Polycationic materials were designed to serve as vehicles for the delivery of therapeutic DNA into cells. Three areas were explored including ionization and buffering control, degradable scaffolds, and new functionality for enhanced cellular uptake. It was found that the delivery ability was greatly influenced by the ionization state of the materials with a range (24–50% ionization at a pH of 7.4) defined as a target in the development of future materials. Use of a degradable scaffold was found to be successful in reducing unwanted toxicity that is present in most delivery vehicles developed to date. Lastly, synthetic strategies were developed for integrating a new functionality, with proven cellular uptake enhancement, into monomers and polymers. Through this work, fundamental studies were conducted that established material design guidelines as well as supported strategies for controlling toxicity and enhancing bioactivity.
|Advisor:||Ashby, Valerie S.|
|Commitee:||Brookhart, Maurice S., DeSimone, Joseph, Johnson, Jeffrey S., Waters, Marcey L.|
|School:||The University of North Carolina at Chapel Hill|
|School Location:||United States -- North Carolina|
|Source:||DAI-B 71/05, Dissertation Abstracts International|
|Subjects:||Biochemistry, Organic chemistry, Polymer chemistry|
|Keywords:||Dienes, Functionalization, Gene delivery, Polycations|
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