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

基本信息

  • 批准号:
    1039531
  • 负责人:
  • 金额:
    $ 6万
  • 依托单位:
  • 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

项目摘要

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.
该方案的研究目的是验证一种假设,即通过粘性沉积、扩散和交联动力学的相互作用进行自组装可以产生一种新的具有环形螺旋内部结构的聚合物微粒,从而为药物的持续释放提供有利条件。更具体地说,在颗粒形成过程中,治疗性蛋白质和多肽同时被包裹到环形螺旋通道中。与目前流行的蛋白质输送方法相比,环形螺旋微粒(TSMPS)可以在温和的条件下(室温、低剪切和低界面张力)完全在水相中形成并负载蛋白质,从而保持微细的大分子构象,从而最大限度地提高生物活性和生物利用度。为了验证这一新想法,从而减轻较长项目的概念性风险,我们请求支持为期一年的研究,以便为未来的常规提案提供更多初步结果。在这里提出的一年时间内,将讨论两个关键方面:(1)蛋白质自负载到环形螺旋粒子中,以及(2)将环形螺旋粒子从毫米级(目前可以实现的)缩小到微米级。在前期实验和理论工作的基础上,我们预计这两项工作都会取得成功。下面的研究计划包括应急计划,以防最初的方法不能如预期那样奏效。智力上的功绩。将实验室研究与多功能计算机模拟相结合,这一建议解决了基本的流体力学和质量传递问题,使一种新类型的聚合物药物输送颗粒能够局部持续释放治疗性蛋白质和多肽。TSMPS将通过复杂缠绕的液体结构的光触发闪光聚合生成。当水可混溶的聚合物液滴在低雷诺数下通过水溶液沉积时,这些液体结构是由水动力形成的。对于任意粘度比和非牛顿流变学,聚合物液滴在水池中的初始冲击(形成涡环的钟形)代表了流体力学中一个很大程度上未知的区域,将应用定量可视化实验和计算机模拟。这些预期的发现将极大地提高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方面实现巨大的飞跃。更广泛的影响。该项目提供了一个技术平台,可以潜在地转化为许多复杂疾病的医疗治疗。研究将通过一门新的研究生微流体学课程、本科生交通现象序列的两个模块和一系列本科生研究项目来影响CHE课程。一个专门的网站(www.microfluidtech.org)将发布一套为大学生和大学预科学生设计的基于Java的教育模块,也将在一篇教育期刊文章中介绍。实验和理论结果的高度可视化,以及生物医学应用的社会相关性,代表了通过与芝加哥土地高中持续的部门关系被招募到化学工程专业的学生的自然吸引力。该项目利用刘和Nitsche在女性和代表性不足的少数族裔学生中正在进行的外展、招聘和留住努力。

项目成果

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Ying Liu其他文献

Low RCS microstrip antenna using polarization-dependent frequency selective surface
使用偏振相关频率选择表面的低 RCS 微带天线
  • DOI:
    10.1109/aps.2014.6905361
  • 发表时间:
    2014-07
  • 期刊:
  • 影响因子:
    1.1
  • 作者:
    Yongtao Jia;Ying Liu;Yuwen Hao;Shuxi Gong
  • 通讯作者:
    Shuxi Gong
spanPhenotypic and genetic evidence for ecological speciation of /spanspan style=line-height:1.5;Aquilegia japonica and A. oxysepala/span
日本耧斗菜和尖萼耧斗菜生态物种形成的表型和遗传证据
  • DOI:
  • 发表时间:
    2014
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Lin-Feng Li;Hua-Ying Wang;Di Pang;Ying Liu;Bao Liu;Hong-Xing Xiao
  • 通讯作者:
    Hong-Xing Xiao
Down regulation of UCP2 expression in RPE cells under oxidative stress
氧化应激下RPE细胞UCP2表达下调
  • DOI:
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Ying Liu;Yuan Ren;Xia Wang;Xu Liu;Yuan He
  • 通讯作者:
    Yuan He
Effects of B on the segregation of Mo at the Fe-Cr-Ni Sigma 5(210) grain boundary
B对Fe-Cr-Ni Sigma 5(210)晶界Mo偏析的影响
  • DOI:
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Jianguo Li;Caili Zhang;Xu Li;Zhuxia Zhang;Nan Dong;Ying Liu;Jian Wang;Yanlu Zhang;Lixia Ling;Peide Han
  • 通讯作者:
    Peide Han
An Effective Entropy Model for Semantic Feature Compression
一种有效的语义特征压缩熵模型
  • DOI:
    10.1109/pcs60826.2024.10566424
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Tianma Shen;Ying Liu
  • 通讯作者:
    Ying Liu

