In this thesis, biodegradable non-viral polymeric nucleic acids delivery vectors were characterized concerning biophysicochemical parameters. In the first part of this research, to answer the questions: why the principle of DNA transfection cannot be directly applied for siRNA transfection, we investigated the complexation and aggregation mechanism of nucleic acids/polycations on the atomic and molecular scale. The MD and ITC data showed us the different nature and the different hierarchical

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... hanism related polycation-siRNA and polycation-pDNA complexes. All our results emphasized one point: lower N/P-ratios are especially effective for polycationic nanocarrier-based siRNA delivery, because siRNA aggregation results in a more uniform and stable complex formation at low N/P ratios already, which lead to increased siRNA delivery efficiency. This could have broad implications for the delivery of siRNA as less toxic and yet efficient delivery systems have been the bottle-neck for the translation of this promising approach into the clinical arena. In chapter 3, novel biodegradable amphiphilic copolymers hy-PEI-g-PCL-b-PEG were prepared by grafting PCL-b-PEG chains onto hyper-branched poly(ethylene imine) as non-viral gene delivery vectors. With the question: how can the graft densities of PCL-b-PEG chains influence the in vitro DNA delivery efficiency, our study began with the characterization of physico-chemical properties and expected that with the introducing of the grafted PCL-b-PEG chains, the in vitro DNA delivery efficiency with the grafted PCL-b-PEG chains could be improved. Of all the experimental results, buffer-capacity has almost exactly the same tendency as transfection efficiency. We assume that in all processes of DNA transfection, the endosomal escape has a really important and rate-limiting role. This opens new persp [...]