Thermoresponsive triblock copolymer aggregates investigated by laser light scattering

Narrowly distributed polystyrene-b-poly(N-isopropylacrylamide)-b-polystyrene (PS-b-PNIPAM-b-PS) triblock copolymer with trithiocarbonate group in the middle of PNIPAM block was synthesized by using reversible addition fragmentation chain transfer (RAFT) polymerization. Such copolymer chains form a micelle-like aggregate with PNIPAM interlocking rings and associating PS blocks as the core and PNIPAM rings as the corona. The hydrolysis of the trithiocarbonate group leads the rings in the corona to be cut into open linear coils. Using laser light scattering, we have investigated the temperature-induced collapse of the aggregates with the rings and coils in the corona. Our results reveal that the former shrink much less than the latter due to the topological effect of PNIPAM blocks in the corona. On the other hand, the aggregates with long coils exhibit a sharper collapse transition than those with shorter coils.     

Interaction of amphiphilic block copolymer micelles with surfactants

An out line and summary of literature studies on interactions between different types of amphiphilic copolymer micelles with surfactants has been given. This field of research is still emerging and it is difficult presently to make generalisations on the effects of surfactants on the copolymer association. The effects are found to be varied depending upon the nature and type of hydrophobic (hp) core and molecular architecture of the copolymers and the hydrocarbon chain length and head group of surfactants. The information available on limited studies shows that both anionic and cationic surfactants (in micellar or molecular form) equally interact strongly with the associated and unassociated forms of copolymers. The beginning of the interaction is typically displayed as critical aggregation concentration (CAC), which lies always below the critical micelle concentration of the respective surfactant. The surfactants first bind to the hydrophobic core of the copolymer micelles followed by their interaction with the hydrophilic (hl) corona parts. The extent of binding highly depends upon the nature, hydropobicity of the copolymer molecules, length of the hydrocarbon tail and nature of the head group of the surfactant. The micellization of poly(ethylene oxide) (PEO)–poly(propylene oxide) (PPO)–poly(ethylene oxide) was found to be suppressed by the added surfactants and at higher surfactant concentrations, the block copolymer micelles get completely demicellized. This effect was manifested itself in the melting of liquid crystalline phases in the high copolymer concentrations. However, no such destabilization was found for the micelles of polystyrene (PS)–poly(ethylene oxide) copolymers in water. On the contrary, the presence of micellar bound surfactant associates resulted in to large super micellar aggregates through induced intra micellar interactions. But with the change in the hydrophobic part from polystyrene to poly(butadiene) (PB) in the copolymer, the added surfactants not only reduced the micellar size but also transformed cylindrical micelles to spherical ones. The mixtures in general exhibited synergistic effects. So varied association responses were noted in the mixed solutions of surfactants and copolymers.     

Interfacial solubilization of model amphiphilic molecules in block copolymer micelles

We investigate the solubilization of 2-nitrodiphenylamine, a hydrophobic but polar dye molecule, in aqueous solutions of polystyrene(310)-b-poly(acrylic acid)(47) micelles. The solubilization capacity of the micelles, which consist of a polystyrene core and poly(acrylic acid) corona, and the micelle-water partition coefficient are evaluated as a function of the solubilizate concentration. The solubilization isotherm shows a nonlinear behavior, and the partition coefficient, instead of being constant, is strongly dependent on the dye concentration. These results are explained by treating solubilization as a binding process, and by fitting the data to a Langmuir adsorption model. In addition, we examine the locus of solubilization of 2-nitrodiphenylamine using its solvatochromic properties and solubility in model solvents, and we identify the micellar interface as the solubilization site. Confirmatory studies, including the dependence of solubilization on the interfacial area of the aggregates, the role of the poly(acrylic acid) corona chains in stabilizing the solubilized molecules, and the effect of the solubilizate structure on the extent of incorporation, were also conducted. The results, consistent with surface localization, show that solubilization is dependent on the interfacial area of the aggregates, and on the affinity of the solubilizate for the micellar interface.     

