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

A series of amphiphilic star-shaped copolymers were prepared by the combination of ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP) based on a six-arm initiator. The molecular weight and structure were characterized by 1H NMR and SEC etc. The self-assembly behavior and drug delivery property of these copolymers were investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM) etc. The combination of polymeric micelles with other materials and its application were also studied. The main results are summarized as follows:(1) Amphiphilic six-arm copolymers named as S(PCL-b-PDEAEMA), containing poly(ε-caprolactone) (PCL) and poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA or PDEA) as the arm and cyclotriphosphazene as the core, were obtained by the combination of ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP) using cyclotriphosphazene derivative (N.3P.3.(OC6H4-p-CH2OH)6) as an initial reagent. The structure and property of these copolymers were characterized by 1H NMR, SEC and DSC etc. Their self-assembly behavior in aqueous solution responding to temperature and pH value was further investigated by a combination of DLS, UV-Vis spectrometry and TEM. The results indicated that a series of amphiphilic star copolymers S(PCL-b-PDEAEMA) were successfully synthesized via ROP and ATRP. The obtained S(PCL-b-PDEAEMA) exhibited the pH-dependent thermo-responsive self-assembly behavior in aqueous solutioa(2) A type of pH-sensitive and good biocompatible mixed micelles was prepared by comicellization of a star block copolymer poly(ε-caprolactone)-block-poly(diethylamino)ethyl methacrylate (S(PCL-b-PDEAEMA)) and a linear block copolymer methoxy polyethylene glycol)-block-poly(ε-caprolactone) (mPEG-b-PCL). It was confirmed by 1H NMR and DLS that the two copolymers self-assembled into mixed micelles with a mixed PDEAEMA/mPEG shell and a common PCL core. As increasing the mPEG-b-PCL content, the size and zeta potential of the mixed micelles were lowered, but the pH-dependent stability and the bio compatibility was improved. The drug release profile demonstrated that the release rate of indomethacin (IND)-loaded mixed micelles at pH 7.4 was faster than that at pH 5.0 due to the collapsed PDEAEMA and the stretched mPEG of the micelles.(3) A series of star-shaped poly(ε-capro lactone) (PCL)-based diblock and triblock copolymers containing 2-(Dimethylamino)ethyl methacrylate (DMAEMA or DMA) and oligo(ethylene glycol) mo no methyl ether methacrylate (OEGMA or OEG) were synthesized by one-pot ATRP. The monomer reactivity ratios for DMAEMA (r1) and OEGMA (r2) were estimated to be near unity and r1×r2=1, indicating the reaction system was a nearly ideal copolymerization. The self-assembly behavior of these copolymers in aqueous solution was investigated by fluorimetry, 1H NMR, DLS, TEM, potentio metric titrations and zeta potential measurements. The results indicated that the star copolymers were stimuli-responsive to both pH and salinity depending on their composition and structure. In vitro release behavior of polymeric micelles was also investigated by using indomethacin (IND) as a model drug. The results showed that the addition of NaCl accelerated the drug release.(4) Micelles/sodium-alginate composite gel beads (micelles/SA beads) were constructed from SA matrix and indomethacin (IND) loaded six-arm block copolymer poly(ε-caprolactone)-b-(dimethylamino)ethyl methacrylate (S(PCL-b-PDMA)6) micelles. The morphology and swelling property of the gel beads was characterized by scanning electron microscopy (SEM) and gravimetric method, respectively. It showed that the composite gel beads were suitable for oral drug delivery. The release behaviors of three matrices including micelles, SA beads and micelles/SA beads were investigated in simulated gastrointestinal (GI) tract. The results showed that the micelles/SA beads used as oral carriers were superior to the micelles and S Abeads, and the release rate of IND could be tuned by the initial concentration of SA and CaCl2.(5) Silver nanoparticles (Ag NPs) were prepared via in situ reduction of silver nitrate (AgNO3.) using S(PCL-b-P(DMA-co-OEG)) and S(PCL-b-PDMA-b-P(DMA-co-OEG)) micelles as nanoreactors. The Ag NPs were characterized by UV-vis spectrum, DLS, TEM, FTIR and TGA measurements. The result revealed that the Ag NPs could be well stabilized by copolymers. The AgNPs were in sphere-like shape with a diameter of about 10-20 nm, which was independent of the AgNO3. concentration, pH value and the architecture of copolymer. Furthermore, the catalytic activity of these Ag NPs was investigated by monitoring the reduction of p-nitrophenol (4-NP) by NaBH4. The result showed that the formation of AgNPs by coordination reduction can be effectively used in catalytic reaction.