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。     

利用Pluronic嵌段共聚物的增溶胶束超滤分离技术

增溶胶束超滤 (MEUF)是新型膜分离技术 ,但迄今仅利用普通烷烃链表面活性剂作为其胶束物质 ,由于这些表面活性剂单体相对分子质量低 ,形成的胶束较小 ,不仅难以有效增溶有机分子 ,还可能透过超滤膜造成对水体的二次污染。聚氧乙烯 -聚氧丙烯 -聚氧乙烯三嵌段共聚物 (Pluronics)是一类重要的功能高分子 ,在合适条件下 ,它们在水溶液中聚集生成具有很大内核的胶束 ,这种胶束能有效增溶水溶液中的有机污染物。其次 ,Pluronic共聚物分子单体的大相对分子质量使其容易被超滤膜隔离 ,加上Pluronic共聚物无毒无刺激性 ,因而这类新型功能高分子适合用于增溶胶束超滤方法 ,实现对水体有机污染物的分离。综述Pluronic嵌段共聚物的胶束化、胶束结构、胶束增溶以及在增溶胶束超滤分离技术中的应用     

二元Pluronic嵌段共聚物相互作用 II.PPO嵌段长度不等的P94/L64二元混合水溶液

用I2 探针增溶分光光度方法 ,考察了Pluronic两亲嵌段共聚物P94/L6 4二元混合水溶液的胶束化行为 ,发现在溶液体相中L6 4的质量摩尔分数XL64 <0 4时 ,由于P94/L6 4混合预胶束的形成 ,导致P94分子在较高浓度时才生成单组分胶束 ;当XL64 >0 4后 ,溶液中生成了P94/L6 4混合胶束。P94和L6 4二种分子PPO嵌段长度不同 ,造成这种不同浓度比例区间内胶束组成的差异。温度升高促进了胶束化行为     

苯酚对Pluronic嵌段共聚物F127胶束化以及胶束增溶蒽的影响

通过紫外 -可见光谱、荧光光谱和黏度等技术测定在苯酚存在下 ,Pluronic嵌段共聚物F12 7水溶液的临界胶束浓度 (CMC)以及胶束结构的变化 ,考察苯酚浓度cph对胶束增溶蒽的影响。实验结果发现F12 7的CMC随cph的增高先增大 ,在cph>3 0× 10 -6 后减小 ,胶束特性黏度[η]则先减小再增大 ,胶束内核中PO成分逐渐增大 ,在cph>3 0× 10 -6 后胶束内核几乎完全由PO构成。蒽与胶束的K1/N值先急剧下降 ,同样在cph>3 0× 10 -6 后转而逐渐增大。结合苯酚对水结构的影响 ,以及与PEO嵌段上醚氧原子的氢键相互作用解释了上述实验现象。     

无机电解质对Pluronic嵌段共聚物胶束化以及增溶萘的影响(II)F108和P94胶束对萘的增溶

无机电解质 K Cl使萘分子和 Pluronic嵌段共聚物 F10 8或 P94空胶束的第一步缔合平衡常数K1值和萘在胶束和水相间的分配系数 KV 值增大 ,即促进了萘的增溶 ,这是由于 KCl使胶束的聚集数增大 ,内核趋向主要由 PO构成所致。KSCN的作用则相反 ,它使胶束的聚集数减小 ,同时降低了内核的 PO含量 ,因而使萘在 F10 8和 P94胶束中的 K1和 KV 值降低     

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     

聚乳酸—聚乙二醇嵌段共聚物胶束的制备及性能研究

分别以聚乙二醇(PEG)及聚乙二醇单甲醚(m PEG)引发L-丙交酯开环聚合得到PLLA(聚乳酸)-PEG-PLLA三嵌段与PLLA-m PEG两嵌段共聚物,通过1H-NMR分析确定共聚物的结构及分子量。采用直接溶解法和有机溶剂挥发法制备PLLA-PEG-PLLA及PLLA-m PEG胶束,并用TEM对其形态进行表征。利用激光粒度分析和染料探针的方法证实了共聚物自组装形成了胶束,且具有较小的临界胶束浓度(CMC),粒径约为100 nm。三嵌段PLLA-PEG-PLLA胶束的粒径小于两嵌段PLLA-m PEG胶束的粒径;有机溶剂挥发法制备的胶束粒径小于直接溶解法制备的胶束粒径。盐酸乌拉地尔胶束的体外释放结果表明,共聚物组成以及载药方式等对胶束载药、释药行为有一定影响,胶束对所包载的盐酸乌拉地尔具有明显的缓释作用。     

