Development of a Biomimetic Lung Surfactant Replacement

仿生肺表面活性剂替代品的开发

• 批准号: 0101195
• 负责人: Annelise Barron
• 金额: $ 27.04万
• 依托单位: Northwestern University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0101195&HistoricalAwards=false
• 关键词: Development; Biomimetic; Lung; Surfactant; Replacement

0101195BarronIn continuation of work that is presently funded by a one-year NSF SGER grant, the PI's propose to elaborate on this novel class of structured, sequence-specific heteropolymers to develop close mimics of natural SP-B and SP-C, that will be stable and biocompatible for in vivo use. This medically-relevant research project offers potential for broad impact on the field of biomaterials engineering, by demonstrating the usefulness of non-natural, sequence-specific polymers for biomimicry. The aims are:(1) To design, synthesize, chromatographically purify, and spectroscopically characteize the secondary strutures of peptoid mimics of helical, amphipathic LS proteins SP-B and SP-C;(2) To perform in vitro biophysical characterization of peptoid SP mimics as spreading agents for biomimetic lipid admixtures, carrying out studies on a pulsating bubble surfactometer and a Langmuir-Wilhelmy surface balance, and making comparisons to LS containing natural petpides;(3) To formulate a therapeutic, biomimetic LS replacement containing both phospholipids and SP mimics, that is effective, bioavailable, biocompatible, and more cost-effective than animal LS;(4) To carry out in vivo testing of optimized biomimetic LS replacements in a murine model of RDS, in collaboration with Brigham and Women's Hospital; and,(5) To deepen the present fundamental understanding of the relationship between LS protein structural features and biophysical functioning in phospholipid surface films.

Barron在目前由一年NSF SGER资助的工作的继续中，PI建议详细说明这类新型结构化的序列特异性杂聚物，以开发天然SP-B和SP-C的紧密模拟物，其对于体内使用将是稳定的和生物相容的。 这个医学相关的研究项目提供了对生物材料工程领域的广泛影响的潜力，通过展示非天然的，序列特异性聚合物的仿生学的有用性。目的是：（1）设计、合成、色谱纯化和光谱表征螺旋两亲性LS蛋白SP-B和SP-C的类肽模拟物的二级结构：（2）进行类肽SP模拟物作为仿生脂质混合物铺展剂的体外生物物理表征，进行脉动气泡表面仪和Langmuir-Wilhelmy表面天平的研究，并与含天然肽的LS进行比较;（3）配制一种治疗性的、含有磷脂和SP模拟物的仿生LS替代物，该替代物是有效的、生物可利用的、生物相容的，并且比动物LS更具成本效益;（4）与Brigham and Women's Hospital合作，在RDS的小鼠模型中进行优化的仿生LS替代物的体内测试;（5）加深对LS蛋白结构特征与磷脂表面膜生物物理功能关系的基本认识。