SCIDOT-08. CHILDREN’S BRAIN TUMOUR DRUG DELIVERY CONSORTIUM (CBTDDC)

Abstract INTRODUCTION The brain tumour community has seen significant progress in the discovery of new therapeutic targets and anticancer drugs. Unfortunately, advances in how to deliver drugs to the brain lag behind. The blood-brain barrier restricts the entry of many small-molecule drugs and nearly all large molecule drugs that have been developed to treat brain disorders. METHODS Following an international CNS drug delivery workshop in 2016, we were awarded funding from Children with Cancer UK to launch the Children’s Brain Tumour Drug Delivery Consortium (CBTDDC; www.cbtddc.org; @cbtddc). RESULTS The CBTDDC launched in 2017 (in Europe and the US) to raise awareness of the challenge of drug delivery in childhood brain tumours, and to initiate and strengthen research collaborations to accelerate the development of drug delivery systems. We ran a Workshop on Drug Delivery to the Brain, attracting 52 delegates from the UK, Belgium, Spain and Portugal. We liaised with UK-based funders over the drug delivery agenda, and with UK policy makers. In the US, we jointly organised the SIGN2019 meeting and we are currently liaising with the leads of Project ‘All In’ DIPG about how we can lend our support to this project. As of June 2019, 150 individuals have registered with the consortium, representing researchers, clinicians, charities, patient groups and industry. These stakeholders represent 70 research institutions, covering 15 countries (France, UK, Italy, Sweden, The Netherlands, USA, Greece, Germany, Belgium, Cuba, Denmark, Spain, Portugal, Israel and Egypt). We host a freely accessible online collaborative research database, containing the details of over 70 researchers. CONCLUSION We believe that collaboration between clinicians and multi-disciplinary researchers is vital to solving the brain tumour drug delivery challenge. We hope to raise awareness of the CBTDDC, and to extend our invitation for collaborators to join the consortium, through SCIDOT’s unrivalled drug delivery platform.

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Foreign States in Domestic Markets

10.1093/oso/9780198786085.001.0001 ◽

2021 ◽

Author(s):

Mark Thatcher ◽

Tim Vlandas

Keyword(s):

Political Economy ◽

Financial Markets ◽

Domestic Politics ◽

National Policy ◽

Sovereign Wealth Funds ◽

Policy Makers ◽

Domestic Markets ◽

The Us ◽

The Uk ◽

Domestic Economies

Political economy debates have focused on the internationalization of private capital. But foreign states increasingly enter domestic markets as financial investors. How do policy makers in recipient countries react? Do they treat purchases as a threat and impose restrictions or see them as beneficial and welcome them? What are the wider implications for debates about state capacities to govern domestic economies in the face of internationalization of financial markets? In response, the book develops the concept of ‘internationalized statism’—governments welcoming and using foreign state investments to govern their domestic economies—and applies it to the most prominent overseas state investors: Sovereign Wealth Funds (SWFs). Many SWFs are from Asia and the Middle East and their number and size have greatly expanded, reaching $9 trillion by 2020. The book examines policies towards non-Western SWFs buying company shares in four countries: the US, the UK, France, and Germany. Although the US has imposed significant legal restrictions, the others have pursued internationalized statism in ways that are surprising given both popular and political economy classifications. The book argues that the policy patterns found are related to domestic politics, notably the preferences and capacities of the political executive and legislature, rather than solely economic needs or national security risks. The phenomenon of internationalized statism underlines that overseas state investment provides policy makers in recipient states with new allies and resources. The study of SWFs shows how and why internationalization and liberalization of financial markets offer national policy makers opportunities to govern their domestic economies.

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Shortcut Approaches to Substance Delivery into the Brain Based on Intranasal Administration Using Nanodelivery Strategies for Insulin

Molecules ◽

10.3390/molecules25215188 ◽

2020 ◽

Vol 25 (21) ◽

pp. 5188

Author(s):

Toshihiko Tashima

Keyword(s):

Drug Delivery ◽

Olfactory Epithelium ◽

Olfactory Nerve ◽

Brain Drug Delivery ◽

Cns Drug Delivery ◽

Capillary Endothelial Cells ◽

Alternative Approaches ◽

Cns Drugs ◽

Direct Delivery ◽

The Brain

The direct delivery of central nervous system (CNS) drugs into the brain after administration is an ideal concept due to its effectiveness and non-toxicity. However, the blood–brain barrier (BBB) prevents drugs from penetrating the capillary endothelial cells, blocking their entry into the brain. Thus, alternative approaches must be developed. The nasal cavity directly leads from the olfactory epithelium to the brain through the cribriform plate of the skull bone. Nose-to-brain drug delivery could solve the BBB-related repulsion problem. Recently, it has been revealed that insulin improved Alzheimer’s disease (AD)-related dementia. Several ongoing AD clinical trials investigate the use of intranasal insulin delivery. Related to the real trajectory, intranasal labeled-insulins demonstrated distribution into the brain not only along the olfactory nerve but also the trigeminal nerve. Nonetheless, intranasally administered insulin was delivered into the brain. Therefore, insulin conjugates with covalent or non-covalent cargos, such as AD or other CNS drugs, could potentially contribute to a promising strategy to cure CNS-related diseases. In this review, I will introduce the CNS drug delivery approach into the brain using nanodelivery strategies for insulin through transcellular routes based on receptor-mediated transcytosis or through paracellular routes based on escaping the tight junction at the olfactory epithelium.

