Size controlled polymersomes by continuous self-assembly in micromixers

The formation of vesicles based on the self-assembly of amphiphilic poly(butadiene)-b-poly(ethylene oxide) (PB₁₃₀-b-PEO₆₆) block copolymer in water has been studied using THF as co-solvent. To obtain a highly controlled mixing process for the polymer/THF- and the water-phase, we employed micro mixers with different mixing geometries. The high impact of this preparation method on the self-assembling process was verified by TEM and DLS characterization of the obtained structures. Spherical micelles, vesicles and worm-like micelles were found depending on the parameters of mixing. By additional parameter adjustment in the vesicle regime, the size of the assembled vesicles was controlled between 45 and 100 nm. This demonstrates the continuous preparation of narrowly distributed vesicle structures with controlled sizes.     

Effect of conformational asymmetry on the self-assembly of amphiphilic diblock copolymer in selective solvent

Three dimensional real-space self-consistent field theory is employed to study the effect of conformational asymmetry on the self-assembly of amphiphilic diblock copolymer in selective solvent. The phase diagrams in wide ranges of interaction parameters and conformational asymmetry were obtained in present study. The results indicate that the conformational asymmetry is an important factor that determines the self-assembly of amphiphilic diblock copolymer in solution. The self-assembled morphology changes from sphere to rod, then to vesicle with an increase of the degree of conformational asymmetry. We found that the entropic contribution of the core-forming block is the main reason for this transition.     

Long-tailed spherical aggregates formed from ABA triblock copolymer by changing the properties of selective solvent

A convenient method of tuning aggregate morphologies from amphiphilic block copolymer by adding second selective solvent is introduced in this paper. Some novel aggregate morphologies, i.e. hierarchical vesicles (and compound spherical micelles) with one or more tails, were formed by introducing a second selective solvent for core-forming blocks into the poly(4-vinyl pyridine)-b-polystyrene-b-poly(4-vinyl pyridine) ABA amphiphilic block copolymer/co-solvent/water systems. Addition of selective solvent (toluene) for core-forming blocks (PS blocks) has significant effect on the aggregate morphologies from the amphiphilic triblock copolymer. The aggregate morphologies changed from spheres to rods, long tailed solid large compound spheres, and to long tailed hierarchical vesicles by adding 0.5, 10 and 30 wt% of toluene to the organic solvent, respectively. There exists an aggregate morphological transition of the long tailed hierarchical vesicles to long tailed solid spheres by decreasing the content of toluene in the organic solvent mixture. The tails disappeared, and irregular vesicular and spherical structures were formed when the toluene content was 20 wt%. The toluene addition is expected to increase the stretching of the core-forming blocks (PS), and to modify the interfacial tension of core-corona interface, which are the main reasons for the aggregate morphology transition. To the best of our knowledge, these tailed vesicles and spherical morphologies have not been found in block copolymer aggregates system up to now.     

The vesicle formation in a binary amphiphilic diblock copolymer/homopolymer solution

The formation of vesicles in a binary blend of an amphiphilic diblock copolymer AB/homopolymer C was studied in a dilute solution using the real space two-dimensional self-consistent field theory (SCFT). Special attention was played to the role played by the homopolymer C in controlling the vesicle formation. In the simulations, it was found that as the averaged volume fraction of homopolymer C was decreased while keeping the total averaged volume fraction of block copolymer AB and homopolymer C unchanged, there was a morphological transition from the bilayer vesicles to rod-like/circle-like micelles. The compound vesicle structure was observed in the simulations. When the averaged volume fraction of block copolymer AB was further increased while the total averaged volume fraction of AB and C remained unchanged, the compound vesicle structure became less favored entropically than the unilamellar vesicle structure. The effect of the degree of polymerization of the homopolymer C on the vesicle formation of the amphiphilic system was examined. By reducing the degree of polymerization of the homopolymer C to unity, the component C became a small solvent molecule immiscible with the bulk solvent. It was found that the small solvent C exerted no influence on the morphological stability of the vesicles.     

