Toroidal-spiral particles (TSPs) for co-delivery of multiple compounds of different sizes

用于共同递送多种不同尺寸化合物的环形螺旋颗粒 (TSP)

• 批准号: 1404884
• 负责人: Ying Liu
• 金额: $ 39万
• 依托单位: University of Illinois at Chicago
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1404884&HistoricalAwards=false
• 关键词: Toroidal; spiral; particles; TSPs; co

Nontechnical: This award by the Biomaterial program in the Division of Materials Research to University of Illinois Chicago is to develop a basic understanding of the materials-science basis for a new polymer-based technology to deliver a cocktail of therapeutic drugs locally to the sites of complex diseases such as brain tumors. Previous generations of polymeric drug-delivery vehicles have faced difficult challenges in encapsulation efficiency of expensive drugs, protecting the bioavailability of delicate protein drugs, and independent tuning of release profiles of multiple drugs for optimum therapeutic effect. Toroidal-spiral particles (donut shaped spiral particles - TSP) solve these problems via the novel internal structure and mechanism of particle formation and drug loading. The visually appealing nature of the experimental and computational results, as well as the societal relevance of the biomedical applications, represents a natural draw for high school students being recruited into chemical engineering. Publicity for educational modules and broader dissemination will occur through: 1) direct outreach to 21 Chicagoland high schools; 2) the annual American Institute of Chemical Engineers Chicago Section Student Symposium; and 3) "Science Minors" student workshops co-organized by the Principal Investigator and the Chicago Museum of Science and Industry.Technical: This award enables research into key materials - science and functionality issues needed to unlock the technological and societal impact of a new polymeric platform for multi-drug delivery: toroidal-spiral particles (TSP). The toroidal-spiral (TS) structure of the particles is self-assembled through competitive kinetics of drop sedimentation, diffusion, and cross-linking. During the formation of the TSP, macromolecules such as therapeutic proteins and oligonucleotides can be auto-entrained into the TS channel, while a small molecular drug can be pre-blended into the polymer drops. Upon solidification into particles, the release of each compound occurs through a separate pathway and can be manipulated independently to reach therapeutic synergy. This project will address three main, enabling aspects of TSP technology: (1) enhance many further biomedical and biotechnical applications, tunable biodegradation of TSP will be studied and measured; (2) independent manipulation of release profiles of cytotoxic drug versus therapeutic proteins will combine laboratory measurements with computational models to ascertain the structure-release relation and to optimize structures for biomedical applications; and (3) in vitro characterization the cellular association and activity of agents released from TSP will use model cell lines for brain tumors and endothelial tissue. In addition to multidisciplinary training of the graduate research assistants involved, fostering undergraduate research opportunities (emphasizing underrepresented minority student participation) and spin-offs in undergraduate engineering education, this project offers multiple avenues for outreach and dissemination among Chicago and grade 6-12 and community-college students.

非技术性：该奖项由材料研究部的生物材料项目授予伊利诺伊芝加哥大学，旨在加深对材料科学基础的基本理解，为基于聚合物的新技术提供局部治疗药物的鸡尾酒，以治疗脑肿瘤等复杂疾病的部位。前几代聚合物给药载体在昂贵药物的包封率、保护脆弱蛋白药物的生物利用度以及独立调整多种药物的释放曲线以实现最佳治疗效果方面面临着严峻的挑战。环状螺旋粒子(TSP)通过其新颖的内部结构和粒子形成和载药机制解决了这些问题。实验和计算结果的视觉吸引力，以及生物医学应用的社会相关性，代表了高中生被招募到化学工程专业的自然吸引力。教育模块的宣传和更广泛的传播将通过以下方式进行：1)直接接触21所芝加哥高中；2)年度美国化学工程师协会芝加哥分部学生研讨会；3)由首席调查员和芝加哥科学与工业博物馆联合举办的“科学未成年人”学生讲习班。技术：该奖项使人们能够研究关键材料--揭示多药物输送的新聚合平台：环形螺旋颗粒(TSP)的技术和社会影响所需的科学和功能问题。粒子的环状螺旋(TS)结构是通过液滴沉积、扩散和交联的竞争动力学而自组装的。在TSP的形成过程中，治疗蛋白和寡核苷酸等大分子可以自动携带到TS通道中，而小分子药物可以预先混合到聚合物液滴中。在固化成颗粒后，每种化合物的释放都通过单独的途径进行，可以独立操作以达到治疗协同作用。该项目将着眼于TSP技术的三个主要方面：(1)加强许多进一步的生物医学和生物技术应用，将研究和测量TSP的可调生物降解；(2)独立操纵细胞毒性药物与治疗蛋白的释放谱，将实验室测量与计算模型相结合，以确定结构-释放关系，并优化生物医学应用的结构；(3)体外表征TSP释放的制剂的细胞结合和活性，将使用脑肿瘤和内皮组织的模型细胞系。除了对所涉及的研究生研究助理进行多学科培训、培养本科生的研究机会(强调少数族裔学生的参与)以及在本科生工程教育中衍生产品外，该项目还提供了在芝加哥、6-12年级和社区大学学生中拓展和传播的多种途径。