Multifunctional intelligent polymers and polymer-inorganic hybrid materials for biomedical applications

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Background: Materials with high biocompatibility and multiple functionalities are very important for biomedical applications including drug delivery and disease detection. However, when used alone, existing materials, such as polymers or inorganic nanoparticles, cannot provide desired properties and functionalities. Thus we propose to develop novel polymers and polymer-inorganic hybrid materials that will provide multiple functions and optimal properties. This proposed research is an expansion and continuation of the applicant's previous and current work. The long-term goal of this research is to advance the science and technology of the design and development of novel polymers, polymer-lipid and polymer-inorganic systems for controlled drug delivery and biomedical imaging. The short-term goal is to develop novel multifunctional intelligent polymers and polymer-inorganic materials for effective drug delivery and disease detection by non-invasive imaging. The specific objectives in this project are: (1) Study the molecular interactions between biocompatible polymers and protein drugs and select leading polymers by CG-MD modeling. From the CG-MD modeling and molecular docking simulation, we will understand the mechanism by which synthetic polymers (e.g. triblock copolymers and zwitterionic polymers) stabilize protein drugs, e.g. insulin and glucagon. Based on the simulation results, we will select or synthesize new polymers for the protein formulation design. (2) Synthesize novel polymers identified in obj.1 and investigate their effect on stabilizing the protein drugs by experiments. Protein-polymer formulations of varying compositions will be examined by HPLC and CD, and then by glucose-regulation activity assay in diabetic rats. (3) Design anti-viral antibody-conjugated terpolymer nanoparticles with chelated paramagnetic metal ions for MR imaging of viral infections in the brain. (4) Design novel pH-responsive amphiphilic polymer microgel particles with conjugated anti-bacterial antibodies and fluorescent dyes for on-site detection of bacterial infections by optical imaging. This project will be supported by the DND/NSERC Supplemental Grant and will be reviewed separately by DND committee. Novelty and Significance: The proposed multifunctional polymers and polymer-inorganic nanocomposite materials have not been reported before. The developed new materials will exhibit useful properties for biomedical applications and will advance the science and technology of biomaterials for drug delivery and medical imaging. Despite their biomedical applications, the synthesis and characterization of new materials will not be funded by health research funding agencies such as CIHR.