Recent approaches and success of liposome-based nanodrug carriers for the treatment of brain tumor

2021 ◽  
Vol 18 ◽  
Author(s):  
Tapan K Shaw ◽  
Paramita Paul
Keyword(s):  
Brain Tumor ◽  
Active Role ◽  
Hydrophilic Drugs ◽  
Enhanced Permeability And Retention ◽  
Blood Brain ◽  
Fruitful Research ◽  
The Brain ◽  
Colloidal Carrier ◽  
Research Domain ◽  
Potential Therapeutics

: Brain tumors are nothing but a collection of neoplasms originated either from areas within the brain or from systemic metastasized tumors of other organs that have spread to the brain. It is a leading cause of death worldwide. The presence of the blood-brain barrier (BBB), blood-brain tumor barrier (BBTB), and some other factors may limit the entry of many potential therapeutics into the brain tissues in tumor area at the therapeutic concentration required for satisfying effectiveness. Liposomes are taking an active role in delivering many drugs through the BBB into the tumor due to their nanosize and their physiological compatibility. Further, this colloidal carrier can encapsulate both lipophilic and hydrophilic drugs due to its unique structure. The surface of the liposomes can be modified with various ligands that are very specific to the numerous receptors overexpressed onto the BBB as well as onto the diseased tumor surface site (i.e., BBTB) to deliver selective drugs into the tumor site. Moreover, the enhanced permeability and retention (EPR) effect can be an added advantage for nanosize liposomes to concentrate into the tumor microenvironment through relatively leaky vasculature of solid tumor in the brain where no restriction of penetration applies compared to normal BBB. Here in this review, we have tried to compilethe recent advancement along with the associated challenges of liposomes containing different anticancer chemotherapeutics across the BBB/BBTB for the treatment of gliomas that will be very helpful for the readers for better understanding of different trends of brain tumor targeted liposomes-based drug delivery and for pursuing fruitful research on the similar research domain.

scholarly journals Molecular Mechanisms of Drug Resistance in Glioblastoma

2021 ◽  
Vol 22 (12) ◽  
pp. 6385
Author(s):  
Maya A. Dymova ◽  
Elena V. Kuligina ◽  
Vladimir A. Richter
Keyword(s):  
Drug Resistance ◽  
Brain Tumor ◽  
Molecular Mechanisms ◽  
Primary Brain Tumor ◽  
Therapeutic Resistance ◽  
Molecular Characteristics ◽  
Blood Brain ◽  
Conventional Radiation ◽  
The Brain ◽  
Made In

Glioblastoma multiforme (GBM) is the most common and fatal primary brain tumor, is highly resistant to conventional radiation and chemotherapy, and is not amenable to effective surgical resection. The present review summarizes recent advances in our understanding of the molecular mechanisms of therapeutic resistance of GBM to already known drugs, the molecular characteristics of glioblastoma cells, and the barriers in the brain that underlie drug resistance. We also discuss the progress that has been made in the development of new targeted drugs for glioblastoma, as well as advances in drug delivery across the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB).

scholarly journals Protection Against Blood-brain Barrier Permeability as a Possible Mechanism for Protective Effects of Thymoquinone Against Sickness Behaviors Induced by Lipopolysaccharide in Rats

2021 ◽  
Vol 16 (2) ◽  
Author(s):  
Rahimeh Bargi ◽  
Mahmoud Hosseini ◽  
Fereshteh Asgharzadeh ◽  
Majid Khazaei ◽  
Mohammad Naser Shafei ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Active Role ◽  
Brain Barrier ◽  
Control Group ◽  
Protective Effects ◽  
Blood Brain ◽  
Immobility Time ◽  
Sickness Behaviors ◽  
Bbb Permeability ◽  
The Brain

Background: Blood-brain barrier (BBB), as well-known protection for the brain, plays an active role in normal homeostasis. It might be changed by a range of inflammatory mediators to have a role in sickness behaviors. Objectives: Regarding the anti-inflammatory effects of thymoquinone (TQ), its protection against BBB permeability, as a possible mechanism for protective effects against sickness behaviors elicited by lipopolysaccharide (LPS), was evaluated in rats. Methods: The animals were grouped as follows and treated (n = 10 in each): (1) control (saline); (2) LPS 1 mg/kg, was injected two hours before behavioral tests for two weeks; (3-5) 2, 5, and 10 mg/kg TQ, respectively was injected 30 min before LPS injection. Open-field (OF), elevated plus-maze (EPM) and Forced Swimming test (FST) were done. Finally, the animals were anesthetized to evaluate for BBB permeability using Evans blue (EB) dye method. Results: Compared with control, LPS decreased the peripheral distance and crossing and also total crossing and distance in OF, (P < 0.01 - P < 0.001). The central crossing and distance and central time in all three treatment groups were more than LPS (P < 0.05 - P < 0.001). LPS also reduced the entries and the time spent in the open arm while increased the time spent in the closed arm in EPM (P < 0.05 - P < 0.001). The effects of LPS were reversed by TQ (P < 0.05 - P < 0.001). In FST, the immobility time and active time were increased and decreased by LPS compared with control (P < 0.001), respectively. In all three TQ-treated groups, the active and climbing times were more while the immobility time was fewer than the LPS (P < 0.05 - P < 0.001). The animals of the LPS group showed more EB dye content in their brain tissue than the control group (P < 0.05 - P < 0.001). TQ significantly reduced EB dye content of the brain tissues (P < 0.05 - P < 0.001). Conclusions: According to this study, protection against BBB permeability as a possible mechanism for the protective effects of TQ against sickness behaviors induced by LPS might be suggested.

