二硫键链接的两亲性嵌段合物的合成及胶束化研究

通过二硫吡啶基活化的聚乙二醇与巯基聚己内酯之间的偶联反应,在聚乙二醇单元与聚己内酯单元间引入二硫键,合成二嵌段共聚物mPEG-SS-PCL,通过核磁氢谱和红外光谱等手段对聚合物的结构进行表征。以阿霉素(DOX)为药物模型,通过紫外分光光度法分析了聚合物对脂溶性药物的包载能力,用激光粒度仪测定胶束粒径、粒径分布。结果表明,空白胶束及载药胶束的平均粒径分别为117.7nm和146.1nm,该聚合物对阿霉素具有良好的药物包载能力,最高载药量为16.28%,包封率为54.26%。     

pH响应型mPEG-PCL嵌段共聚物胶束用作药物运输

该文合成了一种具有pH敏感性,较低毒性的两亲性嵌段共聚物以用于药物运输。聚乙二醇-聚己内酯(mPEG-PCL)是以聚乙二醇单甲醚为引发剂,开环己内酯聚合而成,阿霉素则是通过顺乌头酸裂解键连在聚己内酯的末端。该嵌段聚合物通过核磁共振、红外光谱等进行表征。共轭阿霉素后的嵌段聚合物在水溶液中能够自组装形成胶束,胶束粒径约为45.4 nm,透射电镜显示胶束具有近似的球形结构。阿霉素在pH=4.0下的释放速率明显快于pH=7.4下的释放速率。mPEG-PCL在细胞培养中无细胞毒性,包载阿霉素的胶束在人类MCF-7乳腺癌细胞上表现出迟缓的细胞毒性。通过共聚焦显微镜观察游离阿霉素和mPEG-PCL-DOX胶束在MCF-7细胞内的定位说明载体能够携带阿霉素进入细胞。     

H型两亲性嵌段共聚物的合成与表征

以聚乙二醇(PEG-400)、环氧氯丙烷为原料,氢氧化钾为缚酸剂,十六烷基三甲基溴化铵为相转移催化剂制得聚乙二醇缩水甘油醚(epoxide-PEG-epoxide).然后,在氢氧化钠水溶液中,聚乙二醇缩水甘油醚中的环氧键水解生成分子链两端各含有两个羟基的大分子引发剂((HO)2PEG(OH)2).最终,以辛酸亚锡为催化剂,端羟基大分子引发剂引发ε-己内酯开环聚合,合成了不同相对分子质量的H型两亲性嵌段共聚物((PCL)2PEG(PCL)2).通过红外光谱(FTIR)和核磁共振氢谱(1H-NMR),聚乙二醇缩水甘油醚,端羟基大分子引发剂和H型两亲性嵌段共聚物的结构得到了确认.示差扫描量热法对两亲性嵌段共聚物热性能的研究表明:当亲水段的聚乙二醇分子量为400时,聚合物的熔融温度主要受疏水段的聚己内酯影响,随着聚己内酯链段长度的增加,熔融温度升高.     

三嵌段共聚物大分子引发剂的合成

首先用Novozyme 435作为催化剂合成了聚己内酯-聚乙二醇-聚己内酯三嵌段聚合物,然后通过端基官能化法合成了大分子引发剂。通过核磁表征了三嵌段聚合物和大分子引发剂的结构,从而制备含氟功能五嵌段共聚物,该聚合物在很多领域具有潜在的应用价值。     

pH响应型六臂星形共聚物的制备及药物控释研究

通过开环聚合(ROP)和原子转移自由基聚合(ATRP)设计合成了两种两亲性六臂星形共聚物聚己内酯-b-聚甲基丙烯酸羟基乙酯(6sPCL-b-PHMEA)和聚己内酯-b-聚甲基丙烯酸二乙基氨基乙酯-b-聚甲基丙烯酸羟基乙酯(6s PCL-b-PDEAM-b-PHEMA)。采用傅立叶变换红外光谱(FT-IR)和动态光散射技术(DLS)研究了共聚物的结构和胶束的粒径,并以阿霉素(DOX)为模型药物考察了两种胶束的药物控释动力学。结果表明:两种胶束均具有合适的粒径,可作为DOX载体,6sPCL-b-PHEMA和6s PCL-b-PDEAM-b-PHEMA胶束的载药量分别为11.56%和14.23%。体外释药实验结果表明,与二嵌段星形共聚物相比,三嵌段星形共聚物具有显著的p H敏感性,pH值从7.4降至2.2时,胶束中DOX的累积释药率显著增大。这种p H响应的六臂星形共聚物具有潜在的抗癌药物控释应用前景。     

