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：该奖项由伊利诺伊大学芝加哥材料研究部的生物材料项目授予，旨在对基于聚合物的新技术的材料科学基础进行基本了解，以将治疗药物的鸡尾酒局部递送到脑肿瘤等复杂疾病的部位。前几代聚合物药物递送载体在昂贵药物的包封效率、保护脆弱蛋白质药物的生物利用度以及独立调节多种药物的释放曲线以获得最佳治疗效果方面面临着困难的挑战。环形螺旋颗粒（环形螺旋颗粒- TSP）通过新颖的内部结构和颗粒形成和药物负载的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，代表了被招募到化学工程高中生的自然吸引力。教育模块的宣传和更广泛的传播将通过以下方式进行：1）直接推广到21所芝加哥高中; 2）每年一度的美国化学工程师学会芝加哥分会学生研讨会; 3）由首席研究员和芝加哥科学与工业博物馆共同组织的“未成年科学”学生研讨会。该奖项使研究关键材料-科学和功能性问题所需的解锁技术和社会影响的一种新的聚合物平台的多药物输送：环形螺旋颗粒（TSP）。颗粒的环形螺旋（TS）结构是通过液滴沉降、扩散和交联的竞争动力学自组装的。在TSP的形成过程中，大分子如治疗性蛋白质和寡核苷酸可以自动夹带到TS通道中，而小分子药物可以预混合到聚合物液滴中。在固化成颗粒后，每种化合物的释放通过单独的途径发生，并且可以独立地操纵以达到治疗协同作用。该项目将解决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，TSP的可调生物降解将被研究和测量;（2）细胞毒性药物与治疗性蛋白质的释放曲线的独立操纵将联合收割机与计算模型相结合，以确定结构-释放关系，并优化生物医学应用的结构;和（3）从TSP释放的试剂的细胞缔合和活性的体外表征将使用脑肿瘤和内皮组织的模型细胞系。除了多学科培训的研究生研究助理参与，促进本科生的研究机会（强调代表性不足的少数民族学生的参与）和副产品在本科工程教育，该项目提供了多种途径的推广和传播之间的芝加哥和6-12年级和社区大学的学生。