Chemical tailoring of self-associating poly(ethylene oxide)-block-poly(ester) copolymers for drug delivery applications

用于药物输送应用的自缔合聚（环氧乙烷）-嵌段-聚（酯）共聚物的化学定制

• 批准号: RGPIN-2014-03677
• 负责人: Lavasanifar, Afsaneh
• 金额: $ 1.82万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=566023
• 关键词: Chemical; tailoring; self; associating; poly

The main purpose of this research is to design and develop novel synthetic polymers that can adequately solubilize oily materials, and release them in an appropriate rate and location, but at the same time, are safe, degradable and environmentally friendly. Such compounds may find several applications in different natural science and engineering related fields. For instance, in agriculture, they may be used to deliver pesticides in a controlled manner. In oil industry, they may be used to clean water from oily waste and impurities. And in bio-medical field, they may be used to improve the function of current and emerging pharmaceuticals and/or diagnostic agents used in animals or human. In the previous phases of this NSERC funded project, we have developed and intellectually protected (with patent filings) a library of safe, degradable and environmentally friendly polymers and explored their application as novel pharmaceutical excipients for drug delivery applications. The copolymers within this library have been utilized to form core/shell structures in nanometer size range, namely polymeric micelles, that were able to encapsulate a number of drugs and drug-able genes as well as imaging probes, stabilize them in the harsh biological environment, reduce their exposure to healthy cells/tissues and at the same time direct the incorporated cargo towards target tissues and cells. This has enhanced the performance of incorporated cargo in treating or imaging of the disease (e.g., cancerous tissues). The aim of current proposal is to develop more advanced generations of these polymers and the associated nano-structures which can offer improved function in the solubilization and controlled delivery of diverse chemical structures. We propose to develop "intelligent" nano-materials based on innovative polymers that can keep their integrity and effectively solubilize small or large molecules of interest under normal physiological condition, but sense the presence of specific triggers (such as pH and/or enzymes), and dissociate in response to such triggers. Fulfillment of the objectives of this project will lead to the development of bio-materials that are more effective in solubilization of diverse drugs or imaging agents; and proficient in controlled delivery of incorporated cargo at appropriate rate and/or to the desired location. These materials will be designed to eventually dissociate and get eliminated from the body, not causing short- or long term harm to human or animals upon administration. Materials with such properties have a realistic prospect for use in pharmaceutical industry for the development of better drugs and/or diagnostic imaging tools. Moreover, these new materials can be developed further and optimized for application in other engineering fields as described above. Our specific goals in the current phase of this previously NSERC funded project are: 1. To prepare a new generation of biodegradable and bio-compatible polymers and their associated nano-structures; 2. characterize the efficacy of generated nano-materials for their stability, solubilization capacity and controlled delivery of model oily materials with diverse chemical structures in laboratory setting; and 3. characterize the fate of generated nano-materials and Incorporated cargo in animals.

本研究的主要目的是设计和开发一种新型的合成聚合物，这种聚合物可以充分溶解油性材料，并以适当的速度和位置释放它们，同时又安全、可降解和环保。这些化合物可以在不同的自然科学和工程相关领域中找到几种应用。例如，在农业中，它们可以被用来以一种可控的方式输送农药。在石油工业中，它们可用于清除水中的含油废物和杂质。在生物医学领域，它们可用于改善用于动物或人类的现有和新兴药物和/或诊断试剂的功能。在这个NSERC资助项目的前几个阶段，我们开发了一个安全、可降解和环保的聚合物库，并对其进行了知识保护（并申请了专利），并探索了它们作为药物输送应用的新型药用辅料的应用。该文库中的共聚物已被用于形成纳米尺寸范围内的核/壳结构，即聚合物胶束，能够封装许多药物和可药物基因以及成像探针，在恶劣的生物环境中稳定它们，减少它们对健康细胞/组织的暴露，同时将纳入的货物导向目标组织和细胞。这增强了合并货物在治疗或成像疾病（例如癌组织）方面的性能。目前的建议的目的是开发更先进的这些聚合物和相关的纳米结构，这些纳米结构可以在不同化学结构的增溶和控制输送方面提供改进的功能。我们建议开发基于创新聚合物的“智能”纳米材料，这种材料可以在正常生理条件下保持其完整性并有效地溶解感兴趣的小分子或大分子，但可以感知特定触发因素（如pH和/或酶）的存在，并根据这些触发因素进行解离。该项目的目标实现将导致生物材料的发展，更有效地溶解各种药物或显像剂；并精通以适当的速度和/或到指定地点的控制交付合并货物。这些材料将被设计成最终从体内分离和消除，在给药后不会对人类或动物造成短期或长期的伤害。具有这些特性的材料在制药工业中具有开发更好的药物和/或诊断成像工具的现实前景。此外，这些新材料可以进一步开发和优化应用于上述其他工程领域。在这个之前由NSERC资助的项目的当前阶段，我们的具体目标是：制备新一代生物可降解和生物相容性聚合物及其相关纳米结构；2. 在实验室环境下，表征纳米材料的稳定性、增溶能力和对不同化学结构的油类材料的控制输送；和3。表征生成的纳米材料和动物体内的合成货物的命运。