Synthesis and self-assembly behavior of thermoresponsive triblock copolymer

Block copolymers comprising thermosensitive poly(N-isopropylacrylamide) (PNIPAM) and hydrophobic poly(n-butyl acrylate) (PBA) blocks, were synthesized using the reversible addition-fragmentation chain transfer polymerization (RAFT), their thermosensitive behavior was studied by ultraviolet spectrophotometer (UV) and dynamic light scattering (DLS). The lower critical solution temperature (LCST) was strongly correlated to the hydrophobic/hydrophilic ratio of the copolymers. Their micellization and self-assembly behavior in dilute aqueous solution were studied by surface tension (SFT), DLS and TEM. The resulting block copolymers reversibly formed or deformed micellar assemblies during their LCSTs. The critical micelle concentration (CMC) was controlled by the composition of PBA and PNIPAM, indicating the successful formation of the block copolymers.     

Nanosized Micelles Self-Assembled from amphiphilic dextran-graft-methoxypolyethylene glycol/poly(ε-caprolactone) copolymers

A series of amphiphilic copolymers, dextran-graft-methoxypolyethylene glycol/poly(ε-caprolactone) (Dex-g-mPEG/PCL) were synthesized by grafting both PCL and mPEG chains to dextran, and subsequently the micellar self-assembly behavior of resultant copolymers was investigated. PCL was designed by using Fmoc-protected valine other than organometallic catalyst as the initiator to ring-opening polymerize ε-caprolactone (CL) in view of the safety demand as well as the extra application potential resulting from -NH₂ group introduced after Fmoc deprotection. All the copolymers were characterized by ¹H NMR, FT-IR and GPC measurements. The prepared copolymers are capable of self-assembling into nanosized spherical micelles in aqueous solution with the diameter of around 100-200 nm determined by TEM image and DLS measurement. The critical micellar concentration (CMC) of the graft copolymers is in the range of 10-100 mg/L determined by the fluorescence robe technique using pyrene. The result also indicated that the CMC of self-assembled micelles could be adjusted by controlling the degree of substitution of mPEG and PCL, and these micelles may find great potential as drug carriers in biomedical fields.     

Synthesis and micellar behavior of poly(acrylic acid-b-styrene) block copolymers

Poly(acrylic acid-b-styrene) (PAA-b-PS) amphiphilic block copolymers were synthesized by consecutive telomerization of tert-butyl acrylate, atom transfer radical polymerization (ATRP) of styrene, and hydrolysis. The resulting block copolymers were characterized by ¹H NMR and GPC. These amphiphilic block copolymeric micelles were prepared by dialysis against water. Transmission electron micrograph (TEM) and laser particle sizer measurements were used to determine the morphology and size of these micelles. The results showed that these amphiphilic block copolymers formed spherical micelles with average size of 140–190?nm. The critical micelle concentration (CMC) and the kinetic stability of these micelles were investigated by fluorescence technique, using pyrene as a fluorescence probe. The observed CMC value was in the range of 0.075–0.351?mg/L. Kinetic stability studies showed that the stability of micelles increased with the decrease of the pH value of the solution.     

Methoxy poly(ethylene glycol)-b-poly(valerolactone) diblock polymeric micelles for enhanced encapsulation and protection of camptothecin

Amphiphilic block copolymers, methoxy poly(ethylene glycol)-b-poly(valerolactone) (mPEG-b-PVL), were synthesized via ring opening polymerization of δ-valerolactone in the presence of methoxy poly(ethylene glycol) (mPEG). The copolymers form micelle-like nanoparticles by their amphiphilic characteristics and their structures were examined by Nuclear Magnetic Resonance (NMR). The sizes of nanoparticles ranged from 60 to 120 nm as measured by dynamic light scattering detection, and were larger with higher molecular weight of the copolymers. The Critical Micelle Concentration (CMC) of these nanoparticles in water decreased with increasing molecular weight of hydrophobic segment. Stability analysis showed that the micellar solutions maintain their sizes at 37 °C for six weeks without aggregation or dissociation. The lyophilization method was better than the evaporation method when camptothecin (CPT) was incorporated to the micelles. The former method yielded higher CPT loading efficiency and lower aggregation. The loading efficiency of CPT could be more than 96% and a steady release rate of CPT was kept for twenty six days. Moreover, the mPEG-b-PVL polymeric micelles offered good protection of CPT lactone form at 37 °C for sixteen days. The copolymers showed no cytotoxicity towards L929 mouse muscular cells when incubated for one day. Taken together, the mPEG-b-PVL copolymer has potential to be used for the delivery of CPT or other similar drugs.     

