Synthesis And Application Studies Of Amphiphilic Star-shaped Block Copolymers

Amphiphilic star-shape block copolymers with four and six arms(PTL-PLA-mPEG and DPE-PLA-mPEG) were synthesized and made into micelles asdrug carriers in this research. Linear block copolymers DEG-PLA-mPEG andPLA-mPEG were synthesized as the control groups. The hydrophobic part of themicelle was made up of poly(D, L-lactic acid)(PLA), and methoxy poly (ethyleneglycol)(mPEG) played the part of hydrophilic block. The star polymers weresynthesized by a ring-open polymerization with stannous octoate as the catalyst. Theproducts were comfirmed by nuclear magnetic resonance (1H-NMR), fouriertransform infrared spectroscopy (FTIR) and gel permeation chromatography (GPC).The amphiphilic block copolymers could be self-assembled into micelles by dialysisand solvent evaporation methods.The applications of star-shape and linear polymers as drug delivery carriers wereinvestigated in this thesis. The fluorescence spectroscopy using pyrene as thefluorescent probe was applied to determine the critical micelle concentration (CMC)of polymers, which indicated that the star polymers had lower CMC and higherstablity in aqueous solutions than the linear ones. The morphology of polymermicelles was observed under transmission electron microscopy (TEM), whichexhibited a plenty of spherical nanoparticles in uniform size. Particle size distributionswere investigated by dynamic light scattering (DLS), sizes of linear and star-shapepolymers were all below100nm. Mean sizes of blank star micelles PTL-PLA-Mpegand DPE-PLA-mPEG were53.2nm and59.2nm, which were smaller than theirlinear counterparts whose sizes were around78.1and80.3nm. All the particle sizeswere increased slightly when they were loaded with the model drug.The hydrophobic anti-inflammatory drug indomethcin (IMC) was chosen as themodel drug to be entrapped into micelles. A sustained release was observed by thedrug-loaded star-shape polymer micelles. The release of IMC from micelles lastedmore than45h in simulative physiological environment, and the release rate wasfaster in acidic PBS solution than the neutral environment. The experiments aboutpolymer viscosity showed that the star polymers gained higher inherent viscosities asa result of the higher molecular weight and more branched structures. The hemolysistest confirmed that the amphiphilic copolymers PLA-mPEG, DEG-PLA-mPEG,PTL-PLA-mPEG and DPE-PLA-mPEG were harmless to the blood cells, exhibitinggood biocompatibility.All of the above results stated that the amphiphilic star-shape polymer micellesexhibited better profiles as drug carriers than the linear ones, which indicated that thebranched star polymers could be a promising nanocarrier in drug delivery system.