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Abstract
Polymeric nanoparticles (PNs) including stimuli-responsive nanoparticles, as drug delivery systems, have gained much attention for the last several decades due to their ability to overcome the limitations of conventional therapeutic approaches. These nanoparticles are not only able to protect the active pharmaceutical ingredients (APIs), but they can also release the drugs in response to endogenous and exogenous stimuli, which improves therapeutic efficacy and minimizes adverse effects of the drugs. While stimuli-responsive nanoparticles are used in diverse therapeutic areas, the application of these nanoparticles is an especially advantageous strategy in combating bacterial infections and metabolic syndromes such as iron overload diseases, where the complications particularly accompany the production of specific stimuli such as pH, enzymes, reactive oxygen species (ROS), and toxins. In bacterial infections caused by planktonic bacteria, intracellular bacteria, and bacterial biofilms, stimuli-responsive nanoparticles can take advantage of the stimuli released from the infected areas to overcome both antimicrobial resistance (AMR) and diffusion retardation to enhance the efficacy of antibiotics. In iron-overload disease, where the excess amount of iron accumulation causes multiple organ failure, polymeric nanoparticles can improve bioavailability and blood circulation and pharmacokinetic profiles of iron chelating agents, as well as reduce potential toxicity through target specificity and controlled release properties. In this dissertation, the effectiveness of polymeric nanoparticles as drug-delivery vehicles were investigated. Firstly, a pH-responsive nanoparticle for eliminating bacterial biofilm was studied. Secondly, an orally non-absorbable nanogel-DFO conjugate was evaluated as a potential long-term safe prophylactic treatment in reducing dietary iron absorption for hereditary hemochromatosis.