Synthesis,micellization and gelation of temperature‐responsive star‐shaped block copolymers

A series of amphiphilic temperature‐responsive star‐shaped poly(D,L‐lactic‐co‐glycolic acid)‐b‐methoxy poly(ethylene glycol) (PLGA‐mPEG) block copolymers with different arm numbers were synthesized via the arm‐first method. Gel permeation chromatography data confirmed that star‐shaped PLGA‐mPEG copolymers had narrow polydispersity index, indicating the successful formation of star‐shaped block copolymers. Indirectly, the ¹H NMR spectra in two kinds of solvents and dye solubilization method had confirmed the formation of core‐shell micelles. Further, core‐shell micelles with sizes of about 30–50 nm were directly observed by transmission electron microscopy. Subsequently, the micellar sizes and distributions as a function of concentrations and temperature were measured. At various copolymer concentrations, individual micelles with size of 20–40 nm and grouped micelles with size of 600–700 nm were found. Micellar mechanism of star‐shaped block copolymers in aqueous solution was simultaneously discussed. In addition, sol–gel transition of star‐shaped block copolymers in water was also investigated via the inverting test method. The critical gel temperature (CGT) and critical gel concentration (CGC) values of two‐arm, three‐arm and four‐arm copolymer solutions were markedly higher than ones of one‐arm copolymer. Moreover, the same CGC values of copolymer solution with different molecular weight and the same arm composition were ~15 wt %, and CGT values increased from ~38 to ~47°C with increasing arm numbers. Finally, the temperature‐dependent micellar packing gelation mechanism of star‐shaped block copolymer was schematically illustrated. Copyright © 2013 John Wiley & Sons, Ltd.     

Aggregation behavior of MPEG‐PCL diblock copolymers in aqueous solutions and morphologies of the aggregates

Poly(ethylene glycol)‐b‐polycaprolactone (MPEG‐PCL) diblock copolymers were synthesized via a ring‐opening polymerization of ε‐CL monomers with MPEG as an initiator. Their solubilities and apparent critical micelle concentrations (CMC) in aqueous solution were investigated as well as the determination of the micellar hydrodynamic diameter using dynamic light scattering (DLS). As PCL block length increased, the solubility and CMC decreased while diameters of micelles increased. The gel–sol transition behaviors were investigated using a vial tilting method. Aqueous solutions of copolymers undergo a gel to sol transition with increase in temperature when their polymer concentrations are above a critical gel concentration (CGC). The CGC of the copolymers and gel–sol transition temperature are influenced by the PCL chain length. The tapping mode AFM was performed by imaging the freeze‐dried deposits from the copolymer solutions on mica to investigate a process from free chains to micelles and to gel. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 3406–3417, 2006     

Synthesis,thermo-responsive micellization and caffeine drug release of novel PBMA-<Emphasis Type="Italic">b</Emphasis>-PNIPAAm block polymer brushes

