scholarly journals Cancer Cell Membrane-Coated Nanosuspensions for Enhanced Chemotherapeutic Treatment of Glioma

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 5103
Author(s):  
Yueyue Fan ◽  
Wenyan Hao ◽  
Yuexin Cui ◽  
Mengyu Chen ◽  
Xiaoyang Chu ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Blood Brain Barrier ◽  
Cancer Cell ◽  
Drug Transport ◽  
Immune Escape ◽  
Drug Loading ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Brain

Effective intracerebral delivery is key for glioma treatment. However, the drug delivery system within the brain is largely limited by its own adverse physical and chemical properties, low targeting efficiency, the blood–brain barrier and the blood–brain tumor barrier. Herein, we developed a simple, safe and efficient biomimetic nanosuspension. The C6 cell membrane (CCM) was utilized to camouflaged the 10-hydroxycamptothecin nanosuspension (HCPT-NS) in order to obtain HCPT-NS/CCM. Through the use of immune escape and homotypic binding of the cancer cell membrane, HCPT-NS/CCM was able to penetrate the blood–brain barrier and target tumors. The HCPT-NS is only comprised of drugs, as well as a small amount of stabilizers that are characterized by a simple preparation method and high drug loading. Similarly, the HCPT-NS/CCM is able to achieve targeted treatment of glioma without any ligand modification, which leads it to be stable and efficient. Cellular uptake and in vivo imaging experiments demonstrated that HCPT-NS/CCM is able to effectively cross the blood–brain barrier and was concentrated at the glioma site due to the natural homing pathway. Our results reveal that the glioma cancer cell membrane is able to promote drug transport into the brain and enter the tumor via a homologous targeting mechanism.

Drug transport to the brain: comparison between in vitro and in vivo models of the blood-brain barrier

1995 ◽  
Vol 3 (6) ◽  
pp. 357-365 ◽  
Author(s):  
M.P. Dehouck ◽  
B. Dehouck ◽  
C. Schluep ◽  
M. Lemaire ◽  
R. Cecchelli
Keyword(s):  
Blood Brain Barrier ◽  
Drug Transport ◽  
Brain Barrier ◽  
In Vivo Models ◽  
Blood Brain ◽  
The Brain

Modulators of Blood-Brain Barrier (BBB) Permeability: In Vitro and in Vivo Drug Transport to the Brain

2001 ◽  
pp. 83-97
Author(s):  
A. G. De Boer ◽  
P. J. Gaillard ◽  
I. C. J. Van Der Sandt ◽  
E. C. M. De Lange ◽  
D. D. Breimer
Keyword(s):  
Blood Brain Barrier ◽  
Drug Transport ◽  
Brain Barrier ◽  
Blood Brain ◽  
Bbb Permeability ◽  
The Brain

scholarly journals The Potential Roles of Blood–Brain Barrier and Blood–Cerebrospinal Fluid Barrier in Maintaining Brain Manganese Homeostasis

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1833
Author(s):  
Shannon Morgan McCabe ◽  
Ningning Zhao
Keyword(s):  
Cerebrospinal Fluid ◽  
Blood Brain Barrier ◽  
Blood Circulation ◽  
Critical Role ◽  
Systemic Circulation ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Brain

Manganese (Mn) is a trace nutrient necessary for life but becomes neurotoxic at high concentrations in the brain. The brain is a “privileged” organ that is separated from systemic blood circulation mainly by two barriers. Endothelial cells within the brain form tight junctions and act as the blood–brain barrier (BBB), which physically separates circulating blood from the brain parenchyma. Between the blood and the cerebrospinal fluid (CSF) is the choroid plexus (CP), which is a tissue that acts as the blood–CSF barrier (BCB). Pharmaceuticals, proteins, and metals in the systemic circulation are unable to reach the brain and spinal cord unless transported through either of the two brain barriers. The BBB and the BCB consist of tightly connected cells that fulfill the critical role of neuroprotection and control the exchange of materials between the brain environment and blood circulation. Many recent publications provide insights into Mn transport in vivo or in cell models. In this review, we will focus on the current research regarding Mn metabolism in the brain and discuss the potential roles of the BBB and BCB in maintaining brain Mn homeostasis.

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

2020 ◽  
Vol 13 (10) ◽  
pp. 279
Author(s):  
Dina Sikpa ◽  
Lisa Whittingstall ◽  
Martin Savard ◽  
Réjean Lebel ◽  
Jérôme Côté ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Drug Delivery ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
Radiation Induced ◽  
B2 Receptors ◽  
Peptide Agonist ◽  
The Brain

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.

scholarly journals EXTH-02. THE BLOOD BRAIN BARRIER (BBB) PERMEABILITY IS ALTERED BY TUMOR TREATING FIELDS (TTFIELDS) IN VIVO

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi82-vi82 ◽  
Author(s):  
Ellina Schulz ◽  
Almuth F Kessler ◽  
Ellaine Salvador ◽  
Dominik Domröse ◽  
Malgorzata Burek ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Dce Mri ◽  
Tumor Treating Fields ◽  
Blood Brain ◽  
Vessel Structure ◽  
Bbb Permeability ◽  
The Brain

