Experimental Manipulation of the Blood-Brain ”and Blood-Retinal Barriers

Greenwood, John

doi:10.1007/978-3-642-76894-1_19

Cited by 17 publications

(9 citation statements)

References 127 publications

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“…Several endogenous compounds including neurotransmitters, hormones, and inflammatory mediators can readily open the tight junctions of the BBB. 5 Disruption of the BBB has also been seen in physiological states, such as hypertension, hypoxia, or ischemia. Hypertonic substances including mannitol and biologically active agents, such as bradykinin and angiotensin peptides have also shown to disrupt the BBB.…”

Section: Barrier Disruption Strategies For Enhancing Drug 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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Section: Barrier Disruption Strategies For Enhancing Drug Deliverymentioning

confidence: 99%

Novel Drug Delivery Strategies in Neuro-Oncology

2009

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“…Most of these methods are characterized, for instance, by osmotic BBB opening 1,6 or by the use of biologically active agents (e.g., histamine, serotonin, substance P, free oxygen radicals, nitric oxide, calcium entry blocker, bradykinin, 5-hydroxytryptamine, cytokines, metalloproteinases, endothelin-1, etc.). 7,8 The use of so-called drug carriers, such as liposomes 9 and nanoparticles, 10,11 for targeted drug delivery has been examined. One of the main problems in the targeted drug delivery is the rapid opsonization and uptake of the injected carrier systems by the reticuloendothelial system, by macrophages in liver and spleen.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle Technology for Delivery of Drugs Across the Blood–Brain Barrier

Schröeder¹,

Sommerfeld²,

Ulrich³

et al. 1998

Journal of Pharmaceutical Sciences

262

131

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The Leu-enkephalin dalargin and the Met-enkephalin kyotorphin normally do not cross the blood-brain barrier (BBB) when given systemically. To transport these neuropeptides across the BBB they were adsorbed onto the surface of poly(butylcyanoacrylate) nanoparticles (NPs) and the NPs were coated with polysorbate 80. Central analgesia was measured by the hot plate test in mice. The antidepressant amitriptyline, which normally penetrates the BBB, was used to examine the versatility of the NP method. The concentration of amitriptyline in serum and brain of mice was determined by a gas chromatographic method. Furthermore, NPs were fabricated with different stabilizers. After the adsorption of the peptides on polysorbate 85-stabilized NPs, analgesia was noted after intravenous application when NPs were not coated. The amitriptyline level was significantly enhanced in brain when the substance was adsorbed onto the NP and coated or when the particles were stabilized with polysorbate 85.

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“…There are a number of pathological episodes, such as traumatic brain injury, stroke, epilepsy and the active phase of multiple sclerosis, during which the permeability to these solutes increases, observed as BBB disruption. A number of inflammatory mediators including histamine are released during these conditions (Greenwood, 1992) and have been suggested to contribute to the disruption of the barrier. The principal source of histamine to interact with cerebral endothelium is probably found abluminally in histaminergic neurons.…”

mentioning

confidence: 99%

Regulation of cerebral microvascular permeability by histamine in the anaesthetized rat

Sarker

Easton

Fraser

1998

The Journal of Physiology

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The permeability response of slightly leaky pial venular capillaries to histamine was investigated using the single microvessel occlusion technique. Histamine dose‐response curves showed that concentrations between 5 nm and 5 μM increased permeability, while concentrations from 50 μM to 5 mM reduced it. The H2 receptor antagonist cimetidine (2 μM) blocked the effects of lower concentrations of histamine, while the H1 receptor antagonist mepyramine (3 nM) blocked those of higher concentrations of histamine. The effects of lower doses of histamine were mimicked by the H2 receptor agonist dimaprit, and the effects of higher doses of histamine were mimicked by the H1 receptor agonist α‐2‐(2‐aminoethyl)pyridine (AEP). Low concentrations of histamine, which normally increase the permeability of Lucifer Yellow (PLY), reduced it when co‐applied with the phosphodiesterase 4 (PDE4) inhibitor rolipram. Rolipram also potentiated the response to AEP, but had no effect on that to dimaprit. The effects of dimaprit were blocked by reducing extracellular Ca2+ from 2.5 mM to nominally Ca2+ free, or by applying the calcium entry blocker SKF 96365.

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Experimental Manipulation of the Blood-Brain ”and Blood-Retinal Barriers

Cited by 17 publications

References 127 publications

Novel Drug Delivery Strategies in Neuro-Oncology

Novel Drug Delivery Strategies in Neuro-Oncology

Nanoparticle Technology for Delivery of Drugs Across the Blood–Brain Barrier

Regulation of cerebral microvascular permeability by histamine in the anaesthetized rat

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