scholarly journals Blood-Brain Delivery Methods Using Nanotechnology

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 269 ◽  
Author(s):  
Daniel Teleanu ◽  
Cristina Chircov ◽  
Alexandru Grumezescu ◽  
Adrian Volceanov ◽  
Raluca Teleanu
Keyword(s):  
Multiple Sclerosis ◽  
Carbon Nanotubes ◽  
Drug Development ◽  
Brain Cancer ◽  
Therapeutic Agents ◽  
Brain Delivery ◽  
Delivery Methods ◽  
Selective Permeability ◽  
Blood Brain ◽  
The Brain

Pathologies of the brain, of which brain cancer, Alzheimer’s disease, Parkinson’s disease, stroke, and multiple sclerosis, are some of the most prevalent, and that presently are poorly treated due to the difficulties associated with drug development, administration, and targeting to the brain. The existence of the blood-brain barrier, a selective permeability system which acts as a local gateway against circulating foreign substances, represents the key challenge for the delivery of therapeutic agents to the brain. However, the development of nanotechnology-based approaches for brain delivery, such as nanoparticles, liposomes, dendrimers, micelles, and carbon nanotubes, might be the solution for improved brain therapies.

scholarly journals Characterization of the Blood–Brain Barrier Integrity and the Brain Transport of SN-38 in an Orthotopic Xenograft Rat Model of Diffuse Intrinsic Pontine Glioma

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 399 ◽  
Author(s):  
Catarina Chaves ◽  
Xavier Declèves ◽  
Meryam Taghi ◽  
Marie-Claude Menet ◽  
Joelle Lacombe ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Brain Barrier ◽  
Brain Delivery ◽  
Pontine Glioma ◽  
Anticancer Drug Delivery ◽  
Blood Brain ◽  
The Brain

The blood–brain barrier (BBB) hinders the brain delivery of many anticancer drugs. In pediatric patients, diffuse intrinsic pontine glioma (DIPG) represents the main cause of brain cancer mortality lacking effective drug therapy. Using sham and DIPG-bearing rats, we analyzed (1) the brain distribution of 3-kDa-Texas red-dextran (TRD) or [14C]-sucrose as measures of BBB integrity, and (2) the role of major ATP-binding cassette (ABC) transporters at the BBB on the efflux of the irinotecan metabolite [3H]-SN-38. The unaffected [14C]-sucrose or TRD distribution in the cerebrum, cerebellum, and brainstem regions in DIPG-bearing animals suggests an intact BBB. Targeted proteomics retrieved no change in P-glycoprotein (P-gp), BCRP, MRP1, and MRP4 levels in the analyzed regions of DIPG rats. In vitro, DIPG cells express BCRP but not P-gp, MRP1, or MRP4. Dual inhibition of P-gp/Bcrp, or Mrp showed a significant increase on SN-38 BBB transport: Cerebrum (8.3-fold and 3-fold, respectively), cerebellum (4.2-fold and 2.8-fold), and brainstem (2.6-fold and 2.2-fold). Elacridar increased [3H]-SN-38 brain delivery beyond a P-gp/Bcrp inhibitor effect alone, emphasizing the role of another unidentified transporter in BBB efflux of SN-38. These results confirm a well-preserved BBB in DIPG-bearing rats, along with functional ABC-transporter expression. The development of chemotherapeutic strategies to circumvent ABC-mediated BBB efflux are needed to improve anticancer drug delivery against DIPG.

scholarly journals Nose-to-Brain Delivery

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 138 ◽  
Author(s):  
Paolo Giunchedi ◽  
Elisabetta Gavini ◽  
Maria Cristina Bonferoni
Keyword(s):  
Side Effects ◽  
Blood Brain Barrier ◽  
Neurological Diseases ◽  
Systemic Administration ◽  
Brain Barrier ◽  
Brain Delivery ◽  
Special Issue ◽  
Drug Bioavailability ◽  
Blood Brain ◽  
The Brain

Nose-to-brain delivery represents a big challenge. In fact there is a large number of neurological diseases that require therapies in which the drug must reach the brain, avoiding the difficulties due to the blood–brain barrier (BBB) and the problems connected with systemic administration, such as drug bioavailability and side-effects. For these reasons the development of nasal formulations able to deliver the drug directly into the brain is of increasing importance. This Editorial regards the contributions present in the Special Issue “Nose-to-Brain Delivery”.

