Preparation And Characterization Of PH Responsive Nano-micelles To Build Artificial Oxygen Carriers And Drug-loaded Carriers

Due to the unique structure and properties, block copolymer micelles have been an important particle as artificial oxygen carriers and drug delivery vehicles in biomaterial science. In this dissertation, two kinds of amphiphilic block copolymers were synthesized, and the self-assembly behavior, oxygen binding and releasing and drug release properties were studied. The amphiphilic block copolymers consisting of methoxy poly(ethylene glycol)(mPEG) as a hydrophilic block and either poly(glycidyl methacrylate)(PGMA) as a hydrophobic block. With decoration of N-(3-amino propyl) imidazole (API) or tetraethylenepentamine(TEPA), block copolymers PEG-P(GMA-API) and PEG-P(GMA-TEPA) were synthesized and used as oxygen carriers and drug carriers.Specifically, five sections of work were carried out as follows:(1) Amphiphilic block copolymers of poly(ethylene glycol)-co-poly(glycidyl methacrylate) (PEG-co-P(GMA)) with different DP were synthesized via atom transfer radical polymerization (ATRP). The molecular weight and polydispersity of PEG-co-P(GMA) were determined by 1H NMR and GPC, respectively. The self-assembly behavior of copolymers was characterized by fluorescence spectrum and DLS(Dynamic light scattering).(2) Postpolymerization decoration of reactive epoxy groups in the GMA block with API resulted to a new kind of water soluble copolymer PEG-P(GMA-API)45. The molecular weight and polydispersity of PEG-P(GMA-API)45 were determined with 1H NMR and GPC measurements, respectively. The resulted copolymers could self-assemble into spherical nano-micelles directly in an aqueous medium. The critical micellization concentration (CMC) of the micelles was 4×10-2 g/L, which was significantly influenced by amino and imidazole groups. DLS study showed the diameter of the micelles was about 40 nm and the micelles surface was always positively charged when the pH of the solution increased from 4 to 9.(3) The capacities of the resulted nano-micelles to encapsulate Hb in aqueous solution at pH 7.4 was explored. The encapsulation efficiency of different molar ratios of API and Hb were different. The features of Hb-based micelles were spherical with a diameter of 40 nm, which was larger than that of blank micelles (30 nm). The Hb-based micelles displayed a reversible change in the UV-visible absorption spectrum from the deoxy form to the oxygen-binding one, in response to the partial oxygen pressure of the atmosphere. The characteristic absorption peaks of the encapsulated Hb in different gas-binding states showed no significant change comparing with that of free Hb.(4) Doxorubicin (DOX) was used as a model chemotherapeutic drug to prepare drug-loaded micelles. It was found that DOX could be loaded within the micelles with high entrapment efficiency. DOX release behavior was studied by UV-vis, which indicated that DOX release was abruptly accelerated when pH was lowered below 5.0, and it released slowly when pH was 7.4.(5) Postpolymerization decoration of reactive epoxy groups in the GMA block with TEPA also resulted to a water soluble copolymer PEG-P(GMA-TEPA). The molecular weight and polydispersity of copolymer PEG-P(GMA-TEPA) were determined with 1H NMR and GPC measurements, respectively. The resulted copolymers could also self-assemble into spherical nano-micelles directly in an aqueous medium. The self-assemble behavior was characterized by fluorescence spectrum and DLS. The capacity of the resulted nano-micelles to encapsulate Hb in aqueous solution at pH 7.4 was explored with UV-vis. It demonstrated that Hb could be encapsulated within the micelles and the characteristic absorption peaks of the encapsulated Hb in different gas-binding states showed no significant change comparing with that of free Hb.