Inhaltszusammenfassung

Proteins are natural polymers, which depict promising materials for the preparation of nanoparticles due to their biocompatibility, biodegradability and low toxicity. Moreover, proteins are attractive substances as a result of the simplicity and versatility in their surface modification using bioorganic chemistry. This PhD thesis presents the development of several different protein-based nanoparticle systems, composed of high surface PEGylated enzymes. The modification changes the enzyme so...Proteins are natural polymers, which depict promising materials for the preparation of nanoparticles due to their biocompatibility, biodegradability and low toxicity. Moreover, proteins are attractive substances as a result of the simplicity and versatility in their surface modification using bioorganic chemistry. This PhD thesis presents the development of several different protein-based nanoparticle systems, composed of high surface PEGylated enzymes. The modification changes the enzyme solubility behavior and allows a particle formation by an emulsion-based preparation technique. This process preserves the enzyme structure and activity and the prepared particles need no cross-linking in order to be stable. The preparation technique was advanced to approve the encapsulation of large, hydrophilic enzymes which can act as biotherapeutics in bacterial infection treatment. The encapsulation of the antibacterial payload leads to no activity impairment and the payload can sustained release at the local area of bacterial infections. These results open up the possibility to transfer this particle preparation technique universally to various enzymes as particle material and the encapsulation of diverse hydrophilic payloads. Additionally, the emulsion technique was applied in this work to develop stimuli-responsive protein-based nanoparticle systems, which allows a triggered payload release. An acid-sensitivity was obtained through cleavable vinyl ether groups distributed within the PEG backbone. The prepared particles disassembled in acidic conditions, as it occurs for example in the endo-lysosomal pathway, while they were stable in a physiological neutral environment. After the encapsulation of a hydrophilic payload into these nanoparticles, an acid triggered payload release could be shown. Furthermore, a nanoparticle system was developed with a redox-responsivity, which was obtained using a disulfide linker between the enzyme and PEG. The linker has the additional property of degrading itself after the disulfide cleavage. The prepared nanoparticles have the ability to decompose in reductive conditions, while the nearly unmodified enzyme can be regained due to the linker property. In the future, this enzyme recovery from the particle material could be exploited, that the protein-based nanoparticles itself can be used as a biotherapeutic agent.» weiterlesen» einklappen

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DDC Sachgruppe:
Chemie