Integrated radiomaterials chemistry for simultaneous multi-component tracking of nanomedicines in biological matrices

集成放射性材料化学，用于同时跟踪生物基质中纳米药物的多成分

• 批准号: EP/L02635X/1
• 负责人: Steven Rannard
• 金额: $ 114.23万
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FL02635X%2F1
• 关键词: Integrated; radiomaterials; chemistry; simultaneous; multi

The current global clinical use of nanomedicines benefits patients daily and has considerable market value; global estimates = US$75bn ('11), predicted to be $US160bn by 2015. The decision to develop new nanomedicines balances the needs of patients (are conventional medicinal approaches failing or unable to help?), type of disease/threat to health (is the disease potentially terminal?) and dosing regimes (oral or injectable administration; chronic or acute dosing?). Many therapies require long-term dosing to maintain health over prolonged periods. For example, >33 m people (incl. children) are currently living with HIV/AIDS and the optimised daily dosing (over decades) of highly active antiretroviral therapies helps to prevent progression of HIV to AIDS, and allows a life for many patients that is as close to normal as possible. In contrast, due to the acute nature of cancer (imminent threat to life) short-term interventions, including highly toxic therapies, are required for rapid cure. Cancer research has seen many nanomedicine benefits including the targeting of poorly soluble drugs to solid tumours. Similar contrasts are seen in antiepileptic and cholesterol-lowering therapies (long term health maintenance) versus systemic fungal infections or acute respiratory distress (immediate cure required). Most nanomedicines are enabled by polymer science ranging from polymer-bound drugs through to polymers stabilising drug nanoparticles or forming nanosized drug encapsulants. Nanomedicine expansion to long-term dosage forms and chronic diseases will increase and the behaviour/fate of polymeric materials in the body must be studied to generate safety and toxicology information, to increase the speed-to-clinic (ie patient benefits) and enable decision-making of pharmaceutical companies and regulatory bodies. Currently, the study of low concentrations of polymeric materials in complex environments is extremely difficult. The use of radioactive isotopes for biomedical research is well established with drugs labelled to allow rapid quantification and tracing, however, very few reports describe radiolabelled polymeric components of candidate nanomedicines and facilities for polymer radiochemistry have largely disappeared in UK Universities. The University of Liverpool has created facilities to enable radiomaterials chemistry, providing new academic UK skills and enabling pharmacological studies of polymers used in nanomedicine strategies and other applications. This 3 year programme aims to conduct the first nanomedicine studies that simultaneously monitor drug AND enabling polymeric materials, whilst exploring the synthesis of radiolabelled polymers with the most up-to-date techniques. This will place UK nanomedicine research at the forefront of understanding and provide an engagement platform for global pharmaceutical companies and regulatory bodies as the huge potential for nanomedicine is realised for patients of all ages across multiple disease areas.

目前全球临床使用的纳米药物使患者每天受益，并具有相当大的市场价值;全球估计= 750亿美元（'11），预计到2015年将达到1600亿美元。开发新纳米药物的决定平衡了患者的需求（传统的药物方法是否失败或无法提供帮助？），疾病类型/对健康的威胁（疾病是否可能是晚期？）和给药方案（口服或注射给药;慢性或急性给药？）。许多疗法需要长期给药以在长时间内维持健康。例如，超过3300万人（包括目前，艾滋病毒/艾滋病感染者（儿童）和高效抗逆转录病毒疗法的优化每日剂量（数十年）有助于防止艾滋病毒发展为艾滋病，并使许多患者的生活尽可能接近正常。相比之下，由于癌症的急性性质（对生命的迫在眉睫的威胁），需要短期干预，包括高毒性治疗，以快速治愈。癌症研究已经看到了许多纳米医学的好处，包括将难溶性药物靶向实体瘤。在抗癫痫和降胆固醇治疗（长期健康维护）与系统性真菌感染或急性呼吸窘迫（需要立即治愈）中也观察到类似的对比。大多数纳米医学都是由聚合物科学实现的，从聚合物结合药物到聚合物稳定药物纳米颗粒或形成纳米药物澄清剂。纳米医学扩展到长期剂型和慢性疾病将增加，必须研究聚合物材料在体内的行为/命运，以产生安全性和毒理学信息，提高临床速度（即患者受益），并使制药公司和监管机构能够做出决策。目前，复杂环境中低浓度聚合物材料的研究极为困难。放射性同位素在生物医学研究中的应用已经很成熟，药物被标记以允许快速定量和追踪，然而，很少有报告描述候选纳米药物的放射性标记聚合物组分，并且聚合物放射化学设施在英国大学中基本上消失了。利物浦大学已经建立了设施，使放射性材料化学，提供新的学术英国技能，并使用于纳米医学战略和其他应用的聚合物的药理学研究。这个为期3年的计划旨在进行第一个纳米医学研究，同时监测药物和使聚合物材料，同时探索放射性标记聚合物的合成与最新的技术。这将使英国纳米医学研究处于理解的最前沿，并为全球制药公司和监管机构提供一个参与平台，因为纳米医学的巨大潜力为多个疾病领域的所有年龄段的患者实现。

项目成果

Mucus-responsive functionalized emulsions: design, synthesis and study of novel branched polymers as functional emulsifiers.

• DOI: 10.1039/d0ra05820c
• 发表时间: 2020-08-17
• 期刊: RSC advances
• 影响因子: 3.9

Exploring the homogeneous controlled radical polymerisation of hydrophobic monomers in anti-solvents for their polymers: RAFT and ATRP of various alkyl methacrylates in anhydrous methanol to high conversion and low dispersity

• DOI: 10.1039/c5py00791g
• 发表时间: 2015-01-01
• 期刊: POLYMER CHEMISTRY
• 影响因子: 4.6
• 作者: Dwyer, A. B.;Chambon, P.;Rannard, S. P.
• 通讯作者: Rannard, S. P.

Modulated release from implantable ocular silicone oil tamponade drug reservoirs.

• DOI: 10.1002/pola.28973
• 发表时间: 2018-04-15
• 期刊: Journal of polymer science. Part A, Polymer chemistry
• 作者: Cauldbeck H;Le Hellaye M;McDonald TO;Long M;Williams RL;Rannard SP;Kearns VR
• 通讯作者: Kearns VR

Expanding the monomer scope of linear and branched vinyl polymerisations via copper-catalysed reversible-deactivation radical polymerisation of hydrophobic methacrylates using anhydrous alcohol solvents

• DOI: 10.1039/c9py00777f
• 发表时间: 2019-10-07
• 期刊: POLYMER CHEMISTRY
• 影响因子: 4.6
• 作者: Flynn, Sean;Dwyer, Andrew B.;Rannard, Steve
• 通讯作者: Rannard, Steve

Long-acting injectable atovaquone nanomedicines for malaria prophylaxis.

长效注射型纳米药物可预防疟疾。

• DOI: 10.1038/s41467-017-02603-z
• 发表时间: 2018-01-22
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Bakshi RP;Tatham LM;Savage AC;Tripathi AK;Mlambo G;Ippolito MM;Nenortas E;Rannard SP;Owen A;Shapiro TA
• 通讯作者: Shapiro TA