光敏感三元共聚物的合成及溶液自组装

以一端为肉桂酸酯光交联基元、中间为聚己内酯长柔性链的甲基丙烯酸酯类大单体FM5C为第三单体,与马来酸酐(MAH)及苯乙烯(St)单体以AIBN引发共聚合,制备了光敏感三元共聚物P(FM5C-co-MAH-co-St).该三元共聚物可在选择性溶剂中形成纳米胶体粒子,并可先利用肉桂酸酯基元的光照交联作用使胶体粒子内聚合物交联,进而利用羧酸酐基元与2-氨基吡啶的室温氨解反应改变胶体粒子形态.用FTIR、GPC、1H-NMR等对该聚合物及其氨解产物进行了结构表征.用动态激光光散射(DLS)、透射电镜(TEM)、芘探针等技术研究了该聚合物胶体粒子微观形态、粒径与微环境在光照交联后及氨解后的变化.实验结果表明,P(FM5C-co-MAH-co-St)在选择性溶剂中可自组装成球形胶体粒子,肉桂酸酯光照交联作用使胶体粒子中的聚合物团聚得更加紧密,从而使其粒径更小、疏水区域更加集中;而进一步的室温氨解反应则使聚合物胶体粒子更松散、粒径变大.     

光敏共聚物P(St/VM-co-MA)自组装胶体粒子及其性能

以苯乙烯类光敏单体7-(4-乙烯基苄氧基)-4-甲基香豆素(VM)、苯乙烯(St)、马来酸酐(MA)为共聚单体,采用自由基聚合法制备了光敏性双亲共聚物P(St/VM-co-MA).在选择性溶剂(N,N-二甲基甲酰胺(DMF)/H2O)中对P(St/VM-co-MA)进行自组装,用透射电镜(TEM)和动态激光光散射(DLS)表征了自组装胶体粒子的形态、粒径大小及其分布.利用紫外光照使胶体粒子中香豆素基元发生光二聚反应,形成交联胶体粒子,并用紫外-可见光分光光度计(UV-Vis)跟踪其交联过程.用DLS研究了交联和未经交联胶体粒子的粒径和结构稳定性,用激光扫描共聚焦显微镜(LSCM)和光学显微镜考察了胶体粒子的乳化、包覆性能.结果表明:交联和未经交联胶体粒子均具有乳化性,且在乳化过程中可实现对油溶性染料的包覆.胶体粒子交联后,粒径有所减小,结构稳定性、乳化性能、包覆性能均有所提高.     

双亲性无规共聚物自组装胶束结构及其乳化性能

以不同交联度、溶胀程度的双亲无规共聚物聚[(苯乙烯-alt-马来酸酐)-co-(7-对乙烯基苄氧基-4-甲基香豆素-alt-马来酸酐)](PSMVM)胶束作为聚合物胶束乳化剂稳定甲苯/水体系, 重点研究光交联度对胶束结构及其乳化性能的影响. 结果表明, 胶束交联度、溶胀度和荷电性对胶束结构及乳化性能有较大影响.     

探索光敏性共聚物P(St/CS-alt-MA)的自组装及其乳化行为

以苯乙烯(St)、马来酸酐(MA)、香豆素苯乙烯醚化物(CS)为单体, 通过自由基溶液聚合合成了双亲性交替共聚物P(St/CS-alt-MA), 用凝胶渗透色谱、核磁共振等对聚合物结构进行表征, 并对其溶液自组装及组装体的乳化性进行了研究. 结果表明双亲性P(St/CS-alt-MA)可以在选择性溶剂中进行自组装形成马来酸酐单元为亲水微区、CS与苯乙烯单元为疏水微区的胶体粒子, 用紫外分光光度计, XPS, TEM研究了聚合物胶体粒子性质, 结果显示, P(St/CS-alt-MA)在水溶液中可以形成两亲性聚合物胶体粒子, 亲水单元在胶粒表面富集, 该两亲性聚合物胶体粒子具有良好的乳化性能.     

双亲性光敏感遥爪聚合物C-PNIPAAm的合成与性能

以7-羟基-4-甲基香豆素为原料,依次与环氧氯丙烷、二硫化钠反应得一含香豆素基元的二硫化物(C-S-S-C),并以其与三丁基膦复合体系为链转移剂,偶氮二异丁腈(AIBN)为引发剂,N-异丙基丙烯酰胺(NIPAAm)为单体制备了末端为香豆素光响应基元的双亲性遥爪聚合物(C-PNIPAAm).用傅里叶变换红外(FT-IR)光谱、凝胶渗透色谱(GPC)、氢核磁共振(1H-NMR)等对该聚合物进行了结构表征.研究显示该双亲性遥爪聚合物可在水中直接形成胶束,并以荧光素为疏水性客体考察了聚合物胶束的光控释放行为.在波长大于310 nm的紫外光照射下,聚合物链末端的香豆素单元可进行光二聚,胶束结构随之改变,因而所负载的荧光素可得到逐步有效释放.动态激光光散射(DLS)检测显示,光二聚反应使聚合物胶束平均粒径从56.6 nm增大至101.0 nm.     