scholarly journals Blood–brain barrier shuttle peptides: an emerging paradigm for brain delivery

2016 ◽  
Vol 45 (17) ◽  
pp. 4690-4707 ◽  
Author(s):  
Benjamí Oller-Salvia ◽  
Macarena Sánchez-Navarro ◽  
Ernest Giralt ◽  
Meritxell Teixidó
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Delivery ◽  
Blood Brain ◽  
The Brain

Blood–brain barrier shuttle peptides are increasingly more potent and versatile tools to enhance drug delivery to the brain.

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

2015 ◽  
Vol 38 (3) ◽  
pp. E10 ◽  
Author(s):  
Benjamin K. Hendricks ◽  
Aaron A. Cohen-Gadol ◽  
James C. Miller
Keyword(s):  
Primary Brain Tumor ◽  
Pathological Process ◽  
Therapeutic Interventions ◽  
Delivery Methods ◽  
Ongoing Research ◽  
Functional Capabilities ◽  
Blood Brain ◽  
Natural Protection ◽  
The Brain ◽  
Brain Homeostasis

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. 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.

scholarly journals Nanoparticle brain delivery: a guide to verification methods

Nanomedicine ◽  
2020 ◽  
Vol 15 (4) ◽  
pp. 409-432 ◽  
Author(s):  
Robert A Yokel
Keyword(s):  
Cerebrospinal Fluid ◽  
Extracellular Space ◽  
Brain Parenchyma ◽  
Brain Delivery ◽  
Peripheral Organ ◽  
Blood Brain ◽  
Verification Methods ◽  
Brain Parenchymal ◽  
And Function ◽  
The Brain

Many reports conclude nanoparticle (NP) brain entry based on bulk brain analysis. Bulk brain includes blood, cerebrospinal fluid and blood vessels within the brain contributing to the blood–brain and blood–cerebrospinal fluid barriers. Considering the brain as neurons, glia and their extracellular space (brain parenchyma), most studies did not show brain parenchymal NP entry. Blood–brain and blood–cerebrospinal fluid barriers anatomy and function are reviewed. Methods demonstrating brain parenchymal NP entry are presented. Results demonstrating bulk brain versus brain parenchymal entry are classified. Studies are reviewed, critiqued and classified to illustrate results demonstrating bulk brain versus parenchymal entry. Brain, blood and peripheral organ NP timecourses are compared and related to brain parenchymal entry evidence suggesting brain NP timecourse informs about brain parenchymal entry.

scholarly journals Neuronanomedicine: An Up-to-Date Overview

Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 101 ◽  
Author(s):  
Daniel Mihai Teleanu ◽  
Cristina Chircov ◽  
Alexandru Mihai Grumezescu ◽  
Raluca Ioana Teleanu
Keyword(s):  
Central Nervous System ◽  
Brain Cancer ◽  
Treatment Strategies ◽  
Therapeutic Agents ◽  
Brain Parenchyma ◽  
Brain Disorders ◽  
Central Nervous System Disorders ◽  
Improve Life Expectancy ◽  
The Brain

The field of neuronanomedicine has recently emerged as the bridge between neurological sciences and nanotechnology. The possibilities of this novel perspective are promising for the diagnosis and treatment strategies of severe central nervous system disorders. Therefore, the development of nano-vehicles capable of permeating the blood–brain barrier (BBB) and reaching the brain parenchyma may lead to breakthrough therapies that could improve life expectancy and quality of the patients diagnosed with brain disorders. The aim of this review is to summarize the recently developed organic, inorganic, and biological nanocarriers that could be used for the delivery of imaging and therapeutic agents to the brain, as well as the latest studies on the use of nanomaterials in brain cancer, neurodegenerative diseases, and stroke. Additionally, the main challenges and limitations associated with the use of these nanocarriers are briefly presented.

