Studies On Highly Branched Poly(Ethylene Oxide)s And Their Amphiphilic Copolymers

Since the properties of polymers are determined by their structures,the innovative progress of polymer structure is the key for the development of new multifunctional materials.The topological structures of polymers bring more excellent and unique properties,such as compact molecular stacking,high density of ending groups and abundant intramolecular cavities,which greatly broaden the application field of traditional polymers.Based on the well-designed synthetic methods,exploring the interdependence between structures and properties is highly necessary,which will enable us to design polymer materials with more outstanding properties.Therefore,it is of great significance to developing efficient and controllable methods to synthesize the high branched polymers and study the dependence of properties on the structures.As poly(ethylene oxide)(PEO)has excellent stealth properties in organisms,which can avoid being quickly recognized by the immune system and removed from the body,it is widely applied in the field of drug release.However,the convenient,efficient and controllable synthesis of highly branched PEO and their structure-activity relationship still need to be systematically explored.Similarly,due to biodegradability,absorbability and high biocompatibility,aliphatic polyesters have been widely applied in biodegradable materials and biomedical fields.However,the research on the controllable synthesis and structure-property relationship of highly branched aliphatic polyesters still needs to be improved.Because of the dynamic properties of the linear amphiphilic polymers,more and more studies focus on highly branched amphiphilic polymers,which possess lower critical micelle concentration and higher stability.Currently,the synthesis of highly branched amphiphilic polymers suffers from complicated process and high cost,therefore,the development of efficient and controllable method for the synthesis of amphiphilic polymers and the investigation of structure-property relationship is highly important.Accordingly,based on the "Grafting from" strategy,linear/star-shaped hydroxylated polybutadienes with controllable structures are used as the initiators to successfully synthesized highly branched PEO,highly branched degradable polyesters and highly branched PEOpolyester amphiphilic block copolymers with controllable structures,respectively.The relationship between structures and properties,and the drug-loading properties of highly branched amphiphilic copolymers are systematically investigated.The main content and results of the paper are as follows:(1)By using the hydroxylated polybutadiene macroinitiator with adjustable hydroxyl number initiates the ring-opening polymerization of ethylene oxide monomer with t-BuP4 as catalyst,series of highly branched linear comb/star comb poly(ethylene oxide)with adjustable branch density(23～39 arms)and controllable side chain length(1000～2000 Da)have been synthesized,which possess narrow molecular weight distribution(PDI<1.10).The intrinsic viscosity,crystal structure,crystal morphology and isothermal crystallization kinetics of PEO with different topological structures were systematically analyzed:as the branching degree increases,the intrinsic viscosity of poly(ethylene oxide)and the branching factor(g’)decreased,the branching degree SC-PEO>LC-PEO>S-PEO>L-PEO.As the branching degree increases,the crystallinity decreases(decreased from linear 91.5%to star-comb 65.4%).Under the same super-cooling condition,the radial growth rate G of spherulites decreases with the increase of branching degree.With the increase of side chain length,the radial growth rate G of linear and star-shaped PEO spherulites decreases,while that of comb-shaped PEO increases.The transition temperature from regime Ⅱ to regime Ⅲ(ΔT=15 K)during the crystallization of comb-shaped PEO is higher than that of linear and star-shaped PEO(ΔT=10 K),suggesting a higher degree of super-cooling is required;the nucleation constant Kg decreased,and the fold surface free energy σe decreased from linear 1.53 J/m2 to star-comb shape 2.70 J/m2,with the increase of the side chain length,Kg and σe for linear and star PEO increase,while Kg and σe for comb PEO decrease.Therefore,PEO crystallization is both affected by molecular weight and molecular structure.(2)By using linear/star-shaped hydroxylated polybutadiene as the macromolecular initiator,a series of highly branched linear comb/star comb Caprolactone-Valerolactone random copolymer P(CL-ran-VL)s with high molecular weight,narrow distribution,controllable structure and different compositions(0～100%VL)were efficiently synthesized.The influence of composition and topological structures on their thermal properties,crystallization properties,mechanical properties and enzymatic degradation properties of P(CLran-VL)s were systematically explored:the copolymers exhibit isodimorphic cocrystallization,and the pseudo-eutectic points appear at CL/VL=50 mol%/50 mol%;P(CLran-VL)s possess lower Young’s modulus(111.5 MPa),yield stress(7.6 MPa)and breaking strength(10.5 MPa)but higher elongation at break than homopolymers,which up to 1222.9%.P(CL-ran-VL)s perform faster enzymatic degradation rates,and the enzymatic degradation process conforms to surface degradation mechanism.As the degree of branching increases:the crystallization temperature and melting temperature decrease,and the crystallinity of P(CLran-VL)(85-15)decreases from 41.3%(linear)to 26.1%(star-comb);the elongation at break increases,but the yield stress decreases;the degradation rate increases,and the half-degradation time of P(CL-ran-VL)(15-85)decreases from 58 days(linear)to 16.8 days(star-comb).Therefore,the properties of P(CL-ran-VL)copolymers show composition-and structuredependency,and the polymer properties can be controlled by adjusting the copolymer composition and topological structure.(3)By using linear/star-shaped hydroxylated polybutadiene as the macromolecular initiator,linear comb-/star-comb hyperbranched PEO-b-P(CL-ran-VL)with controllable structure and side chain length was synthesized by the secondary initiation method.These copolymers are characterized by high molecular weight and narrow distribution(PDI<1.20),the composition in hydrophobic segment of CL is 80%.The influence of topological structure and hydrophobic segment composition on the thermal properties,crystallization properties,self-assembly performance,drug loading properties and cytotoxicity of PEO-b-P(CL-ran-VL)random copolymers was systematically explored.The topological structure did not change copolymers’ crystal structure.As the branch length increases,the crystallization temperature,melting temperature,the total crystallization enthalpy as well as melting enthalpy of the polymer increase,suggesting the increasing of crystallinity;as the branching degree increases,the crystallization temperature and melting temperature increase slightly,but the total crystallization enthalpy(88.2 J/g to 48.5 J/g)and melting enthalpy(92.7J/g to 47.4J/g)decrease,suggesting the increasing of crystallinity.The particle size of micelles present narrow distribution(0.101～0.233),the topological structure and side chain length play a synergistic effect on the micelle particle size;with the increase of the side chain length and branching degree,the drug loading and drug loading efficiency increase(8.2%and 39.8%),while the drug release rate decreases,suggesting a sustained release effect.Copolymers have lower cytotoxicity.After drug loading,the cytotoxicity of micelle to PANC-1 increased as the concentration increases,cell viability under 60%at the concentration of 20 μg/mL,and as the degree of branching increases,the inhibiting effect increases.