scholarly journals A review: Brain specific delivery

2020 ◽  
Vol 13 (2) ◽  
pp. 068-079
Author(s):  
Deepti R. Damle ◽  
Dr. Archana D. Kajale ◽  
Dr. Madhuri A. Channawar ◽  
Dr. Shilpa R. Gawande
Keyword(s):  
Side Effects ◽  
Blood Brain Barrier ◽  
Drug Distribution ◽  
Drug Dose ◽  
Brain Barrier ◽  
Brain Targeting ◽  
High Concentration ◽  
Blood Brain ◽  
Clinical Benefits ◽  
The Brain

The overall prevalence rate for CNS pathology has demonstrated that approximately more than one billion people are undergoing from disorders of central nervous system. The most distressing fact about delivery of drugs to the CNS is the presence of blood brain barrier that have a tendency to impair the drug distribution and denotes the major impediment for the development of CNS drugs. Neuropeptides and many drugs which are hydrophilic in nature possibly will encompass the intricacy while passing the blood brain barrier. The net amount of delivered drug (medicinal agent) and its capability to gain access to the pertinent target sites are the main considering points for CNS drug development. Brain targeted drug delivery to the brain is valuable in the diseases of brain. (Alzheimer’s diseases, meningitis, brain abscess, epilepsy, multiple sclerosis, neuromylitis optica, sleeping disorders etc). Whereby high concentration can be gained with lesser side effects that occur because of release of drugs. The simplest method of targeting to brain is to obtain a therapeutic. Brain targeting systems to remain in the brain region by crossing BBB and hence significantly helps in increasing therapeutic activity. There is an increasing attraction towards brain targeting and sue to its immense application in the treatment of various CNS diseases because mostly drugs are unable to cross the BBB. This review article discuss one of the novel technology “nanotechnology” and other aspects that has been developed to target the brain and possess various clinical benefits such as reduced drug dose, less side effects, non-invasive routed, and better patient compliance.

Liposomes: Novel Drug Delivery Approach for Targeting Parkinson’s Disease

2020 ◽  
Vol 26 (37) ◽  
pp. 4721-4737 ◽  
Author(s):  
Bhumika Kumar ◽  
Mukesh Pandey ◽  
Faheem H. Pottoo ◽  
Faizana Fayaz ◽  
Anjali Sharma ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Neural Cells ◽  
Blood Brain ◽  
The Brain

Parkinson’s disease is one of the most severe progressive neurodegenerative disorders, having a mortifying effect on the health of millions of people around the globe. The neural cells producing dopamine in the substantia nigra of the brain die out. This leads to symptoms like hypokinesia, rigidity, bradykinesia, and rest tremor. Parkinsonism cannot be cured, but the symptoms can be reduced with the intervention of medicinal drugs, surgical treatments, and physical therapies. Delivering drugs to the brain for treating Parkinson’s disease is very challenging. The blood-brain barrier acts as a highly selective semi-permeable barrier, which refrains the drug from reaching the brain. Conventional drug delivery systems used for Parkinson’s disease do not readily cross the blood barrier and further lead to several side-effects. Recent advancements in drug delivery technologies have facilitated drug delivery to the brain without flooding the bloodstream and by directly targeting the neurons. In the era of Nanotherapeutics, liposomes are an efficient drug delivery option for brain targeting. Liposomes facilitate the passage of drugs across the blood-brain barrier, enhances the efficacy of the drugs, and minimize the side effects related to it. The review aims at providing a broad updated view of the liposomes, which can be used for targeting Parkinson’s disease.

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 ApoE-Targeting Increases the Transfer of Solid Lipid Nanoparticles with Donepezil Cargo across a Culture Model of the Blood–Brain Barrier

Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 38
Author(s):  
Gizem Rüya Topal ◽  
Mária Mészáros ◽  
Gergő Porkoláb ◽  
Anikó Szecskó ◽  
Tamás Ferenc Polgár ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Solid Lipid Nanoparticles ◽  
Lipid Nanoparticles ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Solid Lipid ◽  
Blood Brain ◽  
Culture Model ◽  
The Brain