Glioblastoma therapeutic approaches were established utilizing contemporary discoveries in delivering medicines to the brain as smart nanoparticles for focused therapy

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Brain Tumor ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Treatment Options ◽  
Brain Targeting ◽  
Cns Drug Delivery ◽  
Blood Brain ◽  
Medication Delivery ◽  
Prospective Application ◽  
The Brain

The blood-brain barrier (primary) and the blood-brain tumor barrier (secondary) are the main barriers for Glioblastoma (GBM) treatment options. Brain design is connected to a critical barrier that restricts medicine delivery to a specific brain region, leaving the rest of the brain without therapeutic chemicals. This requires moving to a different treatment strategy to reach effective therapeutic concentration in brain tumor tissue. Due to more accurate controlled release of medication to the affected area, a continual shift from standard treatment to targeted administration of medication to the brain is attracting more attention these days. GBM's therapeutic approach was established utilizing contemporary discoveries in delivering medicines to the brain as smart nanoparticles for focused therapy. Better knowledge of molecular mechanisms involved in brain targeting and receptor-based therapeutic potential can boost the therapy results. Nonetheless, the most promising technology is still under development, and continual attempts to infer the fundamental process involved in medication delivery will assist hasten nanoparticles' translation into clinical application. Furthermore, numerous complex nanoparticles, including multifunctional smart nanoparticles, have been created to overcome such challenges for CNS drug delivery and their prospective application has been clinically demonstrated or is in the trial phase.

Drug Delivery Systems and Strategies to Overcome the Barriers of Brain

2021 ◽  
Vol 28 ◽  
Author(s):  
Yogesh Garg ◽  
Deepak N Kapoor ◽  
Abhishek Kumar Sharma ◽  
Amit Bhatia
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Brain Barrier ◽  
Olfactory Pathway ◽  
Hydrophilic Drugs ◽  
Blood Brain ◽  
Effective Delivery ◽  
The Brain

Abstract: The transport of drugs to the central nervous system is the most challenging task for conventional drug delivery systems. Reduced permeability of drugs through the blood-brain barrier is a major hurdle in delivering drugs to the brain. Hence, various strategies for improving drug delivery through the blood-brain barrier are currently being explored. Novel drug delivery systems (NDDS) offer several advantages, including high chemical and biological stability, suitability for both hydrophobic and hydrophilic drugs, and can be administered through different routes. Furthermore, the conjugation of suitable ligands with these carriers tend to potentiate targeting to the endothelium of the brain and could facilitate the internalization of drugs through endocytosis. Further, the intranasal route has also shown potential, as a promising alternate route, for the delivery of drugs to the brain. This can deliver the drugs directly to the brain through the olfactory pathway. In recent years, several advancements have been made to target and overcome the barriers of the brain. This article deals with a detailed overview of the diverse strategies and delivery systems to overcome the barriers of the brain for effective delivery of drugs.

Enhanced therapeutic agent delivery through magnetic resonance imaging–monitored focused ultrasound blood-brain barrier disruption for brain tumor treatment: an overview of the current preclinical status

2012 ◽  
Vol 32 (1) ◽  
pp. E4 ◽  
Author(s):  
Hao-Li Liu ◽  
Hung-Wei Yang ◽  
Mu-Yi Hua ◽  
Kuo-Chen Wei
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Brain Tumors ◽  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Therapeutic Agent ◽  
Brain Barrier ◽  
Term Survival ◽  
Blood Brain ◽  
The Brain

