UC San Diego

This thesis describes the development of an alkyne- functionalized poly-lactic acid (PLA) polymer with an acid -sensitive N-ethoxybenzylimidazole (NEBI) linker conjugated to doxorubicin as a drug delivery system (DDS). It also entails the specific qualities of the drug delivery system as a chemotherapeutic regiment. Chapter 1 introduces why drug delivery systems are needed and their desirable properties. In particularly, chapter 1 discusses the roles of [polymeric] carriers and linkers in drug delivery. It also covers some of the drug-delivery strategies specific to chemotherapy. Chapter 2 presents the synthetic route and methodology to produce functionalized PLA, specifically with terminal alkyne moieties. It also covers different strategies to synthesize lactide derivatives with different functional groups. Chapter 3 introduces the synthetic scheme to producing bi-functional N-ethoxybenzylimidazole (NEBI) derivatives. These novel linkers previously displayed accelerated rates of hydrolysis at lower pH. NEBI derivatives also serve as acid-sensitive linkers in the synthesis of my drug delivery system. Chapter 4 discusses the characteristics of my drug delivery system including incorporation percentages, payload, hydrolysis rate and cytotoxicity. The future directions of this project are also elaborated on in that chapter