4-PEG接枝苯乙烯-马来酸酐交替共聚物的合成及功能化

采用普通自由基聚合和可逆加成一断裂链转移（RAFT）自由基聚合方法合成了对位PEG取代苯乙烯（PEG-g-St）和马来酸酐的交替共聚物（P（（PEG—g—St）-alt-MA））,”CNMR分析表明PEG-g-St和马来酸酐单元采取交替的序列结构．利用反应性基团-马来酸酐单元的水解以及胺解可以制备功能性的PEG聚合物．以月桂胺为模型小分子研究了该聚合物的胺解,得到4-PEG-苯乙烯与羧酸基团以及疏水烷烃的交替序列聚合物,该双亲聚合物在水溶液中形成组装体．     

双亲性共聚物P(St/VBT-co-MA)自组装胶束的制备及其乳化性能

以1-(4-乙烯基苄基)胸腺嘧啶(VBT)、苯乙烯(St)、马来酸酐(MA)为共聚单体,采用自由基聚合法制备了双亲性共聚物P(St/VBT-co-MA)(PSVM)。PSVM在选择性溶剂N,N-二甲基甲酰胺(DMF)的水溶液中进行自组装可形成胶束。利用透射电镜(TEM)和动态激光光散射(DLS)表征了自组装胶束的形态和粒径分布。以该胶束作为颗粒乳化剂稳定白油-水体系形成乳液,研究了PSVM胶束浓度、pH、盐浓度等对其乳化性能的影响,并用光学显微镜(OM)表征了其乳液形态。结果表明:通过自由基聚合的方法成功合成了双亲共聚物PSVM,其自组装形成粒径分布均匀的球形胶束;该胶束具有优异的乳化效率,其乳液长期稳定且具有pH响应性及强耐盐性,静置四个月后,乳液仍具有良好的乳化效果且乳液层高度基本不变。     

双亲性无规光敏共聚物的疏水基元对其自组装胶束乳化性能的影响

设计合成了一系列具有不同化学组成的双亲性无规光敏共聚物,聚(7-对乙烯基苄氧基-4-甲基香豆素-r-丙烯酸)(P(VM-r-AA)),通过选择性溶剂法自组装获得纳米胶束,并将纳米胶束用作大分子颗粒乳化剂,研究其在甲苯-水界面的稳定性能。研究表明:聚合物疏水基元含量的增加使自组装胶束结构由溶胀的微凝胶状向刚性颗粒状转变;同时,胶束初始乳化效率增加,但油水界面吸附稳定性显著下降。此外,通过对疏水基元PVM的摩尔分数为12%的胶束进行辐照交联,并研究其在不同pH下的乳化性能,结果表明:胶束表面溶胀的双亲性链段对其乳化性能产生了重要的影响。未交联的胶束保持着良好的乳化性能;而交联的胶束形变能力变差、刚性增强,在碱性条件下,彻底失去乳化能力。     

双亲性无规共聚物P（VM-co-AMPS）的自组装及其性能

以2-丙烯酰胺基-2-甲基丙磺酸（AMPS）和苯乙烯类光敏单体7-（4-乙烯基苄氧基）-4-甲基香豆素（VM）为共聚单体,采用自由基聚合法制备了光敏性双亲共聚物P（VM-co-AMPS）。P（VM-co-AMPS）在溶剂水中自组装胶束化,用原子力显微镜（AFM）表征了自组装胶体粒子的形态、粒径及其分布。紫外光照使胶体粒子中香豆素基元发生光二聚反应,用紫外-可见光分光光度计（UV-Vis）跟踪其光二聚交联过程,用光学显微镜考察了胶体粒子的乳化性能。结果表明：胶体粒子具有较好的紫外吸收性能和较好的乳化性能。该胶束制备工艺简单,条件温和,避免了溶剂的使用。     

光敏感三臂星形聚[甲基丙烯酸2-(二甲氨基)乙酯]的合成及其光敏性能研究

以香豆素为光敏感基元,通过多步反应制备了三臂ATRP引发剂C-Br3,然后以CuBr/PMDETA为催化体系、甲基丙烯酸2-(二甲氨基)乙酯(DMAEMA)为单体,ATRP聚合法制备了三臂星形聚合物C-(PDMAEMA)3.用傅里叶变换红外光谱仪(FTIR)、紫外-可见光分光光度计(UV-Vis)和核磁共振仪(1H-NMR)等对C-Br3及聚合物进行了结构表征.研究表明,该三臂星形聚合物可在水中直接形成胶束,且该聚合物可在365和254 nm交替紫外光照下发生可逆光二聚反应.纳米粒度跟踪显示,光照前其胶束粒径为(87.7±27.8)nm、呈高斯分布;而在365和254 nm光反应后,聚合物胶束粒径大小与分布仅发生微弱变化.这可能是因为在光二聚反应前后,聚合物的双亲结构变化微弱所致.     

