Effect of chain conformational change on micelle structures: experimental studies and molecular dynamics simulations

The effect of chain conformation change on the self-assembly behavior of poly(gamma-benzyl- l-glutamate)-block-poly(ethylene glycol) (PBLG-b-PEG) was studied both experimentally by transmission electron microscopy, laser light scattering, and circular dichroism and computationally using molecular dynamics (MD) simulation. It was found that, by introducing trifluoroacetic acid to the PBLG-b-PEG solution, the conformation of the PBLG chain transforms from alpha-helix to random coil, which results in a change of the micelle structures formed by PBLG-b-PEG from rod to sphere. Meanwhile, the MD simulations were performed by using Brownian dynamics on the self-assembly behavior of model AB-type diblock copolymers with various chain rigidities of the A-block. The results show that, by decreasing the fraction of rigid chain conformation of the A-block, which corresponds to the helix-coil transition in the PBLG-b-PEG sample, the aggregate structure transforms from rod to sphere. The MD simulations also provide chain packing information in the micelles. On the basis of both experimental and MD simulation results, the mechanism regarding the effect of the conformation change of the polypeptide block copolymer on its self-association behavior is suggested.     

Dissipative particle dynamics simulation of gold nanoparticles stabilization by PEO–PPO–PEO block copolymer micelles

Dissipative particle dynamics (DPD) was used to simulate the formation and stabilization of gold nanoparticles in poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (PEO–PPO–PEO) block copolymer micelles. Primary gold clusters that were experimentally observed in the early stage of gold nanoparticle formation were modeled as gold bead in DPD simulation. It showed that gold beads were wrapped by the block copolymer and aggregated into spherical particles inside the micelles and forming stable Pluronic–gold colloids with two-layer structures. Increasing Pluronic concentration, molecular weight, and PPO block length led to the formation of more uniform and more stable gold nanoparticles. Density profiles of water beads suggested that the micelles, especially the hydrophobicity of the micellar cores, played an important role in stabilizing gold nanoparticles. Dynamic process indicated that the formation of gold nanoparticles was controlled by the competition between aggregation of primary gold clusters and the stabilization by micelles of block copolymers.. The DPD simulation results of gold–copolymer–water system agree well with previous experiments, while more structure information on microscopic level could be provided.     

杂臂星型嵌段共聚物在溶液中自组装形成囊泡结构的计算机模拟

利用耗散粒子动力学模拟方法, 研究了杂臂星型嵌段共聚物A_m(B_n)₂在溶液中自组装形成囊泡的行为. 主要分析了自组装过程、亲水分枝和疏水分枝的长度及分子构型对组装结构的影响. 结果表明, 杂臂星型聚合物在溶液中会自组装形成碟状胶束, 之后弯曲闭合形成囊泡. 当亲水部分的分枝较短时, 易于形成囊泡结构; 在可形成囊泡结构的条件下, 双分子层囊泡膜的厚度随分枝长度的增加而增加. 与构成相近的线型嵌段共聚物相比, 杂臂星型嵌段共聚物更易形成囊泡结构, 且形成的囊泡结构较薄.     

Mesoscopic simulations on the aggregation behavior of pH-responsive polymeric micelles for drug delivery

Computer simulations, dissipative particle dynamics (DPD) and mesoscopic dynamics (MesoDyn), are performed to study the aggregation behavior of pH-sensitive micelles self-assembled from amphiphilic polymer poly(methyl methacrylate-co-methacrylic acid)-b-poly(poly-(ethylene glycol) methyl ether monomethacrylate), P(MMA-co-MAA)-b-PPEGMA. Ibuprofen (IBU) is selected as the model drug. It can be seen from DPD simulations that P(MMA-co-MAA)-b-PPEGMA and IBU form spherical core-shell micelles at certain compositions, and IBU molecules distribute inside the core formed by hydrophobic MMA. The polymer molecules aggregate first, and then IBU diffuses into the aggregate, forming drug-loaded nanoparticles. With different compositions of polymer and IBU, aggregate morphologies in water are observed as sphere, column and lamella. From MesoDyn results, with less hydrophobic MMA beads, the polymer chains are more difficult to form ordered aggregates, and the order parameters get equilibrated in a longer time. The pH value also affects the aggregate process. At pH<5, the polymer could form traditional core-shell micelles. But at pH>5, the morphology of micelles is found to be anomalous and loose for releasing drug. MAA aggregates on the surface, instead of the inside. The simulation results are qualitatively consistent with the experimental results.     

