Abstract
Safe and reliable entry to the brain is essential for successful diagnosis and treatment of diseases, but it still poses major challenges. As a result, many therapeutic approaches to treating disorders associated with the central nervous system (CNS) still only show limited success. Nano-sized systems are being explored as drug carriers and show great improvements in the delivery of many therapeutics. The systemic delivery of nanoparticles (NPs) or nanocarriers (NCs) to the brain involves reaching the neurovascular unit (NVU), being transported across the blood–brain barrier, (BBB) and accumulating in the brain. Each of these steps can benefit from specifically controlled properties of NPs. Here, we discuss how brain delivery by NPs can benefit from careful design of the NP properties. Properties such as size, charge, shape, and ligand functionalization are commonly addressed in the literature; however, properties such as ligand density, linker length, avidity, protein corona, and stiffness are insufficiently discussed. This is unfortunate since they present great value against multiple barriers encountered by the NPs before reaching the brain, particularly the BBB. We further highlight important examples utilizing targeting ligands and how functionalization parameters, e.g., ligand density and ligand properties, can affect the success of the nano-based delivery system.
Highlights
The advent of nanomedicine has brought nanoparticles that provide unique ways to control interactions with cells and tissues
The blood–brain barrier (BBB) is rich in TfRs, which have been patient-derived xenografts (PDX) of diffuse intrinsic pontine glioma (DIPG), were observed extensively explored for improving transcytosis, and for improving brain upon administration of vincristine-loaded nanocarriers
The BBB is rich in TfRs, which have been extensively explored for improving transcytosis, and for improving brain delivery
Summary
The advent of nanomedicine has brought nanoparticles that provide unique ways to control interactions with cells and tissues. The design of particle properties ties better enables betterover control over particle interactions within theenvironments biological environments enables control particle interactions within the biological affecting affecting biodistribution, clearance, transport across barriers, uptake, and biodistribution, clearance, transport across barriers, uptake, and therapeutictherapeutic effect. Particle characteristics such ascharge, size, surface charge,ligand and targeting ligand effect. Schematic representation a polymeric drug delivery system and tunable properties This summarizes the main properties of polymer-based nanocarriers for controlling the interaction with biological systems and improving delivery efficacy.
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