Intranasal Pathway for Nanoparticles to Enter the Central Nervous System.

Intranasal administration was previously proposed for delivering drugs for central nervous system (CNS) diseases. However, the delivery and elimination pathways, which are very imperative to know for exploring the therapeutic applications of any given CNS drugs, remain far from clear. Because lipophilicity has a high priority in the design of CNS drugs, the as-prepared CNS drugs tend to form aggregates. Therefore, a PEGylated Fe3O4 nanoparticle labeled with a fluorescent dye was prepared as a model drug and studied to elucidate the delivery pathways of intranasally administered nanodrugs. Through magnetic resonance imaging, the distribution of the nanoparticles was investigated in vivo. Through ex vivo fluorescence imaging and microscopy studies, more precise distribution of the nanoparticles across the entire brain was disclosed. Moreover, the elimination of the nanoparticles from cerebrospinal fluid was carefully studied. The temporal dose levels of intranasally delivered nanodrugs in different parts of the brain were also investigated.

[1]  Ali Mohsin,et al.  Recent Advances of Magnetic Nanomaterials for Bioimaging, Drug Delivery, and Cell Therapy , 2022, ACS Applied Nano Materials.

[2]  Yonghui Wang,et al.  Cholinergic Neuron Targeting Nanosystem Delivering Hybrid Peptide for Combinatorial Mitochondrial Therapy in Alzheimer's Disease. , 2022, ACS nano.

[3]  Huile Gao,et al.  Intranasal Delivery of BACE1 siRNA and Rapamycin by Dual Targets Modified Nanoparticles for Alzheimer's Disease Therapy. , 2022, Small.

[4]  Yi Ji,et al.  “Drug‐Carrier” Synergy Therapy for Amyloid‐β Clearance and Inhibition of Tau Phosphorylation via Biomimetic Lipid Nanocomposite Assembly , 2022, Advanced science.

[5]  Dongtao Ge,et al.  Aβ-responsive metformin-based supramolecular synergistic nanodrugs for Alzheimer's disease via enhancing microglial Aβ clearance. , 2022, Biomaterials.

[6]  Jianping Zhou,et al.  Lipoprotein-Inspired Nanoscavenger for the Three-Pronged Modulation of Microglia-Derived Neuroinflammation in Alzheimer's Disease Therapy. , 2022, Nano letters.

[7]  Mingyuan Gao,et al.  Anchoring Group-Mediated Radiolabeling of Inorganic Nanoparticles─A Universal Method for Constructing Nuclear Medicine Imaging Nanoprobes. , 2022, ACS applied materials & interfaces.

[8]  Fenglei Gao,et al.  Gold Nanorods with Spatial Separation of CeO2 Deposition for Plasmonic-Enhanced Antioxidant Stress and Photothermal Therapy of Alzheimer's Disease. , 2022, ACS applied materials & interfaces.

[9]  R. Saigal,et al.  Drug delivery to the central nervous system , 2021, Nature Reviews Materials.

[10]  T. Massoud,et al.  A Microfluidics-Based Scalable Approach to Generate Extracellular Vesicles with Enhanced Therapeutic MicroRNA Loading for Intranasal Delivery to Mouse Glioblastomas. , 2021, ACS nano.

[11]  B. Tang,et al.  Upregulating Aggregation‐Induced‐Emission Nanoparticles with Blood–Tumor‐Barrier Permeability for Precise Photothermal Eradication of Brain Tumors and Induction of Local Immune Responses , 2021, Advanced materials.

[12]  M. Vannier,et al.  Aerosolized In Vivo 3D Localization of Nose-to-Brain Nanocarrier Delivery Using Multimodality Neuroimaging in a Rat Model—Protocol Development , 2021, Pharmaceutics.

[13]  Steven T. Proulx Cerebrospinal fluid outflow: a review of the historical and contemporary evidence for arachnoid villi, perineural routes, and dural lymphatics , 2021, Cellular and Molecular Life Sciences.

[14]  Guanxun Cheng,et al.  Nanomedicine Directs Neuronal Differentiation of Neural Stem Cells via Silencing Long Noncoding RNA for Stroke Therapy. , 2021, Nano letters.

[15]  M. Allix,et al.  Engineering NIR-IIb fluorescence of Er-based lanthanide nanoparticles for through-skull targeted imaging and imaging-guided surgery of orthotopic glioma , 2020 .

[16]  Han Yang,et al.  A Novel Targeted and High‐Efficiency Nanosystem for Combinational Therapy for Alzheimer's Disease , 2020, Advanced science.

[17]  F. Tang,et al.  Meningeal lymphatic vessels regulate brain tumor drainage and immunity , 2020, Cell Research.

[18]  Y. Anraku,et al.  Nanomaterial-based blood-brain-barrier (BBB) crossing strategies. , 2019, Biomaterials.

[19]  Rajendran J C Bose,et al.  Intranasal delivery of targeted polyfunctional gold-iron oxide nanoparticles loaded with therapeutic microRNAs for combined theranostic multimodality imaging and presensitization of glioblastoma to temozolomide. , 2019, Biomaterials.

[20]  K. T. Householder,et al.  Fate of nanoparticles in the central nervous system after intrathecal injection in healthy mice , 2019, Scientific Reports.

[21]  Feng Ren,et al.  Boosting often overlooked long wavelength emissions of rare-earth nanoparticles for NIR-II fluorescence imaging of orthotopic glioblastoma. , 2019, Biomaterials.

[22]  Y. Nagasaki,et al.  Encapsulation of tissue plasminogen activator in pH-sensitive self-assembled antioxidant nanoparticles for ischemic stroke treatment - Synergistic effect of thrombolysis and antioxidant. , 2019, Biomaterials.

