Date of Award


Document type


Access Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program


First Advisor

Sankaran Thayumanavan

Second Advisor

Craig T. Martin

Third Advisor

Richard W. Vachet

Subject Categories

Polymer Chemistry


The design and engineering of nanoscopic drug delivery vehicles that stably encapsulate lipophilic drug molecules, transport their loaded cargo to specific target sites, and release their payload in a controlled manner are of great interest in therapeutic applications, especially for cancer chemotherapy. This dissertation focuses on chemically cross-linked, water-soluble polymer nanoparticles, termed nanogels, which constitute a promising scaffold and offer the potential to circumvent encapsulation stability issues. A facile synthetic method for a new class of self-cross-linked polymer nanogels, synthesized by an intra/intermolecular disulfide cross-linking reaction in aqueous media, is described here. This simple emulsion-free method affords noncovalent lipophilic guest encapsulation and surface functionalization that may allow for targeted delivery. The encapsulation stability of lipophilic molecules sequestered within these nanoscopic containers is evaluated by a fluorescent resonance energy transfer (FRET) based method developed by our research group. We demonstrate that the encapsulation stability of noncovalently encapsulated guest molecules in disulfide cross-linked polymer nanogels can be tuned and that guest release can be achieved in response to a biologically relevant stimulus (GSH). In addition, varied hydrophobicity in the self-cross-linked nanogels affects the lipophilic loading capacity and encapsulation stability. We reveal that optimal loading capacity is limited by encapsulation stability, where over-loading of lipophilic molecules in the nanoscopic containers may cause undersirable leakage and severely compromise the viability of such systems for drug delivery and other biological applications.