Polymeric Materials Synthesis and Characterization

高分子材料的合成与表征

• 批准号: 10282409
• 负责人: Nathan Claude Gianneschi
• 金额: $ 39.81万
• 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/10282409
• 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.

项目概要 高分子材料合成和表征核心将配制、合成和表征铅 芥子气减排候选者，并为其他核心和项目提供支持和化学专业知识。 核心将由博士共同指导。 Nathan Gianneschi（化学系）和 Stephen Miller（化学系） 微生物学-免疫学）。将采取分层方法来选择和优化此类候选人。最初 将确定增强材料功效的特性，并对材料进行理化分析 将探索感兴趣的材料。其中一个例子是我们丰富自由基清除材料的能力 在化学掺杂水平。其他特性包括表面电荷、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 可以配制为纳米颗粒或表面涂层，并且可以针对其特定的情况优化输送 应用。也就是说，材料可以通过直接应用为液体溶液或浇铸到 薄膜或用于静脉输注的 PLGA 免疫修饰颗粒 (PLGA-IMP)。初次进入后 体外和体内研究，材料将扩大用于临床试验，许多拟议的系统已经 已知适合这种规模的扩大。高分子材料合成与表征核心 将负责推进小分子聚合物等材料的合成，将使 化学修饰以改进先导化合物/材料，并将合成脂质成分 基于自组装材料合成和表征的核心。该核心的目标是开发 主要候选药物（如黑色素、可生物降解的聚合物 PLGA IMP）的配方和递送平台 （将通过封装抗炎细胞因子（IL-10 和 TGF-β）和化合物进行进一步修饰 （例如维生素 D），以及通过改变皮肤和眼睛的生化作用而用于皮肤和眼睛的基于肽的输送系统 特性以及表征材料以进行放大和临床转化。对于高分子材料 合成和表征核心我们提出以下目标： 目标 1：利用黑色素 芥末的修复和吸附；目标 2：用于治疗眼部芥子气的类蛋白质聚合物； 目标 3：带负电、可生物降解的 PLGA 免疫调节剂的生产和表征 用于治疗化学组织损伤的纳米颗粒（PLGA-IMP）。