Synthesis of functional amphiphilic block copolymers as stabilizer for various nanocarriers and further surface functionalization to change protein interactions
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Abstract
Surfactants are known in many daily life products like foods, cosmetics or textiles, because they have the opportunity to mix immiscible liquids by decreasing their surface or interfacial tension due to their amphiphilic nature. Research of surfactants is still present and extended to the use of renewable resources to reach biocompatible and maybe biodegradable stabilizers. Also surfactants which include additional function, e.g. stimuli responsive groups, have been studied recently. One major aspect is here the recovery of the surfactant in a simple way, resulting in less waste production. However, to date, only very few stimuli-responsive and functional surfactants are applied.
In this work several surfactants with different properties for the direct and inverse miniemulsion have been prepared. Polymeric surfactants based on well-defined polyglycerol block copolymers with adjustable length ratios were studied as stabilizers or multifunctional surfmers for various nanocarriers synthesized by water-in-oil (w/o) or oil-in-water (o/w) miniemulsions. Furthermore, the first well-defined amphiphilic block copolymers with several ferrocene units in the side chain are established as non-ionic redox-responsive ferrocenyl surfactants for o/w miniemulsions with destabilization ‘on-demand’ by oxidation.
Nanocarriers generated by w/o miniemulsions, have to be transferred into water after synthesis. Therefore, an additional water-soluble surfactant or a surfactant with stimuli responsive groups is necessary. However, most oil-soluble surfactants are amphiphilic block copolymers without any switchable group, which resulted in shielding of the nanocarrier surface after transfer into water. To decrease such shielding in water a pH-sensitive poly(acrylic acid) homopolymer with pH-sensitive protection group was applied as oil-soluble surfactant for polyurea nanocapsules.
In addition to nanocarrier stabilization research, also surface modification studies have to be investigated especially for their use in biomedical application to increase blood half-life time and specific cell-uptake. Therefore, the surface of the nanocarriers has to be functionalized to decrease the interaction of proteins with the nanocapsule surface. Because polyglycidol has similar protein adsorption properties as PEG, the stability of our polyglycidol functionalized polystyrene nanoparticles in blood plasma were investigated. Besides, the surface of hydroxyethyl starch nanocapsules was modified with different sugar derivatives by copper-free click reaction to reach a completely carbohydrate and biodegradable non-toxic nanocarrier and change the protein composition on the nanocapsule surface. Moreover, the surface of the nanocarriers has to be modified with cell specific linkers like mannose or folic acid to control nanocapsule uptake in the body. Because trimannose is discussed to increase cell uptake into dendritic cells, in this work, trimannose and mannose was introduced on the surface of PEGylated HES nanocapsules by copper-free click reaction to compare their cell uptake into dendritic cells.