Nanoneurology - Drug Delivery across the Brain Protective Barriers

Fymat, A. L.

doi:10.15406/jnmr.2017.05.00105

Cited by 6 publications

(7 citation statements)

References 7 publications

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“…Primary tumors: Of unclear cause, primary tumors can start from normal brain cells in the cerebral white matter then grow quickly, infiltrate small areas of the tumor, spread to other areas, and can become very large before producing symptoms (this is consistent with our current understanding of cancer as braided in our genome [15][16][17][18][19][20][21].…”

Section: On Glioblastoma Multiformmentioning

confidence: 52%

“…The niche protects these cells against therapy by maintaining a relatively hypoxic environment. A biomarker for cells in GBs that exhibits cancer stem cell properties (the transcription factor HES3) has been shown to regulate their number when placed in culture [19][20][21]. Figures 1 & 2 provide a schematic illustration of Glioblastoma and its surgical resection.…”

Section: Introductionmentioning

confidence: 99%

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Surgical and Non-Surgical Management and Treatment of Glioblastoma: I. Primary Tumors

Fymat¹

2017

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Glioblastoma, the most common primary brain tumor in adults, remains an unmet need in oncology. Its management and treatment begin with an understanding of this tumor's morphology, biological types, risk factors, and prognosis. The various surgical and non-surgical modalities devised so far for primary tumors and their metastases are presented and discussed either singly or in combination. For each such therapy, the treatment results obtained in clinical trials and other reported practices are also summarized and discussed. Historically, chemotherapy has provided little durable benefit with tumors recurring within several months, even in the case of more accessible tumors located outside the brain, let alone within the brain behind its protective barriers. More effective therapies involving other options are required either in isolation or more likely in combination. Of these other options, the following are considered here at some length: surgery, conformal radiotherapy, boron neutron therapy, intensity modulated proton beam therapy, antiangiogenic therapy, alternating electric field therapy, immunotherapy without neglecting palliative therapies. A companion paper will discuss the important case of recurring tumors.

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Section: On Glioblastoma Multiformmentioning

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Surgical and Non-Surgical Management and Treatment of Glioblastoma: I. Primary Tumors

Fymat¹

2017

OAJS

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“…d) The inner CSF-brain barrier formed by strap junctions between the neuro-ependymal cells lining the ventricular surfaces. It is present only in early development and absent in the adult [18,19]. The above barriers and the blood retinal barrier (not studied here) are parts of a whole realm of barriers.…”

Section: C)mentioning

confidence: 97%

“…As a result, chemotherapy has historically provided little durable benefit as the tumors recur within several months even in the case of the more accessible tumors that are located outside the brain. For brain tumors, the access is even more challenging because of the presence of the brain protective barriers (BPBs), chiefly the BBB, compounding the difficulties [18,19].…”

Section: C)mentioning

confidence: 99%

Antiangiogenic Targeting of Early Developing Glioblastoma Behind a Weakened Blood Brain Barrier

Fymat

2017

JTMP

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Glioblastoma is the most devastating and most common brain tumor in adults. According to the (US) National Cancer Institute (NCI), there were an estimated 23,380 new cases and 14,320 deaths from brain and other nervous system cancers in the US in 2014. I will emphasize here therapy using Antiangiogenic agents, particularly in the case of tumors in their early development, taking advantage of the associated weakening of the blood brain barrier. As a prelude to this new development, I review below the current lines of treatment for Glioblastoma, making a distinction between primary and secondary tumors, and recurrent tumors. I will also review the brain protective barriers, chiefly the blood brain barrier which, as its name implies, is the primary impediment for the delivery of therapeutic drugs. I will also analyze the drug targeting difficulties and the mechanisms for drug targeting.

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“…In blue color: light: the memory and olfactory area; medium: not specified; and dark: the auditory area). In green color: the visual area [1].…”

Section: Function Of the Blood Brain Barriermentioning

confidence: 99%

Therapeutics Delivery Behind, Through and Beyond the Blood Brain Barrier

Fymat¹

2017

OAJS

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The brain has five protective barriers (BPB) that hinder the delivery of therapeutic drugs. They describe the five main interfaces between the central nervous system (CNS) and the periphery. These include: the blood brain barrier (BBB) that extends down the spinal cord; the brain cerebrospinal fluid (CSF) barrier (B[CSF]B]; the brain-inner CSF barrier (B[iCSF] b); the brain-outer CSF barrier B[oCSF]B; and the brain retinal barrier (B[R]B). We shall mostly be concerned with the BBB and use the denomination BBB as if it applied (though erroneously) to all BPBs.All interfaces are formed by tight junctions. In the case of the BBB, the tight junctions are between the endothelial cells of the primary vasculature with primary manifestation being the impermeability of the capillary wall due to the presence of the junctions and a low endocytic activity. For B [CSF] B, the tight junctions are between the epithelial cells of the choroid plexus. In the case of the B[iCSF]B, the junctions are between the neuroependymal cells lining the ventricular surfaces. As for B[oCSF] B, the junctions are between endothelial cells of the arachnoid vessels (the pia arachnoid). The BPBs hinder the delivery of most pharmaceuticals (diagnostic, therapeutic agents) to the brain. a. Some brain diseases and their effects on the Blood Brain BarrierThere are approximately 400 neural disorders some which being cognitive. Table 1 below shows only some of these, specifically those due to a failure of the BBB as a result of disruption, breakdown, opening, failure, damage (inflammatory) and increased permeability, but also some diseases for which the effect on the BBB is still unknown.. Neurological disorders are

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Nanoneurology - Drug Delivery across the Brain Protective Barriers

Cited by 6 publications

References 7 publications

Surgical and Non-Surgical Management and Treatment of Glioblastoma: I. Primary Tumors

Surgical and Non-Surgical Management and Treatment of Glioblastoma: I. Primary Tumors

Antiangiogenic Targeting of Early Developing Glioblastoma Behind a Weakened Blood Brain Barrier

Therapeutics Delivery Behind, Through and Beyond the Blood Brain Barrier

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