Noncovalent triblock copolymers based on a coiled-coil peptide motif

The formation of a noncovalent triblock copolymer based on a coiled-coil peptide motif is demonstrated in solution. A specific peptide pair (E and K) able to assemble into heterocoiled coils was chosen as the middle block of the polymer and conjugated to poly(ethylene glycol) (PEG) and polystyrene (PS) as the outer blocks. Mixing equimolar amounts of the polymer-peptide block copolymers PS-E and K-PEG resulted in the formation of coiled-coil complexes between the peptides and subsequently in the formation of the amphiphilic triblock copolymer PS-E/K-PEG. Aqueous self-assembly of the separate peptides (E and K), the block copolymers (PS-E and K-PEG), and equimolar mixtures thereof was studied by circular dichroism, dynamic light scattering, and cryogenic transmission electron microscopy. It was found that the noncovalent PS-E/K-PEG copolymer assembled into rodlike micelles, while in all other cases, spherical micelles were observed. Temperature-dependent studies revealed the reversible nature of the coiled-coil complex and the influence of this on the morphology of the aggregate. A possible mechanism for these transitions based on the interfacial free energy and the free energy of the hydrophobic blocks is discussed. The self-assembly of the polymer-peptide conjugates is compared to that of polystyrene-b-poly(ethylene glycol), emphasizing the importance of the coiled-coil peptide block in determining micellar structure and dynamic behavior.     

Self-assembling Behavior of Amphiphilic Copolymer Containing Cross-linked Hydrophilic Block in Ethanol

IntroductionIt is well known that amphiphilic block copolymerscan self-assemble in block-selective solvent to formcore-shell micelle or colloidal size aggregates[1—5].Usually the micelle are preparedviatraditional dialysismethod[6—8]. Besides micellizat…     

Poorly water-soluble drug nanoparticles via an emulsion-freeze-drying approach

In this paper, we examine, by dissipative particle dynamics (DPD) simulation, the interactions between nanoparticles and block copolymer bilayer membranes. The bilayer has a hydrophobic core and hydrophilic head groups on both sides of the core. Nanoparticles without or with a grafted homopolymer are considered. For the conditions investigated, the single nanoparticles and small aggregates are located at the interfaces of the membrane, namely the interfaces between the hydrophilic domains of the membrane and the solvent as well as at the interface between the hydrophobic and hydrophilic domains of the membrane. The large aggregates are located in the hydrophilic domains. By increasing the length of the homopolymer grafted on the nanoparticles, the size of the aggregates in the membrane decreases. At relatively short DPD step times, the particles aggregate in the solvent. As the time increases, the single particles and aggregates penetrate into the membrane.     

聚肽接枝共聚物的自组装行为研究

Polymeric micelles of poly(γ-benzyl L-glutamate)(PBLG)-poly(ethylene oxide)(PEO) graft copolymer were prepared by the dialysis method in deionized water. Fluorescence spectroscopy, nuclear magnetic resonance(NMR) and transmission electron microscope(TEM) were used for the investigation of the self-assembly of PBLG-PEO graft copolymer. Fluorescence spectrosco0y measurements suggest that PBLG-PEO graft copolymer associates to form polymeric micelles in water. ^1H NMR measurements further prove that in aqueous medium PBLG-PEO graft copolymer could assemble into polymeric micelles with PBLG segments as the hydrophobic inner core and PEO segments as the hydrophilic shell. The results of the TEM observations show that the polymeric micelles of PBLG-PEO graft copolymer are almost spindly shaped, which are different from the morphology of the spherical micelles formed by PBLG-PEO block copolymer. Polymeric micelles formed by polypeptide copolymer have potential application as drug carrier in controlled-release delivery system.     