Thermo and pH Dual-Responsive Micelles of N-phthaloylchitosan-g-Poly(N-isopropylacrylamide) and Poly(acrylic acid-co-tert-butyl acrylate) for Drug Delivery

A novel amphiphilic copolymer N-phthaloylchitosan graft poly(N-isopropylacrylamide) and poly(acrylic acid-co-tert-butyl acrylate) (PHCS-g-PNIPAAm&P(AA-co-tBA)) was synthesized. The graft copolymer could form micelles in aqueous medium, and the critical micelle concentration (CMC) of the copolymer was 7.5 × 10^{? 3}mg/mL. The lower critical solution temperature (LCST) of the micelles was measured to be 30°C. Transmission electron microscopy (TEM) image showed that the micelles exhibited a regular spherical shape, and the mean diameter of the micelles was 94.1 ± 0.8 nm as determined by dynamic light scattering (DLS). The potential usefulness of the micelles as drug delivery systems was investigated using anti-inflammation drug prednisone acetate as the model. The drug loading capacity of the micelles was measured to be 22.86 wt%, and the DLS results showed that the mean diameter of the drug-loaded micelles was 133.3 ± 2.4 nm. In vitro drug release studies indicated that the micelles exhibited thermo and pH dual-responsive release profiles.     

Synthesis and properties of monocleavable amphiphilic comblike copolymers with alternating PEG and PCL grafts

Symmetric reduction‐responsive amphiphilic comblike copolymers mid‐disulfide‐functionalized comblike copolymers with alternating copolymer comprised of styrenic unit and N‐(2‐hydroxyethyl) maleimide (HEMI) unit (poly(St‐alt‐HEMI)) backbones and alternating PEG and PCL side chains (S‐CP(PEG‐alt‐PCL)) with poly(St‐alt‐HEMI) backbones and alternating poly(ε‐caprolactone) (PCL) and poly(ethylene glycol) (PEG) side chains were synthesized and used as nanocarriers for in vitro release of doxorubicin. The target copolymers with predetermined molecular weight and narrow molecular weight distribution (M_w/M_n = 1.15–1.20) were synthesized by reversible addition‐fragmentation chain transfer (RAFT) copolymerization of vinylbenzyl‐terminated PEG and N‐(2‐hydroxyethyl) maleimide mediated by a disulfide‐functionalized RAFT agent S‐CPDB, and followed by ring‐opening polymerization of ε‐caprolactone. When compared with linear block copolymer comprised of poly(ethylene glycol) (PEG) and poly(?‐caprolactone) (PCL) segments (PEG‐b‐PCL) copolymers, comblike copolymers with similar PCL contents usually exhibited decreased crystallization temperature, melting temperature, and degree of crystallinity, indicating the significant influence of copolymer architecture on physicochemical properties. Dynamic light scattering measurements revealed that comblike copolymers were liable to self‐assemble into aggregates involving vesicles and micelles with average diameter in the range of 56–226 nm and particle size distribution ranging between 0.07 and 0.20. In contrast to linear copolymer aggregates, comblike copolymer aggregates with similar compositions were of improved storage stability and enhanced drug‐loading efficiency. In vitro drug release confirmed the disulfide‐linked comblike copolymer aggregates could rapidly release the encapsulated drug when triggered by 10 mM DL ‐dithiothreitol. These reduction‐sensitive, biocompatible, and biodegradable aggregates have a potential as controlled delivery vehicles. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Functional and site-specific macromolecular micelles as high potential drug carriers