Brush-like block copolymers with poly(t-butyl methacrylate) (PBMA) and poly(N-isopropylacrylamide) (PNIPAAm) as side arms, PBMA-b-PNIPAAm, were designed and synthesized via a simple free radical polymerization route. The chemical structure and molecular weight of these polymer brushes were characterized and determined by nuclear magnetic resonance (¹H NMR), Fourier transform infrared spectrometry (FTIR) and gel permeation chromatography (GPC). The micellar formation by these polymer brushes in aqueous solutions were detected by a surface tension technique, and the critical micelle concentration (CMC) ranged from 1.53 to 8.06 mg L⁻¹. The morphology and geometry of polymer micelles were investigated by transmission electron microscope (TEM) and dynamic light scattering (DLS). The polymer micelles assume the regularly-spherical core-shell structure with well-dispersed individual nanoparticles, and the particle size was in the range from 36 to 93 nm. The PNIPAAm segments exhibited a thermoreversible phase transition, so the resulting block polymer brushes were temperature-sensitive and the low critical solution temperature (LCST) was determined by UV-vis spectrometer at about 28.82–29.40°C. The characteristic parameters of the polymer micelles such as CMC, micellar size and LCST values were affected by their compositional ratios and the length of hydrophilic or hydrophobic chains. The evaluation for caffeine drug release behavior of the block polymer micelles demonstrated that the self-assembled micelles exhibited thermal-triggered properties in controlled drug release.     

Synthesis of linear and star‐like poly(ε‐caprolactone)‐b‐poly{γ‐2‐[2‐(2‐methoxy‐ethoxy)ethoxy]ethoxy‐ε‐caprolactone} amphiphilic block copolymers using zinc undecylenate

Linear and star‐like amphiphilic diblock copolymers were synthesized by the ring‐opening polymerization of ε‐caprolactone and γ‐2‐[2‐(2‐methoxyethoxy)ethoxy]ethoxy‐ε‐caprolactone monomers using zinc undecylenate as a catalyst. These polymers have potential applications as micellar drug delivery vehicles, therefore the properties of the linear and 4‐arm star‐like structures were examined in terms of their molecular weight, viscosity, thermodynamic stability, size, morphology, and drug loading capacity. Both the star‐like and linear block copolymers showed good thermodynamic stability and degradability. However, the star‐like polymers were shown to have increased stability at lower concentrations with a critical micelle concentration (CMC) of 5.62 × 10^?4 g L^?1, which is less than half the concentration of linear polymer needed to form micelles. The star‐like polymeric micelles showed smaller sizes when compared with their linear counterparts and a higher drug loading capacity of doxorubicin, making them better suited for drug delivery purposes. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3601–3608     

Synthesis and micellar behavior of poly(vinyl alcohol-<Emphasis Type="Italic">b</Emphasis>-styrene) copolymers containing PVA blocks with different syndiotacticity

Poly(vinyl alcohol-b-styrene) (poly(VA-b-St)) diblock copolymers with different syndiotacticity of poly(vinyl alcohol) (PVA) block were synthesized via consecutive telomerization, atom transfer radical polymerization, and saponification. These amphiphilic block copolymeric micelles were prepared by dialysis against water. Dynamic light scattering and transmission electron micrograph measurements confirmed the formation of a micelles, and the size of a micelle was less than 100 nm and increased with the molecular weight of polystyrene (PS) block. From the fluorescence emission spectrum measurements using pyrene as a fluorescence probe, the copolymers formed micelles with critical micelle concentration (CMC) in the range of 0.125–4.47 mg/l. The CMC values increase with decrease of the molecular weight of the PS block and increase of the syndiotacticity of PVA block. Kinetic stability study of micelles showed increased stability for block copolymers containing PVA block with higher syndiotacticity.     

Synthesis and micelle formation of triblock copolymers of poly(methyl methacrylate)-b-poly(ethylene oxide)-b-poly(methyl methacrylate) in aqueous solution

Amphiphilic triblock copolymers of poly(methyl methacrylate)-b-poly(ethylene oxide)-b-poly(methyl methacrylate) (PMMA-b-PEO-b-PMMA) with well-defined structure were synthesized via atom transfer radical polymerization (ATRP) of methyl methacrylate (MMA) initiated by the PEO macroinitiator. The macroinitiator and triblock copolymer with different PMMA and/or PEO block lengths were characterized with ¹H and ¹³C NMR and gel permeation chromatography (GPC). The micelle formed by these triblock copolymers in aqueous solutions was detected by fluorescence excitation and emission spectra of pyrene probe. The critical micelle concentration (CMC) ranged from 0.0019 to 0.016 mg/mL and increased with increasing PMMA block length, while the PEO block length had less effect on the CMC. The partition constant K_v for pyrene in the micelle and in aqueous solution was about 10⁵. The triblock copolymer appeared to form the micelles with hydrophobic PMMA core and hydrophilic PEO loop chain corona. The hydrodynamic radius R_h,app of the micelle measured with dynamic light scattering (DLS) ranged from 17.3 to 24.0 nm and increased with increasing PEO block length to form thicker corona. The spherical shape of the micelle of the triblock copolymers was observed with an atomic force microscope (AFM). Increasing hydrophobic PMMA block length effectively promoted the micelle formation in aqueous solutions, but the micelles were stable even only with short PMMA blocks.     