Redox-mediated synthesis and encapsulation of inorganic nanoparticles in shell-cross-linked cylindrical polyferrocenylsilane block copolymer micelles

Detailed studies of a new approach to the synthesis and encapsulation of silver and silver halide nanoparticles inside shell-cross-linked cylindrical block copolymer polyisoprene-block-polyferrocenyldimethylsilane (PI-b-PFS) micelles (1) through in situ redox reactions are reported. The cylindrical nanostructures 1 were prepared by the solution self-assembly of the PI-b-PFS diblock copolymer in the PI-selective solvent hexane followed by Pt(0)-catalyzed PI shell-cross-linking hydrosilylation reactions. The partial preoxidation of the swollen PFS core using tris(4-bromophenyl)aminium hexachloroantimonate [p-BrC6H4)3N][SbCl6] (2, Magic Blue) followed by redox reaction between the remaining Fe(II) centers in the PFS core and Ag(+) cations led to the formation of silver nanoparticles. High-resolution scanning transmission electron microscopy images of the resulting peapod structures provided a clear indication that the nanoparticles were encapsulated inside the micelles. The composition of the nanoparticles was analyzed by energy-dispersive X-ray spectroscopy (EDX). By combining the evolution of the UV-vis spectra of the reaction mixture and EDX measurements, we surprisingly found that silver halide seed particles were formed through a precipitation reaction at an early stage of the encapsulation process. The size of the silver nanoparticles varied with different amounts of silver ions added to the micelle solution. When I2 was used as the preoxidant, AgI nanoparticles were formed and encapsulated inside the cylinders through the precipitation reaction between iodide anions and silver ions. The packing density of the resulting AgI nanoparticles was increased by an iterative addition method, which utilizes the reversible redox properties of PFS. The small encapsulated AgI nanoparticles were also shown to serve as seeds for the formation of larger Ag nanoparticles when a silver salt was subsequently added.     

Facile synthesis of core‐surface crosslinked nanoparticles by interblock RAFT polymerization

A new, efficient method for synthesizing stable nanoparticles with poly(ethylene oxide) (PEO) functionalities on the core surface, in which the micellization and crosslinking reactions occur in one pot, has been developed. First, amphiphilic PEO‐b‐PS copolymers were synthesized by reversible addition fragmentation chain transfer (RAFT) radical polymerization of styrene using (PEO)‐based trithiocarbonate as a macro‐RAFT agent. The low molecular weight PEO‐b‐PS copolymer was dissolved in isopropyl alcohol where the block copolymer self‐assembled as core‐shell micelles, and then the core‐shell interface crosslink was performed using divinylbenzene as a crosslinking agent and 2,2′‐azobisisobutyronitrile as an initiator. The design of the amphiphilic RAFT agent is critical for the successful preparation of core‐shell interface crosslinked micellar nanoparticles, because of RAFT functional groups interconnect PEO and polystyrene blocks. The PEO functionality of the nanoparticles surface was confirmed by ¹H NMR and FTIR. The size and morphology of the nanoparticles was confirmed by scanning electron microscopy, transmission electron microscopy, and dynamic laser light scattering analysis. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Morphologies of multicompartment micelles formed by ABC miktoarm star terpolymers

Several new multicompartment micellar structures have been identified by cryogenic transmission electron microscopy (cryoTEM) from the aqueous self-assembly of mu-[poly(ethylethylene)][poly(ethylene oxide)][poly(perfluoropropylene oxide)] (mu-EOF) miktoarm star terpolymers. This work extends our previous studies, in which it was found that, upon decreasing the length of the hydrophilic block (O), the resulting micelles evolved from "hamburger" micelles to segmented worms and ultimately to nanostructured bilayers and vesicles. In the terpolymers examined here segmented ribbons and bilayers were found at an intermediate composition between segmented worms and nanostructured bilayers, provided that the fluoropolymer (F) was the minority component in the micelle core. On the other hand, when the F block exceeded the chain length of the hydrocarbon block (E), the superhydrophobic F block imposed a "double frustration" on the self-assembly of the mu-EOF(2-9-5) terpolymer; while F prefers to minimize its interfacial contact with the O corona, it must occupy the majority of the micellar core. Therefore, a richer variety of multicompartment micelles, including well-defined segmented worms, raspberry-like micelles, and multicompartmentalized worms, were formed from one terpolymer, as revealed by cryoTEM. Despite the complexity and variety of the observed aggregate morphologies, a small number of common structural elements can be invoked to interpret the observed micelles and to relate a given structure to the terpolymer composition.     