粘度测定法研究两亲接枝共聚物PMMA-g-PEO在甲苯中的胶束化行为

采用粘度测定法研究了规整性两亲接枝共聚物聚甲基丙烯酸甲酯 g 聚氧乙烯 (PMMA -g -PEO)在选择性溶剂甲苯中的胶束化行为 ,结果表明PMMA -g -PEO在甲苯中可形成胶束。体系的浓度、温度和结构决定了两亲接枝共聚物的聚焦态结构。随着温度的降低或浓度的升高PMMA -g -PEO在甲苯中分别以单分子、小胶束、大胶束的形式存在。在本实验范围内 ,温度越高、PEO含量越大、PEO接枝链越短、PMMA -g -PEO分子量越小、形成胶束的临界胶束化浓度 (CMC)也越小     

基于嵌段共聚物交联制备稳定纳米胶束的研究

两亲嵌段共聚物通过自组装形成纳米胶束,并通过对胶束结构的具体区域进行交联,能够将胶束结构固定下来,对纳米材料的制备及药物的运载、控制释放等带来极大的帮助。本文综述了Wooley,Armes,Liu等在壳交联及核交联方面所做的研究,从制备方法,到功能性胶束的开发以及应用领域的研究进展进行了具体的阐述,并进行了展望。     

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.     

Synthesis and morphology transformation of amphiphilic diblock polyurethane copolymers in aqueous solution

Amphiphilic block copolymers possess both hydrophobic and hydrophilic properties and can form versatile micellar structures in aqueous solution. The aim of the research presented was to prepare a series of non‐ionic amphiphilic diblock polyurethane copolymers (PUn) based on isophorone diisocyanate, monoallyl‐end‐capped poly(ethylene oxide) and poly(propylene oxide) (PPO), followed by an investigation of their micellization properties and morphology transformation in aqueous solution. The PUn samples were synthesized by condensation polymerization. These polyurethanes exhibit surface tension as low as 33.7–37.0 mN m^?1. There is an obvious decrease in critical micelle concentration as the hydrophobic PPO molecular weight increases. According to transmission electron microscopy, the morphology of aggregates of the copolymers can be tuned by varying the concentration in aqueous solution rather than organic solvent. For example, for PU7, large compound micelles are produced instead of vesicles. For PU17, the concentration can be used to control the size and thickness of vesicles. Vesicle size increases from 60 to 500 nm and vesicle thickness from 40 to 60 nm with concentration ranging from 0.003 to 0.03 wt%. The study shows that the copolymers in aqueous solution have excellent surface activities. In addition, they can self‐assemble into large compound micelles or vesicles at certain concentrations. Moreover, the synthesis method described allows one to obtain a desired morphology of aggregates by adjusting the composition of hydrophilic and hydrophobic segments, which provides a novel and simple way to obtain particles on the nanometer scale. Copyright © 2010 Society of Chemical Industry     

Functionalized micelles from new ABC polyglycidol-poly(ethylene oxide)-poly(d,l-lactide) terpolymers

New ABC type terpolymers of poly(ethoxyethyl glycidyl ether)/poly(ethylene oxide)/poly(d,l-lactide) were obtained by multi-mode anionic polymerization. After successive deprotection of the ethoxyethyl groups from the first block, highly hydroxyl functionalized copolymers of polyglycidol/poly(ethylene oxide)/poly(d,l-lactide) were obtained. These copolymers form elongated ellipsoidal micelles by direct dissolution in water. The micelles consist of a poly(d,l-lactide) core and stabilizing shell of polyglycidol/poly(ethylene oxide). The hydroxyl groups of polyglycidol blocks situated at the micelle surface provide high functionality, which could be engaged in further chemical modification resulting in a potential drug targeting agents. The micellization process of the copolymers in aqueous media was studied by hydrophobic dye solubilization, static and dynamic light scattering, and transmission electron microscopy.     

ADSORPTION AND WETTING PROPERTIES OF PLURONIC BLOCK COPOLYMERS ON HYDROPHOBIC SURFACES STUDIED BY OPTICAL WAVEGUIDE LIGHTMODE SPECTROSCOPY AND DYNAMIC TENSIOMETRIC METHOD

Adsorption of four different poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) triblock copolymers (Pluronics®) onto the hydrophobized surface of the sensor was measured by the optical waveguide lightmode spectroscopy (OWLS). Adsorbed amounts of Pluronic PE10300, PE10500, PE6400, and PE6800 determined in the concentration range of 10^-2-10 gdm^-3 were found to follow the order of the hydrophobicity of the Pluronic compounds characterized by their hydrophil-lipophil balance (HLB) values. Wettability of two hydrophobic surfaces, the poly(lactide-co-glycolide), PLGA70/30 copolymer (used as drug carrier in pharmaceutical applications) and silylated glass, in aqueous solutions of the above Pluronics were studied by a dynamic tensiometric method. The significant increase in the wetting tension observed after the adsorption of the surfactants, and hence the decrease of the apparent contact angle as the indication of the wetting effect on both the biopolymer and the hydrophobic glass, was correlated to the poly(ethylene oxide) (PEO) content of the adsorbed layer obtained on the hydrophobized sensor surface by the OWLS method.     

