scholarly journals In silico tool for predicting and designing Blood-Brain Barrier Penetrating Peptides

2021 ◽  
Author(s):  
Vinod Kumar ◽  
Sumeet Patiyal ◽  
Anjali Dhall ◽  
Neelam Sharma ◽  
Gajendra Pal Singh Raghava
Keyword(s):  
Machine Learning ◽  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Protein Sequence ◽  
Web Server ◽  
Brain Barrier ◽  
Blood Brain ◽  
Wide Range ◽  
The Brain ◽  
Brain Barriers

Blood-brain-barrier is a major obstacle in treating brain-related disorders as it does not allow to deliver drugs in the brain. In order to facilitate delivery of drugs in brain, we developed a method for predicting blood-brain-barrier penetrating peptides. These blood-brain barriers penetrating peptides (B3PPs) can act as therapeutic as well as drug delivery agents. We trained, tested, and evaluated our models on blood-brain-barrier peptides obtained from the B3Pdb database. First, we compute a wide range of peptide features then we select relevant peptide features. Finally, we developed numerous machine learning-based models for predicting blood-brain-barrier peptides using selected features. Our model based on random forest performed best on the top 80 selected features and achieved a maximum 85.08% accuracy with 0.93 AUROC. We also developed a web server, B3pred that implements our best models. It has three major modules that allow users to; i) predict B3PPs, ii) scanning B3PPs in a protein sequence, and iii) designing B3PPs using analogs. Our web server and standalone software is freely available at https://webs.iiitd.edu.in/raghava/b3pred/.

scholarly journals B3Pred: A Random-Forest-Based Method for Predicting and Designing Blood–Brain Barrier Penetrating Peptides

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1237
Author(s):  
Vinod Kumar ◽  
Sumeet Patiyal ◽  
Anjali Dhall ◽  
Neelam Sharma ◽  
Gajendra Pal Singh Raghava
Keyword(s):  
Machine Learning ◽  
Drug Delivery ◽  
Random Forest ◽  
Blood Brain Barrier ◽  
Protein Sequence ◽  
Brain Barrier ◽  
Major Obstacle ◽  
Blood Brain ◽  
Wide Range ◽  
The Brain

The blood–brain barrier is a major obstacle in treating brain-related disorders, as it does not allow the delivery of drugs into the brain. We developed a method for predicting blood–brain barrier penetrating peptides to facilitate drug delivery into the brain. These blood–brain barrier penetrating peptides (B3PPs) can act as therapeutics, as well as drug delivery agents. We trained, tested, and evaluated our models on blood–brain barrier peptides obtained from the B3Pdb database. First, we computed a wide range of peptide features. Then, we selected relevant peptide features. Finally, we developed numerous machine-learning-based models for predicting blood–brain barrier peptides using the selected features. The random-forest-based model performed the best with respect to the top 80 selected features and achieved a maximal 85.08% accuracy with an AUROC of 0.93. We also developed a webserver, B3pred, that implements our best models. It has three major modules that allow users to predict/design B3PPs and scan B3PPs in a protein sequence.

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.

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

2020 ◽  
Vol 26 (13) ◽  
pp. 1448-1465 ◽  
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.

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

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.

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

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.

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 Age-Associated Changes in the Immune System and Blood–Brain Barrier Functions

2019 ◽  
Vol 20 (7) ◽  
pp. 1632 ◽  
Author(s):  
Michelle Erickson ◽  
William Banks
Keyword(s):  
Central Nervous System ◽  
Immune System ◽  
Blood Brain Barrier ◽  
Neurological Disorders ◽  
Brain Barrier ◽  
Immune Functions ◽  
Blood Brain ◽  
The Brain ◽  
Brain Barriers

Age is associated with altered immune functions that may affect the brain. Brain barriers, including the blood–brain barrier (BBB) and blood–CSF barrier (BCSFB), are important interfaces for neuroimmune communication, and are affected by aging. In this review, we explore novel mechanisms by which the aging immune system alters central nervous system functions and neuroimmune responses, with a focus on brain barriers. Specific emphasis will be on recent works that have identified novel mechanisms by which BBB/BCSFB functions change with age, interactions of the BBB with age-associated immune factors, and contributions of the BBB to age-associated neurological disorders. Understanding how age alters BBB functions and responses to pathological insults could provide important insight on the role of the BBB in the progression of cognitive decline and neurodegenerative disease.

scholarly journals Permeabilization of the Blood-Brain Barrier via Mucosal Engrafting: Implications for Drug Delivery to the Brain

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e61694 ◽  
Author(s):  
Benjamin S. Bleier ◽  
Richie E. Kohman ◽  
Rachel E. Feldman ◽  
Shreshtha Ramanlal ◽  
Xue Han
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Brain

scholarly journals Rapid and Reversible Enhancement of Blood–Brain Barrier Permeability Using Lysophosphatidic Acid

2013 ◽  
Vol 33 (12) ◽  
pp. 1944-1954 ◽  
Author(s):  
Ngoc H On ◽  
Sanjot Savant ◽  
Myron Toews ◽  
Donald W Miller
Keyword(s):  
Drug Delivery ◽  
Molecular Weight ◽  
Blood Brain Barrier ◽  
Lysophosphatidic Acid ◽  
Near Infrared ◽  
Brain Barrier ◽  
Small Molecular Weight ◽  
Blood Brain ◽  
Bbb Permeability ◽  
The Brain

The present study characterizes the effects of lysophosphatidic acid (LPA) on blood–brain barrier (BBB) permeability focusing specifically on the time of onset, duration, and magnitude of LPA-induced changes in cerebrovascular permeability in the mouse using both magnetic resonance imaging (MRI) and near infrared fluorescence imaging (NIFR). Furthermore, potential application of LPA for enhanced drug delivery to the brain was also examined by measuring the brain accumulation of radiolabeled methotrexate. Exposure of primary cultured brain microvessel endothelial cells (BMECs) to LPA produced concentration-dependent increases in permeability that were completely abolished by clostridium toxin B. Administration of LPA disrupted BBB integrity and enhanced the permeability of small molecular weight marker gadolinium diethylenetriaminepentaacetate (Gd-DTPA) contrast agent, the large molecular weight permeability marker, IRdye800cwPEG, and the P-glycoprotein efflux transporter probe, Rhodamine 800 (R800). The increase in BBB permeability occurred within 3 minutes after LPA injection and barrier integrity was restored within 20 minutes. A decreased response to LPA on large macromolecule BBB permeability was observed after repeated administration. The administration of LPA also resulted in 20-fold enhancement of radiolabeled methotrexate in the brain. These studies indicate that administration of LPA in combination with therapeutic agents may increase drug delivery to the brain.

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