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Special delEVery: Extracellular Vesicles as Promising Delivery Platform to the Brain

Biomedicines ◽

10.3390/biomedicines9111734 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1734

Author(s):

Marie J. Pauwels ◽

Charysse Vandendriessche ◽

Roosmarijn E. Vandenbroucke

Keyword(s):

Drug Delivery ◽

Extracellular Vesicles ◽

Transport Mechanisms ◽

Cell Type ◽

Administration Routes ◽

Brain Drug Delivery ◽

Tissue Targeting ◽

Delivery Platform ◽

The Brain ◽

Cns Targeting

The treatment of central nervous system (CNS) pathologies is severely hampered by the presence of tightly regulated CNS barriers that restrict drug delivery to the brain. An increasing amount of data suggests that extracellular vesicles (EVs), i.e., membrane derived vesicles that inherently protect and transfer biological cargoes between cells, naturally cross the CNS barriers. Moreover, EVs can be engineered with targeting ligands to obtain enriched tissue targeting and delivery capacities. In this review, we provide a detailed overview of the literature describing a natural and engineered CNS targeting and therapeutic efficiency of different cell type derived EVs. Hereby, we specifically focus on peripheral administration routes in a broad range of CNS diseases. Furthermore, we underline the potential of research aimed at elucidating the vesicular transport mechanisms across the different CNS barriers. Finally, we elaborate on the practical considerations towards the application of EVs as a brain drug delivery system.

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Factors for Global Diffusion of the Internet

Encyclopedia of Information Science and Technology, Second Edition ◽

10.4018/978-1-60566-026-4.ch241 ◽

2011 ◽

pp. 1522-1526

Author(s):

Ravi Nath ◽

Vasudeva N.R. Murthy

Keyword(s):

The Internet ◽

Key Factors ◽

Political Leaders ◽

Policy Makers ◽

Overwhelming Evidence ◽

Internet Diffusion ◽

The Us ◽

The World ◽

Diffusion Rates ◽

The Uk

There is overwhelming evidence that the use of the Internetenabled applications and solutions provide unprecedented economic growth opportunities. However, the Internet diffusion rates remain low in many countries. According to the International Telecommunications Union (ITU), in 2004, less than 3% of the Africans used the Internet, whereas the average Internet subscription rate for G8 countries (Canada, France, Germany, Italy, Japan, Russia, the UK, and the US) is about 50%. Also, in nearly 30 countries the Internet penetration rates still remain below 1% (ITU, 2006). So, what are the key factors that explain this wide variation in Internet subscription rates in countries around the world? An understanding of these factors will be highly useful for policy makers, economic developmental agencies and political leaders in establishing and implementing suitable national developmental strategies and policies.

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The Legacy of the Financial Crisis

Productivity and the Bonus Culture ◽

10.1093/oso/9780198836117.003.0001 ◽

2019 ◽

pp. 1-12

Author(s):

Andrew Smithers

Keyword(s):

Financial Crisis ◽

Liberal Democracy ◽

Asset Prices ◽

Central Banks ◽

Living Standards ◽

Policy Makers ◽

The Us ◽

Weak Growth ◽

The Uk ◽

Post Hoc

The reputation of liberal democracy has fallen not only internationally but even within the UK and the US, which on current policies risk a decline in living standards and an even worse outcome should more to populist policies be implemented. Weak growth followed the financial crisis but was not caused by it. Holding otherwise is an example of the ‘post hoc fallacy’. Weak growth was caused solely by adverse changes in demography and poor productivity. Addressing both economists and the wider audience of those concerned with our economic and political future, this chapter shows that the adverse changes in demography and productivity have causes which predate the financial crisis by many years. The financial crisis was due to poor theory which led central banks to ignore the risks of high asset prices and excess debt. Poor theory today inhibits policy makers from recognizing that bonus culture policy has stifled growth.