Pharmacological treatment of central nervous system (CNS) disorders is difficult, because the blood–brain barrier (BBB) restricts the penetration of many drugs into the brain. To solve this unmet therapeutic need, nanosized drug carriers are the focus of research efforts to develop drug delivery systems for the CNS. For the successful delivery of nanoparticles (NPs) to the brain, targeting ligands on their surface is necessary. Our research aim was to design a nanoscale drug delivery system for a more efficient transfer of donepezil, an anticholinergic drug in the therapy of Alzheimer’s disease across the BBB. Rhodamine B-labeled solid lipid nanoparticles with donepezil cargo were prepared and targeted with apolipoprotein E (ApoE), a ligand of BBB receptors. Nanoparticles were characterized by measurement of size, polydispersity index, zeta potential, thermal analysis, Fourier-transform infrared spectroscopy, in vitro release, and stability. Cytotoxicity of nanoparticles were investigated by metabolic assay and impedance-based cell analysis. ApoE-targeting increased the uptake of lipid nanoparticles in cultured brain endothelial cells and neurons. Furthermore, the permeability of ApoE-targeted nanoparticles across a co-culture model of the BBB was also elevated. Our data indicate that ApoE, which binds BBB receptors, can potentially be exploited for successful CNS targeting of solid lipid nanoparticles.

scholarly journals Disease-Induced Modulation of Drug Transporters at the Blood–Brain Barrier Level

2021 ◽  
Vol 22 (7) ◽  
pp. 3742
Author(s):  
Sweilem B. Al Rihani ◽  
Lucy I. Darakjian ◽  
Malavika Deodhar ◽  
Pamela Dow ◽  
Jacques Turgeon ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Drug Transporters ◽  
Neurovascular Unit ◽  
Drug Distribution ◽  
Drug Efficacy ◽  
Brain Barrier ◽  
Protective Function ◽  
Transporter Protein ◽  
Blood Brain ◽  
The Brain

The blood–brain barrier (BBB) is a highly selective and restrictive semipermeable network of cells and blood vessel constituents. All components of the neurovascular unit give to the BBB its crucial and protective function, i.e., to regulate homeostasis in the central nervous system (CNS) by removing substances from the endothelial compartment and supplying the brain with nutrients and other endogenous compounds. Many transporters have been identified that play a role in maintaining BBB integrity and homeostasis. As such, the restrictive nature of the BBB provides an obstacle for drug delivery to the CNS. Nevertheless, according to their physicochemical or pharmacological properties, drugs may reach the CNS by passive diffusion or be subjected to putative influx and/or efflux through BBB membrane transporters, allowing or limiting their distribution to the CNS. Drug transporters functionally expressed on various compartments of the BBB involve numerous proteins from either the ATP-binding cassette (ABC) or the solute carrier (SLC) superfamilies. Pathophysiological stressors, age, and age-associated disorders may alter the expression level and functionality of transporter protein elements that modulate drug distribution and accumulation into the brain, namely, drug efficacy and toxicity. This review focuses and sheds light on the influence of inflammatory conditions and diseases such as Alzheimer’s disease, epilepsy, and stroke on the expression and functionality of the BBB drug transporters, the consequential modulation of drug distribution to the brain, and their impact on drug efficacy and toxicity.

scholarly journals Niosome: A Promising Nanocarrier for Natural Drug Delivery through Blood-Brain Barrier

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Mahmoud Gharbavi ◽  
Jafar Amani ◽  
Hamidreza Kheiri-Manjili ◽  
Hossein Danafar ◽  
Ali Sharafi
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Routes Of Administration ◽  
Packing Factor ◽  
Blood Brain ◽  
Natural Drugs ◽  
Pharmaceutical Uses ◽  
The Brain

Niosomes (the nonionic surfactant vesicles), considered as novel drug delivery systems, can improve the solubility and stability of natural pharmaceutical molecules. They are established to provide targeting and controlled release of natural pharmaceutical compounds. Many factors can influence on niosome construction such as the preparation method, type and amount of surfactant, drug entrapment, temperature of lipids hydration, and the packing factor. The present review discusses about the most important features of niosomes such as their diverse structures, the different preparation approaches, characterization techniques, factors that affect their stability, their use by various routes of administration, their therapeutic applications in comparison with natural drugs, and specially the brain targeting with niosomes-ligand conjugation. It also provides recent data about the various types of ligand agents which make available active targeting drug delivery to the central neuron system. This system has an optimistic upcoming in pharmaceutical uses, mostly with the improving availability of innovative schemes to overcome blood-brain barrier and targeting the niosomes to the brain.

scholarly journals Targeting nanoparticles to the brain by exploiting the blood–brain barrier impermeability to selectively label the brain endothelium

