Super selective intra-arterial cerebral infusion of modern chemotherapeutics after blood–brain barrier disruption: where are we now, and where we are going

D’Amico, Randy S.; Khatri, Deepak; Reichman, Noah; Patel, Nitesh V; Wong, Tamika; Fralin, Sherese; Li, Mona; Ellis, Jason A.; Ortiz, Rafael; Langer, David; Boockvar, John A.

doi:10.1007/s11060-020-03435-6

Cited by 51 publications

(90 citation statements)

References 113 publications

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“…The addition of an infusion of a B2R or dual B1R/B2R agonist prior to chemotherapy infusion would represent a minor modification to our procedure. As recently pointed out by D’Amico et al [ 56 ], i.c. delivery in conjunction with BBB disruption confers advantages notably in allowing delivery of a variety of agents directly to the targeted region, at more effective doses, while potentially sparing the body of systemic side effects.…”

Section: Discussionmentioning

confidence: 69%

Pharmacological Modulation of Blood–Brain Barrier Permeability by Kinin Analogs in Normal and Pathologic Conditions

et al. 2020

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The blood–brain barrier (BBB) is a major obstacle to the development of effective diagnostics and therapeutics for brain cancers and other central nervous system diseases. Peptide agonist analogs of kinin B1 and B2 receptors, acting as BBB permeabilizers, have been utilized to overcome this barrier. The purpose of the study was to provide new insights for the potential utility of kinin analogs as brain drug delivery adjuvants. In vivo imaging studies were conducted in various animal models (primary/secondary brain cancers, late radiation-induced brain injury) to quantify BBB permeability in response to kinin agonist administrations. Results showed that kinin B1 (B1R) and B2 receptors (B2R) agonists increase the BBB penetration of chemotherapeutic doxorubicin to glioma sites, with additive effects when applied in combination. B2R agonist also enabled extravasation of high-molecular-weight fluorescent dextrans (155 kDa and 2 MDa) in brains of normal mice. Moreover, a systemic single dose of B2R agonist did not increase the incidence of metastatic brain tumors originating from circulating breast cancer cells. Lastly, B2R agonist promoted the selective delivery of co-injected diagnostic MRI agent Magnevist in irradiated brain areas, depicting increased vascular B2R expression. Altogether, our findings suggest additional evidence for using kinin analogs to facilitate specific access of drugs to the brain.

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Section: Discussionmentioning

confidence: 69%

Pharmacological Modulation of Blood–Brain Barrier Permeability by Kinin Analogs in Normal and Pathologic Conditions

et al. 2020

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“… 47 Thus, BBB is the main barrier to the transport of drugs from the systemic circulation to the CNS, decreasing bioavailability in the brain and leading to unsuccessful treatment of neurodegenerative diseases. 48 Various strategies that enhance the passage of drugs across the BBB and its delivery into the brain have been studied, 47 , 49 , 50 although with limited success.…”

Section: Treatment Of Alzheimer’s Diseasementioning

confidence: 99%

Improving Drug Delivery for Alzheimer’s Disease Through Nose-to-Brain Delivery Using Nanoemulsions, Nanostructured Lipid Carriers (NLC) and in situ Hydrogels

Cunha¹,

Forbes²,

Lobo³

et al. 2021

IJN

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Current treatments for Alzheimer’s disease (AD) attenuate the progression of symptoms and aim to improve the patient’s quality of life. Licensed medicines are mostly for oral administration and are limited by the difficulty in crossing the blood–brain barrier (BBB). Here in, the nasal route has been explored as an alternative pathway that allows drugs to be directly delivered to the brain via the nasal cavity. However, clearance mechanisms in the nasal cavity impair the delivery of drugs to the brain and limit their bioavailability. To optimize nose-to-brain delivery, formulations of lipid-based nanosystems, namely nanoemulsions and nanostructured lipid carriers (NLC), formulated in situ gelling hydrogels have been proposed as approaches for nose-to-brain delivery. These formulations possess characteristics that facilitate drug transport directly to the brain, minimizing side effects and maximizing therapeutic benefits. It has been recommended that the manufacture of these drug delivery systems follows the quality by design (QbD) approach based on nasal administration requirements. This review provides an insight into the current knowledge of the AD, highlighting the need for an effective drug delivery to the brain. Considering the mounting interest in the use of nanoemulsions and NLC for nose-to-brain delivery, a description of drug transport pathways in the nasal cavity and the application of these nanosystems and their in situ hydrogels through the intranasal route are presented. Relevant preclinical studies are summarised, and the future prospects for the use of lipid-based nanosystems in the treatment of AD are emphasized.

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“…Furthermore, the main limitation lies in the need to overcome the BBB, the reason why the administration route is pivotal. Several studies have proposed innovative methods, such as the implanted intracerebral convection-enhanced deliveries or the superselective intra-arterial cerebral infusion [156][157][158][159][160][161]. The intra-arterial administration is additionally facilitated by the previous destruction of BBB, carried out through osmotic agents, hypertonic solutions and mannitol, or ultrasounds [156,162,163].…”

Section: Limitations and Future Perspectivesmentioning

confidence: 99%

Against the Resilience of High-Grade Gliomas: The Immunotherapeutic Approach (Part I)

Lucifero

Luzzi

2021

Brain Sciences

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The resilience of high-grade gliomas (HGGs) against conventional chemotherapies is due to their heterogeneous genetic landscape, adaptive phenotypic changes, and immune escape mechanisms. Innovative immunotherapies have been developed to counteract the immunosuppressive capability of gliomas. Nevertheless, further research is needed to assess the efficacy of the immuno-based approach. The aim of this study is to review the newest immunotherapeutic approaches for glioma, focusing on the drug types, mechanisms of action, clinical pieces of evidence, and future challenges. A PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis)-based literature search was performed on PubMed/Medline and ClinicalTrials.gov databases using the keywords “active/adoptive immunotherapy,” “monoclonal antibodies,” “vaccine,” and “engineered T cell.”, combined with “malignant brain tumor”, “high-grade glioma.” Only articles written in English published in the last 10 years were selected, filtered based on best relevance. Active immunotherapies include systemic temozolomide, monoclonal antibodies, and vaccines. In several preclinical and clinical trials, adoptive immunotherapies, including T, natural killer, and natural killer T engineered cells, have been shown to be potential treatment options for relapsing gliomas. Systemic temozolomide is considered the backbone for newly diagnosed HGGs. Bevacizumab and rindopepimut are promising second-line treatments. Adoptive immunotherapies have been proven for relapsing tumors, but further evidence is needed.

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Super selective intra-arterial cerebral infusion of modern chemotherapeutics after blood–brain barrier disruption: where are we now, and where we are going

Cited by 51 publications

References 113 publications

Pharmacological Modulation of Blood–Brain Barrier Permeability by Kinin Analogs in Normal and Pathologic Conditions

Pharmacological Modulation of Blood–Brain Barrier Permeability by Kinin Analogs in Normal and Pathologic Conditions

Improving Drug Delivery for Alzheimer’s Disease Through Nose-to-Brain Delivery Using Nanoemulsions, Nanostructured Lipid Carriers (NLC) and in situ Hydrogels

Against the Resilience of High-Grade Gliomas: The Immunotherapeutic Approach (Part I)

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