Intra-CSF administration of chemotherapy medications

Gabay, Michael; Thakkar, Jigisha P.; Stachnik, Joan M; Woelich, Susan K.; Villanó, John L.

doi:10.1007/s00280-012-1893-z

Cited by 18 publications

(6 citation statements)

References 94 publications

(141 reference statements)

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“…Taking into account, this process will pave the road to benefit from ICV drug delivery advantages, as such crossing the blood-brain and blood-CSF barriers with a minimal risk of systemic effects and uniform distribution of the compound in the parenchyma and subarachnoid space [ 49 , 50 ].…”

Section: Clinical Significancementioning

confidence: 99%

Transependymal Cerebrospinal Fluid Flow: Opportunity for Drug Delivery?

et al. 2017

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Drug delivery to the central nervous system (CNS) is complicated by the blood-brain barrier. As a result, many agents that are found to be potentially effective at their site of action cannot be sufficiently or effectively delivered to the CNS and therefore have been discarded and not developed further for clinical use, leaving many CNS diseases untreated. One way to overcome this obstacle is intracerebroventricular (ICV) delivery of the therapeutics directly to cerebrospinal fluid (CSF). Recent experimental and clinical findings reveal that CSF flows from the ventricles throughout the parenchyma towards the subarachnoid space also named minor CSF pathway, while earlier, it was suggested that only in pathological conditions such as hydrocephalus this form of CSF flow occurs. This transependymal flow of CSF provides a route to distribute ICV-infused drugs throughout the brain. More insight on transependymal CSF flow will direct more rational to ICV drug delivery and broaden its clinical indications in managing CNS diseases.

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Section: Clinical Significancementioning

confidence: 99%

Transependymal Cerebrospinal Fluid Flow: Opportunity for Drug Delivery?

et al. 2017

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“…Medulloblastoma cells are notorious for CSF pathway dissemination, which is found in 30-40% of children at initial diagnosis and the majority at recurrence (5)(6)(7). Intrathecal chemotherapy, such as with etoposide or methotrexate, has been attempted for patients having disseminated medulloblastoma, and leptomeningeal metastases (LM) from solid tumors (1,2,5,(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Etoposide-Bound Magnetic Nanoparticles Designed for Remote Targeting of Cancer Cells Disseminated Within Cerebrospinal Fluid Pathways

et al. 2020

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Magnetic nanoparticles (MNPs) have potential for enhancing drug delivery in selected cancer patients, including those which have cells that have disseminated within cerebrospinal fluid (CSF) pathways. Here, we present data related to the creation and in vitro use of new two-part MNPs consisting of magnetic gold-iron alloy cores which have streptavidin binding sites, and are coated with biotinylated etoposide. Etoposide was chosen due to its previous use in the CSF and ease of biotinylation. Etoposide magnetic nanoparticles (“Etop-MNPs”) were characterized by several different methods, and moved at a distance by surface-walking of MNP clusters, which occurs in response to a rotating permanent magnet. Human cell lines including D283 (medulloblastoma), U138 (glioblastoma), and H2122 (lung adenocarcinoma) were treated with direct application of Etop-MNPs (and control particles), and after remote particle movement. Cell viability was determined by MTT assay and trypan blue exclusion. Results indicated that the biotinylated etoposide was successfully bound to the base MNPs, with the hybrid particle attaining a maximum velocity of 0.13 ± 0.018 cm/sec. Etop-MNPs killed cancer cells in a dose-dependent fashion, with 50 ± 6.8% cell killing of D283 cells (for example) with 24 h of treatment after remote targeting. U138 and H2122 cells were found to be even more susceptible to the killing effect of Etop-MNPs than D283 cells. These findings indicate that the novel Etop-MNPs have a cytotoxic effect, and can be moved relatively rapidly at physiologic distances, using a rotating magnet. While further testing is needed, intrathecal administration of Etop-MNPs holds promise for magnetically-enhanced eradication of cancer cells distributed within CSF pathways, particularly if given early in the course of the disease.

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“…More than a century later, this procedure for obtaining cerebrospinal fluid (CSF) directly, at the lumbar level, has become an essential diagnostic tool routinely used in everyday clinical practice [2] . LP is used for diagnosis, but also for therapeutic purposes, for volume depletion or the injection of drugs into the subarachnoid space [3] . Thousands of LPs are undoubtedly performed around the world daily.…”

Section: Introductionmentioning

confidence: 99%

Who Performs Lumbar Puncture, How Many Do They Perform, How and Why? A Retrospective Study of 6,594 Cases

Moisset

Ruet²,

Brochet

et al. 2016

Eur Neurol

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Background: The number and indications of lumbar punctures (LPs) performed nowadays are unknown. The primary aim of this work was to report the number of LPs performed in each of the departments of 2 French university hospitals, their indications and the prevalence of atraumatic spinal needles used. Methods: We carried out a retrospective study of all the LPs performed in 2014. The clinical department in which the intervention was performed and the final diagnosis was made from the Medical Information Department. The type of needles (cutting or atraumatic) used during the study period was also available. Results: In 2014, 6,594 LPs were performed. Overall, 80% were performed for diagnostic purposes. Twenty percent of these LPs were performed in the Neurology Department and were usually carried out at routine check-ups. Overall, atraumatic needles were used in 8.0% of cases. Overall, 1.4 LPs per 100 hospital stays were performed and 0.8 LP for 100 Emergency department admissions. Conclusion: LP is a routine procedure for many clinicians and although neurologists perform the largest number of LPs, they are doing only one fifth of all procedures. Atraumatic needles are underused.

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Intra-CSF administration of chemotherapy medications

Cited by 18 publications

References 94 publications

Transependymal Cerebrospinal Fluid Flow: Opportunity for Drug Delivery?

Transependymal Cerebrospinal Fluid Flow: Opportunity for Drug Delivery?

Etoposide-Bound Magnetic Nanoparticles Designed for Remote Targeting of Cancer Cells Disseminated Within Cerebrospinal Fluid Pathways

Who Performs Lumbar Puncture, How Many Do They Perform, How and Why? A Retrospective Study of 6,594 Cases

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