2020 ◽  
Vol 117 (32) ◽  
pp. 19141-19150 ◽  
Author(s):  
Daniel Gonzalez-Carter ◽  
Xueying Liu ◽  
Theofilus A. Tockary ◽  
Anjaneyulu Dirisala ◽  
Kazuko Toh ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Brain Endothelial Cells ◽  
Brain Endothelium ◽  
Target Proteins ◽  
Blood Brain ◽  
Brain Microvasculature ◽  
The Brain

Current strategies to direct therapy-loaded nanoparticles to the brain rely on functionalizing nanoparticles with ligands which bind target proteins associated with the blood–brain barrier (BBB). However, such strategies have significant brain-specificity limitations, as target proteins are not exclusively expressed at the brain microvasculature. Therefore, novel strategies which exploit alternative characteristics of the BBB are required to overcome nonspecific nanoparticle targeting to the periphery, thereby increasing drug efficacy and reducing detrimental peripheral side effects. Here, we present a simple, yet counterintuitive, brain-targeting strategy which exploits the higher impermeability of the BBB to selectively label the brain endothelium. This is achieved by harnessing the lower endocytic rate of brain endothelial cells (a key feature of the high BBB impermeability) to promote selective retention of free, unconjugated protein-binding ligands on the surface of brain endothelial cells compared to peripheral endothelial cells. Nanoparticles capable of efficiently binding to the displayed ligands (i.e., labeled endothelium) are consequently targeted specifically to the brain microvasculature with minimal “off-target” accumulation in peripheral organs. This approach therefore revolutionizes brain-targeting strategies by implementing a two-step targeting method which exploits the physiology of the BBB to generate the required brain specificity for nanoparticle delivery, paving the way to overcome targeting limitations and achieve clinical translation of neurological therapies. In addition, this work demonstrates that protein targets for brain delivery may be identified based not on differential tissue expression, but on differential endocytic rates between the brain and periphery.

scholarly journals Functionalised LRP1 targeted carbon nanotubes across the blood-brain barrier in vitro and in vivo after intravenous injection

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv3-iv3
Author(s):  
Julie Wang ◽  
Houmam Kafa ◽  
Noelia Rubio ◽  
Sukhvinder Bansal ◽  
Frederic Festy ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Blood Brain Barrier ◽  
Intravenous Injection ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Blood Brain ◽  
The Brain

Abstract Despite extensive research in drug development, brain cancer is still lacking an efficacious cure due to the inability to deliver current therapeutics to the brain across the blood-brain barrier (BBB). Chemically functionalized carbon nanotubes (f-CNT) constitute a novel class of nanomaterials with attractive physical, chemical and electronic properties. The key advantage of f-CNTs is the extremely high surface area to size ratio allowing a high degree of chemical functionalization making them invaluable tools for designing drug delivery systems to the brain. One of the most interesting characteristics of f-CNTs is their ability to translocate across plasma membranes and enter the cells either passively by direct translocation across membranes or actively via endocytosis. Herein, we confirmed the ability of f-CNTs to cross the BBB and reach the brain in in vitro using a co-culture model of PBEC and primary rat astrocytes and in vivo after intravenous injection. Thanks to their unique optical properties, the uptake of f-CNT in brain was confirmed using state-of-the-art spectroscopic imaging techniques such as multi-photon luminescence imaging, fluorescence lifetime microscopy and Raman spectroscopy. Conjugation with angiopep-2 (ANG), a small peptide targeting the LRP1 receptor overexpressed in the BBB and glioma cells, further enhanced brain parenchyma accumulation in healthy brains. Higher uptake in glioma than brain parenchyma was also observed in glioma-bearing mice after intravenous administration. The inherent brain accumulation ability of f-CNTs coupled with improved brain-targeting by ANG favours the future clinical applications of f-CNTs-ANG to deliver active therapeutics for brain glioma therapy.