[23]  O. Ganslandt,et al.  Arachnoid Membranes Around the Cisternal Segment of the Trigeminal Nerve: A Cadaveric Anatomic Study and Intraoperative Observations During Minimally Invasive Microvascular Decompression Surgery. , 2019, World neurosurgery.

[24]  Xiaoyuan Chen,et al.  Fenton-Reaction-Acceleratable Magnetic Nanoparticles for Ferroptosis Therapy of Orthotopic Brain Tumors. , 2018, ACS nano.

[25]  A. Bücker,et al.  Rapid lymphatic efflux limits cerebrospinal fluid flow to the brain , 2018, Acta Neuropathologica.

[26]  R. Thorne,et al.  Delivery of immunoglobulin G antibodies to the rat nervous system following intranasal administration: Distribution, dose‐response, and mechanisms of delivery , 2018, Journal of controlled release : official journal of the Controlled Release Society.

[27]  F. Scholtes,et al.  Aurora A plays a dual role in migration and survival of human glioblastoma cells according to the CXCL12 concentration , 2018, Oncogene.

[28]  F. Caruso,et al.  Overcoming the Blood–Brain Barrier: The Role of Nanomaterials in Treating Neurological Diseases , 2018, Advanced materials.

[29]  Lin Ma,et al.  MRI Probes: Timely Visualization of the Collaterals Formed during Acute Ischemic Stroke with Fe3 O4 Nanoparticle-based MR Imaging Probe (Small 23/2018) , 2018, Small.

[30]  T. Nakada,et al.  Fluid Dynamics Inside the Brain Barrier: Current Concept of Interstitial Flow, Glymphatic Flow, and Cerebrospinal Fluid Circulation in the Brain , 2018, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[31]  D. McGavern,et al.  Advances in Meningeal Immunity , 2018, Trends in Molecular Medicine.

[32]  P. Proost,et al.  The unique structural and functional features of CXCL12 , 2018, Cellular & Molecular Immunology.

[33]  Yong Wang,et al.  MRI‐Visible siRNA Nanomedicine Directing Neuronal Differentiation of Neural Stem Cells in Stroke , 2018 .

[34]  W. Hsu,et al.  Mechanism of intranasal drug delivery directly to the brain , 2018, Life sciences.

[35]  E. Hanse,et al.  Neuromodulation via the Cerebrospinal Fluid: Insights from Recent in Vitro Studies , 2018, Front. Neural Circuits.

[36]  Mengrui Liu,et al.  Progress in brain targeting drug delivery system by nasal route , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[37]  Hong-Yu Zhang,et al.  A strategy for bypassing the blood‐brain barrier: Facial intradermal brain‐targeted delivery via the trigeminal nerve , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[38]  Marijan Klarica,et al.  Role of choroid plexus in cerebrospinal fluid hydrodynamics , 2017, Neuroscience.

[39]  Timothy J Keyes,et al.  Structural and functional features of central nervous system lymphatics , 2015, Nature.

[40]  R. Thorne,et al.  Rapid Transport within Cerebral Perivascular Spaces Underlies Widespread Tracer Distribution in the Brain after Intranasal Administration , 2015, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[41]  S. Hladky,et al.  Mechanisms of fluid movement into, through and out of the brain: evaluation of the evidence , 2014, Fluids and Barriers of the CNS.

[42]  P. Djupesland,et al.  The nasal approach to delivering treatment for brain diseases: an anatomic, physiologic, and delivery technology overview. , 2014, Therapeutic delivery.

[43]  S. Krol,et al.  Therapeutic benefits from nanoparticles: the potential significance of nanoscience in diseases with compromise to the blood brain barrier. , 2013, Chemical reviews.

[44]  F. Fang,et al.  NaGdF4 nanoparticle-based molecular probes for magnetic resonance imaging of intraperitoneal tumor xenografts in vivo. , 2013, ACS Nano.

[45]  L. Hanson,et al.  Intranasal delivery of insulin via the olfactory nerve pathway , 2012, The Journal of pharmacy and pharmacology.

[46]  R. Thorne,et al.  Intranasal delivery of biologics to the central nervous system. , 2012, Advanced drug delivery reviews.

[47]  Z. Ram,et al.  Convection-enhanced delivery catheter placements for high-grade gliomas: complications and pitfalls , 2012, Journal of Neuro-Oncology.

[48]  Mingyuan Gao,et al.  Receptor-mediated delivery of magnetic nanoparticles across the blood-brain barrier. , 2012, ACS nano.

[49]  M. Gilbert,et al.  Molecularly targeted therapies for malignant gliomas: advances and challenges , 2007, Expert review of anticancer therapy.

[50]  R. G. Thorne,et al.  Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration , 2004, Neuroscience.

[51]  B. Jansson,et al.  Visualization of In Vivo Olfactory Uptake and Transfer Using Fluorescein Dextran , 2002, Journal of drug targeting.

[52]  A. Coulthard,et al.  Pictorial review: Trigeminal nerve: anatomy and pathology. , 2001, The British journal of radiology.

[53]  T. Ichimura,et al.  Distribution of extracellular tracers in perivascular spaces of the rat brain , 1991, Brain Research.

[54]  J. McComb,et al.  Ultrastructural morphology of the olfactory pathway for cerebrospinal fluid drainage in the rabbit. , 1986, Journal of neurosurgery.

[55]  G. Bourne,et al.  Perineural Epithelium: A New Concept of its Role in the Integrity of the Peripheral Nervous System , 1966, Science.

[56]  W. Pardridge The blood-brain barrier: Bottleneck in brain drug development , 2005, NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics.

[57]  Tushar K. Vyas,et al.  Recent patents review on intranasal administration for CNS drug delivery. , 2008, Recent patents on drug delivery & formulation.