生物可降解两亲性嵌段共聚物胶束的制备及其对叶酸的控制释放

以甲氧基聚乙二醇(mPEG)为引发剂,在辛酸亚锡催化下引发ε-环己内酯(CL)开环聚合,合成了聚乙二醇-聚己内酯两亲性嵌段共聚物(mPEG-PCL)。通过FTIR、1H-NMR及GPC等表征手段确定了mPEG-PCL的组成及结构。采用芘荧光探针法、透射电镜和动态激光光散射研究了聚合物在水中的自组装行为。结果表明:聚合物在水溶液中能够自组装形成粒径小于100 nm的规则球状胶束,且具有较低的临界胶束浓度(7.35×10-3 g/L);模型药物(叶酸)成功负载于聚合物纳米胶束内,并且能延缓叶酸的释放,其释药速率受载药量和释放介质pH的影响。     

两亲嵌段共聚物聚乙二醇-聚(α-炔丙基-δ-戊内酯)的合成

首次合成了端甲氧基聚乙二醇-聚(α-炔丙基-δ戊内酯)嵌段共聚物。首先用炔丙基溴修饰δ-戊内酯,再以三氟甲磺酸亚锡为催化剂,利用开环聚合的方法,用端甲氧基聚乙二醇引发α-炔丙基-δ-戊内酯开环聚合,合成了侧链带有炔丙基的端甲氧基聚乙二醇-聚(α-炔丙基-δ戊内酯)嵌段共聚物。并用~1H NMR,IR和GPC等方法对所得嵌段聚合物的组成、结构进行了表征。     

两亲扩展型共聚物的合成及中间极性嵌段对乳化性能的影响

采用聚乙二醇单甲醚(Mn=1 900,5 000)分别引发丙交酯和ε-己内酯开环聚合合成了中间嵌段(PLA)聚合度递增的聚乙二醇-聚丙交酯-聚己内酯(MPEG-PLA-PCL)两亲扩展型共聚物和相应的聚乙二醇-聚己内酯(MPEG-PCL)两嵌段共聚物。用FTIR、1HNMR和GPC对产物结构进行了表征,研究了共聚物和常规低分子表面活性剂的乳化性能,探讨了中间极性嵌段的长度对共聚物乳化性能的影响。结果表明,对于甲苯/水体系,共聚物可用于制备稳定的O/W型乳液,且三嵌段共聚物的乳化性能优于低分子表面活性剂;随着引入PLA嵌段聚合度的增加,共聚物的乳化能力呈先增加后减小的趋势;相对于MPEG1900系列共聚物,MPEG5000系列共聚物中需要引入更长的中间嵌段才能获得最佳乳化性能。     

水溶性紫杉醇两亲性共聚物纳米胶束研究

聚乙二醇聚己内酯聚乙二醇采用三嵌段共聚物为载体包载紫杉醇形成纳米胶束,胶束具有明显的核壳结构,有效地改善了紫杉醇的水溶性。研究表明,采用蒸发溶剂法、透析法和熔融法制备的胶束对紫杉醇都呈现良好的包封效果,其中,以熔融法制得的胶束粒径最小,分布最窄。文中还考察了蒸发溶剂法实验条件对胶束的影响,发现低沸点有机溶剂有利于获得小粒径胶束,胶束平均粒径随着载药量的提高相应增大。体外释药的结果表明,载药量高的胶束释药率却相对较小。     

