High-throughput quantification of drug loading into advanced delivery systems at the single particle scale

在单颗粒尺度上对先进递送系统中的药物负载进行高通量定量

• 批准号: 2785685
• 金额: --
• 依托单位: Loughborough University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2785685
• 关键词: throughput; quantification; drug; loading; into

Diseases that affect the skeletal system can be particularly difficult to treat. To enhance drug targeting, attempts have been made to engineer synthetic lipid-based nanoparticle drug delivery systems (DDS, e.g. liposomes). Over the last 25 years, advancements have occurred by varying lipid composition or by engineering the nanoparticle surface through the attachment of tissue-targeting ligands such as antibodies. Nonetheless, biodistribution studies have shown that most of these particles accumulate in the liver (<70%) with a maximum of 0.7% uptake observed in clinical targets. Our bodies have evolved natural networks for the targeted exchange of biological materials. These sophisticated nanoparticle carriers, termed extracellular vesicles, are naturally adapted to avoid clearance by the immune system and traverse complex biological barriers that prohibit the crossing of up to 98% of small molecule drugs. As such, EVs offer a novel and biocompatible alternative for advanced drug delivery that provide enhanced selectivity at sites that are currently difficult or even impossible to reach. Despite the advantages offered by EV technologies, attempts to exploit these particles for the delivery of therapeutic cargos are limited due to a lack of high-throughput analytical methods capable of accurately quantifying drug loading efficiency and localisation. This interdisciplinary project will adapt and optimise a state-of-the-art nano-flow cytometry platform (NanoFCM) to develop a future high-throughput technique capable of quantifying drug loading at the nano-scale.

影响骨骼系统的疾病可能特别难以治疗。为了增强药物靶向性，人们尝试设计合成的基于脂质的纳米粒子药物递送系统（DDS，例如脂质体）。在过去 25 年里，通过改变脂质成分或通过附着组织靶向配体（例如抗体）来设计纳米颗粒表面，已经取得了进展。尽管如此，生物分布研究表明，大多数这些颗粒积聚在肝脏中 (<70%)，在临床目标中观察到的最大吸收率为 0.7%。我们的身体已经进化出用于生物材料有针对性交换的自然网络。这些复杂的纳米颗粒载体（称为细胞外囊泡）天然适合避免被免疫系统清除，并穿越复杂的生物屏障，这些屏障禁止多达 98% 的小分子药物穿过。因此，电动汽车为先进的药物输送提供了一种新颖且生物相容的替代方案，可在目前难以甚至不可能到达的部位提供增强的选择性。尽管电动汽车技术具有诸多优势，但由于缺乏能够准确量化药物装载效率和定位的高通量分析方法，利用这些颗粒来输送治疗货物的尝试受到限制。这个跨学科项目将采用和优化最先进的纳米流式细胞术平台（NanoFCM），以开发未来能够量化纳米级载药量的高通量技术。