UltraSOuNd-controlled drug release from Antimicrobial particles for denTAl tissues

超声波控制牙科组织抗菌颗粒的药物释放

• 批准号: EP/V028553/1
• 负责人: Zoe Pikramenou
• 金额: $ 72.15万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FV028553%2F1
• 关键词: UltraSOuNd; controlled; drug; release; Antimicrobial

Dental caries is the breakdown of the hard dental tissues by the acid produced by bacteria in the mouth. It is recognised that many children and adults suffer unnecessary pain due to the destruction of the tooth and infection of the pulp (nerve). If not treated, then the tooth needs to ultimately be extracted. This non-communicable disease is entirely preventable. Eliminating the established oral biofilm that houses the bacteria that start this destructive process is however a challenge. Once bacteria break through the enamel of the tooth their passage to the pulp of the tooth is helped by the structure of dentine. This hard, dental tissue contains numerous microchannels (dentine tubules), which communicate from the external surface of the tooth to the internal pulp. The biofilm may be prevented by diet and use of fluoride toothpastes but once established is difficult to eradicate. Antibiotics are not very effective as there is no blood supply that enables them to reach the infected area and are therefore misused in the treatment of dental infections. A local treatment is proposed that allows for the rapid release of antibacterial agents at the site of infection.In this research programme we aim to rapidly tackle biofilm infections with an interdisciplinary approach based on a novel particle platform for localised drug-delivery using ultrasound as an external-physical stimulus to trigger the release of an encapsulated antibacterial agent from inside the particles. We have assembled a multidisciplinary team with expertise in chemistry, dentistry and fluid mechanics to study the ultrasound triggered activation and delivery of the silica particles in endodontic model structures, biofilms and explanted teeth. To this end we will use existing dental instruments such as ultrasonic scalers in kHz frequencies which are commonly used in dental clinics. We will employ unique flow characterisation approaches to clarify the effects of ultrasound on particle motion, directing the particles to the biofilm, and on agent release. We have chosen to work with silica particles due to their biocompatibility and the wide applicability of silica materials in dentistry. We will use particle designs to control the entrapment of the antibacterial agent which can only be released upon application of the ultrasound trigger. The particles will be developed with luminescent properties to allow optical detection of their motion in flow and to monitor the antibacterial agent release in solution. We aim to tackle problems in dental healthcare and to accelerate particle based therapies in dental practice through our impact activities. The proposed research will also provide revolutionary ways for antibiotic delivery in other areas of healthcare where localized treatment of infection is challenging (prosthetics, catheters).

龋齿是口腔中细菌产生的酸破坏坚硬的牙齿组织。人们认识到，许多儿童和成人由于牙齿的破坏和牙髓（神经）的感染而遭受不必要的疼痛。如果不治疗，牙齿最终需要拔除。这种非传染性疾病是完全可以预防的。然而，消除已经形成的口腔生物膜是一个挑战，因为生物膜中含有启动这一破坏性过程的细菌。一旦细菌突破牙釉质，它们进入牙髓的通道就得到牙本质结构的帮助。这种坚硬的牙齿组织包含许多微通道（牙本质小管），它们从牙齿的外表面连通到内部牙髓。生物膜可以通过饮食和使用含氟牙膏来预防，但一旦形成就难以根除。抗生素不是很有效，因为没有血液供应使它们能够到达感染区域，因此被滥用于治疗牙齿感染。提出了一种局部治疗方法，可以在感染部位快速释放抗菌剂。在这项研究计划中，我们的目标是快速解决生物膜感染的跨学科方法，该方法基于一种新型的颗粒平台，用于局部给药，使用超声作为外部物理刺激，触发从颗粒内部释放封装的抗菌剂。我们组建了一支具有化学、牙科和流体力学专业知识的多学科团队，研究超声触发的二氧化硅颗粒在牙髓模型结构、生物膜和修复牙齿中的活化和递送。为此，我们将使用现有的牙科仪器，如牙科诊所常用的kHz频率的超声波洁牙机。我们将采用独特的流动表征方法来澄清超声波对颗粒运动的影响，将颗粒导向生物膜，并对试剂释放。我们选择使用二氧化硅颗粒是因为它们的生物相容性和二氧化硅材料在牙科中的广泛适用性。我们将使用颗粒设计来控制抗菌剂的截留，抗菌剂只能在应用超声触发器时释放。将开发具有发光特性的颗粒，以允许光学检测它们在流动中的运动，并监测溶液中的抗菌剂释放。我们的目标是通过我们的影响力活动来解决牙科医疗保健中的问题，并加速牙科实践中的颗粒治疗。拟议的研究还将为其他医疗保健领域的抗生素输送提供革命性的方法，这些领域的感染局部治疗具有挑战性（假肢，导管）。

项目成果

Ultrasonic irrigation flows in root canals: effects of ultrasound power and file insertion depth

• DOI: 10.1038/s41598-024-54611-x
• 发表时间: 2024-03-04
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Koulogiannis，A.;Walmsley，A. D.;Balabani，S.
• 通讯作者: Balabani，S.

Antibiotic entrapment in antibacterial micelles as a novel strategy for the delivery of challenging antibiotics from silica nanoparticles

• DOI: 10.1016/j.micromeso.2023.112841
• 发表时间: 2023-10-10
• 期刊: MICROPOROUS AND MESOPOROUS MATERIALS
• 影响因子: 5.2
• 作者: Muguruza，Asier R.;Odyniec，Maria L.;Pikramenou，Zoe
• 通讯作者: Pikramenou，Zoe