PDE5 Inhibitors Offer Novel Mechanisms in Combination and Solo Cancer Therapy

Lyday, Robert W.; Etters, Abigail M.; Kim, Christopher; Magana, Fernando Alcantar; Pontipiedra, Gabriel M.; Singh, Navjot; Kadavakollu, Samuel

doi:10.2174/1573394713666170731152749

Cited by 4 publications

(3 citation statements)

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“…The increased fenestration or loss of tight junctions between endothelial cells characterizes these vessels. Furthermore, these new vascular endothelial cells are overexpressing caveolae, have increased pinocytotic activity, and are rich in mitochondria [31,32,33]. Nevertheless, the BTB presents continuous fenestrated vessels with a defined pore size, which precludes the entrance of hydrophilic compounds and large molecules to the brain tumor [30,34].…”

Section: Blood-brain and Blood-tumor Barriers (Bbb/btb)mentioning

confidence: 99%

Nasal Drug Delivery of Anticancer Drugs for the Treatment of Glioblastoma: Preclinical and Clinical Trials

et al. 2019

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Glioblastoma (GBM) is the most lethal form of brain tumor, being characterized by the rapid growth and invasion of the surrounding tissue. The current standard treatment for glioblastoma is surgery, followed by radiotherapy and concurrent chemotherapy, typically with temozolomide. Although extensive research has been carried out over the past years to develop a more effective therapeutic strategy for the treatment of GBM, efforts have not provided major improvements in terms of the overall survival of patients. Consequently, new therapeutic approaches are urgently needed. Overcoming the blood–brain barrier (BBB) is a major challenge in the development of therapies for central nervous system (CNS) disorders. In this context, the intranasal route of drug administration has been proposed as a non-invasive alternative route for directly targeting the CNS. This route of drug administration bypasses the BBB and reduces the systemic side effects. Recently, several formulations have been developed for further enhancing nose-to-brain transport, mainly with the use of nano-sized and nanostructured drug delivery systems. The focus of this review is to provide an overview of the strategies that have been developed for delivering anticancer compounds for the treatment of GBM while using nasal administration. In particular, the specific properties of nanomedicines proposed for nose-to-brain delivery will be critically evaluated. The preclinical and clinical data considered supporting the idea that nasal delivery of anticancer drugs may represent a breakthrough advancement in the fight against GBM.

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Section: Blood-brain and Blood-tumor Barriers (Bbb/btb)mentioning

confidence: 99%

Nasal Drug Delivery of Anticancer Drugs for the Treatment of Glioblastoma: Preclinical and Clinical Trials

et al. 2019

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“…The brain tumour barrier is a protective layer formed consequent of an anatomical and physiological alteration of BBB, because of the regeneration of new blood vessels that oxygenate the growing tumour through the loosed-tight junctions of the endothelial cells. These newly formed vessels had some tiny pores that prevented the permeation molecules, including hydrophilic ones [43][44][45]. The affected tissue triggers the release of Vascular Endothelial Growth Factor (VEGF) that facilitated the neoangiogenesis system allowing the tumour to metastases throughout the brain.…”

Section: Brain Tumour Barrier (Btb)mentioning

confidence: 99%

Nose-to-Brain Delivery, a Route of Choice for Targeting Brain Tumors

Shehu

Islam

Singh³

2021

Int J App Pharm

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Brain tumours are the most lethal type of cancer, which is difficult to manage due to the inherent suboptimal bioavailability of the chemotherapy agent at tumour sites, consequent of high levels of protection of physiological blood-brain barrier (BBB), blood tumour barrier (BTB) and blood-cerebrospinal fluid barrier (CSF). Improving the permeability of these barriers would enhance the disease's clinical prognosis and promote patients' quality of life. To this end, scientists have conducted several studies to determine the most suitable route for CNS delivery. Most of which show that the nose-to-brain is proposed to be the most convenient, efficacious and clinically beneficial non-invasive means of delivering chemotherapeutic agents directly to the brain. Therefore, this study compares the therapeutic benefits of intranasal and other conventional brain delivery systems and further evaluates the clinical benefits of using different nanocarriers for brain tumour targeting. However, we surveyed the literature by conducting an in-depth search of the research keywords and their combinations in recognized scientific databases, primarily Science Direct, PubMed, Google Scholar, and Research Gate. Our findings have shown that the nose-to-brain delivery of chemotherapeutics is a breakthrough in bypassing the effects of BBB, BTB, and CSF barriers, improving the delivery of drugs to the brain for specific tumour targeting with desired clinical prognosis.

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“…These vessels are characterized by increased fenestration or loss of tight junctions between endothelial cells. Furthermore vascular endothelial cells are overexpressing caveolae, have increased pinocytotic activity and are rich in mitochondria [31,32,33]. Notwhitstanding, BTB presents continuous fenestrated vessels with a defined pore size, precluding the entrance in brain tumor of hydrophilic compounds and large molecules [30,34].…”

Section: Blood-brain and Blood-tumor Barriers (Bbb/btb)mentioning

confidence: 99%

Nasal Drug Delivery of Anticancer Drugs for the Treatment of Glioblastoma: Preclinical and Clinical Trials

Bruinsmann¹,

Vaz²,

Alves³

et al. 2019

Preprint

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Glioblastoma (GBM) is the most lethal form of brain tumor, characterized by rapid growth and surrounding tissue invasion. The current standard treatment is surgery followed by radiotherapy, and concurrent chemotherapy, typically with temozolomide. Although extensive research has been performed over the past years to develop an effective therapeutic strategy for the treatment of GBM, efforts have not provided major improvements in the overall survival of patients with GBM. Thus, new therapeutic approaches are urgently needed. A major challenge in the development of therapies for central nervous system (CNS) disorders is overcoming the blood–brain barrier (BBB). In this context, the intranasal (IN) route of drug administration has been proposed as a non-invasive alternative route to directly targeting the CNS. In fact, this route of drug administration may bypass the blood-brain barrier and reduce systemic side effects. Recently, formulations have been developed to further enhance nose-to-brain transport, mainly with the use of nano-sized and nanostructured drug delivery systems. The focus of this review will be on the strategies developed to deliver a number of anticancer compounds for the treatment of GBM using the nasal administration. In particular, the specific properties of nanomedicines proposed for the nose-to-brain delivery will be critically evaluated. The number of preclinical and clinical data reviewed support the idea that nasal delivery of anticancer drugs might represent a breakthrough advancement in the fight against GBM.

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PDE5 Inhibitors Offer Novel Mechanisms in Combination and Solo Cancer Therapy

Cited by 4 publications

References 0 publications

Nasal Drug Delivery of Anticancer Drugs for the Treatment of Glioblastoma: Preclinical and Clinical Trials

Nasal Drug Delivery of Anticancer Drugs for the Treatment of Glioblastoma: Preclinical and Clinical Trials

Nose-to-Brain Delivery, a Route of Choice for Targeting Brain Tumors

Nasal Drug Delivery of Anticancer Drugs for the Treatment of Glioblastoma: Preclinical and Clinical Trials

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