Lipid nanocarriers for neurotherapeuticals: Introduction, challenges, blood-brain barrier and promises of delivery approaches

2021 ◽  
Vol 20 ◽  
Author(s):  
Mohammed Aslam ◽  
Md. Noushad Javed ◽  
Hala Hasan Deeb ◽  
Michel Kaisar Nicola ◽  
Aamir Mirza ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Targeted Delivery ◽  
Water Soluble ◽  
Brain Barrier ◽  
Synthetic Drugs ◽  
Blood Brain ◽  
Water Soluble Drugs ◽  
Lipid Nanocarriers ◽  
Disor Ders ◽  
The Brain

: Significant efforts are being made in research to discover newer neurotherapeuticals, but the rate of reported neurological disorders has been increasing at an alarming speed. Neurothera-peuticals delivery in the brain is still posing a significant challenge, owing to the blood-brain barrier and blood-cerebrospinal fluid barrier. These physiological barriers restrict the passage of systemically available fractions of neurotherapeuticals into the brain, owing to low permeability and drug localization factors. Neurotherapeuticals encapsulating lipid carriers favor a significant increase in bioavailability of poorly water-soluble drugs by enhancing solubility in the gastroin-testinal tract and favoring stability. Due to their small size and lipid-based composition, these carriers offer enhanced permeability across the semi-permeable blood-brain barrier to effective-ly transport encapsulated loads, such as synthetic drugs, nutraceuticals, phytoconstituents, herb-al extracts, and peptides, reducing incidences of off-target mediated adverse impacts and tox-icity. The most significant advantage of such lipid-based delivery systems is non–invasive na-ture and targeting of neurotherapeuticals to the central nervous system. Critical attributes of li-pid-based carriers modulate release rates in rate-controlled manners, enable higher penetration through the blood-brain barrier, and bypass the hepatic first-pass metabolism, leading to higher CNS bioavailability neurotherapeuticals. The current review discusses a brief and introductory account of the limitations of neurothera-peuticals, pharmacological barriers, challenges in brain-targeted delivery, and the potential of nanotechnology-processed lipid-based carriers in the clinical management of neuronal disor-ders.

Lipid carriers mediated targeted delivery of nutraceuticals: Challenges, role of blood brain barrier and promises of nanotechnology based ap-proaches in neuronal disorders.

2020 ◽  
Vol 21 ◽  
Author(s):  
Mohammed Aslam ◽  
Md Noushad Javed ◽  
Hala Hasan Deeb ◽  
Michel Kaisar Nicola ◽  
Ayisha Md Sabir ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Targeted Delivery ◽  
Brain Region ◽  
Control Release ◽  
Water Soluble ◽  
Brain Barrier ◽  
Blood Brain ◽  
Bioavailable Fraction ◽  
The Brain ◽  
Neuronal Disorders

: Despite all significant research in discovering new therapeuticals, there has been an alarming rate of reported neurological disorders. However, the delivery of these neurotherapeuticals within the brain region is still a significant chal-lenge in the clinical management of neuronal disorders. Here, characteristic of the blood-brain barrier and blood-cerebrospinal fluid barrier serves the purpose of a physiological barrier to restrict the passage of systemic bioavailable neu-rotherapeuticals inside the brain, owing to low permeability and drug localization issues. The major advantage of such lipid-based delivery systems is that these are effective non–invasive techniques-based approaches that enable targeting of neuro-therapeuticals into the central nervous system. In the case of poorly water-soluble drugs, these lipid-based carriers not onlyfavor to increase bioavailability by enabling better solubility characteristics in the gastrointestinal tract but such encapsulat-ed neurotherapeuticals loads within the systems; may also favor stability. While owing to their small size and lipid-based composition, they offer enhanced permeability across the blood-brain barrier. These lipid-based nanocarriers effectively transport the encapsulated loads such as synthetic drugs, nutraceuticals, phytoconstituents, herbal extracts, or therapeuticalpeptides; across of these impermeable barriers to reduce the incidence of off-target mediated adverse impacts and toxicity. : In this review, we discussed, in brief, the potential of nanotechnology processed and lipid-based carriers, which are not onlyto enable higher penetration through the blood-brain barrier but also to maintain drug plasma levels in the desired range, ow-ing to control release profile. Apart from an increase in the extent of bioavailable fraction of drugs within the brain region, other attributes such as modulation in drug release, better penetration, the incidence of bypassing the first-pass metabolism to elevate half-lives; are further favoring the potential application of these carriers. Hence in this introductory review paper, a brief account of general introduction on limitation of neurotherapeuticals loaded conventional dosage forms, the blood-brain barriers as pharmacological barriers, challenges in brain targeted drug delivery, as well as potentials of different lipid-based nanoparticles and their patents, as emerging delivery solutions for neurotherapeuticals delivery; in the clinical man-agement of neuronal disorders; were thoroughly discussed.

