| Amphiphilic block copolymers are concerned by scientists because of their unique self-assembled morphologies in aqueous media, which have a great application prospects in the field of drug delivery. In this thesis, we have designed and synthesized amphiphilic star-shaped (i.e. Y-shaped and dumbbell-shaped) block copolymers, which have different topological structure and different molecular weight. This topic have chosen biodegradable poly(lactic-co-glycolic acid)(PLGA) as the hydrophobic segment of copolymer, and polyethylene glycol (PEG) as hydrophilic segment, which can avoid protein adsorption and approved by the FDA for clinical application. The copolymers were synthesized by ring-opening polymerization (ROP) of L-lactide and glycolide with double-or tetra-hydroxyl functional PEG as macroinitiator and stannous octoate (Sn(Oct)2) as catalyst. The copolymers self-assembled into nanoscale micellar/vesicular aggregations in phosphate buffer solution at pH7.4. Doxorubicin (DOX), an anthracycline anticancer drug, was loaded into micellar/vesicular nanoparticles, yielding micellar/vesicular nanomedicines. The in vitro release behaviors could be adjusted by topological structure of copolymer, content of hydrophobic polyester, pH of release medium, and self-assembled morphology. In vitro cell experiments showed that the intracellular DOX release could be adjusted by content of hydrophobic polyester, and nanomedicines displayed effective prolification inhibition against HeLa cells with different culture times. Hemolysis tests indicated that the copolymers were hemocompatible, and the presence of copolymers could reduce the hemolysis ratio (HR) of DOX significantly. These results suggested that the anticancer nanomedicines based on DOX and novel amphiphilic star-shaped copolymers were attractive candidates as tumor tissular and intracellular targeting drug delivery systems in vivo with enhanced stability during circulation and accelerated drug release at targeting sites. |
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