The Research On The Synthesis And Properties Of Biodegradable Polyesters And Poly (Amino Acids) Sandwich Copolymer

In recent years, biomedical polymer materials become more and more important in our lives. Fabrication of bioresorbable amphiphilic block copolymers hollow structures has become a hot point in biomedical engineering research. In this context, biocompatible polymers with different architectures, biocompatible, biodegradable, stimuli-responsive and targetable are strongly desired. Polylactide (PLA) and Poly (ε-caprolactone)(PCL) were widely used as drug carrier and tissue engineering scaffold due to their good biocompatibility and degradability. However, their high hydrophobicity and lack of highly reactive functional group as a trigger of chemical reaction on the surface of their matrix which can be easily modified with biologically active moieties limited their applications. Thus the modification of linear polyester is a very important way in the development of biomaterials. Because these biopolymers have potential applications in drug delivery and gene transfection, In this thesis, biocompatible polymers with different architectures have been synthesized by ring-opening polymerization or acylation coupling reaction, and their structure were characterized, at the same time, the thermo stabilities, crystalline properties and self-assembly behaviors in selective solvent of these copolymers were studied. The thesis is composed of five aspects as follow:(1) Synthesis of Amphiphilic Triblock Copolymers Poly(L-lactic acid)-b-Poly(L-lysine)-b-Poly(ethylene glycol) Monomethyl EtherThe amphiphilic triblock copolymer PLA-b-PLL-b-MPEG is prepared in three steps through acylation coupling between the terminal amino groups of PLA-b-PZLL-NH2and carboxyl-terminal MPEG, followed by the deprotection of amines. The block copolymers are characterized via FT-IR,’H NMR, DSC, GPC, and TEM. TEM analysis shows that the triblock polymers can form polymeric micelles in aqueous solution with a homogeneous spherical morphology. The cytotoxicity assay indicates that the final triblock polymer micelles after deprotection show low cytotoxicity against Bel7402human hepatoma cells. MPEG and PLL were introduced into the main chain of PLA affording a kind of ideal bioabsorbable polymer materials, which is expected to be useful in drug and gene delivery.(2) Synthesis and Characterization of Biodegradable Amphiphilic Triblock Copolymers Methoxy-Poly(ethylene glycol)-b-Poly(L-lysine)-b-Poly(L-lactic acid)Starting from MPEG-NH2, a series of amphiphilic triblock copolymers MPEG-b-PLL-b-PLA were synthesized through acylation coupling between the amino-terminated MPEG-b-PZLL-NH2and carboxyl-terminal PLA, followed by deprotection of amines. The block copolymers were characterized by IR,1H NMR, GPC, DSC and TEM. The GPC results indicate that the chain lengths of each block can be controlled by varying the feed ratios of the monomer and initiator, and give polymer samples with a narrow molecular weight distribution (Mw/Mn=1.10～1.25). The TEM analysis shows that the triblock polymers can self-assemble into polymeric micelles in aqueous solution with a homogeneous spherical morphology. The cell-cytotoxicity assay indicates that the triblock polymers show no obvious cytotoxicity against Bel7402human hepatoma cells.(3) Design, Synthesis and Application of Amphiphilic Diblock Copolymers Methoxy-Poly(ethylene glycol)-b-Poly(ε-caprolactone)A series of amphiphilic diblock copolymers MPEG-b-PCL with high molecular weight were synthesized through the ring-opening polymerization of ε-CL using MPEG-OH with fixed chain long as a macroinitiator and with Sn(Oct)2as a catalyst, All the block copolymers were characterized via FT-IR,1H NMR, DSC, GPC, and TEM. The IR,1H NMR and DSC revealed that the successful syntheses of the polymers and all the polymerization yields were more than80%. The GPC results that the chain lengths of each block could be controlled by varying the feed ratios of ε-CL/MPEG. The DSC results show that the subtle phase separation was observed in this series of the copolymers with different composition, when the chain length of MPEG was fixed, the Tm of PCL was raised from59.1℃to62.4℃and the Tm of PEG reduced from50.1℃to39.8℃with the increase of the chain length of PCL. The TEM results show that all the diblock copolymers could selfassemble into polymeric micelles in aqueous solution of homogeneous spherical morphology. The mean particle size of the polymeric micelles was increased with the increase of the chain length of PCL. The cell-cytotoxicity assay indicates that all the diblock polymers were no obvious cytotoxicity against Bel7402human hepatoma cells. So these diblock biodegradable polymers are expected to be useful in drug delivery and tissue engineering.(4) Tetraethoxy-silicone for Controlled Ring-Opening Polymerization of ε-CaprolactoneA series of amphiphilic copolymers TEOS-PCL with high molecular weight were synthesized through the ring-opening polymerization of ε-CL using TEOS as a macroinitiator at the temperature of140℃. The polymeration yield was only77.0%when the feed ratio of ε-CL/TEOS was800:1, and the rest were reached90%in the same condition. All the block copolymers were characterized via FT-IR,1H NMR, DSC, GPC, and TEM. The results show that the chain lengths of PCL block could be controlled by varying the feed ratios of ε-CL/TEOS. The DSC results show that the copolymers TEOS-PCL had evident phase change through the introduction of amorphous part TEOS, which has greatly restricted the PCL crystallization behavior, the melting temperature and the value of the absorption enthalpy of PCL block were affected by changing content of TEOS-PCL. When the contents percentage of TEOS in the copolymers TEOS-PCL changed from0.30%to3.52%, the Tm of PCL block changed from60.28℃to54.65℃and the absorption enthalpy changed from69.73J/g to29.80J/g, the degree of crystallization of PCL changed from51.39%to22.69%. The TEM results show that the copolymers could selfassemble into polymeric micelles in aqueous solution of homogeneous spherical morphology. The mean particle size of the polymeric micelles was in good agreement with the results of the DLS observations. The cell-cytotoxicity assay indicates that the copolymers were no obvious cytotoxicity against Bel7402human hepatoma cells. It was useful as a new kind of targeted drug carrier.(5) Tetraethoxy-silicone-Mediated Controlled Polymerization of α-Amino Acid N-CarboxyanhydridesA series of amphiphilic copolymers TEOS-PZLL with high molecular weight were synthesized through the ring-opening polymerization of Lys (Z)-NCA using TEOS as a macroinitiator at the temperature of80℃, and all polymerization yields were more than90%under the same conditions. All the block copolymers were characterized via FT-IR,1H NMR, DSC, GPC and TEM. The results show that the chain lengths of PZLL block could be controlled by varying the feed ratios of Lys (Z)-NCA/TEOS. Especially the obtained molecular weights agreed perfectly with the expected ones with the Lys (Z)-NCA/TEOS for100:1and150:1. The DSC results show that the copolymers TEOS-PZLL had evident melting temperature change through the introduction of amorphous part TEOS, which has greatly restricted the PZLL crystallization behavior, the Tm of PZLL block in TZLL (1:100) changed to274.9℃, while the Tm of PZLL block in homopolymers was282.4℃, and absorption enthalpy reduced evidently. The TEM results show that the copolymers TZLL could easily selfassemble into polymeric micelles in aqueous solution of homogeneous spherical morphology. The cell-cytotoxicity assay indicates that the copolymers were no obvious cytotoxicity against Bel7402human hepatoma cells. So they are expected to be useful for drug and gene carriers as biodegradable biomedical materials.