新型自组装胶束的制备及其药物释放性能的研究

设计并合成了由亲水链段与疏水链段所组成的新型两亲星形嵌段共聚物.在水溶液中,该星形共聚物能够自组装形成具有核壳结构的纳米胶束粒子.当环境的pH分别为5、7.4、9时,共聚物胶束相应的低临界溶液温度(IESF)分别为32.0、36.6、39.5℃.由于亲水链段具有的温度和pH双响应特性,载药的自组装共聚物胶束也显示出了温度和pH双重响应的药物释放行为.     

ROP和ATRP法制备具有核壳结构的温敏性纳米胶束的研究

结合活性开环聚合(ROP)和原子转移自由基聚合(ATRP)方法,制备了以POSS-OH为核引发剂、PCL为核和PNIPAM为壳的X聚合物纳米胶束。借助GPC,IR,NMR,TEM,UV和DLS对聚合物的分子量、结构、形貌和温敏性进行了分析。结果表明,成功合成了星型嵌段共聚物;当POSS-OH的质量一定时,可以通过[CL]控制POSS-PCL的分子量;纳米胶束具有较为规整的球形和粒径分布均一;纳米胶束具有明显的温敏性与宽的相转变温度。     

两亲性PNIPAM-b-PVC-b-PNIPAM共聚物的合成与自组装

通过单电子转移-蜕化链转移活性自由基聚合合成不同组成的两亲性聚N-异丙基丙烯酰胺-b-聚氯乙烯-b-聚N-异丙基丙烯酰胺(PNIPAM-b-PVC-b-PNIPAM)三嵌段共聚物,并制备共聚物胶束水溶液,采用荧光光谱、动态光散射、透射电镜、紫外-可见光谱等表征共聚物的临界胶束浓度、胶束结构及温度响应性。结果表明,共聚物可在水中形成以PVC为核、PNIPAM为壳的球形胶束,胶束尺寸在75~135 nm;随着共聚物亲水PNIPAM链段含量的增加,临界胶束浓度增大,而胶束尺寸减小。在升温过程中,胶束溶液的透光率逐渐降低,低临界溶解温度随着共聚物亲水链段含量的增加而增大。     

温敏性嵌段聚合物的自组装性能

利用可逆加成-断裂链转移自由基聚合法(RAFT)制备了聚N-异丙基丙烯酰胺/聚丙烯酸乙酯(PNIPAM/PEA)的ABA型和BAB型三嵌段聚合物(A=PNIPAM,B=PEA),考察了共聚物的自组装性能和温度响应性能,探讨了各嵌段组分的用量和嵌段序列对共聚物性能的影响。结果表明:三嵌段共聚物都具有良好的温敏性和自组装性能;BAB型嵌段聚合物溶液的LCST值随着疏水组分PEA的增多呈现先增大后降低;在相同温度下,BAB型的胶束粒径明显小于ABA型的胶束粒径,并能在较低温度下发生相转变。     

新颖的A_2BA_2型温敏(PNIPAM)_2-b-HTPB-b-(PNIPAM)_2嵌段共聚物的合成与自组装研究

采用原子转移自由基聚合法(ATRP)合成了一类具有温敏性的A_2BA_2型嵌段聚合物,聚(N-异丙基丙烯酰胺)2-端羟基聚丁二烯(HTPB)-聚(N-异丙基丙烯酰胺)2[(PNIPAM)_2-b-HTPB-b-(PNIPAM)_2]。通过核磁共振仪(~1H NMR)、红外光谱仪(FTIR)和凝胶渗透色谱仪(GPC)对共聚物进行化学结构表征,确认了合成的目标产物。利用表面张力仪和紫外可见分光光度计对聚合物水溶液的临界胶束浓度(CMC)及低临界溶液温度(LCST)进行了测定,通过透射电子显微镜(TEM)及动态激光光散射技术(DLS)观测了其形态和尺寸。结果表明,合成的嵌段共聚物能够在水溶液中自组装成温敏响应性的纳米尺度胶束,胶束具有低于10 mg/L的CMC、相转变温度33.0~34.5℃、DLS流体力学直径小于150 nm,尺寸分布窄。这些物理化学性质对嵌段共聚物胶束作为药物释放的载体应用是非常有意义的。     

