Chemical and Biomolecular Engineering - Theses
Permanent URI for this collection
Search Results
1 - 1 of 1
-
ItemNanoengineered switchable, multi-responsive carriers for biomedical applications( 2014)Recent progress in material science and nanotechnology has enabled the design of next-generation drug delivery carriers. The implementation of such delivery systems has the potential to significantly enhance the current treatment outcomes, owing to their ability to achieve targeted bio-distribution and enhanced drug payloads. To develop the next generation of drug carriers, it is critical to incorporate a stimuli-responsive trigger into the material design. This allows for the development of “smart” carriers, which can load and release therapeutics in a specific targeted site on demand. Poly(2-diisopropylaminoethyl methacrylate) (PDPA) is a stimuli-responsive polymer that undergoes reversible hydrophobic-hydrophilic phase transition at biological-relevant pH variations. The incorporation of PDPA in the drug delivery systems opens a new route toward advanced drug delivery applications. This thesis focuses on developing several bottom-up approaches to assemble PDPA-based stimuli-responsive delivery systems from a material science perspective. By utilizing Layer-by-Layer (LbL) and self-assembly techniques, switchable, multifunctional systems that responded to various cellular conditions were synthesized. Charge-shifting PDPA capsules were synthesized via LbL assembly and cross-linked using a redox-responsive cross-linker. Dual stimuli-responsive cargo release profiles by pH and redox change were assessed in simulated intracellular conditions. Intracellular degradation kinetics of these capsules was investigated. The tuning of degradation kinetics was achieved by varying the degree of cross-linking density in the capsules, as confirmed by radio scintillation counting. Novel cross-linker free PDPA capsules were later developed. It was found that these capsules could improve the loading ability of drugs as small as 500 Da, and rapidly deconstruct and release cargo upon cellular uptake. Moreover, utilizing self-assembly techniques, multifunctional nanoparticles were synthesized from blending PDPA with an anti-cancer drug and a cell penetrating peptide. By varying the loading ratio in the nanoparticles, tunable cytotoxicity up to 30-fold was achieved. The reported PDPA-based responsive carriers are expected to provide fundamental insights towards the rational deign and synthesis of advanced delivery systems.