitors, such as heparin or polyvinyl sulfate, can help protect CPP-nucleic acid conjugates from nuclease degradation . (4) Conjugation of CPPs with polyethylene glycol (PEG) can increase their stability and circulation time, as well as reduce their susceptibility to nuclease degradation .…”

The Effect of Stereocomplexation and Crystallinity on the Degradation of Polylactide Nanoparticles

“…Polymeric nanoparticles (PNPs) are frequently researched and used in drug delivery, especially for the targeted treatment of tumor or cancer cells through a targeting process [ 5 ]. In this process, specific ligands are attached to the PNP’s shells to guide the drug to its desired site of action [ 6 ].…”