Neutrophil affinity for PGP and HAIYPRH (T7) peptide dual-ligand functionalized nanoformulation enhances the brain delivery of tanshinone IIA and exerts neuroprotective effects against ischemic stroke by inhibiting proinflammatory signaling pathways

2018 ◽  
Vol 42 (23) ◽  
pp. 19043-19061
Author(s):  
Yutao Li ◽  
Chiying An ◽  
Danan Han ◽  
Yanxin Dang ◽  
Xin Liu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Physicochemical Properties ◽  
Signaling Pathways ◽  
Blood Brain Barrier ◽  
Tanshinone Iia ◽  
Brain Barrier ◽  
Brain Delivery ◽  
Neuroprotective Effects ◽  
The Poor ◽  
The Brain

A great challenge to the therapy of ischemic stroke is the poor physicochemical properties and inability of the drug to cross the blood–brain barrier (BBB).

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.

An Angiopep-2 functionalized nanoformulation enhances brain accumulation of tanshinone IIA and exerts neuroprotective effects against ischemic stroke

2018 ◽  
Vol 42 (21) ◽  
pp. 17359-17370 ◽  
Author(s):  
Yutao Li ◽  
Yanxin Dang ◽  
Dandan Han ◽  
Yong Tan ◽  
Xin Liu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Tanshinone Iia ◽  
Effective Intervention ◽  
Neuroprotective Effects ◽  
Neuroprotective Drugs ◽  
The Brain

Effective intervention against ischemic stroke requires delivery of potent neuroprotective drugs to the brain.

scholarly journals Blood-Brain Barrier Dysfunction Amplifies the Development of Neuroinflammation: Understanding of Cellular Events in Brain Microvascular Endothelial Cells for Prevention and Treatment of BBB Dysfunction

2021 ◽  
Vol 15 ◽  
Author(s):  
Fuyuko Takata ◽  
Shinsuke Nakagawa ◽  
Junichi Matsumoto ◽  
Shinya Dohgu
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathways ◽  
Blood Brain Barrier ◽  
Glial Cells ◽  
Inflammatory Mediators ◽  
Brain Barrier ◽  
Brain Endothelial Cells ◽  
Perivascular Cells ◽  
Cellular Components ◽  
The Brain

Neuroinflammation is involved in the onset or progression of various neurodegenerative diseases. Initiation of neuroinflammation is triggered by endogenous substances (damage-associated molecular patterns) and/or exogenous pathogens. Activation of glial cells (microglia and astrocytes) is widely recognized as a hallmark of neuroinflammation and triggers the release of proinflammatory cytokines, leading to neurotoxicity and neuronal dysfunction. Another feature associated with neuroinflammatory diseases is impairment of the blood-brain barrier (BBB). The BBB, which is composed of brain endothelial cells connected by tight junctions, maintains brain homeostasis and protects neurons. Impairment of this barrier allows trafficking of immune cells or plasma proteins into the brain parenchyma and subsequent inflammatory processes in the brain. Besides neurons, activated glial cells also affect BBB integrity. Therefore, BBB dysfunction can amplify neuroinflammation and act as a key process in the development of neuroinflammation. BBB integrity is determined by the integration of multiple signaling pathways within brain endothelial cells through intercellular communication between brain endothelial cells and brain perivascular cells (pericytes, astrocytes, microglia, and oligodendrocytes). For prevention of BBB disruption, both cellular components, such as signaling molecules in brain endothelial cells, and non-cellular components, such as inflammatory mediators released by perivascular cells, should be considered. Thus, understanding of intracellular signaling pathways that disrupt the BBB can provide novel treatments for neurological diseases associated with neuroinflammation. In this review, we discuss current knowledge regarding the underlying mechanisms involved in BBB impairment by inflammatory mediators released by perivascular cells.

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.

scholarly journals Impact of blood-brain barrier permeabilization induced by ultrasound associated to microbubbles on the brain delivery and kinetics of cetuximab: An immunoPET study using 89Zr-cetuximab

2020 ◽  
Vol 328 ◽  
pp. 304-312 ◽  
Author(s):  
Vu Long Tran ◽  
Anthony Novell ◽  
Nicolas Tournier ◽  
Matthieu Gerstenmayer ◽  
Arnaud Schweitzer-Chaput ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Delivery ◽  
Blood Brain ◽  
Kinetics Of ◽  
The Brain

scholarly journals Tailoring Formulations for Intranasal Nose-to-Brain Delivery: A Review on Architecture, Physico-Chemical Characteristics and Mucociliary Clearance of the Nasal Olfactory Mucosa

Pharmaceutics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 116 ◽  
Author(s):  
Stella Gänger ◽  
Katharina Schindowski
Keyword(s):  
Drug Delivery ◽  
Nasal Cavity ◽  
Blood Brain Barrier ◽  
Olfactory Mucosa ◽  
Brain Barrier ◽  
Chemical Characteristics ◽  
Brain Delivery ◽  
Blood Brain ◽  
Physico Chemical ◽  
The Brain

The blood-brain barrier and the blood-cerebrospinal fluid barrier are major obstacles in central nervous system (CNS) drug delivery, since they block most molecules from entering the brain. Alternative drug delivery routes like intraparenchymal or intrathecal are invasive methods with a remaining risk of infections. In contrast, nose-to-brain delivery is a minimally invasive drug administration pathway, which bypasses the blood-brain barrier as the drug is directed from the nasal cavity to the brain. In particular, the skull base located at the roof of the nasal cavity is in close vicinity to the CNS. This area is covered with olfactory mucosa. To design and tailor suitable formulations for nose-to-brain drug delivery, the architecture, structure and physico-chemical characteristics of the mucosa are important criteria. Hence, here we review the state-of-the-art knowledge about the characteristics of the nasal and, in particular, the olfactory mucosa needed for a rational design of intranasal formulations and dosage forms. Also, the information is suitable for the development of systemic or local intranasal drug delivery as well as for intranasal vaccinations.

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