Second CMC in surfactant micellar systems

Experimental reports of surfactant systems displaying a second critical micelle concentration (second CMC) have been surveyed. It turns out that surfactant micelles usually show a growth behavior with some typical features. (i) Micelles grow weakly at low surfactant concentrations but may switch to a much stronger growth behavior at higher concentrations. The second CMC is defined as the point of transition from weakly to strongly growing micelles. (ii) Micelles are found to be non-spherically shaped below the second CMC. (iii) At the second CMC micelles are found to be much smaller, with aggregation numbers typically 100–200, than expected for flexible micelles. (iv) Micelles of intermediate size are present in a narrow concentration regime close to the second CMC. (v) Micelles grow much stronger above the second CMC than expected from a sphere-to-rod transition. The conventional spherocylindrical micelle model predicts a smooth growth behavior that contradicts the appearance of a second CMC. Modifying the model by means of including swollen end caps neither account for the presence of micelles with intermediate size, nor the strong growth behavior above the second CMC. Taking into account micelle flexibility is not consistent with the rather low micelle aggregation numbers observed at the second CMC. On the other hand, a recently proposed alternative theoretical approach, the general micelle model, have been demonstrated to take into account basically all features that are typical of experimentally observed micellar growth behaviors.     

Non-ionic amphiphilic block copolymers by RAFT-polymerization and their self-organization

Water-soluble, amphiphilic diblock copolymers were synthesized by reversible addition fragmentation chain transfer polymerization. They consist of poly(butyl acrylate) as hydrophobic block with a low glass transition temperature and three different nonionic water-soluble blocks, namely, the classical hydrophilic block poly(dimethylacrylamide), the strongly hydrophilic poly(acryloyloxyethyl methylsulfoxide), and the thermally sensitive poly(N-acryloylpyrrolidine). Aqueous micellar solutions of the block copolymers were prepared and characterized by static and dynamic light scattering analysis (DLS and SLS). No critical micelle concentration could be detected. The micellization was thermodynamically favored, although kinetically slow, exhibiting a marked dependence on the preparation conditions. The polymers formed micelles with a hydrodynamic diameter from 20 to 100 nm, which were stable upon dilution. The micellar size was correlated with the composition of the block copolymers and their overall molar mass. The micelles formed with the two most hydrophilic blocks were particularly stable upon temperature cycles, whereas the thermally sensitive poly(N-acryloylpyrrolidine) block showed a temperature-induced precipitation. According to combined SLS and DLS analysis, the micelles exhibited an elongated shape such as rods or worms. It should be noted that the block copolymers with the most hydrophilic poly(sulfoxide) block formed inverse micelles in certain organic solvents.     

New amphiphilic diblock copolymers: surfactant properties and solubilization in their micelles

