PLGA Protein Microspheres: Single Particle Engineering

PLGA 蛋白质微球：单粒子工程

• 批准号: 7454300
• 负责人: DAVID NEEDHAM
• 金额: $ 33.92万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-15 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7454300
• 关键词: Address; Affect; Antibodies; Area; Biochemical; Biological Models; Blood Circulation; Characteristics; Chemicals; Condition; Conotoxin; Controlled Study; Data; Defect; Dehydration; Development; Dose; Drug Delivery Systems; Drug Formulations; Emulsions; Engineering; Ensure; Environment; Event; Figs - dietary; Freeze Drying; Funding; Goals; Half-Life; Hour; Hydrolysis; In Situ; In Vitro; Individual; Industry; Injectable; Injection of therapeutic agent; Invasive; Investigation; Knowledge; Lactic acid; Learning; Left; Localized; Marketing; Measurable; Measurement; Measures; Mechanics; Medical; Methodology; Methods; Microspheres; Modeling; Molecular; Nanosphere; Numbers; Oils; Organic solvent product; Pain management; Patients; Penetration; Peptides; Performance; Pharmaceutical Preparations; Phase; Polymers; Precipitation; Preparation; Process; Property; Proteins; Radial; Rate; Recipe; Research; Research Design; Research Personnel; Sampling; Scientist; Series; Site; Solutions; Solvents; Structure; Subcutaneous Injections; Suspension substance; Suspensions; System; Techniques; Technology; Testing; Therapeutic; Time; Viscosity; Water; Work; base; compliance behavior; day; engineering design; improved; innovation; insight; interfacial; nanoparticle; novel strategies; particle; polylactic acid-polyglycolic acid copolymer; programs; protein degradation; protein function; protein structure; research study; scale up; subcutaneous; technology development; theories; therapeutic protein

DESCRIPTION (provided by applicant): The goal of our proposal is to bring new insights and enabling technology to the principles and practice of handling proteins and peptides as drugs and their formulation as polymer/protein microspheres. With the world-wide demand for innovative protein therapeutics growing at 30% per year, and a market penetration for protein therapeutics estimated to reach $40 billion worldwide by 2018, effective drug delivery becomes the next significant obstacle. In this proposal we are taking a quantitative approach that expands on the existing fund of knowledge already present in this established, yet not fully optimized, field of polymer-based drug and agent delivery. We are following a relatively straightforward research design -single particle studies (experiment and theory) followed by bulk suspension characterization of composition, structure, and function. By studying individual droplets and individual components serially in SA1, the plan is to obtain crucial measurements not easily obtained by any other method, i.e., the dynamic concentration of each component in the droplet, correlated with events such as precipitation, viscous changes, microstructural inclusions, and time for hardening. Microsphere hydrolysis and protein release are also measurable on single microspheres. Specific Aim 2 then looks to correlate these measurements, and modeling with the physical and chemical characteristics and properties of the microspheres as bulk suspensions. And SA3 completes the investigation by directly relating microsphere protein release and protein function, to processs and compositional variables and developed microsphere microstructure. New innovation is developed in SA4 where we will form glassified protein nanospheres for improved protein stability and dispersion. These data will be crucial for developing a sustained release system for conotoxins (SA5) and thus address the important problem of pain control. Upon completion of this project then we aim to provide a more detailed recipe for specific formulations of protein drugs, and in the process, to be able to offer a more complete design engineering methodology, and enabling technology for microsphere brmulation, especially for environment-sensitive proteins and peptides.

描述（由申请人提供）：我们的提案的目的是将新的见解和使技术赋予处理蛋白质和肽作为药物的原理和实践，及其作为聚合物/蛋白质微球的表述。随着全球对创新蛋白质治疗剂每年增长30％的需求，到2018年，蛋白质治疗剂的市场渗透率估计将达到400亿美元，有效的药物输送成为下一个重要的障碍。在此提案中，我们采用了一种定量方法，该方法扩展了这一已建立但尚未完全优化的基于聚合物的药物和剂传递领域中现有的知识基金。我们遵循相对简单的研究设计 - 单一粒子研究（实验和理论），然后是组成，结构和功能的大量悬浮表征。通过研究单个液滴和单个组件在SA1中串行，该计划是获得不容易通过任何其他方法获得的关键测量值，即，液滴中每个成分的动态浓度与降水，粘性变化，微结构夹杂物和耐加工时间相关的事件相关。微球水解和蛋白质释放也可以在单微球上测量。然后，特定的目标2旨在将这些测量值与微球的物理和化学特征和特性相关联，并将其建模为散装悬浮液。 SA3通过将微球蛋白释放和蛋白质功能直接与过程和组成变量以及开发的微球微结构联系起来，从而完成了研究。 SA4在SA4中开发了新的创新，我们将形成玻璃化的蛋白质纳米球，以改善蛋白质的稳定性和分散。这些数据对于开发持续的结合毒素释放系统至关重要（SA5），从而解决了疼痛控制的重要问题。该项目完成后，我们旨在为蛋白质药物的特定配方提供更详细的配方，并在此过程中能够提供更完整的设计工程方法，并为微球促进技术提供技术，尤其是针对环境敏感的蛋白质和肽。