N-异丙基丙烯酰胺嵌段共聚物自组装行为研究进展

具有两亲性和温敏性的嵌段共聚物在选择性溶剂中能够自组装形成独特的微米级甚至纳米级有序结构,具有广泛的潜在应用。聚N-异丙基丙烯酰胺（PNIPAM）是一种典型的温敏性高分子材料,其分子链表现出独特的温敏行为,关于其修饰改性以及自组装行为的研究一直广受关注。以PNIPAM为基点介绍其嵌段共聚物的自组装行为,详细综述影响其行为的诸多因素如组成、分子量、外界刺激条件等,介绍其在生物医药、催化反应等方面的应用,并对其未来的发展方向进行了展望。     

N-异丙基丙烯酰胺嵌段共聚物自组装行为研究进展

具有两亲性和温敏性的嵌段共聚物在选择性溶剂中能够自组装形成独特的微米级甚至纳米级有序结构,具有广泛的潜在应用。聚N-异丙基丙烯酰胺(PNIPAM)是一种典型的温敏性高分子材料,其分子链表现出独特的温敏行为,关于其修饰改性以及自组装行为的研究一直广受关注。以PNIPAM为基点介绍其嵌段共聚物的自组装行为,详细综述影响其行为的诸多因素如组成、分子量、外界刺激条件等,介绍其在生物医药、催化反应等方面的应用,并对其未来的发展方向进行了展望。     

不同拓扑结构嵌段聚合物胶束载药性能的DPD模拟

通过使用耗散粒子动力学(DPD)模拟方法,对不同拓扑结构聚合物自组装胶束包载阿霉素(DOX)的载药性能进行了研究。模拟了五种相同嵌段种类不同拓扑结构的聚合物(PCL_(22)-PDEA_(25)-b-PPEGMA_5)n(n=1,3,4,5,6)自组装载药胶束体系,模拟过程中,不同拓扑结构聚合物都自组装为PCL(核)-PDEA(pH响应)-PEGMA(壳)三层结构的胶束。结果表明,随着聚合物臂数目的增加,具有偶数臂结构的聚合物胶束载药量显著减少,而具有奇数臂结构的聚合物胶束载药量无明显变化;且适当增加六均臂星形聚合物胶束的亲水嵌段比例能够明显提高胶束的稳定性和药物的包载量。     

双亲性无规共聚物自组装胶束化研究

以偶氮二异丁腈(AIBN)为引发剂，由大分子单体己内酯改性丙烯酸酯(FA)、甲基丙烯酸甲酯(MMA)和亲水性单体丙烯酸(AA)在N，N-二甲基甲酰胺(DMF)中通过自由基共聚反应得到双亲性类接枝共聚物(MAF)。将MAF与可生物降解均聚物聚己内酯(PCL)在水溶液中进行自组装，形成以。MAF中PFA链段与PCL为核、MAF中PAA链段为壳的核壳结构复合纳米胶束，进一步对PAA壳进行化学交联，最终得到具有核壳结构的复合纳米微球。动态激光光散射(DLS)和透射电子显微镜(TEM)结果显示胶束为球形，粒径在100nm左右且呈窄分布，有一定的核壳结构。     

两亲性嵌段共聚物胶束的制备及对药物的控制释放

两亲性嵌段共聚物在水溶液中通过自组装可以形成以疏水嵌段为核,以亲水嵌段为壳的胶束。其亲水嵌段对胶束起稳定和保护作用,在胶束中通过物理、化学方式载入药物,可以实现对药物的控制释放。简述了嵌段共聚物胶束化的一些基本途径,如利用氢键,离子间相互作用,改变温度,自由基共聚,改变外部环境pH等,探讨了其对模型药物的控制释放。     

嵌段共聚物聚苯胺-聚乙二醇-聚苯胺水溶液中自组装的介观模拟

用耗散颗粒动力学(DPD)模拟了嵌段共聚物PAn-PEG-PAn在水溶液中的介观相分离。考察了浓度和嵌段比对嵌段共聚物自组装影响的规律,获得了实验难以观察到的介观层次上各嵌段在球面分布情况,并重点研究了嵌段共聚物在稀溶液中自组装成球体的特征和原理。随着PAn链段的摩尔分数的增加,模拟先后获得三种球体,一是憎水段PAn为外壳、亲水段PEG为内核的球体;二是中心为亲水段PEG,中间层为憎水段PAn,最外层是亲水段PEG的三层壳核型球体;三是以亲水段PEG为外壳、憎水段PAn为内核的球体。在高浓度下,水在体系中呈现出有趣的分布现象,即水大部分聚集呈柱状或球状,少部分均匀分散在嵌段共聚物中。结论对实验可以起辅助和指导作用。     

Phase behavior of an amphiphilic molecule in the presence of two solvents by dissipative particle dynamics

