Hydrogel Microparticle Networks for the Controlled Delivery of Nanomedicines

用于纳米药物控制递送的水凝胶微粒网络

• 批准号: EP/M01973X/1
• 负责人: Tom McDonald
• 金额: $ 12.56万
• 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: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FM01973X%2F1
• 关键词: Hydrogel; Microparticle; Networks; Controlled; Delivery

This proposal seeks to combine the advantages of nanomedicines with the proven benefits of sustained drug release, addressing a global unmet need. This will be achieved through the design and development of a new type of implantable drug delivery system which releases drug-containing nanoparticles into the circulation. Such a technology would offer vast benefits for those patients who require long-term treatment. By combining recent developments in materials science, materials chemistry and nanomedicine, options will be studied that may act as future platforms for implantable nanomedicine release systems.Poor compliance, the improper following of a doctor's treatment recommendations is expected for 50% of patients suffering from chronic diseases. The resulting implications of poor compliance are increased ill-health, increased likelihood of negative consequences and the possibly of the disease developing a resistance to the treatment. Poor compliance is a very serious problem, it has been estimated that in the European Union 194,500 deaths a year can be attributed to poor compliance. It is possible to entrap a drug within a material, which can then be implanted in the body to slowly release the drug. Such materials are known as implantable drug delivery systems and can be designed to give sustained drug release over extended periods of time, therefore removing the need for the patient to take repeated drug doses. Implantable drug delivery systems have been shown to be medically very successful in the delivery of contraceptives and for the treatment of a range of diseases including cancer. In addition to removing the problem of poor patient compliance, implantable drug delivery systems can be configured to release drug directly into the surrounding tissue avoiding one of the main issues with orally taken drugs that are prevented from reaching blood circulation (first pass metabolism). In general, patient groups that suffer from poor compliance welcome implantable devices that aid the attainment of positive outcomes from their therapies.While implantable drug delivery systems have been demonstrated for the release of conventional drugs such as small molecules and biopharmaceuticals, release of drugs in the form of nanomaterials (materials with one dimension less than 1000 nm) from implantable drug delivery systems has never been demonstrated. The use of nanomaterials to deliver drugs is known as Nanomedicine, a field that has undergone rapid growth in the past decade. The vast majority of nanomedicines are administered to patients intravenously or orally and therefore currently need to be repeatedly re-administered to maintain the correct drug concentration in the body. Nanomedicine has been found to offer numerous advantages in therapeutic treatment, derived from the properties of the nanomaterials; including enhanced uptake of the drug into the blood stream, reduced side effects and improved delivery of the drug to where it is needed. Currently there are over 40 nanomedicines in clinical use, and over another 100 nanomedicines in medical trials. It is therefore likely that the use of nanomedicines will become more widespread in medicine in the future.This proposal aims to provide a proof of concept system to address the serious issue of poor patient compliance, for the delivery of present and future nanomedicines, with the goal of attracting further developmental and research activities in order to progress towards actual patient benefits.

该提案旨在将纳米医学的优势与药物持续释放的已证实益处联合收割机相结合，以解决全球未满足的需求。这将通过设计和开发一种新型的植入式药物输送系统来实现，该系统将含有药物的纳米颗粒释放到循环中。这种技术将为那些需要长期治疗的患者提供巨大的好处。通过结合材料科学、材料化学和纳米医学的最新发展，将研究可能作为植入式纳米药物释放系统未来平台的选择。依从性差，预计50%的慢性病患者会不正确地遵循医生的治疗建议。依从性差的后果是健康状况不佳的情况增加，产生负面后果的可能性增加，疾病可能对治疗产生抗药性。不遵守是一个非常严重的问题，据估计，在欧洲联盟，每年有194，500人死亡可归因于不遵守。可以将药物包埋在材料中，然后将其植入体内以缓慢释放药物。这种材料被称为可植入药物递送系统，并且可以被设计为在延长的时间段内提供持续的药物释放，因此消除了患者重复服用药物剂量的需要。植入式药物递送系统已被证明在递送避孕药和治疗包括癌症在内的一系列疾病方面在医学上非常成功。除了消除患者依从性差的问题之外，可植入药物递送系统可以被配置为将药物直接释放到周围组织中，从而避免口服药物被阻止到达血液循环（首过代谢）的主要问题之一。一般来说，依从性差的患者群体欢迎植入式设备，这些设备有助于从他们的治疗中获得积极的结果。虽然植入式药物递送系统已被证明用于释放常规药物，如小分子和生物药物，以纳米材料的形式释放药物（一维小于1000 nm的材料）从可植入药物递送系统中分离的方法从未得到证实。使用纳米材料来提供药物被称为纳米医学，这是一个在过去十年中经历了快速增长的领域。绝大多数纳米药物都是静脉注射或口服给药，因此目前需要反复重新给药，以保持体内正确的药物浓度。纳米医学已被发现在治疗性治疗中提供了许多优势，这些优势来自于纳米材料的特性;包括增强药物进入血流的吸收，减少副作用和改善药物向需要的地方的递送。目前有超过40种纳米药物在临床使用，另有100多种纳米药物在医学试验中。因此，很可能纳米医学的使用将在未来的医学中变得更加广泛。该提案旨在提供一个概念验证系统，以解决患者依从性差的严重问题，用于提供当前和未来的纳米医学，其目标是吸引进一步的开发和研究活动，以实现患者的实际利益。

项目成果

Using the hydrolysis of anhydrides to control gel properties and homogeneity in pH-triggered gelation

• DOI: 10.1039/c5ra22253b
• 发表时间: 2015-01-01
• 期刊: RSC ADVANCES
• 影响因子: 3.9
• 作者: Draper, Emily R.;Mears, Laura L. E.;Adams, Dave J.
• 通讯作者: Adams, Dave J.

Dual-stimuli responsive injectable microgel/solid drug nanoparticle nanocomposites for release of poorly soluble drugs.

• DOI: 10.1039/c6nr07858c
• 发表时间: 2017-05
• 期刊: Nanoscale
• 影响因子: 6.7
• 作者: A. Town;Marco Giardiello;R. Gurjar;M. Siccardi;M. Briggs;R. Akhtar;Tom O. McDonald

Tuning HIV drug release from a nanogel-based in situ forming implant by changing nanogel size.

通过改变纳米凝胶尺寸来调节基于纳米凝胶的原位形成植入物的 HIV 药物释放。

• DOI: 10.1039/c8tb01597j
• 发表时间: 2019
• 期刊: Journal of materials chemistry. B
• 作者: Town AR

Facile production of nanocomposites of carbon nanotubes and polycaprolactone with high aspect ratios with potential applications in drug delivery.

• DOI: 10.1039/c7ra13553j
• 发表时间: 2018-05-07
• 期刊: RSC advances
• 影响因子: 3.9
• 作者: Niezabitowska E;Smith J;Prestly MR;Akhtar R;von Aulock FW;Lavallée Y;Ali-Boucetta H;McDonald TO
• 通讯作者: McDonald TO