两亲Janus纳米片的制备及胶体与界面性质研究进展

该文首先综述了两亲Janus纳米片制备方法的研究进展，包括界面保护法、乳液界面自组装溶胶-凝胶法、模板辅助溶胶-凝胶法以及嵌段共聚物自组装法。接着，系统介绍了两亲Janus纳米片在水溶液中的胶体特性及其在油水体系中的界面特性。最后，简要介绍了两亲Janus纳米片的应用领域，并对未来两亲Janus纳米片制备方法和胶体与界面特性的研究方向进行了展望。     

Nanostructured thermosets from self‐assembled amphiphilic block copolymer/epoxy resin mixtures: effect of copolymer content on nanostructures

Nanostructure formation in thermosets can allow the design of materials with interesting properties. The aim of this work was to obtain a nanostructured epoxy system by self‐assembly of an amphiphilic diblock copolymer in an unreacted epoxy/amine mixture followed by curing of the matrix. The copolymer employed was polystyrene‐block‐poly(methyl methacrylate) (PS‐b‐PMMA). The thermoset system, formed by a diglycidyl ether of bisphenol A‐type epoxy resin and diaminodiphenylmethane hardener, was chosen to ensure the miscibility of most of the PMMA block until matrix gelation. Transparent materials with microphase‐separated domains were obtained for copolymer contents lower than 40 wt%. In systems containing 20 and 30 wt% block copolymer, the PS block formed spherical micelles or worm‐like structures before curing, which were stabilized through curing by the more compatible PMMA block phase. Nanostructured thermoset systems were successfully synthesized for self‐assembled amphiphilic block copolymer–epoxy/amine mixtures for copolymer contents lower than 40 wt%. Copyright © 2009 Society of Chemical Industry     

Synthesis of Miktoarm Dumbbell-Like Amphiphilic Triblock Copolymer by Combination of Consecutive RAFT Polymerizations and ATRP

Summary  A novel synthetic route, combining three reversible addition-fragmentation chain transfer (RAFT) and one atom transfer radical polymerization (ATRP) processes, for the preparation of a miktoarm dumbbell-like amphiphilic triblock copolymer, poly(poly(ethylene glycol) methyl ether methacrylate)-b-polystyrene-b-(poly(4-vinylbenzyl chloride)-g-polystyrene) (PPEGMA-b-PS-b-(PVBC-g-PS)), was developed using 2-cyanoprop-2-yl 1-dithionaphthalate (CPDN) as a RAFT agent, and the benzyl chloride group of the VBC units in the PVBC block as active ATRP macroinitiators, respectively. The structures of the obtained (co)polymers were characterized by ¹H NMR spectroscopy. The obtained PPEGMA-b-PS-b-(PVBC-g-PS) amphiphilic triblock graft copolymer could self-assemble into spherical micelles with 100-300 nm diameters in a selective solvent.     

Vesicular and micellar self‐assembly of stimuli‐responsive poly(N‐isopropyl acrylamide‐b‐9‐anthracene methyl methacrylate) amphiphilic diblock copolymers

Dually responsive amphiphilic diblock copolymers consisting of hydrophilic poly(N‐isopropyl acrylamide) [poly(NIPAAm)] and hydrophobic poly(9‐anthracene methyl methacrylate) were synthesized by reversible addition fragmentation chain‐transfer (RAFT) polymerization with 3‐(benzyl sulfanyl thiocarbonyl sulfanyl) propionic acid as a chain‐transfer agent. In the first step, the poly(NIPAAm) chain was grown to make a macro‐RAFT agent, and in the second step, the chain was extended by hydrophobic 9‐anthryl methyl methacrylate to yield amphiphilic poly(N‐isopropyl acrylamide‐b‐9‐anthracene methyl methacrylate) block copolymers. The formation of copolymers with three different hydrophobic block lengths and a fixed hydrophilic block was confirmed from their molecular weights. The self‐assembly of these copolymers was studied through the determination of the lower critical solution temperature and critical micelle concentration of the copolymers in aqueous solution. The self‐assembled block copolymers displayed vesicular morphology in the case of the small hydrophobic chain, but the morphology gradually turned into a micellar type when the hydrophobic chain length was increased. The variations in the length and chemical composition of the blocks allowed the tuning of the block copolymer responsiveness toward both the pH and temperature. The resulting self‐assembled structures underwent thermally induced and pH‐induced morphological transitions from vesicles to micelles and vice versa in aqueous solution. These dually responsive amphiphilic diblock copolymers have potential applications in the encapsulation of both hydrophobic and hydrophilic drug molecules, as evidenced from the dye encapsulation studies. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46474.     