scholarly journals Quantum Dots Application in Neurodegenerative Diseases

Thrita ◽  
2021 ◽  
Vol 9 (2) ◽  
Author(s):  
Behnam Hasannejadasl ◽  
Farkhondeh Pooresmaeil Janbaz ◽  
Edris Choupani ◽  
Mahmood Fadaie ◽  
Mohammad Ali Hamidinejad ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Quantum Dots ◽  
Neurodegenerative Diseases ◽  
Small Molecules ◽  
Bright Light ◽  
Therapeutic Agents ◽  
High Quantum Yield ◽  
High Emission ◽  
Image Production ◽  
The Brain

: Quantum dots (QDs) are nanoparticles (NPs) with electronic and optical properties such as emitting bright light and fluorescence. They also carry specific characters such as photostability, high quantum yield, high emission, and size-turnable. Nowadays, a great interest is given to the extensive use of theranostic-NPs for sensing and imaging, as well as drug delivery. Moreover, QDs may yield great potential for the diagnosis and treatment of various central nervous system (CNS) diseases (e.g., Parkinson’s disease, Alzheimer’s disease, and multiple sclerosis). The blood-brain barrier (BBB) protects the brain tissue. Only certain small molecules like water and gases can cross BBB, whereas larger molecules enter via receptors, but many drugs are incapable of passing the barrier. A series of great advances have been achieved concerning using different NPs (e.g., QDs) to deliver drugs to the brain and CNS imaging. In this review, we discussed a wide variety of QDs along with their production, passive or active delivery of therapeutic agents for neurodegenerative diseases, and different image production.

scholarly journals Noncovalent Strategy with Cell-Penetrating Peptides to Facilitate the Brain Delivery of Insulin through the Blood–Brain Barrier

2018 ◽  
Vol 41 (4) ◽  
pp. 546-554 ◽  
Author(s):  
Noriyasu Kamei ◽  
Ai Yamaoka ◽  
Yukiko Fukuyama ◽  
Rei Itokazu ◽  
Mariko Takeda-Morishita
Keyword(s):  
Blood Brain Barrier ◽  
Cell Penetrating Peptides ◽  
Brain Barrier ◽  
Brain Delivery ◽  
Blood Brain ◽  
Cell Penetrating ◽  
The Brain

Brain delivery and activity of a lysosomal enzyme using a blood-brain barrier transport vehicle in mice

2020 ◽  
Vol 12 (545) ◽  
pp. eaay1163 ◽  
Author(s):  
Julie C. Ullman ◽  
Annie Arguello ◽  
Jennifer A. Getz ◽  
Akhil Bhalla ◽  
Cathal S. Mahon ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Lysosomal Enzyme ◽  
Brain Barrier ◽  
Enzyme Treatment ◽  
Brain Delivery ◽  
In Vivo Models ◽  
Blood Brain ◽  
Brain Exposure ◽  
Transport Vehicle ◽  
The Brain

Most lysosomal storage diseases (LSDs) involve progressive central nervous system (CNS) impairment, resulting from deficiency of a lysosomal enzyme. Treatment of neuronopathic LSDs remains a considerable challenge, as approved intravenously administered enzyme therapies are ineffective in modifying CNS disease because they do not effectively cross the blood-brain barrier (BBB). We describe a therapeutic platform for increasing the brain exposure of enzyme replacement therapies. The enzyme transport vehicle (ETV) is a lysosomal enzyme fused to an Fc domain that has been engineered to bind to the transferrin receptor, which facilitates receptor-mediated transcytosis across the BBB. We demonstrate that ETV fusions containing iduronate 2-sulfatase (ETV:IDS), the lysosomal enzyme deficient in mucopolysaccharidosis type II, exhibited high intrinsic activity and degraded accumulated substrates in both IDS-deficient cell and in vivo models. ETV substantially improved brain delivery of IDS in a preclinical model of disease, enabling enhanced cellular distribution to neurons, astrocytes, and microglia throughout the brain. Improved brain exposure for ETV:IDS translated to a reduction in accumulated substrates in these CNS cell types and peripheral tissues and resulted in a complete correction of downstream disease-relevant pathologies in the brain, including secondary accumulation of lysosomal lipids, perturbed gene expression, neuroinflammation, and neuroaxonal damage. These data highlight the therapeutic potential of the ETV platform for LSDs and provide preclinical proof of concept for TV-enabled therapeutics to treat CNS diseases more broadly.

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