Structural evolution of mixed micelles due to interchain complexation and segregation investigated by laser light scattering

Polystyrene-b-poly(acrylic acid) (PS-b-PAA) diblock copolymers form micelles in toluene with PAA as the core and PS as the corona. The introduction of poly(methyl methacrylate)-b-poly(ethylene oxide) (PMMA-b-PEO) solution in toluene leads to mixed micelles due to the hydrogen-bonding complexation between PAA and PEO. By using a combination of static and dynamic laser light scattering, we have investigated the evolution of the mixed micelles. Our results revealed that the complexation between PAA and PEO in the core and the segregation between PS and PMMA in the corona as a function of the molar ratio (r) of PEO to PAA manipulate the evolution. At r < approximately 1.0, the mixed micelles hold a spherical structure after a long-time standing. However, at r > approximately 1.0, the average radius of gyration Rg, the average hydrodynamic radius , and the ratio / of the mixed micelles increase with time, whereas the molar mass (Mw) does not change. The facts indicate that the mixed micelle has evolved from a spherical structure to a hyperbranched structure.     

A microfluidic platform for integrated synthesis and dynamic light scattering measurement of block copolymer micelles

Microfluidic devices were developed that integrate the synthesis of well defined block copolymers and dynamic light scattering (DLS) measurement of their micelle formation. These metal devices were designed to operate in contact with organic solvents and elevated temperatures for long periods, and thus were capable of continuous in-channel atom transfer radical polymerization (ATRP) of styrene and (meth)acrylate homopolymers and block copolymers. These devices were equipped with a miniaturized fiber optic DLS probe that included several technology improvements, including a measurement volume of only 4 microlitres, simple alignment, and reduced multiple scattering. To demonstrate the integrated measurement, poly(methyl methacrylate-b-lauryl methacrylate) and poly(methyl methacrylate-b-octadecyl methacrylate) block copolymers were processed on the device with a selective solvent, dodecane, to induce micelle formation. The in situ DLS measurements yielded the size and aggregation behavior of the micelles. For example, the block copolymer solutions formed discrete micelles (D(H) approximately = 25 nm) when the corona block was sufficiently long (f(MMA) < 0.51), but the micelles aggregated when this block was short. This study demonstrates the utility of these new devices for screening the solution behavior of custom synthesized polymeric surfactants and additives.     

Light scattering and luminescence studies on self-aggregation behavior of amphiphilic copolymer micelles

The self-aggregation behavior of three amphiphilic graft copolymers, oligo(9,9-dihexyl)fluorence-graft-poly(ethylene oxide) (OHF-g-PEO), with different architectures was studied by dynamic and static light scattering (DLS and SLS) in combination with fluorescence spectroscopy and transmission electron microscopy (TEM). The formation of self-assembled polymeric micelles was confirmed by SLS and TEM. DLS and SLS analyses showed that the architecture of graft copolymers has a dramatic effect on critical aggregation concentration (CAC), micelle size distribution, apparent aggregation number (Nagg app), and apparent molecular weight of polymer aggregates (Mw,agg app). An architecture-dependent excimer emission, resulting from the pi-pi stacking of the oligofluorene backbones, was also observed from the photoluminescence spectra of the micelle aqueous solutions, which indicated a strong intermolecular interaction among the polymeric molecules. The excimer emission was further investigated by time-resolved fluorescence spectroscopy.     