Abstract OBJECTIVE For glioblastoma patients Tumor Treating Fields (TTFields) have been established as adjuvant therapy. The blood brain barrier (BBB) tightly controls the influx of the majority of compounds from blood to brain. Therefore, the BBB may block delivery of drugs for treatment of brain tumors. Here, the influence of TTFields on BBB permeability was assessed in vivo. METHODS Rats were treated with 100 kHz TTFields for 72 h and thereupon i.v. injected with Evan’s Blue (EB) which directly binds to Albumin. To evaluate effects on BBB, EB was extracted after brain homogenization and quantified. In addition, cryosections of rat brains were prepared following TTFields application. The sections were stained for tight junction proteins Claudin-5 and Occludin and for immunoglobulin G (IgG) to assess vessel structure. Furthermore, serial dynamic contrast-enhanced DCE-MRI with Gadolinium contrast agent was performed before and after TTFields application. RESULTS TTFields application significantly increased the EB accumulation in the rat brain. In TTFields-treated rats, the vessel structure became diffuse compared to control cryosections of rat brains; Claudin 5 and Occludin were delocalized and IgG was found throughout the brain tissue. Serial DCE-MRI demonstrated significantly increased accumulation of Gadolinium in the brain, observed directly after 72 h of TTFields application. The effect of TTFields on the BBB disappeared 96 h after end of treatment and no difference in contrast enhancement between controls and TTFields treated animals was detectable. CONCLUSION By altering BBB integrity and permeability, application of TTFields at 100 kHz may have the potential to deliver drugs to the brain, which are unable to cross the BBB. Utilizing TTFields to open the BBB and its subsequent recovery could be a clinical approach of drug delivery for treatment of brain tumors and other diseases of the central nervous system. These results will be further validated in clinical Trials.

scholarly journals Permeability of the windows of the brain: feasibility of dynamic contrast-enhanced MRI of the circumventricular organs

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Inge C. M. Verheggen ◽  
Joost J. A. de Jong ◽  
Martin P. J. van Boxtel ◽  
Alida A. Postma ◽  
Frans R. J. Verhey ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Gray Matter ◽  
Circumventricular Organs ◽  
Brain Barrier ◽  
Dce Mri ◽  
Dynamic Contrast Enhanced ◽  
Blood Brain ◽  
Contrast Enhanced ◽  
The Brain

Abstract Background Circumventricular organs (CVOs) are small structures without a blood–brain barrier surrounding the brain ventricles that serve homeostasic functions and facilitate communication between the blood, cerebrospinal fluid and brain. Secretory CVOs release peptides and sensory CVOs regulate signal transmission. However, pathogens may enter the brain through the CVOs and trigger neuroinflammation and neurodegeneration. We investigated the feasibility of dynamic contrast-enhanced (DCE) MRI to assess the CVO permeability characteristics in vivo, and expected significant contrast uptake in these regions, due to blood–brain barrier absence. Methods Twenty healthy, middle-aged to older males underwent brain DCE MRI. Pharmacokinetic modeling was applied to contrast concentration time-courses of CVOs, and in reference to white and gray matter. We investigated whether a significant and positive transfer from blood to brain could be measured in the CVOs, and whether this differed between secretory and sensory CVOs or from normal-appearing brain matter. Results In both the secretory and sensory CVOs, the transfer constants were significantly positive, and all secretory CVOs had significantly higher transfer than each sensory CVO. The transfer constants in both the secretory and sensory CVOs were higher than in the white and gray matter. Conclusions Current measurements confirm the often-held assumption of highly permeable CVOs, of which the secretory types have the strongest blood-to-brain transfer. The current study suggests that DCE MRI could be a promising technique to further assess the function of the CVOs and how pathogens can potentially enter the brain via these structures. Trial registration: Netherlands Trial Register number: NL6358, date of registration: 2017-03-24

scholarly journals Drug transport across the blood–Brain barrier: In Vitro and In Vivo techniques

Drug Delivery ◽  
1998 ◽  
Vol 5 (2) ◽  
pp. 153-153 ◽  
Author(s):  
de Boer A. G ◽  
W. Sutanto ◽  
William M. Pardridge
Keyword(s):  
Blood Brain Barrier ◽  
Drug Transport ◽  
Brain Barrier ◽  
Blood Brain

Drug transport to the brain: key roles for the efflux pump P-glycoprotein in the blood–brain barrier

2002 ◽  
Vol 38 (6) ◽  
pp. 339-348 ◽  
Author(s):  
Michel Demeule ◽  
Anthony Régina ◽  
Julie Jodoin ◽  
Alain Laplante ◽  
Claude Dagenais ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Drug Transport ◽  
Efflux Pump ◽  
Brain Barrier ◽  
P Glycoprotein ◽  
Blood Brain ◽  
The Brain
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