Several series of amphiphilic diblock copolymers are investigated as macrosurfactants in comparison to reference low-molar-mass and polymeric surfactants. The various copolymers share poly(butyl acrylate) as a common hydrophobic block but are distinguished by six different hydrophilic blocks (one anionic, one cationic, and four nonionic hydrophilic blocks) with various compositions. Dynamic light scattering experiments indicate the presence of micelles over the whole concentration range from 10(-4) to 10 g x L(-1). Accordingly, the critical micellization concentrations are very low. Still, the surface tension of aqueous solutions of block copolymers decreases slowly but continuously with increasing concentration, without exhibiting a plateau. The longer the hydrophobic block, the shorter the hydrophilic block, and the less hydrophilic the monomer of the hydrophilic block is, the lower the surface tension is. However, the effects are small, and the copolymers reduce the surface tension much less than standard low-molar-mass surfactants. Also, the copolymers foam much less and even act as anti-foaming agents in classical foaming systems composed of standard surfactants. The copolymers stabilize O/W emulsions made of methyl palmitate as equally well as standard surfactants but are less efficient for O/W emulsions made of tributyrine. However, the copolymer micelles exhibit a high solubilization power for hydrophobic dyes, probably at their core-corona interface, in dependence on the initial geometry of the micelles and the composition of the block copolymers. Whereas micelles of copolymers with strongly hydrophilic blocks are stable upon solubilization, solubilization-induced micellar growth is observed for copolymers with moderately hydrophilic blocks.     

Conductive properties of TiO2/bacterial cellulose hybrid fibres

In this article, we report the first micellization study of amphiphilic copolymers composed of bacterial medium chain length poly(3-hydroxyalkanoates) (mcl-PHAs). A series of diblock copolymers based on fixed poly(ethylene glycol) (PEG) block (5000 g mol(-1)) and a varying poly(3-hydroxyoctanoate-co-3-hydroxyhexanoate) (PHOHHx) segment (1500-7700 g mol(-1)) have been synthesized using "click" chemistry. These copolymers self-assembled to form micelles in aqueous media. The influence of PHOHHx block molar mass on the hydrodynamic size and on the critical micelle concentration (CMC) has been studied using dynamic light scattering and fluorescence spectroscopy, respectively. With increasing PHOHHx length, narrowly distributed micelles with diameters ranging from 44 to 90 nm were obtained, with extremely low CMC (up to 0.85 mg/L). Cryogenic transmission electron microscopy (Cryo-TEM) showed that micelles took on a spherical shape and exhibited narrow polydispersity. Finally, the colloidal stability of the micelles against physiological NaCl concentration has been demonstrated, suggesting they are promising candidates for drug delivery applications.     

Enhancement of cellular uptake and antitumor efficiencies of micelles with phosphorylcholine

Internalization of drug delivery micelles into cancer cells is a crucial step for antitumor therapeutics. Novel amphiphilic star-shaped copolymers with zwitterionic phosphorylcholine (PC) block, 6-arm star poly(ε-caprolactone)-b-poly(2-methacryloyloxyethyl phosphorylcholine) (6sPCL-b-PMPC), have been developed for encapsulation of poorly water-soluble drugs and enhancement of their cellular uptake. The star-shaped copolymers were synthesized by a combination of ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP). The copolymers self-assembled to form spherical micelles with low critical micelle concentration (CMC). The sizes of the micelles range from 80 to 170 nm and increase 30 ≈ 80% after paclitaxel (PTX) loading. Labeled with fluorescein isothiocyanate (FITC), the micelles were confirmed by fluorescence microscopy to have been internalized efficiently by tumor cells. Direct visualization of the micelles within tumor cells by transmission electron microscopy (TEM) confirmed that the 6sPCL-b-PMPC micelles were more efficiently uptaken by tumor cells compared to PCL-b-PEG micelles. When incorporated with PTX, the 6sPCL-b-PMPC micelles show much higher cytotoxicity against Hela cells than PCL-b-PEG micelles, in response to the higher efficiency of cellular uptake.     

羧甲基纤维素-十二烷基醇聚氧乙烯醚丙烯酸酯共聚物表面活性剂在水溶液中的胶束形态

采用动态激光光散射及环境扫描电镜研究了羧甲基纤维素型高分子表面活性剂在水溶液中的胶束形态 .结果表明 ,共聚物在水溶液中的形态完全不同于羧甲基纤维素分子 ,亲水疏水链段的引入 ,使共聚物分子聚集形成了以疏水链段为核心的棍状胶束结构 .高分子表面活性剂水溶液体系的归一化一级相关函数不符合单指数衰减 ,表明胶束形态的多分散性 .在 0 .0 0 5%～ 1 %浓度范围内 ,胶束粒子大小均分布在两个区域 ,随共聚物浓度增大 ,低粒径区保持在 3 0～ 1 0 0nm范围 ,为单分子区 ;而高粒径区随浓度增大移向更高值 ,表明多分子胶束不断长大 .     