Recent Advancements in Nanodiamond Mediated Brain Targeted Drug Delivery and Bioimaging of Brain Ailments: A Holistic Review

2021 ◽  
Vol 10 ◽  
Author(s):  
Mohini Singh ◽  
Bhaskar Mazumder
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Targeted Drug Delivery ◽  
Building Blocks ◽  
Biological Properties ◽  
Brain Barrier ◽  
Brain Targeting ◽  
Blood Brain ◽  
Targeted Drug ◽  
The Brain

Background: The brain is a vital and composite organ. By nature, the innate make-up of the brain is such that in anatomical parlance, it is highly protected by the “Blood-Brain Barrier”, which is a nexus of capillary endothelial cells, basement membrane, neuroglial membrane and glialpodocytes. The same barrier, which protects and isolates the interstitial fluid of the brain from capillary circulation, also restricts the therapeutic intervention. Many standing pharmaceutical formulations are ineffective in the treatment of inimical brain ailments because of the inability of the API to surpass and subsist inside the Blood Brain Barrier. Objective: This is an integrated review that emphasizes on the recent advancements in brain-targeted drug delivery utilizing nanodiamonds (NDs) as a carrier of therapeutic agents. NDs are a novel nanoparticulate drug delivery system, having carbon moieties as their building blocks and their surface tenability is remarkable. These neoteric carbon-based carriers have exceptional, mechanical, electrical, chemical, optical, and biological properties, which can be further rationally modified and augmented. Conclusion: NDs could be the next“revolution ”in the field of nanoscience for the treatment of neurodegenerative disorders, brain tumors, and other pernicious brain ailments. What sets them apart from other nanocarriers is their versatile properties like diverse size range and surface modification potential, which makes them efficient enough to move across certain biological barriers and offer a plethora of brain targeting and bioimaging abilities. Lay Summary: The blood-brain barrier (BBB) poses a major hurdle in the way of treating many serious brain ailments. A range of nanoparticle based drug delivering systems have been formulated, including solid lipid nanoparticles, liposomes, dendrimers, nanogels, polymeric NPs, metallic NPs (gold, platinum, andironoxide) and diamondoids (carbonnanotubes). Despite this development, only a few of these formulations have shown the ability to cross the BBB. Nanodiamonds, because of their small size, shape, and surface characteristics, have a potential in moving beyond the diverse and intricate BBB, and offer a plethora of brain targeting capabilities.

Influence of nanoparticle size on blood-brain barrier penetration and the accumulation of anti-seizure medicines in the brain

2021 ◽  
Author(s):  
Qian Meng ◽  
Hongmei Meng ◽  
Yong Pan ◽  
Jiayu Liu ◽  
Jiaai Li ◽  
...  
Keyword(s):  
Side Effects ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Nanoparticle Size ◽  
Blood Brain ◽  
Barrier Penetration ◽  
The Brain

Anti-seizure medicines constitute a common yet important modality to treat epilepsy. However, some of them are associated with serious side effects including hepatotoxicity and hypersensitivity. Furthermore, the blood-brain barrier (BBB)...

scholarly journals Design of Biopolymer-Based Interstitial Therapies for the Treatment of Glioblastoma

2021 ◽  
Vol 22 (23) ◽  
pp. 13160
Author(s):  
Erik S. Pena ◽  
Elizabeth G. Graham-Gurysh ◽  
Eric M. Bachelder ◽  
Kristy M. Ainslie
Keyword(s):  
Blood Brain Barrier ◽  
Drug Distribution ◽  
Brain Barrier ◽  
Morbidity Rate ◽  
Interstitial Therapy ◽  
Blood Brain ◽  
Polymer Implant ◽  
Intermolecular Bonding ◽  
Multiple Drugs ◽  
The Brain

Glioblastoma multiforme (GBM) is the most common form of primary brain cancer and has the highest morbidity rate and current treatments result in a bleak 5-year survival rate of 5.6%. Interstitial therapy is one option to increase survival. Drug delivery by interstitial therapy most commonly makes use of a polymer implant encapsulating a drug which releases as the polymer degrades. Interstitial therapy has been extensively studied as a treatment option for GBM as it provides several advantages over systemic administration of chemotherapeutics. Primarily, it can be applied behind the blood–brain barrier, increasing the number of possible chemotherapeutic candidates that can be used and reducing systemic levels of the therapy while concentrating it near the cancer source. With interstitial therapy, multiple drugs can be released locally into the brain at the site of resection as the polymer of the implant degrades, and the release profile of these drugs can be tailored to optimize combination therapy or maintain synergistic ratios. This can bypass the blood–brain barrier, alleviate systemic toxicity, and resolve drug resistance in the tumor. However, tailoring drug release requires appropriate consideration of the complex relationship between the drug, polymer, and formulation method. Drug physicochemical properties can result in intermolecular bonding with the polymeric matrix and affect drug distribution in the implant depending on the formulation method used. This review is focused on current works that have applied interstitial therapy towards GBM, discusses polymer and formulation methods, and provides design considerations for future implantable biodegradable materials.

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