Self-assembly of amphiphilic liquid crystal block copolymers containing a cholesteryl mesogen: Effects of block ratio and solvent

We report on the self-assembly, in water and in bulk, of amphiphilic liquid crystal block copolymers consisting of a cholesterol-based smectic LC polymer block (PAChol) and poly(ethylene glycol) (PEG) block. Two series of block copolymers, PEG₄₅-b-PAChol and PEG₁₁₄-b-PAChol (45 and 114 are the degree of polymerization of PEG blocks) with different hydrophilic/hydrophobic weight ratios were synthesized and characterized in detail. Depending on the diblock composition, smectic polymer vesicles and/or nanofibers were formed by adding water into a dilute solution of copolymers in dioxane. If THF is used instead of dioxane as solvent, solid spherical aggregates were obtained upon water addition for PEG₄₅-b-PAChol series, while macroscopic precipitation occurred for PEG₁₁₄-b-PAChol series. The mesomorphic and microphase segregation structures of the block copolymers in bulk were studied by X-ray scattering, DSC and POM. The interdigital smectic A (SmA_d) phase with a lamellar period of 4.25 nm was detected in all block copolymers. For PEG₁₁₄-b-PAChol₅ (PEG/PAChol weight ratio = 66/34) and PEG₁₁₄-b-PAChol₁₂ (45/55), lamellar type of microphase segregation was observed.     

Self-assembling of star-like amphiphilic block copolymers with polyelectrolyte blocks. Effect of pH

The self-assembling behaviour of a four-arm amphiphilic star block copolymer, (PMMA₇₃-b-PAA₁₄₃)₄, with poly(methyl methacrylate) inner blocks and poly(acrylic acid) outer blocks in ratio 1:2 (PMMA:PAA) has been investigated in aqueous solutions as a function of pH by dynamic light scattering and cryo-transmission electron microscopy. At low pH (pH ≤ 5) the amphiphile forms in the presence of salt both spherical and worm-like micellar aggregates that coexist in solution. At high pH (pH > 12) the solution contains mainly spherical micelles and a small number of larger aggregates that have ‘pearl-necklace’ structure, indicating the disintegration of the worm-like species. In addition to the experiments, computer simulations of the four-arm amphiphilic star block copolymer with the same ratio of the blocks as above were conducted using a coarse-grained model. The simulations predict the formation of the worm-like micellar aggregates at low pH and the spherical ones at high pH. The changes in the morphology of the aggregates are related to the higher degree of ionization of poly(acrylic acid) blocks at high pH and to the swelling of the corona of the micelles by the higher osmotic pressure due to trapped counterions.     

Amphiphilic star block copolymers: Influence of branching on lyotropic/interfacial properties

How can the degree of branching influence the lyotropic properties of amphiphilic block copolymers? In order to provide a qualitative answer to this question, we have prepared a library of poly(propylene sulfide)-bl-poly(ethylene glycol) (PPS-PEG) block copolymers, varying the hydrophobic block (PPS) length and its branching degree and thus producing diblock, triblock (that can be seen as two-armed star), tri-armed star and tetra-armed star structures. The PEG block, on the contrary, was kept constant (linear PEG2000).Although all the polymers exhibited a qualitatively similar lyotropic behaviour, an increased degree of branching of the hydrophobic block caused clear differences in the rheology of lyotropic phases, with an increasingly softer character, and in the organisation of the PEG chains, which appeared to adopt possibly more extended and dehydrated conformations.     

Synthesis and self-association in aqueous media of poly(ethylene oxide)/poly(ethyl glycidyl carbamate) amphiphilic block copolymers

New temperature sensitive AB, ABA, and BAB amphiphilic block copolymers consisting of hydrophilic poly(ethylene oxide) and hydrophobic poly(ethyl glycidyl carbamate) blocks were synthesized by anionic polymerization followed by chemical modification reactions. The self-association of the block copolymers in aqueous media was studied by UV-vis spectroscopy and dynamic and static light scattering. The obtained block copolymers spontaneously form micelles in aqueous media. The critical micellization concentration varied from 0.5 to 4 g/L depending on the copolymer architecture and composition. The influence of the temperature upon the self-association of the block copolymers was investigated. The increase of temperature did not affect the value of the critical micellization concentration, but led to the formation of better defined micelles with narrow size distribution.     

