Synthesis, Degradation And Drug Controlled Release Properties Of Copolyanhydrides

In this thesis, poly(sebacic anhydride-co-octadecanoic anhydride)(P(SA-OA)), poly(sebacic anhydride-co-glycol) (PSAG), poly(sebacic anhydride-co-glycol-co- glycerin) (PSAGGM ) and MPEG-PSA-MPEG were synthesized by melt codensation. The intrinsic viscosities of copolymers were detected by Ubbelohde viscometer, and the structures of polymers were characterized by Fourier-transform infrared spectroscopy (FTIR) , ~1H-nuclear magnetic resonance spectra (~1H-NMR), wide angle X-ray diffraction (WAXD) and scanning electron microscopy (SEM). The drug controlled release properties of the prepared copolymers were examined by using salicylic acid, paclitaxol, fluorouracil and dexamethasone as model drugs. The results show that the degradation rate of P(SA-OA) decreases with the increasing of OA fraction. When the molar ratio of SA/OA in P(SA-OA) is 5/5, only 68.9% weight is lost in 13 days. Salicylic acid and paclitaxol were used as model drugs to detect the drug controlled release of the prepared copolymers. The drug release rate of paclitaxol is consistent with the degradation rate of the copolymer, whereas the drug release rate of salicylic acid is faster than the degradation rate of copolymer. The influences of chain extenders on drug release of PSA, PSAG and PSAGGM were studied with salicylic acid and dexamethasone as model drugs. The results show that the release rate of salicylic acid from PSAG is the fastest and that from PSA is the slowest. The drug release rate from PSA,PSAG and PSAGGM decreases with the increasing in the fraction of salicylic acid. The dexamethasone release rate from PSAG and PSAGGM are slower than that from PSA and increase with the increasing in the fraction of dexamethasone.In situ gel of triblock copolymer with polyanhydride as hydrophobic chain was also studied. Aqueous solution (20 wt % concentration) of MPEG-PSA-MPEG triblock copolymer presents sol-gel transition property. The phase transition temperature is 28-42℃. The in situ gel of MPEG-PSA-MPEG can control the release of fluorouracil. The drug release rate keeps constantly in former 32h and the release amount accumulates to 63.4%.