Polymeric Materials Synthesis and Characterization

高分子材料的合成与表征

• 批准号: 10490414
• 负责人: Nathan Claude Gianneschi
• 金额: $ 31.97万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-17 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10490414
• 关键词: Adsorption; Amino Acids; Angiogenic Peptides; Anti-Inflammatory Agents; Binding; Biological Assay; Biopolymers; Cell Culture Techniques; Cells; Charge; Chemical Injury; Chemicals; Chemistry; Clinical; Clinical Trials; Collaborations; Encapsulated; Exposure to; Exudative age-related macular degeneration; Eye; Film; Formulation; Free Radical Scavenging; Glycolates; Goals; Human; Immune; Immunology; In Vitro; Inflammation; Inflammatory; Interleukin-10; Intravenous infusion procedures; Laboratories; Lead; Lipids; Liquid substance; Mechlorethamine; Melanins; Microbiology; Modeling; Modification; Mustard; Mustard Gas; Nature; Peptides; Play; Polymers; Porosity; Positioning Attribute; Preparation; Production; Property; Proteins; Redness; Retina; Role; Site; Skin; Skin injury; Solubility; Surface; System; Technology; Testing; Therapeutic; Tissues; Transforming Growth Factor beta; Translating; Universities; Validation; Vitamin D; Work; base; biocompatible polymer; biodegradable polymer; carboxylate; clinical translation; cytokine; direct application; experimental study; improved; in vivo; innovation; interest; keratinocyte; lead candidate; macrophage; materials science; monocyte; monomer; nanomaterials; nanoparticle; novel; particle; protein aminoacid sequence; remediation; scale up; skin burn; small molecule; surface coating; therapeutic nanoparticles; tissue injury; tool; ultraviolet irradiation; uptake

Project Summary The Polymeric Materials Synthesis and Characterizations Core will formulate, synthesize, and characterize lead candidates for the mitigation of mustards and provide support and chemical expertise to other cores and projects. The Core will be co-directed by Drs. Nathan Gianneschi (Dept. of Chemistry) and Stephen Miller (Dept. of Microbiology-Immunology). A tiered approach will be taken to select and optimize such candidates. Initially properties that enhance the efficacy of the materials would be determined and physiochemical analysis on the materials of interest would be probed. One such example is our ability to enrich materials for radical scavenging at the chemical doping level. Other properties would include surface charge, porosity, binding capacity, and solubility of materials. Depending on the material and application for the skin or eyes, the candidate material will be formulated as a nanoparticle, or as a surface coating and the delivery could be optimized for its specific application. That is, materials can be prepared for delivery via direct application as a liquid solution or cast into a film or in the case of PLGA Immune Modifying Particles (PLGA-IMPs) for intravenous infusion. After initial in vitro and in vivo studies, materials will be scaled-up for clinical trials, with many of the proposed systems already known to be amenable to that kind of scale-up. The Polymeric Materials Synthesis and Characterizations Core will be responsible for advancing the synthesis of materials such as polymers from small molecules, will make chemical modifications to improve lead compounds/materials, and will synthesize components for the Lipid- Based Self-Assembled Materials Synthesis and Characterization Core. The goals of this core are to develop formulations and delivery platforms for lead candidates such as melanin, biodegradable polymeric PLGA IMPs (which will be further modified by encapsulating anti-inflammatory cytokines (IL-10 and TGF-β) and compounds (e.g. Vitamin D), and peptide-based delivery systems for the skin and eyes by modifying their physiochemical properties and by characterizing materials for scale-up and clinical translation. For the Polymeric Materials Synthesis and Characterizations Core we propose the following Aims: Aim 1: Utilizing melanin for the remediation and adsorption of mustards; Aim 2: Protein-Like Polymers for treatment of mustard gas in the eye; and Aim 3: Production and characterization of negatively-charged, biodegradable PLGA Immune-Modifying Nanoparticles (PLGA-IMPs) for therapeutic treatment of chemical tissue injury.

项目摘要 聚合物材料合成和表征核心将制定、合成和表征铅 该项目将成为缓解芥末病的候选方案，并为其他核心和项目提供支持和化学专业知识。 《核心》将由Nathan Gianneschi博士(Dep.化学系)和Stephen Miller(系的 微生物学-免疫学)。将采取分层的方法来选择和优化这些候选人。最初 将对增强材料功效的性能进行测定并对其进行物理化学分析 将对感兴趣的材料进行探测。一个这样的例子是我们为激进分子清除而丰富材料的能力 在化学掺杂水平上。其他性质包括表面电荷、孔隙率、结合能力和 材料的溶解度。根据皮肤或眼睛的材料和应用，候选材料将 可以配制成纳米颗粒或表面涂层，并且可以根据其特定的特性优化输送 申请。也就是说，材料可以准备好通过直接应用于液体溶液或浇铸成 用于静脉输液的薄膜或PLGA免疫修饰颗粒(PLGA-IMPS)。在初始输入之后 体外和体内研究，材料将扩大到临床试验，许多拟议的系统已经 已知能够适应这种规模的扩大。聚合物材料的合成与表征 将负责推进从小分子合成聚合物等材料，将使 化学修饰以改进先导化合物/材料，并将合成用于脂类的成分- 基于自组装材料的合成与表征核心。这个核心的目标是开发 用于黑色素、可生物降解的聚合物IMPS等候选铅的制剂和输送平台 (将通过包裹抗炎细胞因子(IL-10和转化生长因子-β)和化合物来进一步修改 (例如，维生素D)和基于多肽的皮肤和眼睛给药系统，通过改变它们的物理化学 通过对用于放大和临床翻译的材料进行表征来确定其特性。关于聚合物材料 合成和表征核心我们提出以下目标：目标1：利用黑色素 修复和吸附芥末；目标2：用于治疗眼睛中芥子气的类蛋白质聚合物； 和目标3：带负电荷的可生物降解的PLGA免疫修饰剂的制备和表征 用于治疗化学组织损伤的纳米粒(PLGA-IMPS)。