Pluronic嵌段共聚物胶束作为靶向药物载体

聚氧乙烯 聚氧丙烯 聚氧乙烯 (PEO PPO PEO)三嵌段共聚物 (商品名为Pluronics)在水溶液中能自发生成多分子聚集的胶束 ,这些胶束主要以疏水的PPO嵌段为内核 ,PEO嵌段环绕在外构成外壳 ,这种胶束可以有效地增溶油溶性药物。Pluronic嵌段共聚物无毒、无刺激、无免疫原性 ,胶束外壳的PEO嵌段能阻止血小板的聚集。胶束尺寸和病毒相仿 ,其大小适合在体内传输。初步尝试表明 ,胶束表面嵌上合适的抗体可以将增溶了模型药物的Pluronic胶束定向输送到动物脑部 ,从而提高了药效 ,降低了副作用。实验表明 ,Pluronic嵌段共聚物胶束可能成为将多种药物导向特定部位的有效载体。     

EO-PPO-PEO嵌段共聚物的表面活性

采用吊环法测量了PEO–PPO–PEO 嵌段共聚物溶液的表面张力,观测到嵌段共聚物溶液的表面张力随着时间延长逐渐降低. 根据嵌段共聚物在气液界面形成分子刷的结构模型, 解释了嵌段共聚物溶液的表面张力随浓度的变化.     

PE0一PP0一PE0 嵌段共聚物的表面活性

采用吊环法测量了PEO－PPO－PEO嵌段共聚物溶液的表面张力,观测到嵌段共聚物溶液的表面张力随着时间延长逐渐降低。根据嵌段共聚物在气液界面形成分子刷的结构模型,解释了嵌段共聚物溶液的表面张力随浓度的变化。     

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。     

Pluronic嵌段共聚物胶束化行为及其胶束增溶

两亲性质的Pluronic嵌段共聚物在合适条件下能自发形成内核很大的稳定胶束 ,其胶束化行为复杂 ,初步的研究深化了对两亲分子自组织机理的认识。实验发现这类胶束具有很强的增溶油溶性物质的能力 ,由于这些分子单体和胶束化行为的特点 ,可望利用这类嵌段共聚物实现在增溶应用场合中的突破。综述Pluronic嵌段共聚物的胶束化行为和胶束增溶规律的当前研究进展     

氟碳化合物FC-77在Pluronic嵌段共聚物胶束中包封与缓释

采用乙醇注入法制备FC-77的载药纳米胶束,通过动态光散射、透射电子显微镜表征了载药纳米胶束的粒径和形貌;通过紫外可见光谱研究了FC-77在嵌段共聚物P123中的包封率和释放曲线。结果表明,含1%P123的FC-77载药纳米胶束粒径为270 nm,呈球形分布,包封率为50%6,00 min时的释放量为92.2%。进一步地,通过调节嵌段共聚物的组成、浓度等可以改变载药纳米胶束的粒径和包封率。结果证明,嵌段共聚物胶束体系能作为FC-77载药制剂的载体,并且通过调整嵌段共聚物胶束体系配方,可以得到理想的FC-77药物载体。     

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。     

二元Pluronic嵌段共聚物相互作用 I.PPO嵌段长度相近的P94/L92和F108/L92二元混合水溶液

以I2 作为探针 ,用可见光度方法测定不同浓度比例的P94/L92和F10 8/L92二元Pluronic嵌段共聚物水溶液的临界胶束浓度。实验结果表明 ,这些PPO嵌段长度相近的分子在全部浓度比例范围内都发生相互作用 ,生成了混合胶束。由于这些分子的PEO嵌段长度不等 ,随着具有较短PEO嵌段的L92分子加入 ,P94/L92和F10 8/L92混合胶束外壳的EO基团数减少 ,从而使混合胶束水化度降低     

新型嵌段共聚物的合成及其作为药物载体的应用研究

通过调控嵌段共聚物的嵌段组成可实现水-油两亲,并可在水相中形成的稳定的胶束,从而为难溶性药物的负载提供了可能。该研究合成一种新型的两嵌段的聚丙烯酸异丁酯-b-聚甲基丙烯酸吗啉乙酯共聚物PMAQ-b-PMEMA。并对两亲性嵌段共聚物PMAQ-b-PMEMA胶束的物理性能和对紫杉醇的负载能力进行了研究。研究结果表明,PMAQ-b-PMEMA胶束稳定性良好,负载紫杉醇能力较强,是一种优良的难溶药物载体。     

