Abstract
The first part of this thesis focuses on mixed hydrogels. The mixed micelles were formed by mPEG-PLGA and mPEG-PCL, the mixed micelles aggregated to form hydrogels under certain temperature and concentration above 15 wt%. The mixed hydrogels can successfully encapsulate a typical hydrophilic drug (vancomycin). Experimental results show that the mixed hydrogels have the features of stable durg release properties and slow degradation. The second part of this thesis focuses on polyanhydride hydrogels. The thermosensitive micelles mPEG-PLCPPA and mPEG-PLCPHA copolymers compose of methoxy polyethylene glycol (mPEG), polylactic acid (PLA) and 1,3-bis(p-carboxyphenoxy)propane (CPP) or 1,6-bis (p-carboxyphenoxy) hexane (CPH) are fabricated for application as a novel hydrophilic drug carrier. The copolymer can self-assemble into micelles in phosphate buffered saline (PBS) by hydrophobic interaction. The sol-gel transition profiles were investigated by the tube flipped upside method and a rheometer. The drug release profiles were investigated in PBS at 37°C with different concentrations of mPEG- PLCPPA and mPEG-PLCPHA solution. The in vitro and in vivo biocompatibility were also evaluated. Bacterial inhibition zone assay was performed by encapsulation of vancomycin and cefazolin. The diameters of these micelles increased as the temperature increased. The micelles increased in viscosity because of the aggregation of hydrophobic segments while temperature increased from the room temperature to the body temperature. The micelle properties of hydrogel containing vancomycin or cefazolin compared with hydrogel without drug loading were not significant difference. During the in vitro degradation process, hydrogels demonstrated a lower degradation rate and a light decrease in pH value. The in vitro and in vivo cytotoxicity results showed that the copolymer micelles had excellent biocompatibility. In vitro drug release profiles revealed a stable vancomycin release for 10 days and a stable cefazolin release for 30 days. The hydrogel encapsulating vancomycin and cefazolin had good antibacterial effects. Based on the results, mPEG-PLCPPA and mPEG-PLCPHA are promising as injectable depot gels for drug delivery.