Molecule-responsive block copolymer micelles

Ring-opening metathesis polymerization was used to generate an ABC triblock copolymer, containing complementary diamidopyridine (DAP) and thymine (THY) outer blocks, which assembles into spherical aggregates held together by DAP-THY noncovalent interactions. Addition of THY-containing small guest molecules results in complete opening and deaggregation of the block copolymer micelle. This molecular recognition and macroscopic response shows high selectivity to the guest structure, and tolerates only a small amount of conformational mobility in the THY guest. On the other hand, addition of a small DAP-containing guest does not break the aggregates, but instead, results in new micelles which show a different selectivity profile from the parent morphology. We have examined the effect of a number of structural features in the block copolymers, on both the extent and selectivity of their macroscopic response to guests (that is, opening of the micelle). This study has resulted in a set of structural guidelines, which help in the design of effective molecule-responsive micelles for applications in selective drug delivery, sensing, and surface patterning.     

Bactericidal block copolymer micelles

Block copolymer micelles with bactericidal properties were designed to deactivate pathogens such as E. coli bacteria. The micelles of PS‐b‐PAA and PS‐b‐P4VP block copolymers were loaded with biocides TCMTB or TCN up to 20 or 30 wt.‐%, depending on the type of antibacterial agent. Bacteria were exposed to loaded micelles and bacterial deactivation was evaluated. The micelles loaded with TCN are bactericidal; bacteria are killed in less than two minutes of exposure. The most likely interpretation of the data is that the biocide is transferred to the bacteria by repeated micelle/bacteria contacts, and not via the solution.

     

Deformation of copolymer micelles induced by amphiphilic dimer particles

Combining self-consistent-field theory and density-functional theory,we systematically study the deformation of copolymer micelles induced by the presence of amphiphilic dimer particles.Due to the amphiphilic nature,dimer particles tend to accumulate onto the interface of the copolymer micelle.With increasing concentration of the symmetric dimer particles,which are made of two identical spherical particles,the micelle deforms from the initial sphere to ellipse,dumbbell, and finally separates into two micelles.Furthermore,asymmetric dimer particles,composed by two particles with different sizes,are considered to investigate the influence of geometry of dimer particles on the deformation of the micelle.It is found that the micelle inclines to deform into dumbbell due to the additional curvature originating in the gathering of asymmetric dimer particles onto the interface of the micelle.The present study on the deformation of micelles is useful to understand the possible shape variation in the course of cell division/fusion.     

Spontaneous generation of amphiphilic block copolymer micelles with multiple morphologies through interfacial Instabilities

We introduce a method for the formation of block copolymer micelles through interfacial instabilities of emulsion droplets. Amphiphilic polystyrene-block-poly(ethylene oxide) (PS-PEO) copolymers are first dissolved in chloroform; this solution is then emulsified in water and chloroform is extracted by evaporation. As the droplets shrink, the organic solvent/water interface becomes unstable, spontaneously generating a new interface and leading to dispersion of the copolymer as micellar aggregates in the aqueous phase. Depending on the composition of the copolymer, spherical or cylindrical micelles are formed, and the method is shown to be general to polymers with several different hydrophobic blocks: poly(1,4-butadiene), poly(-caprolactone), and poly(methyl methacrylate). Using this method, hydrophobic species dissolved or suspended in the organic phase along with the amphiphilic copolymer can be incorporated into the resulting micelles. For example, addition of PS homopolymer, or a PS-PEO copolymer of different composition and molecular weight, allows the diameter and morphology of wormlike micelles to be tuned, while addition of hydrophobically coated iron oxide nanoparticles enables the preparation of magnetically loaded spherical and wormlike micelles.     

