Synthesis,Characterization And Properties Of Amphiphilic Star-Shaped Block Copolymers And Their Hybrid Micelles Based On Poly(ε-Caprolactone)

A series of amphiphilic star-shaped block copolymers were prepared by ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP) with pentaerythritol as initiator. The molecular weight and structures were confirmed by’H NMR and GPC. The degradation behavior, self-assembly behavior, hybrid micellizaiton and drug delivery properties of these copolymers were investigated by dynamic light scattering (DLS), Zeta potential, Differential Scanning Calorimeter (DSC), scanning electron microscope (SEM) and transmission electron microscope (TEM) etc. The main results are summarized as follows:(1) Miktoarm star copolymers (PCL)2-b-(PLLA)2were synthesized by ROP and protection/deprotection reaction, confirmed by1H NMR and GPC. Then the copolymers microspheres were prepared by oil-in-water (O/W) emulsion solvent extraction/evaporation method. DSC and SEM were used to study the degradation behavior of (PCL)2-b-(PLLA)2microspheres. The results indicated that the fast degradation of PLLA block had autocatalytic effect on the degradation of microspheres. The microsphere morphologies were changed from spheroid with rough surface to irregular broken parts. Combined with weight loss and molecular weight, the degradation behavior was a combined degradation of surface erosion and bulk degradation.(2) Amphiphilic star copolymers s(PCL-b-PDEAEMA)4were synthesized by ROP and ATRP, confirmed by1H NMR and GPC. Their micelles were prepared in water with different pH values. Fluorescence spectrum, DLS and TEM were used to investigate the CMC, hydrodynamic diameters and morphologies of copolymer micelles in different pH values. The results showed that the micelles had pH sensitivity. The micelles diameters were200nm at pH2.0to7.0and more than1000nm above pH9.0. The drug release profile demonstrated that the DLC and EE were22%and44%, respectively. The cumulative releases at36hours were53%.(3) Amphiphilic star copolymers s(PDMAEMA-b-P(HEMA-g-PCL))4were synthesized by ROP and ATRP, confirmed by1H NMR and GPC. Their micelles in different pH values were examined by fluorescence spectrum, DLS, Zeta potential and TEM. The results illustrated that the CMCs of copolymer micelles were decreased with the increasing PCL content. The micelles diameters were around100nm at pH2.0to7.0but more than1000nm above pH9.0. Compared with s(PCL-b-PDEAEMA)4, the diameters of s(PDMAEMA-b-P(HEMA-g-PCL))4micelles were more lower, which might be caused by the molecular structure of inner-hydrophilic/outer-hydrophobic. The drug release profile demonstrated that the DLC and EE were25%and50%, respectively, and the cumulative releases at36hours were62%, which were better than s(PCL-b-PDEAEMA)4. MTT results showed that the addition of PCL could decrease the cytotoxicity of polycationics.(4) The hybrid micelles of mPEG-b-PAA with s(PCL-b-PDEAEMA)4or s(PDMAEMA-b-P(HEMA-g-PCL))4were prepared by electrostatic interaction between PAA and polycationics. Fluorescence spectrum, DLS, Zeta potential and TEM were applied to monitor the hybrid micelles. All the hybrid micelles showed their pH sensitivities and the s(PDMAEMA-b-P(HEMA-g-PCL))4hybrid micelles were more suitable for drug delivery. The drug release profile demonstrated that the DLC and EE were26%and55%, respectively, and the cumulative releases at36hours were above60%. MTT results indicated that the addition of mPEG chain and the combination of PAA and polycationics could decrease the cytotoxicity of polycationics.(5) The linear-hyperbranched block copolymer mPEG-b-hPCL were synthesized by ROP and esterification. DSC results showed a broad melting range of PCL between30℃to50℃. The copolymers were dispersed in water and methanol in same condition. The results illustrated that the micelles diameters from water were300nm while those from methanol were150nm. TEM identified the aggregates formed from water were micelles but those from methanol were nanoparticles. The drug release profile demonstrated that the DLC and EE were15%and33%, respectively. The cumulative releases at36hours were decreased with the increasing PCL content, because the hyperbranch structure enhanced the interaction between drug and PCL chain.