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 为缓解气候变化的候选项目提供支持，并为其他核心项目和项目提供化学专业知识。 核心将由Nathan Gianneschi博士（部门）共同指导。化学）和斯蒂芬米勒（系。的 微生物学-免疫学）。将采取分层办法来挑选和优化这些候选人。最初 将确定增强材料功效的特性，并对材料进行理化分析。 将探测感兴趣的材料。一个这样的例子是我们丰富清除自由基的材料的能力 在化学掺杂水平上。其他性质将包括表面电荷、孔隙率、结合能力和 材料的溶解性。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，或作为表面涂层，并且可以针对其特异性优化递送。 应用程序.也就是说，材料可以通过直接施加作为液体溶液或浇铸成液体溶液来制备用于递送。 膜或在PLGA免疫修饰颗粒（PLGA-IMP）的情况下用于静脉内输注。初始输入后 体外和体内研究，材料将扩大临床试验，许多拟议的系统已经 我们知道它可以被放大。高分子材料合成与表征核心 将负责推进从小分子合成聚合物等材料， 化学修饰，以改善先导化合物/材料，并将合成脂质的组分， 基于自组装材料的合成与表征核心。这个核心的目标是发展 用于主要候选物如黑色素、可生物降解聚合物PLGA IMP的制剂和递送平台 （其将通过包封抗炎性细胞因子（IL-10和TGF-β）和化合物来进一步修饰 (e.g.维生素D）以及通过改变皮肤和眼睛的物理化学性质的基于肽的递送系统 性能和表征材料的放大和临床翻译。对于聚合物材料 合成和表征核心我们提出以下目的：目的1：利用黑色素用于制备 目的2：用于治疗眼睛中芥子气的蛋白质样聚合物; 目的3：制备和表征带负电荷的可生物降解的PLGA免疫修饰剂 用于化学组织损伤的治疗性处理的纳米颗粒（PLGA-IMP）。