两亲性杂臂星型嵌段共聚物胶束的制备、表征及载药性能研究

以溴代异丁酰溴与3,5-二羟基苯甲酸制备3,5-二(2-溴-2丙酰氧基)苯甲酸,再与聚乙二醇单甲醚酯化,合成含溴大分子引发剂PEG-Br2。以苯乙烯为单体,利用原子转移自由基聚合方法(ATRP)合成了两种不同亲疏水段比例的两亲性星型杂臂嵌段共聚物PEG-b-(PS)2。本实验利用FTIR、1H-NMR、GPC等技术对聚合物的分子结构及分子量进行表征,利用透析法制备聚合物胶束;采用AFM对聚合物胶束的纳米结构进行观察;采用荧光探针法测得其临界胶束浓度(CMC)分别为0.99 mg·L-1和0.59 mg·L-1;利用DLS测得聚合物胶束粒径为150 nm左右;以疏水型抗肿瘤药物氨甲喋呤(MTX)为模型药物,对载药胶束的体外释药行为进行了研究,测得聚合物胶束的载药量分别为为13.32%和10.00%,包封率分别为61.75%和46.82%。结果表明,随着疏水段的增大,星型杂臂嵌段共聚物胶束药物包载量及CMC随之降低,且在人体pH条件下药物释放较低;同时发现两种载药胶束在肿瘤细胞酸性条件下释药速率增加。综上,此类结构的聚合物胶束作为抗肿瘤药物MTX的载体分子具有很好的应用前景。     

Sphere-to-rod transition of non-surface-active amphiphilic diblock copolymer micelles: a small-angle neutron scattering study

Micellization behavior of amphiphilic diblock copolymers with strong acid groups, poly(hydrogenated isoprene)-block-poly(styrenesulfonate), was investigated by small-angle neutron scattering (SANS). We have reported previously (Kaewsaiha, P.; Matsumoto, K.; Matsuoka, H. Langmuir 2005, 21, 9938) that this strongly ionic amphiphilic diblock copolymer shows almost no surface activity but forms micelles in water. In this study, the size, shape, and internal structures of the micelles formed by these unique copolymers in aqueous solution were duly investigated. The SANS data were well described by the theoretical form factor of a core-shell model and the Pedersen core-corona model. The micellar shape strongly depends on the hydrophobic chain length of the block copolymer. The polymer with the shortest hydrophobic chain was suggested to form spherical micelles, whereas the scattering curves of the longer hydrophobic chain polymers showed a q-1 dependence, reflecting the formation of rodlike micelles. Furthermore, the addition of salt at high concentration also induced the sphere-to-rod transition in micellar shape as a result of the shielding effect of electrostatic repulsion. The corona thickness was almost constant up to the critical salt concentration (around 0.2 M) and then decreased with further increases in salt concentration, which is in qualitatively agreement with existing theories. The spherical/rodlike micelle ratio was also constant up to the critical salt concentration and then decreased. The micelle size and shape of this unique polymer could be described by the common concept of the packing parameter, but the anomalously stable nature of the micelle (up to 1 M NaCl) is a special characteristic.     

Scattering from block copolymer micelles

Small-angle neutron and X-ray scattering are techniques, which are frequently used for studying the structure and interactions of block copolymer micelles. Recent developments of models for the analysis of small-angle scattering data are reviewed. The most recent models, based on Monte Carlo simulations, are able to provide information on shape, aggregation number, polydispersity, core size, core solvation, corona shape/size, and on the interactions between the chains in the corona.     

pH/Temperature-responsive behavior of amphiphilic block copolymer micelles prepared using two different methods

The pH- and temperature-responsive behavior of amphiphilic block copolymer poly(L-lactide)-b-poly(2-(dimethylamino)ethyl methacrylate) (PLLA-b-PDMAEMA) in aqueous solutions is investigated using static and dynamic light scattering. Electrostatic force, hydrophobic interaction, and hydrogen bonding coexist in the system. Micelles with different structures are prepared using water addition (WA) and direct dissolution (DD) methods. The aggregation from loose micelles into large micellar clusters is observed above the transition temperature under basic conditions. Only micellar clusters from the DD method could disaggregate when temperature was decreased to 24.3 °C after heating. The behavior of the micelles prepared with the DD method indicates that only the outer parts of the PLLA-b-PDMAEMA chains in the corona are solvated.     