Dissipative particle dynamics simulation on a ternary system with nanoparticles, double-hydrophilic block copolymers, and solvent

Dissipative particle dynamics (DPD) simulations are performed to study the aggregation of hydrophobic nanoparticles in the presence of double-hydrophilic block copolymer (DHBC). A single compact spherical nanoparticle aggregate is formed in the absence of DHBC. The response of the aggregate to a continuous increase in the concentration of DHBC has been investigated in detail. We observe the evolvement from single spherical aggregate, through single ellipsoidal aggregate, single platelike aggregate, single long and curly rod, dispersed aggregates, then to hexagonally packed cylinders, and ultimately to ordered lamellar structures upon slow addition of DHBC chains. However, when nanoparticles and DHBCs are added into the system simultaneously at the beginning of simulation, we only obtain single spherical aggregate, dispersed aggregates, hexagonally packed cylinders, and ordered lamellar structures at different concentrations of DHBC. Phase diagrams of structures against concentration of DHBC are presented for these two methods, and the stabilities of structures obtained with the two methods are compared.     

Self‐assembled complexes of poly(acrylic acid) and poly(styrene)‐block‐poly(4‐vinyl pyridine)

Polymer complexes were prepared from high molecular weight poly(acrylic acid) (PAA) and poly(styrene)‐block‐poly(4‐vinyl pyridine) (PS‐b‐P4VP) in dimethyl formamide (DMF). The hydrogen bonding interactions, phase behavior, and morphology of the complexes were investigated using Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), dynamic light scattering (DLS), atomic force microscopy (AFM), and transmission electron microscopy (TEM). In this A‐b‐B/C type block copolymer/homopolymer system, P4VP block of the block copolymer has strong intermolecular interaction with PAA which led to the formation of nanostructured micelles at various PAA concentrations. The pure PS‐b‐P4VP block copolymer showed a cylindrical rodlike morphology. Spherical micelles were observed in the complexes and the size of the micelles increased with increasing PAA concentration. The micelles are composed of hydrogen‐bonded PAA/P4VP core and non‐bonded PS corona. Finally, a model was proposed to explain the microphase morphology of complex based on the experimental results obtained. The selective swelling of the PS‐b‐P4VP block copolymer by PAA resulted in the formation of different micelles. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 1192–1202, 2009     

Hierarchical mesostructures of biodegradable triblock copolymers via evaporation-induced self-assembly directed by alkali metal ions

Hierarchical mesostructures of poly(ε-caprolactone)-b-poly(ethylene oxide)-b-poly(ε-caprolactone) (PCL-PEO-PCL) triblock copolymers have been grown from evaporation-induced self-assembly directed by alkali metal ions. The self-assembly process began with a dilute homogeneous solution of the triblock copolymers in a mixture of tetrahydrofuran (THF) and water. THF preferentially evaporated under reduced pressure and induced the formation of amphiphilic polymer micelles. The spherical polymer micelles formed both in deionized water and NaOH aqueous solution. However, different mesostructures were discovered during the film depositing process for scanning electron microscopy observation. The polymer micelles were observed for the deposition sample in deionized water while sisal-like hierarchical mesostructures resulted from the film deposition of polymer micelles in NaOH aqueous solution. The sisal-like mesostructures and their formation process were observed through scanning electron microscopy, transmission electron microscopy, fluorescent microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. Detailed study revealed that during evaporation-induced self-assembly of PCL-PEO-PCL amphiphilic triblock copolymer directed by alkali metal ions, the sodium ions and polymer micelles increasingly concentrated in NaOH aqueous solution and the solvent quality for the diblock progressively decreased, which resulted in the stronger coordination between alkali metal ions and PEO ligands in the block copolymer and PEO segment crystallization.     

