EAGER: Preliminary Study on Novel self-assembled Toroidal-Spiral MicroParticles (TSMPs) for sustained release of therapeutic proteins and peptides: theory and experiments

EAGER：用于持续释放治疗性蛋白质和肽的新型自组装环形螺旋微粒（TSMP）的初步研究：理论和实验

• 批准号: 1039531
• 负责人: Ying Liu
• 金额: $ 6万
• 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: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1039531&HistoricalAwards=false
• 关键词: EAGER; Preliminary; Study; Novel; self

The research objective of the proposal is to test the hypothesis that self-assembly by interaction of viscous sedimentation, diffusion, and cross-linking kinetics can produce a new category of polymeric micro-particles with a toroidal-spiral internal structure that offers advantages for sustained drug release. More specifically, during the particle formation, therapeutic proteins and peptides are simultaneously encapsulated into the toroidal-spiral channels. In contrast with prevailing protein delivery methods, toroidal-spiral micro-particles(TSMPs) can be formed and loaded with proteins entirely within the aqueous phase, under benign conditions (room temperature, low shear and low interfacial tensions) that preserve delicate macromolecular conformations and thereby maximize bioactivity and bioavailability. To validate this novel idea, and thereby mitigate conceptual risk for the longer project, we request support for one-year of research to provide more preliminary results for a regular proposal in future. Within the one-year period proposed here, two key aspects will be addressed: (1) protein self-loading into the toroidal-spiral particles, and (2) scaling down toroidal-spiral particles from the millimeter scale (currently achievable) to micron dimensions. On the basis of preliminary experimental and theoretical work, we expect success in both endeavors. The research plan below includes contingency plans in case the initial approach does not work as anticipated. Intellectual Merit. Integrating laboratory investigation with versatile computer simulations, this proposal addresses the fundamental fluid mechanics and mass transfer that enable a new category of polymeric drug-delivery particles for local sustained release of therapeutic proteins and peptides. TSMPs will be generated by light-triggered flash polymerization of intricately wound liquid structures. These liquid structures form by hydrodynamic forces when a water-miscible, polymeric drop sediments at low Reynolds number through an aqueous solution. The initial impact of the polymeric droplets into the aqueous pool (forming bell shapes of vortex rings) for arbitrary viscosity ratio and non-Newtonian rheology represents a largely unexplored regime in fluid mechanics, to which both quantitative visualization experiments and computer modeling will be applied. The anticipated findings will greatly enhance our quantitative understanding of new self-assembly processes, thereby providing a quantum leap in producing microparticles with novel structures. Broader Impacts. This project provides a technological platform that can potentially be translated into medical treatments for many complex diseases. Research will impact the ChE curriculum through a new graduate microfluidics course, two modules for the undergraduate Transport Phenomena sequence and a sequence of undergraduate research projects. A dedicated website (www.microfluidtech.org) will publish a suite of Java-based educational modules designed for college and pre-college students, also to be described in an educational journal article. The highly visual nature of the experiments and theoretical results, as well as the societal relevance of the biomedical applications, represent a natural draw for students being recruited into chemical engineering through ongoing departmental relationships with Chicago land high schools. This project leverages ongoing outreach, recruitment and retention efforts by Liu and Nitsche among women and underrepresented minority students.

该提案的研究目的是检验以下假设：通过粘性沉积，扩散和交联动力学的相互作用自组装可以产生具有带环状刺激性内部结构的新类别的聚合微粒粒子，从而为持续药物释放提供了优势。更具体地说，在颗粒形成期间，治疗蛋白和肽同时封装在环形螺旋通道中。与流行的蛋白质递送方法相反，在良性条件下（室温，低剪切和低界面张力），可以完全在水相中形成环形 - 螺旋微粒（TSMP），并完全在水相中，可保留纯净的大分子构象，从而可最大程度地生物活力，并最大程度地提高生物活性。为了验证这一新颖的想法，从而减轻了较长项目的概念风险，我们要求对一年的研究支持，以为将来的常规建议提供更多的初步结果。在此处提出的一年期间，将解决两个关键方面：（1）蛋白质自我载荷到环形螺旋颗粒中，（2）（2）从毫米尺度（目前可实现的）缩小环形螺旋颗粒到微米尺寸。在初步实验和理论工作的基础上，我们期望这两项努力成功。下面的研究计划包括应急计划，以防初始方法无法按预期工作。 智力优点。该提案将实验室研究与多功能计算机模拟整合在一起，解决了基本的流体力学和传质，从而使一类新类别的聚合药物递送颗粒可以局部持续释放治疗蛋白和肽。 TSMP将通过复杂的液体结构的光触发闪光聚合产生。这些液体结构是由流体动力形成的，当时在低雷诺数下通过水溶液在低雷诺数处的聚合物滴沉积物时。聚合物液滴对任意粘度比和非牛顿风湿病的水池（形成涡旋环的形成钟形形状）的初始影响代表了流体力学中的一个未开发的方案，对量化的可视化实验和计算机建模都将在其上均未开发。预期的发现将大大增强我们对新的自组装过程的定量理解，从而在生产具有新结构的微粒时提供了量子飞跃。 更广泛的影响。该项目提供了一个技术平台，可以将其转化为许多复杂疾病的医疗治疗。研究将通过新的研究生微流体课程，两个用于本科运输现象序列的模块以及一系列本科研究项目来影响CHE课程。专门的网站（www.microfluidtech.org）将出版一套基于Java的教育模块，该模块为大学和大学前学生设计，也将在教育期刊文章中进行描述。实验和理论结果的高度视觉性质以及生物医学应用的社会相关性，是通过与芝加哥土地高中的持续部门关系招募到化学工程的学生的自然吸引力。该项目利用了刘和尼茨在妇女和代表性不足的少数族裔学生中的持续推广，招募和保留工作。