Abstract
Cancer is one of the leading causes of death worldwide, and anticancer treatments are also known to cause side effects that can affect life quality of the patients severely. Novel drug delivery systems (DDS), e.g., polymeric nanoparticles as carriers of drug, hold great potential in this field, as they can promote selective accumulation or activation of anticancer drug. This reduces the harm anticancer drugs could bring to the rest of the body. The unique biological properties that cancer tissue display have been exploited to develop more effective and selective DDS. In this thesis, properties of a pH-responsive supramolecular self-assembling system consisting of cyclodextrin grafted linear-poly(ethylenimine) and trimethylsilyl-containing di-copolymer were studied. The idea was to design an anticancer DDS that can utilize both the enhanced permeability and retention-effect (EPR-effect) and the lower extracellular pH values that solid tumors display. The pH-responsiveness was studied by nuclear magnetic resonance (NMR) spectroscopy experiments, which revealed that the trimethylsioxyl groups of poly ((trimethylsioxyl 2- ethylmethacrylate-co-poly (ethyl glycol) methyl ether methacrylate)) (P(TMSHEMA-co- OPEG9MA)) copolymer hydrolyzes rapidly and completely in light water solutions irrespective of pH, whereas the hydrolysis is much slower in heavy water solutions. The degradation rate in heavy water was further studied with respect to different pH levels. A pH-rate profile for the degradation of (P(TMSHEMA-co-OPEG9MA)) in heavy water solutions was determined. It revealed that the polymer does not display the desired pH-responsiveness in heavy water. The complexation of the two polymers were studied by dynamic light scattering measurements on P(TMSHEMA-co-OPEG9MA) and β-cyclodextrin-grafted-linear-poly (ethylenimine), (β- CD-g-lPEI), both alone and in mixtures with different ratios and concentrations. Both polymers showed extensive self-aggregation issue, as the intensity fluctuation measured were dominated by large particles. These particles were larger than 100 nm in hydrodynamic radius (Rh). This made it difficult to determine whether there was any complex formation.