Supramolecular self-assembly of block copolymer based on rigid surfactant

The supramolecular self-assembling of pyridine-containing amphiphilic block copolymers (PS-b- P4VP and PS-PI-P2VP) and 4-biphenylcarboxylic acid (BPCA) in selective solvents has been systematically studied. BPCA molecules are able to complex with the vinylpyridine (VP) moieties through hydrogen bonding, which leads to a transformation of spherical block copolymer micelles into structured nanofibers in solutions. The effects of molar ratio of BPCA to the VP repeat units, solvent selectivity, and copolymer composition on the supramolecular complex nanofiber formation have been systematically investigated by atomic force microscopy (AFM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The formation mechanism of supramolecular self-assembly nanofibers was discussed.     

Self-assembly behavior of pH- and thermosensitive amphiphilic triblock copolymers in solution: experimental studies and self-consistent field theory simulations

We investigated, both experimentally and theoretically, the self-assembly behaviors of pH- and thermosensitive poly(L-glutamic acid)- b-poly(propylene oxide)-b-poly(L-glutamic acid) (PLGA-b-PPO-b-PLGA) triblock copolymers in aqueous solution by means of transmission electron microscopy (TEM), scanning electron microscopy (SEM), dynamic light scattering (DLS), circular dichroism (CD), and self-consistent field theory (SCFT) simulations. Vesicles were observed when the hydrophilic PLGA block length is shorter or the pH value of solution is lower. The vesicles were found to transform to spherical micelles when the PLGA block length increases or its conformation changes from helix to coil with increasing the pH value. In addition, increasing temperature gives rise to a decrease in the size of aggregates, which is related to the dehydration of the PPO segments at higher temperatures. The SCFT simulation results show that the vesicles transform to the spherical micelles with increasing the fraction or statistical length of A block in model ABA triblock copolymer, which corresponds to the increase in the PLGA length or its conformation change from helix to coil in experiments, respectively. The SCFT calculations also provide chain distribution information in the aggregates. On the basis of both experimental and SCFT results, the mechanism of the structure change of the PLGA- b-PPO- b-PLGA aggregates was proposed.     

Application of solid phase peptide synthesis to engineering PEO–peptide block copolymers for drug delivery

This work describes a simple, versatile solid-phase peptide-synthesis (SPPS) method for preparing micelle-forming poly(ethylene oxide)-block-peptide block copolymers for drug delivery. To demonstrate its utility, this SPPS method was used to construct two series of micelle-forming block copolymers (one of constant core-composition and variable length; the other of constant core length and variable composition). The block copolymers were then used to study in detail the effect of size and composition on micellization. The various block copolymers were prepared by a combination of SPPS for the peptide block, followed by solution–phase conjugation of the peptide block with a proprionic acid derivative of poly(ethylene oxide) (PEO) to form the PEO-b-peptide block copolymer. The composition of each block component was characterized by mass spectrometry (MALDI and ES-MS). Block copolymer compositions were characterized by ¹H NMR. All the block copolymers were found to form micelles as judged by transmission electron microscopy (TEM) and light scattering analysis. To demonstrate their potential as drug delivery systems, micelles prepared from one member of the PEO-b-peptide block copolymer series were physically loaded with the anticancer drug doxorubicin (DOX). Micelle static and dynamic stability were found to correlate strongly with micelle core length. In contrast, these same micellization properties appear to be a complex function of core composition, and no clear trends could be identified from among the set of compositionally varying, fixed length block copolymer micelles. We conclude that SPPS can be used to construct biocompatible block copolymers with well-defined core lengths and compositions, which in turn can be used to study and to tailor the behavior of block copolymer micelles.     

