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

点击翻译按钮获取中文摘要

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.