Design, Synthesis And Characterization Of Biodegradable Block Copolymers

Biodegradable block copolymers become the great potential materials for develop -ing new drug carrier beacause of good biocompatibility, good biodegradability, the ratio of the block can be formed by adjusting and the physical and chemical properties can be controlled by joining to meet the requirements of the new block, With further research, biodegradable block copolymer drug delivery system has been widely used carrier.Biodegradable block copolymers as drug delivery carrier have many unique advantages, the paper designed and synthesized a series of block copolymers by methoxy poly（ethylene glycol）（MPEG） and poly（ethylene glycol）（PEG） as original materials. Characterization of products were determined by IR, 1H NMR and GPC analysis. The thesis is composed of three parts as follow:（1） Synthesis and characterization of MPEG-PCL and PCL-PEG-PCL block copolymer. MPEG-PCL block copolymer and a series of PCL-PEG -PCL block copolymers of different molecular weight were synthesized in good yields by ring opening polymerization ofε-caprolactone with use of poly（ethylene glycol）（PEG） or methoxy poly（ethylene glycol）（MPEG） as the initiator and stannous octoate（Sn（Oct）2） as catalyzed. The target products MPEG-PCL and PCL-PEG-PCL were determined by 1H NMR, IR and GPC analysis.（2） Synthesis and characterization of MPEG-b-PZLL-NH₂ diblock copolymer and MPEG-b-PBLG- NH₂ diblock copolymer Amino-terminated poly（ethylene glycol） monomethyl ether（MPEG-NH₂） was synthesized from MPEG by esterification with p-toluenesulfonyl chloride, and then reacting with sodium azide at high temperature and reflow followed by basification with acetonitrile, lastly, MPEG-NH₂ was synthesized from polyethylene glycol monomethyl ether azide（MPEG-N3） and triphenylphosphine in THF and water. N-caboxy-（Nε-benzyloxycarbonyl）-L-lysine anhydride （Lys（Z）-NCA） and N-caboxy-γ-benzyl-L-glutamate anhydride （BLG-NCA） were synthesized by triphosgene in THF. Diblock copolymer MPEG-b-PZLL-NH₂ was synthesized by ring-opening polymeri -zation of Lys（Z）-NCA with single-amino PEG as the initiator in CHCl3. Diblock copolymer MPEG-b-PBLG-NH₂ could be obtained by ring-opening polymerization of BLG-NCA with amino-terminated MPEG as macroinitiator in CHCl3. The product structure was characterized by IR, 1H NMR and GPC.（3） Synthesis and characterization of PEG-b-PZLL-b-PLA block copolymer and PEG-b-PBLG-b-PLA block copolymer Amino-terminated poly（ethylene glycol）（PEG-NH₂） was synthesized with reference to MPEG-NH₂. Triblock copolymer PEG-b-PZLL-NH₂ was synthesized by ring-opening polymerization of Lys（Z）-NCA with double-amino PEG as the initiator in CHCl3. Triblock copolymer PEG-b-PBLG-NH₂ was synthesized by ring-opening polymerization of BLG-NCA with double-amino PEG as the initiator in CHCl3. The target block copolymer PEG-b-PZLL-b-PLA and PEG-b-PBLG-b-PLA was synthesiz -ed by activated carboxyl-terminal poly（L-lactic acid）PLA-COOH with PEG-b-PZLL -NH₂ and PEG-b-PBLG-NH₂. The structures of the copolymers were confirmed by IR, 1H NMR and GPC.