SELF-ASSEMBLY OF ROD-COIL DIBLOCK COPOLYMERS——INFLUENCE OF THE ROD LENGTH

The self-assembly of five narrowly distributed novel rod-coil diblock copolymers, poly(styrene-block-(2, 5-bis[4-methoxy-phenyl]oxycarbonyl) styrene) (PS-b-PMPCS), in p-xylene, a selective solvent at room temperature, was studied. Therod-coil copolymers, which have the same PS length but different PMPCS length, were synthesized by 2,2,6,6-tetramethyl-I-piperidinyloxy (TEMPO) mediated living free radical polymerization. The influence of the rod length on the self-assemblymorphology was studied by transmission electron microscopy (TEM). At a concentration of 2.0 mg/mL, those copolymerswith relatively shorter PMPCS length (copolymers 1 and 2) form individual spherical micelles; those with relatively longerPMPCS length (copolymer 3 and 4) form "pearl chains" coexisting with individual spherical micelles; the ones with longestPMPCS length form "pearl chains" coexisting with occasionally formed nanofibers. The diameter of all the morphologieswas controlled by the rod length. This gives us a way to govern the self-assembly morphology by altering the length of oneblock in the block copolymer.     

Nanotubes from the self-assembly of asymmetric crystalline-coil poly(ferrocenylsilane-siloxane) block copolymers

Block copolymers with a high asymmetry normally give spherical starlike micelles in a solvent selective for the longer block. We have discovered that samples of poly(ferrocenyldimethylsilane-b-dimethylsiloxane) (PFS-b-PDMS) with block ratios of 1:12 form nanotubes in n-hexane and n-decane, which are poor solvents for PFS. Two block copolymer samples PFS(40)-b-PDMS(480) (M(n) = 45 300, PDI = 1.01) and PFS(80)-b-PDMS(960) (M(n) = 90 500, PDI = 1.01) were synthesized by sequential anionic polymerization. When self-assembly occurs, the PFS blocks aggregate and crystallize to form a shell with a cavity in the middle of the tube, while the PDMS blocks form the corona. The nature of these structures was elucidated by conventional transmission electron microscopy and dark-field scanning transmission electron microscopy. Time- and temperature-dependence studies revealed that a variety of morphologies are formed initially depending on the conditions of sample preparation, but most of them eventually rearrange to form nanotubules. The lengths of the tubes can be varied with time and with the choice of solvents. We have been able to grow nanotubes with lengths reaching 0.1 mm. The presence of the hollow core was confirmed by trapping tetrabutyllead in the cavity and performing energy-dispersive X-ray measurements on the resulting structure.     

Dynamic and static light scattering studies on self-aggregation behavior of biodegradable amphiphilic poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene oxide) triblock copolymers in aqueous solution

The self-aggregation behavior of two amphiphilic poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene oxide) (PEO-PHB-PEO) triblock copolymer samples with nearly identical PHB block lengths but different PEO block lengths, PEO-PHB-PEO(2000-810-2000) and PEO-PHB-PEO(5000-780-5000), was studied with dynamic and static light scattering (DLS and SLS), in combination with fluorescence spectroscopy and transmission electron microscopy (TEM). The formation of polymeric micelles by the two PEO-PHB-PEO triblock copolymers was confirmed with fluorescence technique and TEM. DLS analysis showed that the hydrodynamic radius (R(h)) of the monodistributed polymeric micelles increased with an increase in PEO block length. The relative thermostability of the triblock copolymer micelles was studied by SLS and DLS at different temperatures. The aggregation number and the ratio of the radius of gyration over hydrodynamic radius were found to be independent of temperature, probably due to the strong hydrophobicity of the PHB block. The combination of DLS and SLS studies indicated that the polymeric micelles were composed of a densely packed core of hydrophobic PHB blocks and a corona shell formed by hydrophilic PEO blocks. The aggregation numbers were found to be approximately 53 for PEO-PHB-PEO(2000-810-2000) micelles and approximately 37 for PEO-PHB-PEO(5000-780-5000) micelles. The morphology of PEO-PHB-PEO spherical micelles determined by DLS and SLS measurements was further confirmed by TEM.