About this Research Topic
Central nervous system (CNS)-related disorders, including brain cancer, lysosomal storage disorders, traumatic brain or spinal cord injury, chronic pain, or chronic neurodegenerative diseases, such as Alzheimer’s, Parkinson’s disease or Amyotrophic Lateral Sclerosis, still represent a major burden for the society and demand innovative and more efficacious therapeutic approaches. Indeed, delivering therapeutics to the CNS is challenging since the blood-brain barrier (BBB) must be overcome to gain access to brain cells. Moreover, monitoring drug biodistribution or target engagement is rarely feasible if not impossible, due to the limited accessibility to tissue sampling, with the exception of the cerebrospinal fluid (CSF). However, CSF analysis is not always fully informative, especially for those conditions where the analyte is not a soluble compound released in biological fluids.
Recent advances in nanomaterial science and nanoparticles (NPs) technology have provided a great breakthrough in pharmacology allowing: i) increased selectivity for target cells, thus reducing the risk of potential side effects; ii) multiple-drug delivery, ranging from small molecules to oligonucleotides, full genes or small proteins; iii) controlled drug release over time; and iv) traceability in vivo. Despite some interesting examples demonstrating the possibility to improve brain penetration for compounds encapsulated in NPs, little is known on the factors affecting the behavior of NPs (in terms of biodistribution and/or drug release) when they are administered in a complex matrix such as the brain, especially in pathological conditions, when the neurodegenerative processes and neuroinflammation radically affect the microenvironment.
This Research Topic aims at attracting studies that deepen our understanding of the critical features that influence NPs biodistribution, or that dictate the uptake by specific cell types (including neurons, oligodendrocytes, astrocytes, microglia or neural stem cells) or selective CNS drug or gene release in healthy versus pathological conditions. Review articles, describing the state of the art of CNS-targeted therapeutics are welcome. We especially encourage innovative approaches or technologies, such as i) new routes or refined/less invasive modalities of NPs administration to the CNS; ii) modifications of NPs surface features allowing better brain penetration; iii) development of NPs formulations improving the pharmacodynamic or pharmaco-toxicological profile of specific potentially therapeutic compounds; iii) tools to monitor NPs biodistribution, or control drug release.
Potential topics include but are not limited to the following:
● Nano-pharmacological tools designed to obtain selective uptake in specific cell types or CNS compartments;
● Methods to achieve selective or controlled drug release, with a focus on the influence of the microenvironment (e.g. disruption of the BBB, changes of the pH or the redox state of the extracellular matrix, innate or adaptive immune response,...);
● Comparison of different routes of administration, with special emphasis on the chances or challenges for successful translation to the clinical setting;
● New approaches to track NPs biodistribution in vivo by non-invasive imaging methods, including but not limited to MRI, PET, bioluminescence, near-infrared or others;
● New technologies allowing modulation of drug release, e.g. by changing NPs biodegradation profile or by exploiting pH- or temperature-sensitive materials or caged compounds.
Keywords: central nervous system, brain, blood-brain-barrier, nanotechnologies, neurodegeneration, microglia, astrocytes, neurons
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