Self-assembly of polystyrene-b-poly(4-vinylpyridine) in deoxycholic acid melt

It is well known that amphiphilic block copolymers in selective solvents self-assemble into micellar structures, where solvophilic blocks tend to contact with solvents while solvophobic blocks are shielded from the solvents. Different from the conventional micellization in liquid systems, we report that the block copolymer, polystyrene-b-(4-vinylpyridine) (PS-b-P4VP), can self-assemble in melted deoxycholic acid (DCA) at high temperatures and the structures are retained in “solid state” after being cooled down to room temperature. Probing by transmission electron microscopy (TEM), we found that a series of self-assembled structures, including spherical micelles, wormlike micelles and vesicles can be obtained by varying the length of the block copolymers and the morphologies are dependent on the annealing temperature and time. We also demonstrate how to extract the structures that are trapped in solid state by removing DCA using appropriate solvents. The extracted vesicles, which are loaded with solid molecules, are potential for applications in nanocapsules and controlled release.     

Hydrogen bond‐mediated self‐assembly and supramolecular structures of diblock copolymer mixtures

This review summarizes recent advances in the preparation of hydrogen bonding block copolymer mixtures and the supramolecular structures they form through multiple hydrogen bonding interactions. Hydrogen bonding in block copolymer mixtures that form nanostructures and have unusual electronic, photonic and magnetic properties is a topic of great interest in polymer science. Combining the self‐assembly of block copolymers with supramolecular structures offers unique possibilities to create new materials with tunable and responsive properties. The self‐assembly of structures from diblock copolymer mixtures in the bulk state is readily controlled by varying the weight fraction of the block copolymer mixture and the copolymer composition; in solution, the morphologies are dependent on the copolymer composition, the copolymer concentration, the nature of the common solvent, the amount of the selective solvent and, most importantly, the hydrogen bonding strength. Copyright © 2008 Society of Chemical Industry     

Polymeric nanoparticles with tunable architecture formed by biocompatible star shaped block copolymer

An amphiphilic star shaped block copolymer, based on well known biocompatible components, was synthesized using branched poly(ε-caprolactone) as hydrophobic core and branched poly(ethyleneglycol) as hydrophilic corona. The composition of this macromolecule, based on two well differentiated blocks, conferred amphiphilic behavior to the whole system that acted as driving force for its self-assembling in aqueous media. Depending on the polymer concentration it was possible to obtain different architectures. The TEM micrographs permitted to follow the evolution of the system from single vesicles toward necklace entanglements. In this work, we discuss the mechanism that would be involved in the evolution of the system's morphology as a function of the block copolymer concentration. In addition, the proposed star shaped block copolymer presented good solubilizing properties that were used to disperse in water, poorly soluble molecules such as chlorine-carbazoles, which were used to investigate the suitability of the self-assembled nanostructures as drug nano-carriers.     

Synthesis and characterization of pH/temperature-sensitive block copolymers via atom transfer radical polymerization

In order to prepare well-defined pH-sensitive block copolymers with a narrow molecular weight distribution (MWD), we synthesized a pH-sensitive block copolymer via atom transfer radical polymerization (ATRP) of sulfamethazine methacrylate monomer (SM) and amphiphilic diblock copolymers by the ring-opening polymerization of d,l-lactide/?-caprolactone (LA/CL), and their sol-gel phase transition was investigated. SM, which is a derivative of sulfonamide, was used as a pH responsive moiety, while PCLA-PEG-PCLA was used as a biodegradable, as well as a temperature sensitive one, amphiphilic triblock copolymer. The pentablock copolymer, OSM-PCLA-PEG-PCLA-OSM, was synthesized using Br-PCLA-PEG-PCLA-Br as an ATRP macroinitiator. The number average molecular weights of SM were controlled by adjusting the monomer/initiator feed ratio. The macroinitiator was synthesized by the coupling of 2-bromoisobutyryl bromide with PCLA-PEG-PCLA in the presence of triethyl amine catalyst in dichloromethane. The resultant block copolymer shows a narrow polydispersity. The block copolymer solution shows a sol-gel transition in response to a slight pH change in the range of 7.2-8.0. Gel permeation chromatography (GPC) and NMR were used for the characterization of the polymers that were synthesized.     

Synthesis of amphiphilic block copolymer of acrylamide with styrene using free radical interfacial copolymerization

A novel free radical interfacial copolymerization was proposed and used to prepare the amphiphilic block copolymer of acrylamide (AM) with styrene (S). In this copolymerization, a synthesized new kind of initiator, namely, amphiphilic bifunctional initiator, which has not only a hydrophilic and a hydrophobic group but also two functional groups generating radicals in both ends of its molecule, was used to initiate the interfacial copolymerization. The generated amphiphilic block copolymer was characterized by infrared analysis, differential scanning calorimetry, elemental analysis, and dissolution behavior. The migration of generated copolymer from interface to water phase was discussed. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 69: 443–449, 1998     

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.     