嵌段共聚物的合成及其组装行为

嵌段共聚物在选择性溶剂中可逆缔合形成以不溶性链段为核 ,溶解性链段为壳的胶束。广泛用作表面活性剂、增溶剂、药物载体和纳米材料等。综述了嵌段共聚物的合成方法 ,着重分析了浓度、温度、嵌段长度、溶剂、添加物及电荷等因素对嵌段共聚物在选择性溶剂中组装行为的影响及其形成机理。展望了嵌段共聚物组装行为的应用前景     

Effect of vortex-induced physical stress on fluorescent properties of dye-containing poly(ethylene glycol)-block-poly(lactic acid) micelles

The effect of vortex-induced mechanical stresses on the fluorescent properties of dye-containing poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA) block copolymer micelles has been investigated. PEG-b-PLA block copolymer micelles containing fluorescent dyes, 3,3′-dioctadecyloxacarbocyanine perchlorate (DiO) and/or 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI), are prepared by a simple one-step procedure that involves the self-assembly of block copolymers and spontaneous incorporation of hydrophobic dyes into the core of the micelles. Upon vortexing, the micelle dispersion samples showed a decrease in fluorescence intensity in a rotational speed- and time-dependent manner. The results demonstrated that the vortexing can alter the fluorescent properties of the dye-containing PEG-b-PLA block copolymer micelle dispersion samples, suggesting the potential utility of block copolymer micelles as a mechanical stress-responsive nanomaterial.     

Fluorescence studies of pyrene-labelled, pH-responsive diblock copolymer micelles in aqueous solution

Fluorescence spectroscopic techniques, and time-resolved anisotropy measurements (TRAMS) in particular, have provided valuable information regarding micelle formation in luminescently labelled pH-responsive diblock copolymers of 2-(diethylamino)ethyl methacrylate (DEA) and 2-(dimethylamino)ethyl methacrylate (DMA). A pyrenyl derivative, located at the DEA block, allowed motion of this site to be monitored via TRAMS in aqueous solution: a significant reduction in the mobility of this label was apparent at concentrations in excess of the critical micelle concentration, CMC, of the diblock copolymer. This is consistent with the labelled DEA block being located in the core of the micelles. At concentrations below the CMC, unimers were detected in solution. The micelle size estimated from TRAMS is approximately half of that determined from dynamic light scattering measurements. This suggests that the chain ends of the block copolymer are not “frozen” into position but that limited motion may occur due to fluidity within the micelle core. This is reasonable given the low T_g of the DEA block. Alternatively, a model is proposed which suggests that the interior of the micelle is a hard sphere, surrounded by flexible, fast-moving corona, which imparts little viscous drag on the core.     

胶束共聚合法合成丙烯酰胺/4-乙烯基吡啶共聚物

以十二烷基苯磺酸钠为表面活性剂 ,过硫酸钾 /亚硫酸氢钠为引发剂 ,进行丙烯酰胺 - 4-乙烯基吡啶胶束共聚合 ,合成了双亲共聚物 ,用1H NMR分析法、差示扫描量热量 ( DSC)对其进行表征 ,并分析了共聚物形成机理。     

Styrene–isoprene block copolymers. II. Hydrogenation and solution properties

Styrene–isoprene block copolymers with a different degree of monomer distribution are hydrogenated with homogeneous catalysts. The products are characterized by means of IR and ¹H-NMR spectroscopy, GPC, viscometry, and light scattering. Hydrogenation proceeds without destruction and selectively for olefinic unsaturation. The hydrogenated copolymers are homogeneous in molecular weights and chain composition. The influence of the copolymer structure on the solution properties in selective solvents is established. In cyclohexane an equilibrium between micelle associates and individual polymer coils, monomolecular micelles, or micelle aggregates are observed, depending on the type of the copolymer. The micellization in base-lubricating oil leads to micelle fractions with a different degree of association.     

Phase diagram of polymer blends containing block copolymers

The phase transition and phase separation behavior occurring in mixtures containing an A–B block copolymer and an A homopolymer is discussed. With a pure block copolymer an order-disorder transition can be induced by raising the temperature, whereby the ordered lattice of segregated microdomains becomes unstable and gives way to a homogeneous liquid structure. Small amounts of a homopolymer added to a block copolymer can be accommodated in the microdomains consisting of the same type of monomeric units, up to a solubility limit that depends on the relative lengths of the homopolymer and the copolymer block and on the temperature. The order-disorder transition temperature of the block copolymer is also affected by the added homopolymer. At the other extreme of concentration, spherical micelles of block copolymer are formed when a small amount of the copolymer is added in the bulk homopolymer, and the critical micelle concentration again depends on the relative lengths of the molecules and blocks involved and on the temperature. Measurements were made with light scattering and small-angle X-ray scattering techniques to determine the phase behavior of mixtures containing a styrene-butadiene block copolymer and either a polystyrene or a polybutadiene. The resulting phase diagram exhibits a fascinating complexity. Comparison with recent theories treating these phenomena shows that a good agreement is generally obtained on a qualitative or semi-quantitative level, but a quantitative agreement is often not attained.     

