Therapies directed toward the central nervous system remain difficult to translate into improved clinical outcomes. This is largely due to the blood-brain barrier (BBB), arguably the most tightly regulated interface in the human body, which routinely excludes most therapeutics. Advances in the engineering of nanomaterials and their application in biomedicine (i.e., nanomedicine) are enabling new strategies that have the potential to help improve our understanding and treatment of neurological diseases. Herein, the various mechanisms by which therapeutics can be delivered to the brain are examined and key challenges facing translation of this research from benchtop to bedside are highlighted. Following a contextual overview of the BBB anatomy and physiology in both healthy and diseased states, relevant therapeutic strategies for bypassing and crossing the BBB are discussed. The focus here is especially on nanomaterial-based drug delivery systems and the potential of these to overcome the biological challenges imposed by the BBB. Finally, disease-targeting strategies and clearance mechanisms are explored. The objective is to provide the diverse range of researchers active in the field (e.g., material scientists, chemists, engineers, neuroscientists, and clinicians) with an easily accessible guide to the key opportunities and challenges currently facing the nanomaterial-mediated treatment of neurological diseases.
We
report the assembly of metal-polyphenol complex (MPC) films
and capsules through the sequential deposition of iron(III) ions (Fe(III)) and a natural polyphenol, tannic acid (TA), driven by
metal–ligand coordination. Stable Fe(III)/TA films
and capsules were formed, indicating lateral and longitudinal cross-linking
of TA by Fe(III) in the film structure. Quartz crystal
microbalance, ultraviolet–visible (UV-vis) spectrophotometry,
and X-ray photoelectron spectroscopy were carried out to quantitatively
analyze the film growth. A comparison of the MPC capsules prepared
through multistep assembly with those obtained through one-step deposition,
as reported previously [Ejima et al., Science
2013, 341, 154–156], reveals substantial
differences in the nature of complexation and in their physicochemical
properties, including permeability, stiffness, and degradability.
This study highlights the importance of engineering MPC films with
different properties through implementing different assembly methods.
Historical details regarding the genesis of SET-LRP and the evolution from single electron degenerative transfer living radical polymerization (SET-DTLRP) have been addressed in detail in the aforementioned review and will not be revisited herein. The mechanistic debate will also be critically discussed; however, it is not the main focus of this current contribution.
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