Synthesis Of Amphiphilic Block Copolymers By Organocatalyst And Study On Nanomicelles

Poly(L-lactide)(PLLA)is an important aliphatic polyester and has been used in the diverse biomedical applications such as tissue engineering,drug controlled release systems and surgical suture lines due to its biocompatibility and bioresorbable.Howerer,hydrophobicity and poor elasticity have limited the applications of PLLA.In the view of the consideration,one of the possible and promising approaches to overcome above problems is to introduce hydrophilic units into PLLA to control the hydrophilicity and degradablity.Dihydroxy poly(ethylene glycol)(PEG)and 4-armed poly(ethylene glycol)(4-armPEG-OH)were approved by the US Food and Drug Adminstration(FDA)because of the excellent biocompatibity,hydrophilicity and good security.They can also be metabolized in human body under molecular weight of 3×104 g/mol.In this paper,2,3,6,7-tetrahydro-5H-thiazolo[3,2-a] pyrimidine(ITU 1)was synthesized and used to catalyze ring-opening homopolymerizations and copolymerizations of L-lactide(LLA)to obtain PLLA homopolymers,amphiphilic poly(L-lactide)-poly(ethylene glycol)-poly(L-lactide)(PLLA-b-PEG-b-PLLA)and four-armed poly(ethylene glycol)-poly(L-lactide)(4-armPEG-b-PLLA)copolymers by the molecular design.The main contents are listed below.(1)PLLA homopolymers were prepared by ring-opening polymerization of LLA catalyzed by ITU 1 in benzyl alcohol as initiator in dichloromethane.The effects of polymerization conditions,such as monomer concentration,monomer to catalyst molar ratio,reaction time and temperature on the yield and molecular weight of PLLA were discussed in detail.The optimum conditions for the polymerization are: [LLA] = 2.0 mol/L,molar ratio of [LLA]/[C]/[I] = 20:1:0.1 molar ratio,30 ?,62 h,in dichlornethane.PLLA homopolymer with molecular weight of 1.23×104 g/mol and molecular weight distribution of 1.10 can be prepared.The structure and property of PLLA were characterized and analyzed by FTIR,NMR,XRD and DSC.The results of NMR and DSC confirmed no inversion of the configuration of the asymmetric carbon atoms of LLA under the reaction conditions and formation of isotactic PLLA with 100% optical purity.The XRD analystic result confirmed ?-crystal structure of PLLA(2)PLLA-b-PEG-b-PLLA triblock copolymers were successfully obtained using ITU 1 as a catalyst,PEG as a macroinitiator.The effects of different conditions on the polymerization of LLA with ITU 1 were explored in detail.The optimum conditions can be described as: [LLA] = 3.0 mol/L,[LLA]/[C] = 30 molar ratio,30 ?,56 h,in dichloromethane,under which PLLA-b-PEG-b-PLLA with Mn = 2.78×104 g/mol can be obtained.The spectra of FTIR and 1H NMR proved the formation of triblock copolymer.The properties of PLLA-b-PEG-b-PLLA were characterized by DSC and TGA.TGA curves showed that decomposition temperature of copolymers was improved due to introducing PEG segment into PLLA.DSC measurement showed the melting point of PLLA gradually increased with the increasing of Mn of triblock copolymers.When the molecular weight of the block copolymer reached the maximum,the melting temperature of the PLLA segment was close to PLLA homopolymer and PEG melting peak was not observed.The reason was that with increasing molecular weight of PLLA-b-PEG-b-PLLA,the PLLA segment at both ends of PEG blocks hindered folding of PEG chain and PEG could't form the nuclei and could't crystallize.(3)4-ArmPEG-b-PLLA star-shaped copolymers were prepared utilizing ITU 1 as a catalyst,4-armPEG-OH as a macroinitiator.The effects of various factors on the molecular weight and yield of the copolymer were investigated detailedly.The structure of 4-armPEG-b-PLLA was characterized by FTIR and 1H NMR.The performance of the synthesized star copolymers were analysized by DSC and contact angle.The experimental results suggest that with increasing molecular weight of 4-armPEG-b-PLLA,the melting temperature of the copolymers gradually approaches the PLLA homopolymer.The contact angle of copolymers gradually becomes smaller because of introducing 4-armPEG-OH units into PLLA to improve the hydrophilicity of PLLA.(5)The PLLA-b-PEG-b-PLLA and 4-armPEG-b-PLLA nanomicelles were obtained through the dialysis method.The size and size distribution of micelles were determined by dynamic light scatter(DLS)technology.The morphology of micelles was observed by transmission electron microscopy.The results show that the nanomicelles are formed by self-assembly in the aqueous solution.The particle size distributions are uniform and the particle sizes are within 100 nm.The nanomicelles are promising in biomedical drug carrier.