ADSORPTION AND WETTING PROPERTIES OF PLURONIC BLOCK COPOLYMERS ON HYDROPHOBIC SURFACES STUDIED BY OPTICAL WAVEGUIDE LIGHTMODE SPECTROSCOPY AND DYNAMIC TENSIOMETRIC METHOD

Adsorption of four different poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) triblock copolymers (Pluronics®) onto the hydrophobized surface of the sensor was measured by the optical waveguide lightmode spectroscopy (OWLS). Adsorbed amounts of Pluronic PE10300, PE10500, PE6400, and PE6800 determined in the concentration range of 10^?2?10?gdm^?3 were found to follow the order of the hydrophobicity of the Pluronic compounds characterized by their hydrophil–lipophil balance (HLB) values. Wettability of two hydrophobic surfaces, the poly(lactide-co-glycolide), PLGA70/30 copolymer (used as drug carrier in pharmaceutical applications) and silylated glass, in aqueous solutions of the above Pluronics were studied by a dynamic tensiometric method. The significant increase in the wetting tension observed after the adsorption of the surfactants, and hence the decrease of the apparent contact angle as the indication of the wetting effect on both the biopolymer and the hydrophobic glass, was correlated to the poly(ethylene oxide) (PEO) content of the adsorbed layer obtained on the hydrophobized sensor surface by the OWLS method.     

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.     

Pluronic F68胶束水溶液对稠环芳烃的增溶

PluronicF6 8嵌段共聚物在 5 0℃的水溶液中可形成外壳良好水化的胶束 ,其内核组成中PO和EO的质量分数分别为 80 %和 2 0 %。该胶束和稠环芳烃的结合能力顺序为芘 >蒽 >萘。三者在F6 8胶束和水相间的分配系数KV 分别为 8 74× 10 2 (芘 )、7 94× 10 2 (蒽 )和 2 5 4× 10 2(萘 )。     

PEO-PPO-PEO嵌段共聚物在水溶液中的自组装行为及其应用

聚氧乙烯-聚氧丙烯-聚氧乙烯(PEO-PPO-PEO)嵌段共聚物是一类重要的非离子表面活性剂,在选择性溶剂中可以自组装成多种形貌的介观结构。对PEO-PPO-PEO嵌段共聚物在水溶液中自组装行为进行了综述,介绍了其自组装行为的实验研究技术;阐明了嵌段共聚物构型、分子量、温度、浓度、添加剂等因素对PEO-PPO-PEO嵌段共聚物聚集行为的调控和作用机理;介绍了嵌段共聚物自组装特性的热力学模型、分子模拟及计算机预报等研究方法和研究进展;重点介绍了PEO-PPO-PEO嵌段共聚物在介孔材料制备、药物载体、生物大分子分离、嵌段共聚物修饰等方面的应用。     

Synthesis and characterization of temperature and pH-responsive pentablock copolymers

A family of amphiphilic ABCBA pentablock copolymers based on commercially available Pluronic^® F127 block copolymers and various amine containing methacrylate monomers was synthesized via Cu(I) mediated controlled radical polymerization. The block architecture and chemical composition of the pentablock copolymers were engineered to exhibit both temperature and pH responsive self-assembly by exploiting the lower critical solution temperature of the poly(ethylene oxide)/poly(propylene oxide) blocks and the polycationic property of the poly(amine methacrylate) blocks, respectively. In aqueous solutions, the pentablock copolymers formed temperature and pH-responsive micelles. Concentrated aqueous solutions of the copolymer formed a pH-responsive, thermoreversible gel phase. The controlled radical synthesis route yielded well-defined copolymers with narrow molecular weight distributions with the benefit of mild reaction conditions. Small angle X-ray scattering, laser light scattering, cryogenic transmission electron microscopy and dynamic mechanical analysis have been used to characterize the self-assembled structures of the micellar solution and gel phases of the aqueous copolymer system. These copolymers have potential applications in controlled drug delivery and non-viral gene therapy due to their tunable phase behavior and biocompatibility.