Nano-container assembled thin films with time-programmed release of hydrophobic dyes

We introduce an all nano-container assembled multilayer thin films for controlling the release of hydrophobic functional materials. Two complementary charged block copolymer micelles were used as a nano-container for layer-by-layer assembly of thin films. Block copolymer micelles were composed of positively charged hairy polystyrene-block-poly(4-vinylpyridine) and negatively charged hairy (long corona region relative to the hydrophobic core part) or crew-cut (huge hydrophobic core chains, compared with the hydrophilic corona region) polystyrene-block-poly(acrylic acid) micelles. Two different fluorescent dye-incorporated block copolymer micelles multilayer films deconstructed when rehydrated in physiological condition, phosphate buffer saline solutions, releasing block copolymer micelles as a hydrophobic material carrier, suggesting that the detachment behavior of block copolymer micelles integrated into the multilayer films differs according to layer-by-layer assembled block copolymer micelle combinations. These results indicate the suitability of thin films for applications including the controlled release of hydrophobic materials. Atomic force microscope analysis suggested the successful preparation of block copolymer micelles. Film growth and release of fluorescence dyes were monitored by UV-Vis spectra.     

Polymeric micelles formed by polypeptide graft copolymer and its mixtures with polypeptide block copolymer

Polymeric micelles based on poly(γ-benzyl-l-glutamate)-poly(ethylene glycol) graft copolymer (PBLG-g-PEG) with various degrees of grafting and the mixtures composed of PBLG-g-PEG and poly(γ-benzyl-l-glutamate)-poly(ethylene glycol) block copolymer (PBLG-b-PEG) were prepared by the dialysis method in deionized water. Fluorescence spectroscopy and transmission electron microscope (TEM) have been used to study the self-assembly behavior. The experimental results revealed that the degree of grafting exerts marked effect on the critical micelle concentration (CMC) and the morphology of the micelle formed by PBLG-g-PEG. With increasing the degree of grafting, the CMC value becomes larger and the morphology of formed micelle changes from irregular shape to spindle. It was also found that mixtures of PBLG-g-PEG/PBLG-b-PEG can associate into hybrid polymeric micelle with various shapes.     

Synthesis and micellization of a new amphiphilic star-shaped poly(D,L-lactide)/polyphosphoester block copolymer

A new amphiphilic 4-arm star-shaped poly(D,L-lactide)/poly(ethyl ethylene phosphate) (ssPLA-b-PEEP) block copolymer was synthesized by ring-opening polymerization of ethyl ethylene phosphate (EEP) with hydroxyl terminated 4-arm star-shaped poly(D,L-lactide) (ssPLA) as a macroinitiator, which was prepared by ring-opening polymerization of D,L-lactide (LA) initiated by pentaerythrite using stannous octoate as catalyst. The structures of the block copolymers were confirmed by IR, ¹H-NMR and GPC analysis. Fluorescence measurements were applied to determine the critical micelle concentration (CMC) of the copolymer micelle solutions. The diameter and the distribution of micelles were characterized by dynamic light scattering (DLS) and the shape was perceived by transmission electron microscopy (TEM). The results indicated those copolymers formed nano-micelles in aqueous solution with hydrophobic poly(D,L-lactide) core and hydrophilic poly(ethyl ethylene phosphate) shell. The CMC of the copolymer solutions increased with the increments of the proportion of PEEP segments. TEM images demonstrated that all micelles were spherical.     

Phase behavior of ordered mesoporous silica film prepared by Brij-76 block copolymer

Phase behavior of ordered mesoporous silica film was investigated according to the solvent and Brij-76 block copolymer molar ratio. From grazing incidence small angle X-ray scattering and transmission electron microscopy analysis, we found that the lyotropic mesophase diagram exhibited body-centered cubic (bcc), two-dimensional hexagonal and lamellar structures with a mixed phase region. The existence of the mixed phase region indicated fast structuration during spin coating. The ordered mesoporous silica film using Brij-76 block copolymer had a three-dimensional pore structure with distorted bcc arrangement in a wide composition range, while the ordered mesoporous silica using Brij-76 block copolymer displayed a three-dimensional mesophase with a hexagonal close-packed or cubic close-packed arrangement. We suggest that the thick ethylene oxide chains in the corona region govern micelle aggregation behavior, favoring the formation of the less tightly coordinated bcc structure during the fast structuration process.