We examine the phase behavior of A_mB_n amphiphilic molecules in the presence of two solvents X₂ and Y₂, which are strongly selective for A and B, respectively, by dissipative particle dynamics (DPD). We find that increasing the immiscibility parameter between the two solvents not only drives a macrophase separation into two phases X₂-rich and Y₂-rich for systems at less concentrated regimes, but also expands the ordered microphase region at more concentrated regimes. It even induces a sequential transition of various ordered structures. This is not surprising since increasing the solvent immiscibility parameter enhances the preferentiality of X₂ for A and Y₂ for B, and thus qualitatively varies the degree of molecular asymmetry in the amphiphilic molecules. In general, our current results reveal that the DPD simulation method has successfully captured the phase separation behavior of an amphiphilic molecule in the presence of two solvents. However, we find that the packing order of the spherical micelles is greatly affected by the finite size of the simulation box. As such, it becomes difficult to examine the most stable packing array of spheres via the DPD method. Still, DPD reveals a possible spherical order of A15, which has been observed in some amphiphilic molecule systems.     

Dissipative particle dynamics study on the multicompartment micelles self-assembled from the mixture of diblock copolymer poly(ethyl ethylene)-block-poly(ethylene oxide) and homopolymer poly(propylene oxide) in aqueous solution

Dissipative particle dynamics (DPD) method is applied to model the self-assembly of diblock copolymer poly(ethyl ethylene)-block-poly(ethylene oxide) (PEE-b-PEO) and homopolymer poly(propylene oxide) (PPO) in aqueous solution. In this study, several segments are coarse-grained into a single simulation bead based on the experimental density. For the self-assembly of pure diblock copolymer PEE-b-PEO in dilute solution, the DPD simulation results are in good agreement with experimental data of micelle morphologies and sizes. The chain lengths of the block copolymers and the volume ratios between PPO and PEE-b-PEO are varied to find the conditions of forming multicompartment micelles. The micelles with core-shell-corona structure and the micelles with two compartments are both formed from the mixture of PEE-b-PEO and PPO in aqueous solution.     

双亲纳米颗粒在选择性溶剂中的自组装行为：耗散粒子动力学模拟

接枝聚合物纳米颗粒在构筑多级功能性纳米材料方面具有很大潜力,但其在选择性溶剂中自组装相图却鲜见报道。利用耗散粒子动力学模拟研究了溶剂选择性、接枝聚合物链长度以及亲水、疏水聚合物链比例等因素对双亲纳米颗粒自组装行为的影响,并绘制了自组装形态相图。结果显示,随着浓度的增大,双亲纳米颗粒逐渐自组装成球状、棒状、二维膜、纳米膜孔等丰富纳米结构。不仅如此,溶剂与亲水、疏水聚合物相容性差异较小时（a_S-HL=40k_BT/R_c,a_S-HB=50k_BT/R_c）,双亲纳米颗粒自组装形成层状纳米结构,在较高浓度时,形成规则的多孔网络结构。研究发现,双亲纳米颗粒浓度和接枝聚合物的链长以及亲水、疏水聚合物链比例是调控双亲纳米颗粒自组装形态的关键因素。鉴于双亲纳米颗粒丰富的自组装行为,它在气体分离、检测、载药、催化剂载体等领域有着很大的潜在应用价值。     

Synthesis and characterization of dual stimuli-responsive block copolymers based on poly(N-isopropylacrylamide)-b-poly(pseudoamino acid)

The current study synthesized amphiphilic thermal/pH-sensitive block copolymers PNiPAAm-b-PHpr by condensation polymerization of trans-4-hydroxy-l-proline (Hpr) initiated from hydroxy-terminated poly(N-isopropylacrylamide) (PNiPAAm) as the macroinitiator in the presence of the catalyst, SnOct₂. ¹H NMR, FTIR, and gel permeation chromatography (GPC) characterized these copolymers. Their solutions showed reversible changes in optical properties: transparent below a lower critical solution temperature (LCST) and opaque above the LCST. The LCST values depended on the polymer composition and the media. With critical micelle concentrations (CMCs) in the range of 1.23-3.73 mg L⁻¹, the block copolymers formed micelles in the aqueous phase owing to their amphiphilic characteristics. Increased hydrophobic segment length or decreased hydrophilic segment length in an amphiphilic diblock copolymer produced lower CMC values. The current work proved the core-shell structure of micelles by ¹H NMR analyses of the micelles in D₂O. Transmission electron microscopy analyzed micelle morphology, showing a spherical core-shell structure. The micelles had an average size in the range of 170˜210 nm (blank), and 195˜280 nm (with drug). Observations showed high drug entrapment efficiency and drug-loading content for the drug micelles.     

