Nanoparticles with Surfaces Consisting of Polyoxazolines

Polymeric nano- and microparticles of definite size have become a topic of intense research during the last decade. Potential applications of such particles exist in the biomedical field for use in drug delivery systems, drug carriers, diagnostic carriers and resonance imaging agents. We plan to generate three different types of nanoparticles with a focus on addressing their biocompatibility: vesicles, polymerized vesicles, comb- and hyperbranched polymers and stabilized block-copolymeric micelles. Polyoxazolines (POZO) will be attached to the surface (or also form the structural basis of) such particles in order to achieve biocompatibility by steric stabilization effects, similar to that known in polyethyleneglycols. The strategy of synthesis will exploit the living mechanism of the polymerization of 2-oxazolines, thus giving way to an easy access to various types of lipid-POZO conjugates and POZO-polymers. Vesicles will be formed by incorporation of lipid-POZO conjugates into lipid mixtures consisting of DPPC and cholesterol. In order to increase the stability of the lipid bilayer special lipid-POZO conjugates with polymerizable groups (i.e: 1,3-diynes, acrylates) will be synthesized and incorporated into vesicles, whose lipid bilayer is then polymerized by UV- irradiation or radical initiator molecules. Another approach will form the synthesis of comb- and hyperbranched polymers as well as block-copolymers consisting of polyoxazolines. Here the design and branching ability of specially 2-substituted oxazolines will be investigated. In addition stabilized nanoparticles will be formed from block-copolymeric micelles. The structure, formation and stability of the resulting vesicles, polymerized vesicles, comb- and hyperbranched polymers and stabilized block-copolymeric micelles will be investigated by static and dynamic light scattering methods, transmission electron microscopy (TEM) and fluorescence spectroscopy. The structural information thus obtained will form the basis for in vivo tests for the evaluation of biostability and biocompatibility.