Minimalist Protocell Design: A Molecular System Based Solely on Proteins that Form Dynamic Vesicular Membranes Embedding Enzymatic Functions

Life in its molecular context is characterized by the challenge of orchestrating structure, energy and information processes through compartmentalization and chemical transformations amenable to mimicry of protocell models. Here we present an alternative protocell model incorporating dynamic membranes based on amphiphilic elastin-like proteins (ELPs) rather than phospholipids. For the first time we demonstrate the feasibility of combining vesicular membrane formation and biocatalytic activity with molecular entities of a single class: proteins. The presented self-assembled protein-membrane-based compartments (PMBCs) accommodate either an anabolic reaction, based on free DNA ligase as an example of information transformation processes, or a catabolic process. We present a catabolic process based on a single molecular entity combining an amphiphilic protein with tobacco etch virus (TEV) protease as part of the enclosure of a reaction space and facilitating selective catalytic transformations. Combining compartmentalization and biocatalytic activity by utilizing an amphiphilic molecular building block with and without enzyme functionalization enables new strategies in bottom-up synthetic biology, regenerative medicine, pharmaceutical science and biotechnology.     

两亲性嵌段共聚物的合成及其在离子液体中的自组装行为

采用阴离子开环聚合法合成了嵌段共聚物PCL—PEG—PCL（聚己内醋-聚乙二醇-聚己内酯）。用1HNMR和GPC等对产物的分子量和组成进行表征,将其在离子液体中配成胶束,通过透射电镜（TEM）观察胶束的微观结构。研究结果表明,当疏水链段长度固定时,胶束的自组装形状主要依赖于亲水链的长度。     

Vesicular aggregation and morphologic evolvement of a flexible-rigid block hydrogen-bonding complex

In this paper, we selected a flexible poly(ethylene oxide) (PEO) connected to a stilbazole head group and a semi-rigid dendron of gallic acid with three alkyl chains to prepare an amphiphilic complex through hydrogen bonding. The structure of flexible-rigid complex has been characterized by ¹H NMR, IR and DLS. From the calculation of the binding interaction, the bonded complex occupies ca. 59.5% of total amount of molecules at the molar ratio of 1:1 of its two components, accompanied by the stability constant K_sc about 369 L/mol. The complex displays vesicular aggregation in toluene mixed with a certain amount of DMSO and the structural characterization indicates a symmetrical bilayer with PEO component locating outside towards the solution based on the analysis of contact angle. More interesting, tubular architecture of the complex is observed and found with the similar bilayer structure as that of the vesicular aggregation. The tubules are confirmed to derive from the vesicular aggregation through aging the vesicular structure. It is believed that the present investigation is helpful for the understanding of the dynamics of the vesicle evolvement based on the flexible-rigid complex.     

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。     

Solution study of novel diblock copolymers: Morphology and structural transition

The solution behavior and morphology of the nanostructures formed by novel block copolymers based on 1-cetyl[2-(acryloyloxy)ethyl]dimethylammonium bromide (ADHA) and 2-hydroxyethylacrylate (HEA) or N-isopropylacrylamide (NIPAM) have been studied using small angle X-ray scattering (SAXS), dynamic light scattering (DLS), and transmission electron microscopy (TEM). In these block copolymers the pADHA block consists of long hydrophobic C₁₆ tails connected to a positively charged quaternary ammonium group, making it amphiphilic, while the second block is either fully hydrophilic (pHEA) or thermoresponsive (pNIPAM). Using SAXS, we demonstrate that the morphology of block copolymer nanostructures is dependent on the solute concentration and on the length and composition of the blocks. In the case of thermoresponsive pADHA-b-pNIPAM, two types of ordered structures are formed and their characteristics are also defined by the temperature. Complementary information is obtained from DLS, showing large particles with the size up to 280 nm, which is beyond the resolution of the SAXS data. Loss of ordering around the lower critical solution temperature followed by ordering restoration at the higher temperature was observed for the pADHA-b-pNIPAM block copolymers. The differences in the structural order in the block copolymer solutions are directly related to their ability to coat hydrophobic metal nanoparticles.     

Polymeric nanoparticles,micelles and polymersomes from amphiphilic block copolymer

Block copolymers are made up of blocks of different polymerized monomers. Among the block copolymers, amphiphilic block copolymers can self-assemble to form nano-sized vehicles, such as micelles, nanoparticles, polymersomes, in aqueous or non-aqueous media. This review describes the synthesis, formation, and major applications of amphiphilic block copolymer and corresponding vehicles in order to provide an overview of the current features of functionalized block copolymers for drug delivery applications.