星形共聚物聚己内酯-聚丙烯酸羟基乙酯的合成与载药性能

通过原子转移自由基聚合(ATRP)制备了两亲性线形共聚物聚己内酯-聚丙烯酸羟基乙酯(LPCLPHEA)及四臂星形共聚物聚己内酯-聚丙烯酸羟基乙酯(4s PCL-PHEA),以芘为荧光探针,测定两种聚合物的临界胶束浓度(CMC),并以阿霉素(DOX)为模型药物,分析探讨聚合物的载药能力。实验通过红外光谱(FT-IR)、荧光分光光度计、马尔文激光粒度仪等对聚合物的结构、粒径、Zeta电位、载药等性能进行表征。结果表明,两种聚合物都能形成稳定的载药胶束,其中四臂星形结构聚合物比线形聚合物具有较低的粒径和临界胶束浓度、较高的载药量和包封率,可作为药物载药材料进行进一步研究。     

Drug release from nanoparticles of Poly(DL-lactide-co-glycolide)

Nanoparticles of poly(DL-lactide-co-glycolide) (PLGA) were prepared by dialysis method without surfactant. The size of PLGA nanoparticles prepared from dimethylacetamide (DMAc), dimethylformamide (DMF), and dimethylsulfoxide (DMSO) as an initial solvent was smaller than that of acetone or 1,4-dioxane. Selected initial solvent used to dissolve the copolymer significantly affects the size of nanoparticles. Also, the size of PLGA nanoparticles was changed according to the copolymer composition. It was shown that PLGA nanoparticles have spherical shapes from the results of scanning electron microscope (SEM) and transmission electron microscope (TEM) observations. From these results was shown the potential that the PLGA nanoparticles could be formed successively by dialysis method without surfactant. The drug-loading contents were also dependent on the copolymer composition and initial feeding amount of the drug. The greater lactide ratio on the copolymer composition led to higher drug loading contents. Also, the higher the initial feeding amount of drug, the higher the drug loading contents. Clonazepam (CNZ) was used as a model drug. CNZ was slowly released in higher lactide ratio in the copolymer composition and in the higher drug loading contents.     

Nonfouling biomaterials based on polyethylene oxide‐containing amphiphilic triblock copolymers as surface modifying additives: Synthesis and characterization of copolymers and surface properties of copolymer–polyurethane blends

The objective of this work is to develop nonfouling biomaterials by blending polyethylene oxide (PEO)‐containing block copolymers with a polyurethane (PU) matrix; it is expected that the PEO component will migrate to the tissue‐material interface. Three amphiphilic triblock copolymers, PEO‐PU‐PEO, in which the PEO MW was 550 (copolymer 1), 2000 (copolymer 2), and 5000 (copolymer 3), respectively, were synthesized. XPS data showed that the polymer/vacuum interfaces of copolymers 2 and 3 were enriched in the PU block, whereas that of copolymer 1 was enriched in the PEO block. In contact with water, the PEO blocks for all three copolymers migrated to the surface as indicated by water contact angles. Blends of the copolymers with a segmented polyurethane were investigated. Surface enrichment of the copolymers occurred and increased over time up to a limit; the degree of enrichment was dependent on PEO block size and copolymer content. At copolymer content <10%, enrichment decreased with increasing PEO block size. For the copolymer 2 and copolymer 3 blends, enrichment increased with increasing copolymer content; at 20% copolymer the surfaces consisted essentially of pure copolymer. For the copolymer 1 blends, the surface was completely covered by copolymer at content ≥ 1%. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

High PVC film‐forming composite latex particles via miniemulsification,part 2: Efficiency of encapsulation

The application of a density gradient column (DGC) method using sodium polytungstate (SPT) solutions as the medium was investigated for determining the encapsulation efficiency of 11–30% pigment volume concentration (PVC)) latex particles prepared by the miniemulsification process. The encapsulation efficiencies for 11, 20, and 30% PVCs were found to be 100% of the TiO₂ encapsulated inside 86.3, 98, and 98.9% of the styrene/n‐butyl acrylate copolymer, respectively. The copolymer not participating in the encapsulation (free copolymer) was found in the 1.04 g/mL density layer of the DGC. Particle size analysis by DLS (dynamic light scattering) showed that the encapsulated particle size increased with increasing density. Thus, the number of TiO₂ particles (primary particles) inside each encapsulated particle increased to accommodate both the increased size and density. The results obtained by DLS for each DGC layer of the 30% PVC system were confirmed qualitatively by TEM in terms of the increasing encapsulated particle size and broadening of the size distribution as the density increased in the DGC. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 4517–4525, 2006     