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Nanotechnology Approaches for Enhanced CNS Drug Delivery in the Management of Schizophrenia

Advanced Pharmaceutical Bulletin ◽

10.34172/apb.2022.052 ◽

2021 ◽

Author(s):

Rajalakshmi R ◽

Krishnakumar N Menon ◽

Sreeja C Nair

Keyword(s):

Drug Delivery ◽

Targeted Drug Delivery ◽

Symptomatic Relief ◽

Therapeutic Strategies ◽

Review Article ◽

Visual Hallucinations ◽

Cns Drug Delivery ◽

The Central Nervous System ◽

The Brain

Schizophrenia is a neuropsychiatric disorder mainly affecting the central nervous system, presented with auditory and visual hallucinations, delusion and withdrawal from society. Abnormal dopamine levels mainly characterise the disease; various theories of neurotransmitters explain the pathophysiology of the disease. The current therapeutic approach deals with the systemic administration of drugs other than the enteral route, altering the neurotransmitter levels within the brain and providing symptomatic relief. Fluid biomarkers help in the early detection of the disease, which would improve the therapeutic efficacy. However, the major challenge faced in CNS drug delivery is the blood-brain barrier. Nanotherapeutic approaches may overcome these limitations, which will improve safety, efficacy, and targeted drug delivery. This review article addresses the main challenges faced in CNS drug delivery and the significance of current therapeutic strategies and nanotherapeutic approaches for a better understanding and enhanced drug delivery to the brain, which improve the quality of life of schizophrenia patients.

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Permeation Challenges of Drugs for Treatment of Neurological Tuberculosis and HIV and the Application of Magneto-Electric Nanoparticle Drug Delivery Systems

Pharmaceutics ◽

10.3390/pharmaceutics13091479 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1479

Author(s):

Sinaye Mhambi ◽

David Fisher ◽

Moise B. Tchoula Tchokonte ◽

Admire Dube

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Anatomical Structure ◽

Invasive Approach ◽

Non Invasive ◽

Cns Drug Delivery ◽

Immunodeficiency Virus ◽

The Central Nervous System ◽

Nanoparticle Drug Delivery ◽

The Brain

The anatomical structure of the brain at the blood–brain barrier (BBB) creates a limitation for the movement of drugs into the central nervous system (CNS). Drug delivery facilitated by magneto-electric nanoparticles (MENs) is a relatively new non-invasive approach for the delivery of drugs into the CNS. These nanoparticles (NPs) can create localized transient changes in the permeability of the cells of the BBB by inducing electroporation. MENs can be applied to deliver antiretrovirals and antibiotics towards the treatment of human immunodeficiency virus (HIV) and tuberculosis (TB) infections in the CNS. This review focuses on the drug permeation challenges and reviews the application of MENs for drug delivery for these diseases. We conclude that MENs are promising systems for effective CNS drug delivery and treatment for these diseases, however, further pre-clinical and clinical studies are required to achieve translation of this approach to the clinic.

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EPCT-08. TRIAL WORKING GROUPS FOR PAEDIATRIC BRAIN TUMOURS

Neuro-Oncology ◽

10.1093/neuonc/noab090.194 ◽

2021 ◽

Vol 23 (Supplement_1) ◽

pp. i48-i48

Author(s):

Ruman Rahman ◽

David Walker ◽

Emma Campbell ◽

Kristian Aquilina

Keyword(s):

Drug Delivery ◽

Clinical Trials ◽

Brain Tumour ◽

Brain Tumours ◽

International Workshop ◽

Convection Enhanced Delivery ◽

Children With Cancer ◽

Cns Drug Delivery ◽

Working Groups ◽

Paediatric Brain Tumours

Abstract Introduction Brain tumours are the biggest cancer killer in children and young adults. Several recent developments have the potential to change the treatment of brain tumours in children. These include ultrasound-mediated blood-brain barrier disruption, convection enhanced delivery, polymer delivery systems and electric field therapy, as well as intra-arterial, intra-CSF and intra-nasal chemotherapy. To date, there have been very few clinical trials to evaluate any of these. The science and technology underlying these developments is not traditionally embedded within the standard paediatric neuro-oncology network. In addition, custom-built hardware, novel surgical procedures and, in some cases, the testing and licensing of implantable devices, add difficulty at the regulatory level. Methods The authors participated in an international workshop funded by the charity Children with Cancer UK in 2016, where different experimental techniques aimed at optimising CNS drug delivery were discussed. Following this workshop and two subsequent workshops run by the CBTDDC (Children’s Brain Tumour Drug Delivery Consortium) in 2018 and 2020, the CBTDDC and the recently developed ITCC (Innovative Therapies for Children with Cancer) brain tumour group started working together to set up a new initiative. This aims to develop CNS-delivery-focused trial working groups for paediatric brain tumours. Results We have assembled a prestigious steering group, comprising international researchers and clinicians with expertise in diverse aspects of translational and clinical research in CNS drug delivery. At our first group meeting in March, participants will discuss the most effective ways of translating the emerging drug delivery modalities into clinical trials. Prioritised actions will be taken forward and the group will reconvene to discuss developments and next steps at a workshop in the Autumn. Conclusion We present this abstract to the SNO Paediatric conference to raise awareness of this initiative with the large number of relevant stakeholders who will be attending the event.

