Development of novel polymeric architectures for applications in drug delivery and studies towards the synthesis of perfect polymers by iterative exponential growth "Plus" (IEG+)

Abstract

Polymeric materials are ubiquitous in numerous facets of everyday life, and their applications will only become increasingly prevalent as the field of polymer science advances. The first chapter of this thesis describes the use of polymeric nanoparticles to overcome challenges in traditional drug delivery. Specifically, a series of novel acid-cleavable bisnorbornene crosslinkers were synthesized and evaluated as building blocks for the formation of acid-degradable brush-arm star polymers (BASPs) via the brush-first ring-opening metathesis polymerization (ROMP) method. A bis-norbornene acetal structure was identified that, when employed in conjunction with a poly(ethylene glycol) (PEG) macromonomer, provided highly controlled BASP formation reactions. Combination of this new crosslinker with a novel acid-labile doxorubicin (DOX)-branch-PEG macromonomer provided BASPs that simultaneously degrade and release DOX in cell culture. In vitro cell viability studies using HeLa cells confirmed that these constructs are cytotoxic. Even though polymeric materials have found widespread use in current times, polymer science must overcome certain challenges to contend with the needs of next-generation technologies. In particular, newer polymer applications require the use of macromolecules with precisely defined structure and degree of polymerization--challenges that synthetic polymer chemistry has yet to conquer. The second chapter of this thesis describes a novel synthetic methodology (IEG+) that gives polymers with defined molar mass and sequence using synthetic procedures that are precise, scalable, and amenable to diversification. The IEG+ method utilized monomers equipped with orthogonal protecting groups: epoxides and alkynyl silanes. The epoxide functionality served both as a protecting group and as a masked synthon for alcohols, which allowed for side-chain functionalization of the IEG+ scaffold. Combing R- and Smonomers afforded complete stereochemical control of the IEG backbone. Oligomers of unimolecular molar mass and precise chemical structure were successfully prepared.