Self-assemblies formed by four-arm star copolymers with amphiphilic diblock arms in aqueous solutions

The self-assembly of two star copolymers, each consisting of four diblock arms of either poly(?-caprolactone)-block-poly(ethylene oxide), PCL-PEO, or polylactide-block-poly(ethylene oxide), PLA-PEO, with PEO blocks in the centers of the stars, have been studied by a combination of light scattering, atomic force microscopy, fluorometry and ¹H NMR spectroscopy. Results of the study show that despite the very similar architecture of both star copolymers, the structures of their self-assembled nanoparticles differ. Unlike the (PLA-PEO)₄ star copolymer which forms core/shell flower-like micelles, the association of the (PCL-PEO)₄ copolymer leads to large micellar aggregates in which individual micelles are interconnected by shared unimers, having joint coronas formed by hydrophilic centers of the stars.     

Preparation and evaluation of novel amphiphilic glycopeptide block copolymers as carriers for controlled drug release

In the present study we describe a synthesis and self-assembly and an in vitro evaluation of a kind of novel amphiphilic glycopeptide block copolymers as carriers for controlled drug release. Initially, an amphiphilic ABA triblock copolymer comprising polytetrahydrofuran (PTHF) as a central hydrophobic block flanked by poly(l-lysine)s (PLLs) as outer hydrophilic blocks was synthesized through the ring-opening polymerization of ?-benzyloxycarbonyl-l-lysine N-carboxyanhydride with a distal amine-terminated PTHF as a macroinitiator, followed by removal of the protecting group. Afterwards the resulting triblock copolymer was allowed to react with d-gluconolactone and lactobionolactone in the varying feeding ratios in the presence of diisopropylethylamine leading to the target glycopeptide block copolymers with high yields. They were found to easily self-assemble into nano-sized aggregates in water. The critical aggregation concentrations (CACs) were assessed by fluorescence measurement with N-phenyl-1-naphthylamine employed as a molecular probe. The particle sizes of the aggregates before and after doxorubicin loading were determined by dynamic light scattering (DLS) and the aggregate morphologies were evidenced by transmission electron microscopy (TEM) measurements. Finally, the in vitro doxorubicin loading capacity and release behavior were investigated with these glycopeptide copolymers as carriers for controlled release.     

两亲嵌段共聚物的合成及其自组装研究进展

作者介绍了两亲嵌段共聚物的活性阴离子聚合、基团转移聚合、开环歧化聚合、活性阳离子聚合、活性／可控自由基聚合、缩聚法、嵌段共聚物化学改性法等合成方法,并对其自组装形成聚合物纳米胶束的制备方法、形成机理以及在药物控制释放领域的应用进行了综述,并对其未来发展趋势进行了展望。     

pH- and temperature-responsive amphiphilic diblock copolymers of 4-vinylpyridine and oligoethyleneglycol methacrylate synthesized by RAFT polymerization

Diblock copolymers of 4-vinylpyridine (4VP) and oligoethyleneglycol methyl ether methacrylate (OEGMA) were synthesized for the first time using RAFT polymerization technique as potential drug delivery systems. Effects of the number of ethylene glycol units in OEGMA, chain length of hydrophobic P4VP block, pH, concentration and temperature on the solution behavior of the copolymers were investigated comprehensively. Copolymer chains formed micelles at pH values higher than 5 whereas unimeric polymers were observed to exist below pH 5, owing to the repulsion between positively charged P4VP blocks. The size of the micelles was dependent on the relative length of blocks, P4VP and POEGMA. Thermo-responsive properties of copolymers were investigated depending on the pH and length of P4VP block. The increase in the length of P4VP block decreased the LCST substantially at pH 7. At pH 3, LCST of copolymers shifted to higher temperatures due to the increased interaction of copolymers with water through positively charged P4VP block.     

Multiple morphologies of self-assembled star aggregates of amphiphilic PEO-b-PNPMA diblock copolymers in solution, synthesis and micellization

Novel amphiphilic block copolymers, poly(ethylene oxide)-b-poly(p-nitrophenyl methacrylate) (PEO-b-PNPMA) with controlled molecular weights and narrow molecular weight distribution were successively synthesized by ATRP of NPMA using PEO-Br as initiator. Self-assembling of the diblock copolymer PEO₁₁₃-b-PNPMA₂₈ in the different solvent mixtures yielded various morphologies of star micelle-like aggregates, such as spheres, vesicles, cauliflower-like aggregates and rod-like aggregates, which are determined by the nature of the common solvents and the selective solvents. Thus the critical selective solvent contents and the solvent contents in PNPMA-rich phase were measured, and they have the following order: ethanol > methanol > water, and THF > CH₃NO₂ > DMSO. The probable self-assembling mechanism is discussed. This method is convenient for preparation of multiple morphological star micelle-like aggregates in solution, especially from the amphiphilic block copolymers with relatively longer block shell.     

