Synthesis Of Six-arm Star PLGA And Amphiphilic Six-arm Star-PLGA-PEG Block Copolymer, Characterization And Used As A Drug Carrier

PLGA has been approved using as drug carrier in medicine by FDA for years, it is low toxic, good biocompatibale and biodegradable. However, some problems still remain: for example, for linear PLGA, it has little modification of the reactive functional groupsit can be phagocytosed by reticuloendothelial system (RES) easily, reduces the bioavailability of drugs in the body. So lots of researchers focus on modified linear PLGA. In our study, we synthesised star shaped PLGA and amphiphilic star shaped PLGA-PEG polymer, then studied the advantages of modified PLGA. Consequently, the major contents of this thesis elaborating my experiments in three portions are shown as follows:The six arm star-shaped poly (lactide-co-glycolide) was synthesized via the ring-opening polymerization of D, L-lactide and glycolide, with inositol as a multifunctional initiator and stannous2-ethylhexanoate as a catalyst. And then a series of amphiphilic star shaped PLGA-PEG was prepared using classical DCC condensation reaction in the mild condition. Polymers were characterized by NMR and GPC method. The results showed that the structure of6-s-PLGA was demonstrated by13C NMR, and1H NMR demonstrated the successful couple of6-s-PLGA and PEG. GPC results showed the polymer molecular weight was unimodal and had good uniformity.As for6-s-PLGA, we designed orthogonal experiment to study the effect of factor such as:polymer concentration, sonication time, PVA concentration and the ratio of oil phase to water phase, and optimize the best preparation condition. At the best preparation condition, we prepared nanoparticles loading paclitaxel using emulsion solvent evaporation method. We characterized the nanoparticle size and morphology and loading efficiency. We also compared release of linear PLGA nanopaticles and6-s-PLGA nanoparticles in vitro and the inhibition effect on smooth muscle cell proliferation. The results showed that the best condition for preparation nanoparticles was:polymer concentration30mg/mL, sonication time8min, PVA concentration was1%, the oil and water phase ratio was1:3. The in vitro release indicated that6-s-PLGA-PTX-NP had a slower and longer release profile than L-PLGA-PTX-NP. MTT assay showed that6-s-PLGA-PTX-NP had a long and last effect on smooth muscle cell proliferation.As for the amphiphilic star shaped PLGA-PEG, pyrene fluorescence was employed to inspect the critical micelle concentration of each polymers. Micelles were then prepared from PLGA-PEG copolymers using solvent evaporation method. The biocompatibility of polymer was studied by MTT assay. The morphology and the size of the micelles were characterized by Transmission Electron Microscope (TEM) and dynamic light scattering (DLS). We also examined the stability of the micelles loading Paclitaxel (PTX), tested about the in vitro release profiles of nanoparticles loading PTX of6-s-PLGA (6-s-PLGA-PTX-NP) and nanomicelles loading PTX of6-s-PLGA-PEG (6-s-PLGA-PEG-PTX-NP). The inhibition of smooth muscle cell proliferation was tested using MTT assay. The results showed the CMC of each copolymer was0.994μg/L、0.7559μg/L and0.5098μg/L, and the polymer had a good biocompatibility, the micelles loading PTX were spherical shape, and the size were uniform. And6-s-PLGA-PEG-PTX-NP had a faster and more complete release and also had a stronger inhibition effect to SMC cells than that of6-s-PLGA-PTX-NP.All the results above support the fact that both6-s-PLGA polymer and6-s-PLGA-PEG copolymer can be hopeful drug carrier candidate.