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

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.

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

Current Pharmaceutical Design ◽

10.2174/1381612826666200128145124 ◽

2020 ◽

Vol 26 (37) ◽

pp. 4721-4737 ◽

Cited By ~ 4

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.

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

Pharmaceutics ◽

10.3390/pharmaceutics13010038 ◽

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.

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

Pharmaceutical Nanotechnology ◽

10.2174/2211738510666211222111938 ◽

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.

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Brain Drug Delivery: Overcoming the Blood-brain Barrier to Treat Tauopathies

Current Pharmaceutical Design ◽

10.2174/1381612826666200316130128 ◽

2020 ◽

Vol 26 (13) ◽

pp. 1448-1465 ◽

Cited By ~ 1

Author(s):

Jozef Hanes ◽

Eva Dobakova ◽

Petra Majerova

Keyword(s):

Drug Delivery ◽

Blood Brain Barrier ◽

Neurodegenerative Disorders ◽

Brain Barrier ◽

Neuronal Function ◽

Brain Drug Delivery ◽

Naturally Occurring ◽

Blood Brain ◽

Traditional Approaches ◽

The Brain

Tauopathies are neurodegenerative disorders characterized by the deposition of abnormal tau protein in the brain. The application of potentially effective therapeutics for their successful treatment is hampered by the presence of a naturally occurring brain protection layer called the blood-brain barrier (BBB). BBB represents one of the biggest challenges in the development of therapeutics for central nervous system (CNS) disorders, where sufficient BBB penetration is inevitable. BBB is a heavily restricting barrier regulating the movement of molecules, ions, and cells between the blood and the CNS to secure proper neuronal function and protect the CNS from dangerous substances and processes. Yet, these natural functions possessed by BBB represent a great hurdle for brain drug delivery. This review is concentrated on summarizing the available methods and approaches for effective therapeutics’ delivery through the BBB to treat neurodegenerative disorders with a focus on tauopathies. It describes the traditional approaches but also new nanotechnology strategies emerging with advanced medical techniques. Their limitations and benefits are discussed.

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P10.02 Combined methods of a micropump system and a chronic cranial window allows tumor observation with multi photon laser scanning microscopy under continuous treatment

Neuro-Oncology ◽

10.1093/neuonc/noab180.095 ◽

2021 ◽

Vol 23 (Supplement_2) ◽

pp. ii28-ii28

Author(s):

S Weil ◽

E Jung ◽

D Domínguez Azorín ◽

J Higgins ◽

J Reckless ◽

...

Keyword(s):

Drug Delivery ◽

Tumor Cells ◽

Blood Brain Barrier ◽

Laser Scanning ◽

Laser Scanning Microscopy ◽

New Drugs ◽

Brain Barrier ◽

Cranial Window ◽

Blood Brain ◽

The Brain

Abstract BACKGROUND Glioblastomas are notoriously therapy resistant tumors. As opposed to other tumor entities, no major advances in therapeutic success have been made in the past decades. This has been calling for a deeper biological understanding of the tumor, its growth and resistance patterns. We have been using a xenograft glioma model, where human glioblastoma cells are implanted under chronic cranial windows and studied longitudinally over many weeks and months using multi photon laser scanning microscopy (MPLSM). To test the effect of (new) drugs, a stable and direct delivery system avoiding the blood-brain-barrier has come into our interest. MATERIAL AND METHODS We implanted cranial windows and fluorescently labeled human glioblastoma stem-like cells into NMRI nude mice to follow up on the tumor development in our MPLSM model. After tumor establishment, an Alzet® micropump was implanted to directly deliver agents via a catheter system continuously over 28 days directly under the cranial window onto the brain surface. Using the MPLSM technique, the continuous delivery and infusion of drugs onto the brain and into the tumor was measured over many weeks in detail using MPLSM. RESULTS The establishment of the combined methods allowed reliable concurrent drug delivery over 28 days bypassing the blood-brain-barrier. Individual regions and tumor cells could be measured and followed up before, and after the beginning of the treatment, as well as after the end of the pump activity. Fluorescently labelled drugs were detectable in the MPLSM and its distribution into the brain parenchyma could be quantified. After the end of the micropump activity, further MPLSM measurements offer the possibility to observe long term effects of the applied drug on the tumor. CONCLUSION The combination of tumor observation in the MPSLM and concurrent continuous drug delivery is a feasible and reliable method for the investigation of (novel) anti-tumor agents, especially drugs that are not blood-brain-barrier penetrant. Morphological or even functional changes of individual tumor cells can be measured under and after treatment. These techniques can be used to test new drugs targeting the tumor, its tumor microtubes and tumor cells networks, and measure the effects longitudinally.

