Variables affecting convection-enhanced delivery to the striatum: a systematic examination of rate of infusion, cannula size, infusate concentration, and tissue—cannula sealing time

Chen, Mike Y.; Lonser, Russell R.; Morrison, Paul F.; Governale, Lance S.; Oldfield, Edward H.

doi:10.3171/jns.1999.90.2.0315

Cited by 299 publications

(213 citation statements)

References 16 publications

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“…These devices can lead to reflux, or backflow, along the outside of the catheter and unpredictable drug distributions [39]. The amount of reflux decreases as the diameter of the device is made smaller [29,7]. In a previous study we showed that a microfabricated device with cross-sectional area of 100 μm × 100 μm mitigates backflow at relatively high flow rates [31].…”

Section: Discussionmentioning

confidence: 99%

Dilation and degradation of the brain extracellular matrix enhances penetration of infused polymer nanoparticles

et al. 2007

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This study investigates methods of manipulating the brain extracellular matrix (ECM) to enhance the penetration of nanoparticle drug carriers in convection-enhanced delivery (CED). A probe was fabricated with two independent microfluidic channels to infuse, either simultaneously or sequentially, nanoparticles and ECM-modifying agents. Infusions were performed in the striatum of the normal rat brain. Monodisperse polystyrene particles with a diameter of 54 nm were used as a model nanoparticle system. Because the size of these particles is comparable to the effective pore size of the ECM, their transport may be significantly hindered compared with the transport of low molecular weight molecules. To enhance the transport of the infused nanoparticles, we attempted to increase the effective pore size of the ECM by two methods: dilating the extracellular space and degrading selected constituents of the ECM. Two methods of dilating the extracellular space were investigated: co-infusion of nanoparticles and a hyperosmolar solution of mannitol, and pre-infusion of an isotonic buffer solution followed by infusion of nanoparticles. These treatments resulted in an increase in the nanoparticle distribution volume of 50% and 123%, respectively. To degrade hyaluronan, a primary structural component of the brain ECM, a pre-infusion of hyaluronidase (20,000 U/mL) was followed after 30 min by infusion of nanoparticles. This treatment resulted in an increase in the nanoparticle distribution of 64%. Our results suggest that both dilation and enzymatic digestion can be incorporated into CED protocols to enhance nanoparticle penetration.

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Section: Discussionmentioning

confidence: 99%

Dilation and degradation of the brain extracellular matrix enhances penetration of infused polymer nanoparticles

et al. 2007

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“…Fluctuation in this V d :V i linearity correlate with failure of infusate distribution as demonstrated previously by us in NHPs (Varenika et al, 2008) and in a clinical brainstem infusion case, where nonlinearity was caused by leakage into the surrounding ventricular space . Along with infusate leakage , other factors such as infusion rate and cannula size have been shown to affect the efficacy of CED (Chen et al, 1999). It should also be noted that V d :V i ratios are also affected by the composition of various anatomical regions, perhaps dependent on whether these regions are structurally composed of mainly gray or white matter (Szerlip et al, 2007).…”

Section: Aguilar Salegio Et Almentioning

confidence: 99%

Magnetic Resonance Imaging-Guided Delivery of Adeno-Associated Virus Type 2 to the Primate Brain for the Treatment of Lysosomal Storage Disorders

et al. 2010

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Gene replacement therapy for the neurological deficits caused by lysosomal storage disorders, such as in Niemann-Pick disease type A, will require widespread expression of efficacious levels of acid sphingomyelinase (ASM) in the infant human brain. At present there is no treatment available for this devastating pediatric condition. This is partly because of inherent constraints associated with the efficient delivery of therapeutic agents into the CNS of higher order models. In this study we used an adeno-associated virus type 2 (AAV2) vector encoding human acid sphingomyelinase tagged with a viral hemagglutinin epitope (AAV2-hASM-HA) to transduce highly interconnected CNS regions such as the brainstem and thalamus. On the basis of our data showing global cortical expression of a secreted reporter after thalamic delivery in nonhuman primates (NHPs), we set out to investigate whether such widespread expression could be enhanced after brainstem infusion. To maximize delivery of the therapeutic transgene throughout the CNS, we combined a single brainstem infusion with bilateral thalamic infusions in naive NHPs. We found that enzymatic augmentation in brainstem, thalamic, cortical, as well subcortical areas provided convincing evidence that much of the large NHP brain can be transduced with as few as three injection sites.

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“…31 Furthermore, CED within the defined infusion measurements does not produce cerebral edema or measurable increases in intracranial pressure. 32 For CED, one or more catheters are generally stereotactically implanted through a burr hole into or adjacent to either the enhancing portion of a tumor and/or the nonenhancing infiltrative surrounding tissue. A pressuredriven flow of the drug is achieved via an infusion pump, and the agent is directly infused into the target tissue at a predetermined concentration, rate, and duration.…”

Section: Convection-enhanced Deliverymentioning

confidence: 99%

Novel Drug Delivery Strategies in Neuro-Oncology

2009

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Summary: Treatment of malignant gliomas represents one of the most formidable challenges in oncology. Despite treatment with surgery, radiation therapy, and chemotherapy, the prognosis remains poor, particularly for glioblastoma, which has a median survival of 12 to 15 months. An important impediment to finding effective treatments for malignant gliomas is the presence of the blood brain barrier, which serves to prevent delivery of potentially active therapeutic compounds. Multiple efforts are focused on developing strategies to effectively deliver active drugs to brain tumor cells. Blood brain barrier disruption and convectionenhanced delivery have emerged as leading investigational delivery techniques for the treatment of malignant brain tumors. Clinical trials using these methods have been completed, with mixed results, and several more are being initiated. In this review, we describe the clinically available methods used to circumvent the blood brain barrier and summarize the results to date of ongoing and completed clinical trials. Key Words: Convection-enhanced delivery, blood brain barrier disruption, brain neoplasm, drug delivery system.

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Variables affecting convection-enhanced delivery to the striatum: a systematic examination of rate of infusion, cannula size, infusate concentration, and tissue—cannula sealing time

Cited by 299 publications

References 16 publications

Dilation and degradation of the brain extracellular matrix enhances penetration of infused polymer nanoparticles

Dilation and degradation of the brain extracellular matrix enhances penetration of infused polymer nanoparticles

Magnetic Resonance Imaging-Guided Delivery of Adeno-Associated Virus Type 2 to the Primate Brain for the Treatment of Lysosomal Storage Disorders

Novel Drug Delivery Strategies in Neuro-Oncology

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