scholarly journals Addressed delivery of valproic acid to target cells in treatment of epilepsy using aptamers

2021 ◽  
pp. 108-112
Author(s):  
T.N. Zamay ◽  
◽  
D.V. Dmitrenko ◽  
N.A. Shnaider ◽  
E.A. Narodova ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Status Epilepticus ◽  
Blood Brain Barrier ◽  
Targeted Delivery ◽  
Brain Barrier ◽  
Target Cells ◽  
Treatment Of Epilepsy ◽  
Blood Brain ◽  
Pilocarpine Model ◽  
The Brain

The aim of the research. To develop a drug based on aptamers that cross the blood-brain barrier, targeting the delivery of valproic acid to the brain. Material and methods. We used the Brain 1 and Co 451 aptamers passing through the blood-brain barrier, obtained using the in vivo-SELEX technology, the affi nity of which was determined using fl ow cytometry fl uorescence microscopy. Th e drug for targeted delivery of valproic acid was obtained using the conjugation of Konvulex, biotinylated aptamers, and streptavidin protein. Th e antiepileptic effi cacy of the drug was evaluated in ICR mice with a lithium-pilocarpine model of the development of epilepsy. Aft er the injection of pilocarpine, the animals were monitored using round-the-clock video recording. For the treatment of epilepsy, a valproic acid dose of 130 μg / g of animal weight was used. During treatment with a drug for targeted delivery, the dose of valproic acid was reduced to 5 μg / g. Evaluation of status epilepticus in mice was performed using the Racine Scale. Results. In animals, using the lithium-pilocarpine model, status epilepticus was formed at diff erent stages - from the 1st to the 5th. In all groups of animals, complete overcoming of status epilepticus did not occur in 120 min. In the group of mice treated with valroic acid, no change in their status occurred within 80 minutes. When mice were treated with conjugates based on the Brain 1 and Co 451 aptamers, the blockade of status epilepticus in mice, despite the lower (26 times) doses of the administered antiepileptic drug, occurred faster. Conclusion. A scientifi c platform has been developed for the development of drugs for targeted delivery of antiepileptic drugs with high effi ciency and low toxicity

scholarly journals The Role of P-Glycoprotein in Transport of Danshensu across the Blood-Brain Barrier

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Peng-Fei Yu ◽  
Wen-Yan Wang ◽  
Gaowa Eerdun ◽  
Tian Wang ◽  
Lei-Ming Zhang ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Salvia Miltiorrhiza ◽  
Water Soluble ◽  
Brain Barrier ◽  
Saline Control ◽  
Control Group ◽  
P Glycoprotein ◽  
Blood Brain ◽  
The Brain

Danshensu (3-(3, 4-dihydroxyphenyl) lactic acid), a water-soluble active component isolated from the root ofSalvia miltiorrhizaBunge, is widely used for the treatment of cerebrovascular diseases. The present study aims to investigate the role of P-glycoprotein in transport of Danshensu across the blood-brain barrier. Sprague-Dawley rats were pretreated with verapamil at a dose of 20 mg kg−1(verapamil group) or the same volume of normal saline (control group). Ninety minutes later, the animals were administrated with Danshensu (15 mg kg−1) by intravenous injection. At 15 min, 30 min, and 60 min after Danshensu administration, the levels of Danshensu in the blood and brain were detected by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The results showed that Danshensu concentrations in the brain of the rats pretreated with verapamil were significantly increased. In addition, the brain-plasma ratios of the group pretreated with verapamil were much higher than that of the control group. There was no difference in Danshensu level in plasma between the verapamil group and control group. The findings indicated that Danshensu can pass the blood-brain barrier, and P-glycoprotein plays an important role in Danshensu transportation in brain.

scholarly journals Magnetic Enhancement of Stem Cell–Targeted Delivery into the Brain Following MR-Guided Focused Ultrasound for Opening the Blood–Brain Barrier