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Recent Advances in Targeted Drug Delivery Approaches using Lipidic and Polymeric Nanocarriers for the management of Alzheimer’s Disease

Current Pharmaceutical Design ◽

10.2174/1381612827666210927163258 ◽

2021 ◽

Vol 27 ◽

Author(s):

Dhara Lakdawala ◽

Md Abdur Rashid ◽

Farhan Jalees Ahmad

Keyword(s):

Alzheimer’S Disease ◽

Drug Delivery ◽

Alzheimer's Disease ◽

Blood Brain Barrier ◽

Targeted Drug Delivery ◽

Brain Barrier ◽

Polymeric Nanocarriers ◽

Blood Brain ◽

Targeted Drug ◽

The Brain

: Drug delivery to the brain has remained a significant challenge in treating neurodegenerative disorders such as Alzheimer's disease due to the presence of the blood-brain barrier, which primarily obstructs the access of drugs and biomolecules into the brain. Several methods to overcome the blood-brain barrier have been employed, such as chemical disruption, surgical intervention, focused ultrasound, intranasal delivery and using nanocarriers. Nanocarrier systems remain the method of choice and have shown promising results over the past decade to achieve better drug targeting. Polymeric nanocarriers and lipidic nanoparticles act as a carrier system providing better encapsulation of drugs, site-specific delivery, increased bioavailability and sustained release of drugs. The surface modifications and functionalization of these nanocarrier systems have greatly facilitated targeted drug delivery. The safety and efficacy of these nanocarrier systems have been ascertained by several in vitro and in vivo models. In the present review, we have elaborated on recent developments of nanoparticles as a drug delivery system for Alzheimer's disease, explicitly focusing on polymeric and lipidic nanoparticles.

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The Blood-Brain Barrier and Brain Drug Delivery

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2006.441 ◽

2006 ◽

Vol 6 (9) ◽

pp. 2712-2735 ◽

Cited By ~ 55

Author(s):

J. M. Koziara ◽

P. R. Lockman ◽

D. D. Allen ◽

R. J. Mumper

Keyword(s):

Drug Delivery ◽

Blood Brain Barrier ◽

Present Report ◽

Drug Carriers ◽

Brain Barrier ◽

Brain Targeting ◽

Anatomy And Physiology ◽

Brain Drug Delivery ◽

Blood Brain

The present report encompasses a thorough review of drug delivery to the brain with a particular focus on using drug carriers such as liposomes and nanoparticles. Challenges in brain drug delivery arise from the presence of one of the strictest barriers in vivo—the blood-brain barrier (BBB). This barrier exists at the level of endothelial cells of brain vasculature and its role is to maintain brain homeostasis. To better understand the principles of brain drug delivery, relevant knowledge of the blood-brain barrier anatomy and physiology is briefly reviewed. Several approaches to overcome the BBB have been reviewed including the use of carrier systems. In addition, strategies to enhance brain drug delivery by specific brain targeting are discussed.

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

Chemical Society Reviews ◽

10.1039/c6cs00076b ◽

2016 ◽

Vol 45 (17) ◽

pp. 4690-4707 ◽

Cited By ~ 146

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.

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An overview of nanomedicines for neuron targeting

Nanomedicine ◽

10.2217/nnm-2020-0088 ◽

2020 ◽

Vol 15 (16) ◽

pp. 1617-1636 ◽

Cited By ~ 2

Author(s):

Jesus Garcia-Chica ◽

West Kristian D Paraiso ◽

Shihori Tanabe ◽

Dolors Serra ◽

Laura Herrero ◽

...

Keyword(s):

Drug Delivery ◽

Blood Brain Barrier ◽

Neuronal Cells ◽

Brain Barrier ◽

Brain Targeting ◽

Brain Cells ◽

Medical Treatments ◽

Blood Brain

Medical treatments of neuron-related disorders are limited due to the difficulty of targeting brain cells. Major drawbacks are the presence of the blood–brain barrier and the lack of specificity of the drugs for the diseased cells. Nanomedicine-based approaches provide promising opportunities for overcoming these limitations. Although many previous reviews are focused on brain targeting with nanomedicines in general, none of those are concerned explicitly on the neurons, while targeting neuronal cells in central nervous diseases is now one of the biggest challenges in nanomedicine and neuroscience. We review the most relevant advances in nanomedicine design and strategies for neuronal drug delivery that might successfully bridge the gap between laboratory and bedside treatment in neurology.

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