Hyperbranched poly (amine-ester)-poly(ε-caprolactone) copolymer and their nanoparticles as camptothecin delivery system

A new amphiphilic hyperbranched poly (amine-ester)-poly(ε-caprolactone) copolymer (HPAE-co-PCL) was synthesized by ring-opening polymerization of ε-caprolactone and branched poly (amine-ester) (HPAE-OHs) with Sn(Oct)₂ as catalyst. The chemical structures of copolymers were determined by FT-IR, ¹H-NMR (¹³C-NMR), thermo gravimetric analysis apparatus (TGA) and differential scanning calorimetry (DSC). Camptothecin (CPT)-loaded copolymer nanoparticles were prepared by the oil-in water (o/w) emulsion technique method. Their physicochemical characteristics, e.g. morphology and nanoparticles size distribution were then evaluated by means of fluorescence spectroscopy, environmental scanning electron microscopy (ESEM), and dynamic light scattering (DLS). CPT-loaded nanoparticles assumed a spherical shape and have unimodal size distribution. It was found that the chemical composition of the nanoparticles was a key factor in controlling nanoparticles size, drug-loading content, and drug release behavior. As the molar ratio of ε-caprolactone to HPAE increased, the nanoparticles size and drug-loading content increased, and the drug release rate decreased. The antitumor activity of the CPT-loaded HPAE-co-PCL nanoparticles against human hepatoma HEPG2 cells was evaluated by 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The CPT-loaded HPAE-co-PCL nanoparticles showed comparable anticancer efficacy with the free drug.     

Copolymers of 3,3,3‐trifluoropropene and vinyl acetate: Synthesis,characterization, and hydrolysis

Copolymers based on 3,3,3‐trifluoropropene (TFP) and vinyl acetate (VAc) were synthesized in supercritical carbon dioxide(sc? CO₂). The copolymers were characterized by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and differential scanning calorimetry (DSC) as the thermal analysis method. The copolymer compositions were estimated by three techniques: mass balance, NMR and electric potential analysis. The mole fraction of TFP in the copolymer increased with the feeding TFP added from 12.1% to 76.4% and almost unchanged with a feeding TFP increase from 76.4% to 89.7%. After partial carboxyl groups turned to hydroxyl groups by hydrolysis, the P(TFP‐co‐VAc) copolymer turned into terpolymers, P(TFP‐VAc‐VA). Dispersed in water, the hydrolyzed copolymer obtained emulsion by self‐emulsifying. The size distribution and the morphology of the latex were also investigated. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Preparation of stable polyurethane-polystyrene copolymer emulsions via RAFT polymerization process

Stable polyurethane-polystyrene (PU-PS) copolymer emulsions were prepared by the polymerization of 2-hydroxyethyl acrylate (HEA)-capped PU macromonomer and styrene, using azobis(isobutyronitrile) (AIBN), a radical initiator, and 4-((benzodithioyl)methyl)benzoic acid, a reversible addition-fragmentation chain transfer (RAFT) agent. As the molar ratio of the RAFT agent to AIBN increased, the zeta potential of the resulting copolymer emulsion increased, but the average size and size distribution of the emulsion droplets decreased. A living polymerization of HEA end-capped PU macromonomer and styrene was characterized by a linear increase in the molecular weight and decrease in the molecular weight distribution with consumption of monomers. The tensile strength, hardness and water-resistance of the copolymer films, prepared from the PU-PS copolymer emulsions, were much greater than those of the films prepared from the pure PU emulsion. The copolymer emulsions, prepared via the RAFT polymerization process, are expected to exhibit better storage stability than those prepared via the conventional free radical polymerization process, due to the presence of carboxyl groups derived from the RAFT agent at the PS block termini.     

