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.
| Identifer | oai:union.ndltd.org:UMASS/oai:scholarworks.umass.edu:open_access_dissertations-1375 |
| Date | 13 May 2011 |
| Creators | Jiwpanich, Siriporn |
| Publisher | ScholarWorks@UMass Amherst |
| Source Sets | University of Massachusetts, Amherst |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Open Access Dissertations |
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