Novel delivery methods bypassing the blood-brain and blood-tumor barriers

Abstract

<jats:p>Glioblastoma (GBM) is the most common primary brain tumor and carries a grave prognosis. Despite years of research investigating potentially new therapies for GBM, the median survival rate of individuals with this disease has remained fairly stagnant. Delivery of drugs to the tumor site is hampered by various barriers posed by the GBM pathological process and by the complex physiology of the blood-brain and blood–cerebrospinal fluid barriers. These anatomical and physiological barriers serve as a natural protection for the brain and preserve brain homeostasis, but they also have significantly limited the reach of intraparenchymal treatments in patients with GBM.</jats:p> <jats:p>In this article, the authors review the functional capabilities of the physical and physiological barriers that impede chemotherapy for GBM, with a specific focus on the pathological alterations of the blood-brain barrier (BBB) in this disease. They also provide an overview of current and future methods for circumventing these barriers in therapeutic interventions. Although ongoing research has yielded some potential options for future GBM therapies, delivery of chemotherapy medications across the BBB remains elusive and has limited the efficacy of these medications.</jats:p>

Bradykinin increased the permeability of BTB via NOS/NO/ZONAB-mediating down-regulation of claudin-5 and occludin

“…Treatments for glioma include surgical resection followed by radiotherapy and chemotherapy which is assuming an increasingly important role in the treatment [2]. However, it has severely affected the chemotherapeutic effect that blood-tumor barrier (BTB) has restricted the anti-tumor drug from entering the CNS [3]. Studies demonstrated small dose of bradykinin (BK) can selectively open BTB without affecting the permeability of normal brain tissue [4].…”

Fluorescein sodium-guided surgery of malignant brain tumors: history, current concepts, and future projects

“…An intact BBB defends the central nervous system (CNS) from intrusion of foreign substances and maintains CNS homeostasis, including ionic and fluid balances (18). Abbott et al could show that the balance of this microenvironment is disrupted by cerebral lesions such as gliomas.…”

New therapeutic strategies regarding endovascular treatment of glioblastoma, the role of the blood–brain barrier and new ways to bypass it

“…Malignant brain tumors, including GBM, alter the normal BBB by secreting humoral factors such as bradykinin, histamine, serotonin, and platelet-activating factor,14 thereby deregulating vascular permeability, producing hypoxia-induced changes, and modifying carrier-mediated efflux 13. The alterations in vascular permeability are related to diffuse upregulation and redistribution of aquaporin 4 on astrocyte membranes, decreased claudin and occludin expression within the tight junction complex, basal membrane disruption, and leaky neovascularization 13.…”