Since several years, macromolecular micelles based on amphiphilic block copolymers have attracted much interest as drug carriers. These micelles show a long term blood circulation time resulting from their small diameter and the steric repulsion created by the poly(ethylene oxide) chains which constitute micelle corona, as well as from their high thermodynamic stability. Besides this long term blood circulation time generating a passive targeting, an active targeting, chemical or physical affinity targeting, might allow the preparation of more efficient drug carriers. In order to obtain such double targeting properties, we have prepared two kinds of macromolecular micelles. The first one is based on amphiphilic poly(ethylene oxide)/poly(β-benzyl -aspartate) ---PEO/PBLA--- block copolymers having hydroxy groups at the free end of PEO chains. As a result of their structure, such micelles have hydroxy groups on their outer-shell which can be further modified in order to introduce a targeting moiety (sugar, etc.). The characteristics (diameter, critical micellar concentration (cmc), drug loading capacity) have been determined. Moreover, doxorubicin loaded -hydroxy PEO/PBLA micelles have been shown to be slightly more cytotoxic than the corresponding -methoxy PEO/PBLA micelles. The second type of micelles is based on thermosensitive amphiphilic poly(N-isopropyl acrylamide)/polystyrene ---PIPAAm/PSt--- block copolymers. Such micelles have a small diameter and a low cmc in addition to thermosensitivity properties which are similar to those of PIPAAm.     

两种双亲性聚合物自组装胶束复合水溶液的乳化性能

以苯乙烯(St)、含香豆素光敏单体(VM)、丙烯酸(AA)为单体,偶氮二异丁腈(AIBN)为引发剂引发自由基共聚,合成了双亲性光敏无规共聚物P(St-co-VM-co-AA)(简称PSVA);又以St及甲基丙烯酸二甲胺乙酯(DMAEMA)为单体,AIBN为引发剂引发自由基共聚,制得二元双亲性无规共聚物P(St-co-D...     

两亲性梳形共聚物PASP-Na-g-DDA的合成及接枝率对其水溶液胶束性质的影响

天冬氨酸自身缩聚产物聚琥珀酰亚胺(PSI)与十二胺(DDA)发生氨解反应,该氨解产物在碱性条件下水解,制得了一种两亲性梳形共聚物PASP-Na-g-DDA.通过改变DDA与PSI的比例,合成了一系列不同接枝率的两亲性梳形共聚物.用核磁共振(1H-NMR)及凝胶渗透色谱(GPC)对共聚物的结构进行了表征.随着疏水链段DD...     

Micellization of non-surface-active diblock copolymers in water. Special characteristics of poly(styrene)-block-poly(styrenesulfonate)

Strongly ionized amphiphilic diblock copolymers of poly(styrene)-b-poly(styrenesulfonate) with various hydrophilic and hydrophobic chain lengths were synthesized by living radical polymerization, and their properties and self-assembling behavior were systematically investigated by surface tension measurement, foam formation, hydrophobic dye solubilization, X-ray reflectivity, dynamic light scattering, small-angle neutron scattering, small-angle X-ray scattering, and atomic force microscope techniques. These copolymer solutions in pure water did not show a decrease of surface tension with increasing polymer concentration. The solutions also did not show foam formation, and no adsorption at the air/water interface was confirmed by reflectivity experiments. However, in 0.5 M NaCl aq solutions polymer adsorption and foam formation were observed. The critical micelle concentration (cmc) was observed by the dye solubilization experiment in both the solutions with and without added salt, and by dynamic light scattering we confirmed the existence of polymer micelles in solution, even though there was no adsorption of polymer molecules at the water surface in the solution without salt. By the small-angle scattering technique, we confirmed that the micelles have a well-defined core-shell structure and their sizes were 100-150 A depending on the hydrophobic and hydrophilic chain length ratio. The micelle size and shape were unaffected by addition of up to 0.5 M salt. The absence of polymer adsorption at the water surface with micelle formation in a bulk solution, which is now known as a universal characteristic for strongly ionized amphiphilic block copolymers, was attributed to the image charge effect at the air/water interface due to the many charges on the hydrophilic segment.     

Amphiphilic Block‐Graft Copolymers Poly(ethylene glycol)‐b‐(polycarbonates‐g‐palmitate) Prepared via the Combination of Ring‐Opening Polymerization and Click Chemistry

Amphiphilic block‐graft copolymers mPEG‐b‐P(DTC‐ADTC‐g‐Pal) were synthesized by ring‐opening polymerization of 2,2‐dimethyltrimethylene carbonate (DTC) and 2,2‐bis(azidomethyl)trimethylene carbonate (ADTC) with poly(ethylene glycol) monomethyl ether (mPEG) as an initiator, followed by the click reaction of propargyl palmitate and the pendant azido groups on the polymer chains. Stable micelle solutions of the amphiphilic block‐graft copolymers could be prepared by adding water to a THF solution of the polymer followed by the removal of the organic solvent by dialysis. Dynamic light scattering measurements showed that the micelles had a narrow size distribution. Transmission electron microscopy images displayed that the micelles were in spherical shape. The grafted structure could enhance the interaction of polymer chains with drug molecules and improve the drug‐loading capacity and entrapment efficiency. Further, the amphiphilic block‐graft copolymers mPEG‐b‐P(DTC‐ADTC‐g‐Pal) were low cytotoxic and had more sustained drug release behavior. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012