Single-molecule force spectroscopy of selenium-containing amphiphilic block copolymer: toward disassembling the polymer micelles

Selenium-containing polymers are a new type of responsive polymer material. Here, a selenium-containing amphiphilic block copolymer (PEG-PUSe-PEG) has been investigated using atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS). The deviation between force-extension curves of PEG-PUSe-PEG in water and in DMSO is found to be related to the disassembly of the micellar structures in water. SMFS experiments on PEG-PUSeox-PEG suggest that the change from selenide to oxidized selenone contributes significantly to the change in amphiphilicity, without obviously influencing the single-chain elasticity.     

Light scattering study of solubilization of organic molecules by block copolymer micelles in aqueous media

Block copolymers, when dissolved in a selective solvent, form spherical micelles. These micelles can selectively solubilize organic molecules otherwise insoluble in the pure solvent. In this study, we report solubilization of organic molecules by styrene-methacrylic acid block copolymer micelles in aqueous buffers. A light scattering technique was developed to determine the extent of micellar solubilization. Our results indicate that the extent of micellar solubilization depends on the chemical nature of organic molecules, specifically, on the interactions between the organic compound and polystyrene. A thermodynamic model has been developed to describe micellar solubilization. The theoretical calculation agrees reasonably well with the experimental results for two micellar samples examined. ©1995 John Wiley & Sons, Inc.     

Thermoresponsive polymersome from a double hydrophilic block copolymer

The article describes synthesis and thermally triggered self‐assembly of a Poly (ethylene oxide)‐block‐poly (N‐insopropylacrylamide) (PEO‐b‐PNIPAm) in aqueous medium. At rt, the polymer remains as unimer, however, at lower critical solution temperature (LCST) of PNIPAm (32 °C), it forms a rather large undefined aggregate which at slightly elevated temperature (～40 °C) converges to well defined polymersome structure (Critical aggregation concentration = 0.45 mg/mL) with hydrodynamic diameter of 40–50 nm. By lowering the temperature, initial swelling of the compact vesicle followed by reversible disassembly to unimer was noticed. The polymersome exhibits encapsulation ability to a hydrophilic dye Calcein which can be spontaneously released by lowering the temperature below cloud point. Likewise a hydrophobic dye namely 8‐Anilino‐1‐naphthalenesulfonic acid (ANS) can also be encapsulated and released by thermal trigger. Detail photoluminescence studies reveal ANS dye can be used as a generalized probe molecule for detecting LCST of a thermoresponsive polymer by “fluorescence on” above LCST even by cursory observation. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2444–2451     

NMR studies of block copolymer micelles

Block copolymers dissolved in selective solvent often self-assemble. We review the use of NMR to study this process and to characterize the aggregates formed. We stress the need to consider the polydispersity of the polymers and the fact that the increase in NMR relaxation rates observed upon aggregation can be assigned to contributions from the block copolymer micelle tumbling.     

Cross-linking of cationic block copolymer micelles by silica deposition

Diblock copolymer micelles comprising cationic poly(2-(dimethylamino)ethyl methacrylate) (PDMA) coronas and hydrophobic poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) cores are used as nanosized templates for the deposition of silica from aqueous solution at pH 7.2 and 20 degrees C. Both noncross-linked and shell cross-linked (SCL) micelles can be coated with silica without loss of colloid stability. Under optimized conditions, the silica deposition is confined to the partially quaternized cationic PDMA chains, leading to hybrid copolymer-silica particles of around 35 nm diameter with well-defined core-shell morphologies. 1H NMR studies confirmed that the PDPA cores of these copolymer-silica particles became protonated at low pH and deprotonated at high pH, which suggests possible encapsulation and controlled release applications. Moreover, in situ silica deposition effectively stabilizes the PDPA-PDMA micelles, which remain intact on lowering the solution pH (whereas the original noncross-linked PDPA-PDMA micelles dissociate in acidic solution). This suggests a convenient route to silica-stabilized SCL micelles under mild conditions.