ReviewMolecular pharmaceutics2013
Physiology of the intrathecal bolus: the leptomeningeal route for macromolecule and particle delivery to CNS.
Review in Molecular pharmaceutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Intrathecal drug delivery in the era of nanomedicine.Advanced drug delivery reviews · 2020Pooled it
- A phase I/II study on intracerebroventricular tralesinidase alfa in patients with Sanfilippo syndrome type B.The Journal of clinical investigation · 2023Trial
- A phase I/II study of intrathecal idursulfase-IT in children with severe mucopolysaccharidosis II.Genetics in medicine : official journal of the American College of Medical Genetics · 2016Trial
- The impact of spinal cord nerve roots and denticulate ligaments on cerebrospinal fluid dynamics in the cervical spine.PloS one · 2014Trial
- Bridging the blood-brain barrier: strategies to improve delivery of biologics to tumors in the brain.Fluids and barriers of the CNS · 2026Review
- Breaking the neuroinflammatory loop with intrathecal dexamethasone in FIRES.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- Article
- Mixed-dimensional fluid-structure interaction simulations reveal key mechanisms of cerebrospinal fluid dynamics in the spinal canal.Fluids and barriers of the CNS · 2025Article
- Pia Mater-Penetrable Lipopolymer Nanoparticles for Gliocyte-Targeted IL-10 mRNA Therapy Alleviate Paclitaxel-Induced Peripheral Neuropathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Intrathecal administration of Anti-Nogo-A antibody in macaque monkeys: Pharmacokinetics, tissue penetration and target interaction.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Advances in Intrathecal Nanoparticle Delivery: Targeting the Blood-Cerebrospinal Fluid Barrier for Enhanced CNS Drug Delivery.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Article
- A perspective: neuraxial therapeutics in pain management: now and future.Frontiers in pain research (Lausanne, Switzerland) · 2024Article
- Brain Targeting Nanomedicines: Pitfalls and Promise.International journal of nanomedicine · 2024Review
- Anatomical Targeting of Anticancer Drugs to Solid Tumors Using Specific Administration Routes: Review.Pharmaceutics · 2023Review
- Nanoparticles-based anti-aging treatment of Alzheimer's disease.Drug delivery · 2022Review
- Retrograde Axonal Transport of Liposomes from Peripheral Tissue to Spinal Cord and DRGs by Optimized Phospholipid and CTB Modification.International journal of molecular sciences · 2022Article
- Article
- Intrathecal amyloid-beta oligomer administration increases tau phosphorylation in the medial temporal lobe in the African green monkey: A nonhuman primate model of Alzheimer's disease.Neuropathology and applied neurobiology · 2022Article
- Drug delivery to the central nervous system.Nature reviews. Materials · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
Presently, there are no effective treatments for several diseases involving the CNS, which is protected by the blood-brain, blood-CSF, and blood-arachnoid barriers. Traversing any of these barriers is difficult, especially for macromolecular drugs and particulates. However, there is significant experimental evidence that large molecules can be delivered to the CNS through the cerebrospinal fluid (CSF). The flux of the interstitial fluid in the CNS parenchyma, as well as the macro flux of CSF in the leptomeningeal space, are believed to be generally opposite to the desirable direction of CNS-targeted drug delivery. On the other hand, the available data suggest that the layer of pia mater lining the CNS surface is not continuous, and the continuity of the leptomeningeal space (LMS) with the perivascular spaces penetrating into the parenchyma provides an unexplored avenue for drug transport deep into the brain via CSF. The published data generally do not support the view that macromolecule transport from the LMS to CNS is hindered by the interstitial and CSF fluxes. The data strongly suggest that leptomeningeal transport depends on the location and volume of the administered bolus and consists of four processes: (i) pulsation-assisted convectional transport of the solutes with CSF, (ii) active "pumping" of CSF into the periarterial spaces, (iii) solute transport from the latter to and within the parenchyma, and (iv) neuronal uptake and axonal transport. The final outcome will depend on the drug molecule behavior in each of these processes, which have not been studied systematically. The data available to date suggest that many macromolecules and nanoparticles can be delivered to CNS in biologically significant amounts (>1% of the administered dose); mechanistic investigation of macromolecule and particle behavior in CSF may result in a significantly more efficient leptomeningeal drug delivery than previously thought.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.