Malignant glioma is a severe primary CNS cancer with a high recurrence and mortality rate. The current strategy of surgical debulking combined with radiation therapy or chemotherapy does not provide good prognosis, tumor progression control, or improved patient survival. The blood-brain barrier (BBB) acts as a major obstacle to chemotherapeutic treatment of brain tumors by severely restricting drug delivery into the brain. Because of their high toxicity, chemotherapeutic drugs cannot be administered at sufficient concentrations by conventional delivery methods to significantly improve long-term survival of patients with brain tumors. Temporal disruption of the BBB by microbubble-enhanced focused ultrasound (FUS) exposure can increase CNS-blood permeability, providing a promising new direction to increase the concentration of therapeutic agents in the brain tumor and improve disease control. Under the guidance and monitoring of MR imaging, a brain drug-delivery platform can be developed to control and monitor therapeutic agent distribution and kinetics. The success of FUS BBB disruption in delivering a variety of therapeutic molecules into brain tumors has recently been demonstrated in an animal model. In this paper the authors review a number of critical studies that have demonstrated successful outcomes, including enhancement of the delivery of traditional clinically used chemotherapeutic agents or application of novel nanocarrier designs for actively transporting drugs or extending drug half-lives to significantly improve treatment efficacy in preclinical animal models.

scholarly journals A Mathematical Model for Prediction of Drug Molecule Diffusion Across the Blood-Brain Barrier

2004 ◽  
Vol 31 (4) ◽  
pp. 520-527 ◽  
Author(s):  
Jonathan Burns ◽  
Donald F. Weaver ◽  
Jonathan Burns ◽  
Donald F. Weaver
Keyword(s):  
Mathematical Model ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Topological Descriptors ◽  
Final Model ◽  
Drug Molecules ◽  
Blood Brain ◽  
Brain Uptake Index ◽  
The Brain ◽  
Potential Therapeutics

Background:Predicting the ability of drugs to enter the brain is a longstanding problem in neuropharmacology. The first step in creating a much-needed computational algorithm for predicting whether a drug will enter brain is to devise a rigorous mathematical model.Methods:Employing two experimental measures of blood-brain barrier (BBB) penetrability (brain/plasma ratio and the brain-uptake index) and 14 theoretically derived biophysical predictors, a mathematical model was developed to quantitatively correlate molecular structure with ability to traverse the BBB.Results:This mathematical model employs Stein's hydrogen bonding number and Randic's topological descriptors to correlate structure with ability to cross the BBB. The final model accurately predicts the ability of test molecules to cross the BBB.Conclusion:A mathematical method to predict blood-brain barrier penetrability of drug molecules has been successfully devised. As a result of bioinformatics, chemoinformatics and other informatics-based technologies, the number of small molecules being developed as potential therapeutics is increasing exponentially. A biophysically rigorous method to predict BBB penetrability will be a much-needed tool for the evaluation of these molecules.

scholarly journals Focused Ultrasound and Microbubbles-Mediated Drug Delivery to Brain Tumor

Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 15
Author(s):  
Sheng-Kai Wu ◽  
Chia-Lin Tsai ◽  
Yuexi Huang ◽  
Kullervo Hynynen
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Focused Ultrasound ◽  
Therapeutic Agents ◽  
Non Invasive ◽  
Long Period ◽  
Blood Brain ◽  
Invasive Method ◽  
The Brain

The presence of blood–brain barrier (BBB) and/or blood–brain–tumor barriers (BBTB) is one of the main obstacles to effectively deliver therapeutics to our central nervous system (CNS); hence, the outcomes following treatment of malignant brain tumors remain unsatisfactory. Although some approaches regarding BBB disruption or drug modifications have been explored, none of them reach the criteria of success. Convention-enhanced delivery (CED) directly infuses drugs to the brain tumor and surrounding tumor infiltrating area over a long period of time using special catheters. Focused ultrasound (FUS) now provides a non-invasive method to achieve this goal via combining with systemically circulating microbubbles to locally enhance the vascular permeability. In this review, different approaches of delivering therapeutic agents to the brain tumors will be discussed as well as the characterization of BBB and BBTB. We also highlight the mechanism of FUS-induced BBB modulation and the current progress of this technology in both pre-clinical and clinical studies.

scholarly journals Formation of the blood–brain barrier: Wnt signaling seals the deal

2008 ◽  
Vol 183 (3) ◽  
pp. 371-373 ◽  
Author(s):  
Paul Polakis
Keyword(s):  
Tight Junction ◽  
Wnt Signaling ◽  
Blood Brain Barrier ◽  
Active Role ◽  
Brain Barrier ◽  
Structural Elements ◽  
Mechanistic Insight ◽  
Blood Brain ◽  
The Brain ◽  
Gain Access

Capillaries in the brain are especially selective in determining which blood-borne components gain access to neurons. The structural elements of this blood–brain barrier (BBB) reside at the tight junction, an intercellular protein complex that welds together adjacent endothelial cell membranes in the microvasculature. In this issue, Liebner et al. (Liebner, S., M. Corada, T. Bangsow, J. Babbage, A. Taddei, C.J. Czupalla, M. Reis, A. Felici, H. Wolburg, M. Fruttiger, et al. 2008. J. Cell Biol. 183: 409–417) report that Wnt signaling plays an active role in the development of the BBB by regulating expression of key protein constituents of the tight junction. Such mechanistic insight has implications for a variety of neuropathological states in which the BBB is breached.

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