Synthesis And Characterization Of Environmentally Responsive Amphiphilic Micelles

Drug treatment is one of the most important ways to cure illnesses. In order to make the efficacy of the drugs to be fully exploited, the way of the drugs acting on human body should be emphasized. Conventional methods, such as oral medication and injection, could lead to fluctuations in blood drug concentration. Environmentally responsive polymer micelles, which have the advantage of controlled drug release, can be used as drug carriers to regulate the drug concentration in blood in an appropriate range. Photo-responsive amphiphilic polyester block copolymers and reduction-responsive poly(disulfide) micelles are good choices to be used as drug carriers because of excellent biocompatibility and biodegradability in order not to harm the human body.In this thesis, strategies for the construction of two kind of environmentally responsive amphiphilic block copolymers micelles were developed and the properties of the micelles were further investigatedFirstly, photo-responsive block copolymer mPEG-b-Poly(Tyr)-g-NB was prepared by introduction of o-nitrobenzyl ester group into the side chain of amphiphilic poly(ethylene glycol)-b-poly(a-hydroxy acids)(mPEG-b-poly(Tyr)) containing pendent alkynyl group via copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction. The amphiphilic mPEG-b-poly(Tyr) was synthesized via the ring-opening polymerization (ROP) of O-carboxyanhydirdes with monomethoxy poly(ethylene glycol)(mPEG) as macroinitiator. The molecular structure, self-assembly, and photo-controlled release of the obtained mPEG-b-Poly(Tyr)-g-NB were thoroughly investigated. mPEG-b-Poly(Tyr)25-g-NB could self-assemble into spherical micelles in water with an average diameter of250.6nm and a critical micelle concentration of0.0095mg mL-1, while mPEG-b-Poly(Tyr)50-g-NB self-assemble into spherical micelles with an average diameter of259.7nm and a critical micelle concentration of0.0090mg mL-1. As demonstrated by UV-vis spectroscopy, SEM and DLS,, the o-NB ester group in the side chain proceeded the photoisomerization into o-nitrosobenzaldehyde and free carboxylic acid upon365nm UV irradiation, resulting the disassembly of micelles. Controlled release of encapsulated NR molecules was verified by fluorescence spectroscopy.Secondly, a reduction-responsive amphiphilic triblock copolymer mPEG-b-PDS-b-mPEG was synthesized via polycondensation between a dithiol and dipyridyl disulfide, followed by a selective thiol-disulfide exchange reaction. The molecular structures, selfassembly, and reduction-triggered release of mPEG-b-PDS-b-mPEG were thoroughly investigated. mPEG-b-PDS(1)-b-mPEG could self-assemble into spherical micelles in water with an average size of～30nm and a critical micelle concentration of0.024mg mL-1. The reduction-triggered release of Nile Red by DTT was further demonstrated using fluorescence spectroscopy.