聚含氟丙烯酸酯/聚氨酯共聚物细乳液的制备及表征

以甲苯二异氰酸酯(TDI)和甲基丙烯酸羟乙酯(HEMA)为原料,合成了丙烯酸酯/聚氨酯(PUA)预聚体;采用细乳液聚合法,合成了聚含氟PUA细乳液。使用红外光谱(FT-IR)和核磁共振(1H-NMR)表征了PUA预聚体及共聚物的结构组成,用激光光散射粒度仪(PCS)分析了乳胶粒的粒径及其分布,并考察了氟单体用量对乳胶膜的吸水率和表面性能的影响。研究结果表明,乳胶粒的粒径随着PUA预聚体用量的增加而增大;当氟单体质量分数由0增至20%时,乳胶膜的吸水率由10.3%降至4.2%,表面自由能由34.89mJ/m2降至15.66mJ/m2,说明氟单体的加入较好地改善了乳胶膜的表面性能。     

Synthesis of thermoresponsive copolymer/silica-coated magnetite nanoparticle composite and its application for heavy metal ion recovery

To enhance chemical stability and suppress of aggregation of magnetite nanoparticles (MNPs), which are used as a support for thermoresponsive copolymer immobilization, silica coating of the MNPs is applied via the electrooxidation method. Although the resulting silica coated-MNPs also formed aggregates, the size distribution of the aggregate shifted to smaller size range. Because of that, the surface area available for copolymer immobilization increased approximately 6.7 times at maximum as compared with that of the uncoated MNPs. It contributed to the increase of the amount of the immobilized copolymer on the silica-coated MNPs, which is approximately four times larger than that on the uncoated MNPs. Fe₃O₄ dissolution test confirmed enhancement of chemical stability of MNPs. The thermoresponsive copolymer immobilized on the silica-coated MNPs shows the ability to recycle Cu(II) ion from Cu(II) containing solution by changing temperature with significantly shorter time than those in other thermoresponsive adsorbents in gel form.     

Phenyl acrylates and divinyl benzene cross-linked copolymers as basic novel supports: Synthesis and characterization

Suspension Copolymerization of glycidyl methacrylate (GMA), phenyl methacrylate (PhMA), 2,4,6-tribromophenyl acrylate (TBPA), and 4-acetylphenyl acrylate (APA) with divinyl benzene (DVB) was carried out at 80 ± 1°C in aqueous medium, as basic supports for possible applications in polymer-supported chemistry. The resulting copolymer heads were characterized with various techniques. The identification of monomers in the copolymer was attempted using FTIR and ¹³C-CP/MAS-NMR spectroscopic techniques. The optical and scanning electron microscopic methods were used to study the shape, size, and surface morphology of the beaded copolymers. The particle-size distribution was measured, and the average particle size of the particulate copolymers were carried out using a Malvern particle-size analyzer. The decomposition temperatures and energy of activation involved in the thermal degradation were studied with thermogravimetry. The solvent imbibition of the polymer supports in various solvents was carried out with a centrifuge method.     

Impact strength and melt viscosity of bisphenol-a polycarbonate and styrene-maleic-anhydride copolymer blends

Mixtures of 90, 80, and 70 percent by weight bisphenol-A-polycarbonate (PC) and 10, 20, and 30 percent by weight styrene maleic anhydride (SMA) copolymer were melt-blended in a single screw extruder. Differential scanning calorimetry (DCS) and scanning electron microscopy (SEM) were used to determine the miscibility of the blends. The viscosity, as a function of shear rate and temperature, was measured by an Instron capillary viscometer. The notched impact strength as a function of temperature was measured by an Izod impact tester. The results of DSC showed two glass transition temperatures which merged slightly towards each other, indicating marginal miscibility of these blends. There was a decrease in viscosity as the fraction of SMA copolymer was increased. The most significant decrease occurred with the initial addition of SMA copolymer. The viscosity also decreased with increases in temperature. The impact strength of the blends was also dependent on SMA copolymer content. The blends showed six to ten times lower impact strengths at room temperature than the 100 percent polycarbonate. SEM analysis helped to determine the reason why the impact strength was lower for the blends. High magnification showed the presence of SMA copolymer inclusions dispersed throughout the PC matrix. These inclusions, which increased in size as SMA copolymer content was increased, acted as defects in the system.