Formation of micelles of Pluronic block copolymers in PEG 200

The formation of micelles of Pluronic block copolymers in poly(ethylene glycol) (PEG) was studied using fluorescence, solubilization measurements, and frozen fracture electron microscopy (FFEM) methods at 40 degrees C. It was discovered that surfactants L44 (EO(10)PO(23)EO(10)), P85 (EO(26)PO(40)EO(26)), and P105 (EO(37)PO(56)EO(37)) can form micelles in PEG 200 (PEG with a nominal molecular weight of 200), and the critical micellization concentration (CMC) decreases with increasing molecular weight of the surfactants. The size of the micelles formed by these Pluronic block copolymers is in the range of 6-35 nm. The CMC values in PEG 200 are higher than those in aqueous solutions.     

Micellization and gelation of aqueous solutions of star-shaped PEG-PCL block copolymers consisting of branched 4-arm poly(ethylene glycol) and polycaprolactone blocks

Star-shaped block copolymers consisting of non-toxic poly(ethylene glycol) and biodegradable polycaprolactone ((PEG5K-PCL)₄) were synthesized by ring-opening polymerization of the ε-caprolactone monomer with hydroxyl-terminated 4-armed PEG as initiator. These biodegradable, amphiphilic star block copolymers showed micellization and sol-gel transition behaviors in aqueous solution with varying concentration and temperature. In the dilute aqueous solutions of star block copolymers, micellization behavior occurred over specific concentration. The 1,6-diphenyl-1,3,5-hexatriene (DPH) solubilization method was used to determine the critical micellization concentration (CMC) of star block copolymers. The obtained micelle size increased with increasing hydrophobic PCL block length. In high-concentration solutions, the star block copolymers showed temperature-sensitive sol-gel transition behavior. The morphology of the micelle and gel was investigated by atomic force microscopy (AFM). As a result, the micelles showed a core-corona spherical structure at concentration near CMC, while the gel showed a mountain-chain-like morphology picture. It was proposed that with increasing the micelle concentration the worm-like micelle clusters formed firstly and the gel was constructed by the packing of micelle clusters.     

药物包载对两亲嵌段共聚物胶束形态的影响

以聚(ε-己内酯-b-L-丙交酯)/聚乙二醇单甲醚(P(CL-b-LLA)-b-mPEG)和聚(ε-己内酯-b-D,L-丙交酯)/聚乙二醇单甲醚(P(CL-b-DLLA)-b-mPEG)两种两亲嵌段共聚物为载体,选择了物理状态完全不同、而疏水性相近的吲哚美辛和维生素E为模型药物,研究了药物包载对高分子胶束形态的影响.发现两种药物在高分子胶束内部的增溶均会导致胶束形态发生显著改变,变化行为与胶束内核的结晶性和药物疏水性有关.另外,还研究了两种嵌段共聚物的载药性能,发现非结晶性疏水内核共聚物的药物包载率明显大于可结晶疏水内核的共聚物.     

Thermodynamic Characteristics of the Micellization in Droplet and Quasi-Droplet Models of Surfactant Molecular Aggregates with Account of Experimental Data on Equilibrium Micelle Distribution

Formuals for the thermodynamic characteristics of micellization in the droplet and quasi-droplet models of surfactant molecular aggregates are derived. These formulas account for the experimental data on the mean size of micelles and average statistical scatter of their sizes in the equilibrium state. These formulas cover critical micellization concentration corresponded to the onset of surfactant accumulation in micelles and higher (than CMC) concentrations at which micelles incorporate noticeable or even the largest portion of surfactant in micellar solution. Analytical dependence of thermodynamic characteristics of micellization on the initial parameters of droplet and quasi-droplet models of molecular aggregates at critical micellization concentration is disclosed.