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COVID-19 and people's health-wealth preferences: Information effects and policy implications

10.31235/osf.io/mz67j ◽

2020 ◽

Author(s):

Shaun Hargreaves Heap ◽

Christel Koop ◽

Konstantinos Matakos ◽

Asli Unan ◽

Nina Sophie Weber

Keyword(s):

Information Provision ◽

Policy Implications ◽

Health Costs ◽

Survey Experiment ◽

Public Preferences ◽

Policy Makers ◽

Trade Off ◽

The Us ◽

The Uk ◽

Relative Valuation

Policy makers responding to COVID-19 need to know people’s relative valuation of health over wealth. Loosening and tightening lockdowns moves a society along a (perceived) health-wealth trade-off and the associated changes have to accord with the public’s relative valuation of health and wealth for maximum compliance. In our survey experiment (N=4,618), we randomize information provision on economic and health costs to assess public preferences over this trade-off in the UK and the US. People strongly prioritize health over wealth, but the treatment effects suggest these priorities will change as experience of COVID-19 deaths and income losses evolves. Information also has heterogeneous/polarizing effects. These results encourage policy caution. Individual differences in health-wealth valuation highlight this study’s importance because they map onto compliance with current lockdown measures.

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Trial working groups for paediatric brain tumours

Neuro-Oncology ◽

10.1093/neuonc/noab195.020 ◽

2021 ◽

Vol 23 (Supplement_4) ◽

pp. iv9-iv9

Author(s):

Kristian Aquilina ◽

Ruman Rahman ◽

David Walker ◽

Emma Campbell

Keyword(s):

Drug Delivery ◽

Clinical Trials ◽

Brain Tumour ◽

Brain Tumours ◽

Delivery Systems ◽

Children With Cancer ◽

Cns Drug Delivery ◽

Oncology Research ◽

Steering Group ◽

Paediatric Brain Tumours

Abstract Aims Children's brain tumours are the biggest cancer killer in children and young adults. Several recent developments have the potential to change the treatment of brain tumours in children. These include intra-CSF chemotherapy, ultrasound-mediated blood-brain barrier disruption, convection enhanced delivery, polymer delivery systems and electric field therapy, as well as intra-arterial and intra-nasal chemotherapy. To date, there have been very few clinical trials to evaluate any of these. The science and technology underlying these developments is not traditionally embedded within the standard paediatric neuro-oncology network. In addition, custom-built hardware, novel surgical procedures and, in some cases, the testing and licensing of implantable devices, add difficulty at the regulatory level. Method The authors participated in an international workshop funded by the charity Children with Cancer UK in 2016, where different experimental techniques aimed at optimising CNS drug delivery were discussed. Following this workshop and two subsequent workshops run by the CBTDDC (Children’s Brain Tumour Drug Delivery Consortium) in 2018 and 2020, the CBTDDC and the recently developed ITCC (Innovative Therapies for Children with Cancer) brain tumour group started working together to set up a new initiative. Called the ‘Clinical Trials Working Group for Central Nervous System Drug Delivery’, this aims to accelerate clinical trials to assess the safety and effectiveness of drug delivery devices for the treatment of paediatric brain tumours. On March 1st, 2021, CBTDDC with guest chair, Mr Kristian Aquilina (Consultant Paediatric Neurosurgeon at Great Ormond Street Hospital), hosted the first virtual meeting of this group. Results We have assembled a prestigious steering group, comprising international researchers and clinicians with expertise in diverse aspects of translational and clinical research in CNS drug delivery. At our first group meeting on March 1st, 2021, 38 leading brain tumour research scientists and clinicians from the UK, EU and US tackled the challenges head-on, with commitment and a driving passion to identify and move forwards with the most effective ways of translating drug delivery modalities into clinical trials. Attendees were split into three break-out sessions based on distinct drug delivery systems, and lots of insightful comments were collated. Conclusion The ideas generated during the 1st March meeting will help form the basis of a CBTDDC ‘Clinical Trials’ workshop in the autumn of 2021. In particular, there was an agreed consensus that a key objective will be the creation of a ‘Roadmap’ document for pre-clinical to clinical translation which would be shared with the paediatric neuro-oncology research community. CBTDDC look forward to working with steering group as we act on their recommendations to address the current challenges faced by translational drug delivery research. We present this abstract to the BNOS Annual 2021 Meeting to raise awareness of this initiative with the large number of relevant stakeholders who will be attending the event.

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