Ying Liu的其他文献

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{{ truncateString('Ying Liu', 18)}}的其他基金

EAGER: Resolving the issue of pairing symmetry in Sr2RuO4
EAGER:解决 Sr2RuO4 中的配对对称性问题
  • 批准号:
    2312899
  • 财政年份:
    2023
  • 资助金额:
    $ 6万
  • 项目类别:
    Standard Grant
ERI: Generative Adversarial Networks for Video Coding
ERI:用于视频编码的生成对抗网络
  • 批准号:
    2138635
  • 财政年份:
    2022
  • 资助金额:
    $ 6万
  • 项目类别:
    Standard Grant
I-CORPS: Scalable Production of Polymeric Nanoparticles Encapsulating Hydrophobic Compounds
I-CORPS:封装疏水性化合物的聚合物纳米颗粒的可规模化生产
  • 批准号:
    1566113
  • 财政年份:
    2015
  • 资助金额:
    $ 6万
  • 项目类别:
    Standard Grant
CAREER: Understanding Nanoprecipitation - Scalable Production of Polymeric Nanoparticles Encapsulating Hydrophobic Compounds
职业:了解纳米沉淀 - 封装疏水性化合物的聚合物纳米颗粒的规模化生产
  • 批准号:
    1350731
  • 财政年份:
    2014
  • 资助金额:
    $ 6万
  • 项目类别:
    Standard Grant
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
  • 财政年份:
    2014
  • 资助金额:
    $ 6万
  • 项目类别:
    Standard Grant
Materials World Network: Novel Physical Phenomena in Unusual Mesoscopic Superconductors
材料世界网络:异常介观超导体中的新物理现象
  • 批准号:
    0908700
  • 财政年份:
    2009
  • 资助金额:
    $ 6万
  • 项目类别:
    Standard Grant
US-France Cooperative Research: Search for Edge Currents and Domain Walls in SrRu0
美法合作研究:寻找SrRu0中的边缘电流和畴壁
  • 批准号:
    0340779
  • 财政年份:
    2004
  • 资助金额:
    $ 6万
  • 项目类别:
    Standard Grant
Experimental Studies of Nanoscopic Superconductors: Half-flux Quantum, Metallic State of Cooper Pairs, and the Berry's Phase
纳米超导体的实验研究:半通量量子、库珀对金属态和贝里相
  • 批准号:
    0202534
  • 财政年份:
    2002
  • 资助金额:
    $ 6万
  • 项目类别:
    Continuing Grant
Determination of the Exact Symmetry of the Pairing State in Sr2RuO4
Sr2RuO4 中配对态精确对称性的测定
  • 批准号:
    9974327
  • 财政年份:
    1999
  • 资助金额:
    $ 6万
  • 项目类别:
    Continuing Grant
CAREER: Mesoscopic Physics of Disordered Superconductors: An Arena for Research and Education
职业:无序超导体的介观物理:研究和教育的舞台
  • 批准号:
    9702661
  • 财政年份:
    1997
  • 资助金额:
    $ 6万
  • 项目类别:
    Continuing Grant

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Exploring the concept of dyadic health in Thai couples coping with breast cancer: A preliminary study of a partnered approach to physical activity in breast cancer survivors and spouse care partners
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