PTPFCBBMA-b-PEG-b-PTPFCBBMA amphiphilic triblock copolymer: Synthesis and self-assembly behavior

We present the synthesis and self-assembly behavior of a new semi-fluorinated amphiphilic triblock copolymer. A series of perfluorocyclobutyl aryl ether-based amphiphilic ABA triblock copolymer containing hydrophilic poly(ethylene glycol) segment as the middle block were synthesized by atom transfer radical polymerization (ATRP). ATRP of 4-(4′-p-tolyloxyperfluorocyclobutoxy)benzyl methacrylate was initiated by PEG-based bifunctional macroinitiators with different molecular weights to obtain the desired copolymers with narrow molecular weight distributions (M_w/M_n ≤ 1.30) and the number of perfluorocyclobutyl linkage can be tuned by the feed ratio and the conversion of the fluorine-containing methacrylic monomer. The critical micelle concentrations of these amphiphilic ABA triblock copolymers in aqueous media were determined by fluorescence probe technique. They could aggregate to form spherical and cylindrical micelles visualized by TEM with varying the content of hydrophobic segment.     

Synthesis and self-assembly behavior of POSS tethered amphiphilic polymer based on poly(caprolactone) (PCL) grafted with poly(acrylic acid) (PAA) via ROP,ATRP, and CuAAC reaction

This investigation reports the preparation and self-assembly behavior of polyhedral oligomeric silsesquioxane (POSS) containing poly(caprolactone)-graft-poly(acrylic acid) (POSS-PCL-graft-PAA) polymer. This article focuses on the self-assembly behavior of POSS tethered amphiphilic graft copolymer. In this investigation, POSS tethered alkyne functionalized polycaprolactone (PCL) was prepared by strategic ring opening polymerization (ROP) of ε-caprolactone and α-propargyl-ε-caprolactone using hydroxyl-terminated POSS as an initiator. Azide-terminated poly(tert-butyl acrylate) (P ^t BA) was grafted onto functional PCL via Cu-catalyzed azide-alkyne “click” (CuAAC) reaction. Finally, hydrolysis of the tert-butyl ester group into acid furnished the POSS tethered PCL-graft-PAA polymer. This amphiphilic graft copolymer was characterized by GPC, NMR, and FT-IR analyses and the morphology of the graft copolymer analyzed by HRTEM and FESEM analyses. On changing the graft copolymer concentration (low to high) in water, the morphology of the final graft copolymer changed from micelles to worm-like and core-shell. The structural motif of POSS plays an important role in this morphological transformation. The pH sensitivity was studied using DLS analysis as well as via release profile of rhodamine B as a model compound.     

Synthesis and micelle behavior of (PNIPAm-PtBA-PNIPAm)m amphiphilic multiblock copolymer

A linear amphiphilic multiblock copolymer (PNIPAm-PtBA-PNIPAm)_m was successfully synthesized by a two-step reversible addition-fragmentation transfer (RAFT) polymerization in the presence of a cyclic trithiocarbonate as RAFT agent. The micelle behavior of (PNIPAm-PtBA-PNIPAm)_m multiblock copolymer in aqueous solution was then investigated by means of normal TEM, cryo-TEM, static and dynamic light scattering. The morphology, size, and size distribution of (PNIPAm-PtBA-PNIPAm)_m micelles were found to be dependent on the initial concentration of multiblock copolymer in THF. Spherical micelles, associated aggregates of spherical micelles, cage-like micelles, layered structures, and vesicular micelles were experimentally observed, which were in good agreement with the prediction of theory and simulations on linear amphiphilic multiblock copolymer in selective solvent. The (PNIPAm-PtBA-PNIPAm)_m micelles also exhibit thermo-sensitive behavior in aqueous solution because of the PNIPAm blocks.     

超临界CO_2反相微乳体系的介观模拟研究

研究水/表面活性剂/超临界CO2(ScCO2)的结构自组装对于设计和应用基于ScCO2流体的反胶束微乳化过程有着重要的理论指导意义。文中采用耗散粒子动力学(DPD)模拟方法,对双链离子型表面活性剂[琥珀酸酯磺酸钠(d i-HCF4)]+水+CO2(溶剂)体系进行介观模拟。模拟观测了在ScCO2中表面活性剂不同组成下的聚集形态,以及反相微乳结构形成的动态过程,同时考察了微乳体系的相形态与温度和压力的关系。模拟结果表明:温度升高,有利于反相微乳结构的形成;压力升高,会破坏反相微乳结构。