2017 ◽  
Vol 26 (7) ◽  
pp. 1235-1246 ◽  
Author(s):  
Wei-Bin Shen ◽  
Pavlos Anastasiadis ◽  
Ben Nguyen ◽  
Deborah Yarnell ◽  
Paul J. Yarowsky ◽  
...  
Keyword(s):  
Stem Cell ◽  
Blood Brain Barrier ◽  
Targeted Delivery ◽  
Focused Ultrasound ◽  
Brain Barrier ◽  
Blood Brain ◽  
Magnetic Enhancement ◽  
The Brain

Neuropsychological Disorders and their Nanocarriers

2020 ◽  
Vol 26 (19) ◽  
pp. 2247-2256 ◽  
Author(s):  
Surbhi Sharma ◽  
Shweta Dang
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Targeted Delivery ◽  
Antipsychotic Drugs ◽  
Effective Drug ◽  
Brain Barrier ◽  
Neuropsychological Disorders ◽  
Blood Brain ◽  
The People ◽  
The Brain

Neuropsychological disorders are now growing rapidly worldwide among the people of diverse backgrounds irrespective of age, gender, and geographical region. Such disorders not only disturb the normal life and functionality of an individual but also impact the social relationships of the patient and the people associated with them, and if not treated in time, it may also result in mortality in severe conditions. Various antipsychotic drugs have been developed but their use is often limited by issues related to effective drug delivery at the site of action i.e. brain, mainly because of the blood-brain barrier. To resolve these issues, researchers and scientists have been working to develop a more effective drug delivery system where drugs can cross the blood-brain barrier and reach the brain in more effective concentrations. Drugs have been modified and formulated into nano-carriers and experimental studies for efficient and targeted delivery of drugs have been conducted. This review focuses on certain common neuropsychological diseases and their nanocarriers developed for drug delivery in the brain and are discussed with a brief description of various experimental in vitro and in vivo studies. This review also focuses on the intranasal route for the delivery of antipsychotic drugs and constraints faced due to the blood-brain barrier by the drugs.

scholarly journals Targeted Delivery of Neural Stem Cells to the Brain Using MRI-Guided Focused Ultrasound to Disrupt the Blood-Brain Barrier

PLoS ONE ◽  
2011 ◽  
Vol 6 (11) ◽  
pp. e27877 ◽  
Author(s):  
Alison Burgess ◽  
Carlos A. Ayala-Grosso ◽  
Milan Ganguly ◽  
Jessica F. Jordão ◽  
Isabelle Aubert ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Blood Brain Barrier ◽  
Targeted Delivery ◽  
Focused Ultrasound ◽  
Brain Barrier ◽  
Blood Brain ◽  
Mri Guided ◽  
The Brain

Ligand and Structure-based Modeling of Passive Diffusion through the Blood-Brain Barrier

2018 ◽  
Vol 25 (9) ◽  
pp. 1073-1089 ◽  
Author(s):  
Santiago Vilar ◽  
Eduardo Sobarzo-Sanchez ◽  
Lourdes Santana ◽  
Eugenio Uriarte
Keyword(s):  
Blood Brain Barrier ◽  
In Silico ◽  
Passive Diffusion ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
Different Types ◽  
The Brain

Background: Blood-brain barrier transport is an important process to be considered in drug candidates. The blood-brain barrier protects the brain from toxicological agents and, therefore, also establishes a restrictive mechanism for the delivery of drugs into the brain. Although there are different and complex mechanisms implicated in drug transport, in this review we focused on the prediction of passive diffusion through the blood-brain barrier. Methods: We elaborated on ligand-based and structure-based models that have been described to predict the blood-brain barrier permeability. Results: Multiple 2D and 3D QSPR/QSAR models and integrative approaches have been published to establish quantitative and qualitative relationships with the blood-brain barrier permeability. We explained different types of descriptors that correlate with passive diffusion along with data analysis methods. Moreover, we discussed the applicability of other types of molecular structure-based simulations, such as molecular dynamics, and their implications in the prediction of passive diffusion. Challenges and limitations of experimental measurements of permeability and in silico predictive methods were also described. Conclusion: Improvements in the prediction of blood-brain barrier permeability from different types of in silico models are crucial to optimize the process of Central Nervous System drug discovery and development.

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.

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