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Nanoparticles for the Targeted Delivery of Therapeutic Agents to the Brain for the Treatment of Dementias.

用于将治疗药物靶向输送至大脑以治疗痴呆症的纳米颗粒。

基本信息

批准号：
EP/G061521/1
负责人：
Stephen Hart
金额：
$ 173.33万
依托单位：
University College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2009
资助国家：
英国
起止时间：
2009 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FG061521%2F1
关键词：
Nanoparticles Targeted Delivery Therapeutic Agents

项目摘要

This project focuses on the development of nanotechnologies for the targeted delivery of novel therapies for Alzheimer's disease, the major cause of dementia in the elderly. The most common symptoms of dementias are gradual memory loss, confusion, and changes in personality, mood and behaviour. There are currently about 700,000 dementia patients in the UK and approximately 450,000 of those have Alzheimer's disease. There are no cures for dementias, only drugs that treat the symptoms and temporarily stabilize the disease progression so patients become more dependent on care. The cost of formal healthcare services (e.g., residential care, NHS support services) for dementia patients at 4Bn in 2002 are formidable, and expected to grow to 13Bn by 2031. However, when informal care contributions from families of patents are considered, estimated costs escalate to about 17Bn. There is a further economic and social toll from the impact of patient care on the careers of carers. Dementia is therefore a growing medical, social and economic problem for the UK and beyond. The current level of research activity into the understanding and treatment of dementias does not reflect the enormity of the growing challenge. Dementia is one of the major causes of disability in later life, contributing 11.2% of all years lived with disability over the age of 60, compared to 2.4% for cancer. Since 2002, however, only 1.4% of published research papers on disabilities concerned dementias, compared to 23.5% for cancers. Increased research funding and activity in dementias is therefore an urgent priority. We aim in this project to harness nanotechnologies for the design and delivery of new therapeutics for the treatment of Alzheimer's disease. Nanoparticles are formulations of synthetic, chemical components that self-assemble on mixing into particles of less than 100 nm. They can be used to package a variety of drugs, including genes, proteins and RNA molecules. The nanoparticle components that will be designed and synthesised will comprise novel peptides and lipids with smart properties, such as receptor targeting, stealth coatings, bioresponsive linkers for disassembly, and biocompatibility. The uptake of nanoparticles into the brain from the circulation is impeded by the blood brain barrier so we will optimise a method called convection enhanced delivery (CED). In CED the blood-brain barrier is physically bypassed by injecting reagents directly into the brain through a fine needle under constant pressure. CED has already been used to administer therapeutics, achieving widespread dispersal through the brain, but has not been optimised for nanoparticle delivery. The project combines basic studies into nanoparticle materials and biology of the brain in relation to CED, and more applied studies into nanoparticle formulation and CED-mediated dispersal studies using MRI. The output of this study will be a nanoparticle platform technology and delivery method compatible with a range of therapeutic options for Alzheimer's disease and other forms of dementia. The research team comprises scientific experts in chemistry, drug and nanoparticle formulations as well as clinical expertise in brain pathology, surgery and experimental clinical trials, and has the capabilities to succeed both in this project and a future Stage 2 therapeutic study into Alzheimer's disease. This new capability could transform the management of patients with dementias with enormous potential benefits to UK society and the economy.

该项目的重点是开发纳米技术，用于针对老年痴呆症的主要原因阿尔茨海默病的新疗法。痴呆症最常见的症状是逐渐的记忆丧失，意识模糊，以及个性，情绪和行为的变化。目前英国约有70万痴呆症患者，其中约45万患有阿尔茨海默病。痴呆症没有治愈方法，只有治疗症状并暂时稳定疾病进展的药物，因此患者变得更加依赖护理。正规医疗服务的成本（例如，2002年，为痴呆症患者提供的40亿人的家庭护理、NHS支持服务）令人生畏，预计到2031年将增长到130亿人。然而，当考虑到专利家庭的非正式护理贡献时，估计成本上升到约170亿美元。病人护理对护理人员职业的影响造成了进一步的经济和社会损失。因此，痴呆症是英国及其他地区日益严重的医疗、社会和经济问题。目前对痴呆症的理解和治疗的研究活动水平并没有反映出日益增长的挑战的紧迫性。痴呆症是晚年残疾的主要原因之一，占60岁以上残疾人的11.2%，而癌症占2.4%。然而，自2002年以来，发表的关于残疾的研究论文中只有1.4%涉及痴呆症，而癌症的比例为23.5%。因此，增加痴呆症的研究资金和活动是一个紧迫的优先事项。我们在这个项目中的目标是利用纳米技术来设计和提供治疗阿尔茨海默病的新疗法。纳米颗粒是合成的化学成分的制剂，其在混合成小于100 nm的颗粒时自组装。它们可用于包装各种药物，包括基因、蛋白质和RNA分子。将被设计和合成的纳米颗粒组分将包括具有智能特性的新型肽和脂质，例如受体靶向、隐形涂层、用于拆卸的生物响应连接体和生物相容性。纳米颗粒从血液循环进入大脑的吸收受到血脑屏障的阻碍，因此我们将优化一种称为对流增强递送（CED）的方法。在CED中，通过在恒定压力下通过细针将试剂直接注射到脑中，从而物理绕过血脑屏障。CED已经被用于给药治疗，实现了通过大脑的广泛分散，但尚未优化纳米颗粒递送。该项目结合了纳米颗粒材料和脑生物学与CED的基础研究，以及更多的应用研究纳米颗粒制剂和CED介导的分散研究使用MRI。这项研究的成果将是一种纳米颗粒平台技术和递送方法，与阿尔茨海默病和其他形式的痴呆症的一系列治疗选择兼容。该研究团队包括化学、药物和纳米颗粒制剂方面的科学专家，以及脑病理学、手术和实验性临床试验方面的临床专业知识，有能力在该项目和未来的阿尔茨海默病第二阶段治疗研究中取得成功。这种新的能力可以改变痴呆症患者的管理，为英国社会和经济带来巨大的潜在利益。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Trichain cationic lipids: the potential of their lipoplexes for gene delivery.

DOI：
10.1039/c8bm00965a
发表时间：
2018-12-18
期刊：
Biomaterials science
影响因子：
6.6
作者：
Kudsiova L;Mohammadi A;Mustapa MFM;Campbell F;Welser K;Vlaho D;Story H;Barlow DJ;Tabor AB;Hailes HC;Lawrence MJ
通讯作者：
Lawrence MJ

Systematic Comparisons of Formulations of Linear Oligolysine Peptides with siRNA and Plasmid DNA.