Zwitterionic Polymers and Their Derivatives as Drug and Gene Delivery Carriers and Implantable Materials
MetadataShow full item record
This dissertation mainly focuses on the development of zwitterionic-based materials and their biomedical applications, particularly, multifunctional zwitterionic-based nanoparticles (NPs) for targeted imaging and drug delivery, microparticles for DNA vaccine delivery, and <italic>in vivo</italic> evaluation of zwitterionic-based nanoparticles and hydrogel implants. In the multifunctional nanoparticle work, stealthy and functionalizable magnetic nanoparticles were first developed by coating them with polycarboxybetaine (PCBMA) using a biomimetic adhesive linkage. After conjugation with a targeting ligand, the PCBMA coated NPs could efficiently enter cells and be imaged with magnetic resonance imaging (MRI). Second, degradable PCBMA nanogels were developed using a reduction-sensitive crosslinker. The nanogels could encapsulate both imaging reagents and macromolecule drugs. They were degradable and able to release their payload spontaneously after entering the intracellular reducing environment. The degraded products could be excreted from the body via renal clearance, making the nanogels a safe and ideal platform for targeted imaging and drug delivery. In the DNA vaccine delivery work, microparticles were developed using a CBMA ethyl ester (CBMA-EE) monomer and its tertiary amine analogue. Gene transfection results showed that microparticles with a 1:1 molar ratio of the two monomers had the best transfection efficiency, which was twelve times higher than commercially developed PLGA-CTAB microparticles. Together with their low toxicity and passive targeting effect to macrophage cells, the microparticles developed in this work could potentially be used as a suitable platform for DNA vaccine delivery. In the <italic>in vivo</italic> evaluation work, <italic>in vivo</italic> circulation time of PCBMA nanogels and the foreign body reaction to PCBMA hydrogel implants were studied. Results of PCBMA nanogels showed that they exhibit an extended circulation time in a rat model. Furthermore, it was found that softer nanogels were able to more effectively pass through splenic filtration and had a longer circulation time. <italic>In vivo</italic> implantation studies show that that PCBMA holds great promise as an ideal coating for implantable medical devices.
- Chemical engineering