Polymeric Materials Synthesis and Characterization

高分子材料的合成与表征

• 批准号: 10682623
• 负责人: Nathan Claude Gianneschi
• 金额: $ 31.93万
• 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/10682623
• 关键词: Adsorption; Amino Acids; Angiogenesis Inhibitors; 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; Macrophage; 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; biocompatible polymer; biodegradable polymer; carboxylate; carboxylation; clinical translation; cytokine; direct application; experimental study; improved; in vivo; innovation; interest; keratinocyte; lead candidate; materials science; monocyte; monomer; nanomaterials; nanoparticle; novel; particle; protein aminoacid sequence; remediation; scale up; self assembly; skin burn; small molecule; surface coating; technology platform; 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 聚合物材料的合成和特征核心将制定，合成和表征铅 减轻芥末的候选人，并为其他核心和项目提供支持和化学专业知识。 核心将由DRS共同指导。内森·吉安尼斯基（Nathan Gianneschi）（化学系）和斯蒂芬·米勒（Stephen Miller） 微生物 - 免疫学）。将采用分层方法来选择和优化此类候选人。最初 将确定提高材料效率的特性，并在理化分析上 感兴趣的材料将被研究。一个这样的例子是我们能够丰富材料进行根本清除的能力 在化学掺杂水平上。其他特性将包括表面电荷，孔隙度，结合能力，并且 材料的溶解度。根据皮肤或眼睛的材料和应用，候选材料将 以纳米颗粒或表面涂层的形式配方，并且可以针对其特异性进行优化 应用。也就是说，可以准备通过直接应用作为液体溶液或施放的材料 在PLGA免疫修饰颗粒（PLGA-IMP）的情况下，用于静脉输注。初始in 体外研究和体内研究，将对临床试验进行扩展，许多拟议的系统已经进行 已知可以适应这种规模。聚合物材料合成和特征核心 将负责推进材料的合成，例如小分子的聚合物，将使 化学修饰以改善铅化合物/材料，并将合成脂质的成分合成 基于自组装的材料合成和表征核心。该核心的目标是发展 黑色素，可生物降解的聚合PLGA IMPS等铅候选者的配方和交付平台 （将通过封装抗炎细胞因子（IL-10和TGF-β）和化合物来进一步修改。 （例如，维生素D），以及通过修饰物理化学的皮肤和眼睛的基于胡椒的递送系统 特性以及通过表征用于扩展和临床翻译的材料。对于聚合物材料 综合和特征核心我们提出以下目的：目标1：利用黑色素为 芥末的修复和增加； AIM 2：蛋白质样聚合物用于治疗眼睛中的芥末气体； 和目标3：产生和表征负收集的，可生物降解的PLGA免疫修饰 用于化学组织损伤治疗的纳米颗粒（PLGA-IMP）。