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

这项研究的主要目的是设计和开发新型的合成聚合物，能够充分溶解油性材料，并以适当的速度和位置释放它们，同时又是安全、可降解和环境友好的。这类化合物可能在不同的自然科学和工程相关领域中有多种应用。例如，在农业中，它们可能被用来以受控的方式输送杀虫剂。在石油工业中，它们可以用来净化含油废物和杂质中的水。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/或诊断剂的功能。**在这个由NSERC资助的项目的前几个阶段，我们开发了一个安全、可降解和环境友好的聚合物库，并探索了它们作为药物输送应用的新型药物辅料的应用。该文库中的共聚物已被用来形成纳米尺度的核/壳结构，即聚合物胶束，能够包裹一些药物和可药物基因以及成像探针，使它们在恶劣的生物环境中稳定下来，减少它们对健康细胞/组织的暴露，同时将被包裹的货物引导到靶组织和细胞。这提高了联合货物在治疗或成像疾病(例如，癌症组织)方面的性能。**目前提议的目的是开发更先进的一代此类聚合物和相关的纳米结构，这些结构可以在增溶和控制各种化学结构的传递方面提供更好的功能。我们建议开发基于创新聚合物的“智能”纳米材料，这种材料可以保持其完整性，并在正常生理条件下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物(如pH和/或酶)的存在，并对这些触发物做出反应而解离。该项目目标的实现将导致开发更有效地溶解各种药物或成像剂的生物材料；并熟练地以适当的速度和/或所需位置控制地运送合并的货物。这些材料将被设计为最终解离并从体内消除，在给药后不会对人类或动物造成短期或长期伤害。具有这种性质的材料在制药工业中用于开发更好的药物和/或诊断成像工具具有现实的前景。此外，这些新材料还可以进一步开发和优化，以应用于上述其他工程领域。**我们在这个先前由NSERC资助的项目的当前阶段的具体目标是：1.制备新一代可生物降解和生物兼容的聚合物及其相关的纳米结构；2.在实验室环境下表征产生的纳米材料的稳定性、增溶能力和对具有不同化学结构的模型油性材料的受控输送的有效性；以及3.表征产生的纳米材料和包含在动物中的货物的命运。

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.