Honeycomb structured porous films from amphiphilic block copolymers prepared via RAFT polymerization

The synthesis of polystyrene-block-poly(N,N-dimethylacrylamide) (PS-b-PDMA) via RAFT polymerization was investigated in detail. Two different RAFT agents - benzyl dithiobenzoate and 3-(benzylsulfanylthiocarbonylsufanyl) propionic acid, were employed to prepare polystyrene macroRAFT agents with molecular weights varying between 3000 g mol⁻¹ and 62,000 g mol⁻¹ and polydispersities between 1.1 and 1.4. Chain extensions with N,N-dimethylacrylamide (DMA) were carried out using a constant monomer to RAFT agent concentration ([DMA]/[RAFT] = 500), to compare the rate of polymerization in dependency of the polystyrene chain length. A decreasing rate of polymerization with increasing block length was observed. Depending on the sizes of the first block and type of RAFT agents used, chain extension polymerization with DMA was found to be incomplete, leading to significant low molecular weight tailing in the GPC analyses. Block copolymers prepared using 3-(benzylsulfanylthiocarbonylsufanyl) propionic acid, followed the expected molecular weight evolutions with polydispersity indices of 1.2-1.4. In contrast, block copolymers using benzyl dithiobenzoate clearly showed bimodal molecular weight distributions, especially when the longest PS macroRAFT agent with a molecular weight of 38,000 g mol⁻¹ was employed. These amphiphilic block copolymers were used to fabricate honeycomb structured porous films using the breath figure technique. The regularity of the film was considerably influenced by the humidity of the environment, which could be controlled by the rate of the airflow or the humidity in the casting chamber. The interaction between the hydrophilic block copolymer and the humidity was found responsible for the delicate equilibrium during the casting process, which prevented high pores regularity at very low (below 50%) and at elevated (above 80%) humidity. The interactions of the hydrophilic block with the humidity were observed to superimpose an additional nano-scaled order onto the hexagonal micron-sized porous array. Pores, which are created by encapsulation of water droplets, were found to be more hydrophilic than the surface. Confocal microscopy studies were employed to locate hydrophilic blocks within the film using a fluorescence labeled PDMA polymer.     

Synthesis and properties of amphiphilic star block copolymers with star macroinitiators based on a one‐pot approach

Previously, star polystyrenes (PSs) have been prepared by atom transfer radical polymerization (ATRP) of N‐[2‐(2‐bromoisobutyryloxy)ethyl]maleimide (BiBEMI) with a large excess of styrene (St) in one pot. But linear PSs were also present during the formation of the star polymers. In the work reported here, we found that control of the formation of star polymers using a one‐pot approach can be improved by using a two‐step process. The polymerization was conducted first at a low temperature to form multifunctional cores by copolymerization of BiBEMI and St. Second, on increasing the temperature, homopolymerization of St occurred to grow PS arms. Then a series of amphiphilic star polystyrene‐block‐poly(acrylic acid)s, (S₁₄A_x)₁₆, were prepared by ATRP of tert‐butyl acrylate with the star PSs as macroinitiators, followed by selective acidolysis of the poly(tert‐butyl acrylate) blocks. Their micellization was studied using dynamic light scattering, which suggested that (S₁₄A₁₁₂)₁₆ amphiphilic star block copolymers could form unimolecular micelles in a basic aqueous solution. Then pyrene molecules were encapsulated using the (S₁₄A₁₁₂)₁₆ amphiphilic star copolymers and the loading capacity was investigated with UV and fluorescence spectroscopy. © 2013 Society of Chemical Industry     

Synthesis and characterization of biodegradable and biocompatible amphiphilic block copolymers bearing pendant amino acid residues

Polylactide (PLA)-based biodegradable and biocompatible amphiphilic block copolymers bearing pendant amino acid residues were synthesized through a relatively easy and efficient way. The composition and structure of these copolymers were characterized by gel permeation chromatography (GPC) and ¹H nuclear magnetic resonance (¹H NMR) spectroscopy. The self-assembly behavior of the copolymers was investigated by fluorescence (FL), dynamic light scattering (DLS), and transmission electron microscope (TEM). It was shown that aggregates less than 100 nm in average size were formed by these copolymers, which changed from micelles to vesicles with the variation of the block length. In addition, the in vitro cytotoxicity of these copolymers was determined and compared with that of PEO-b-PLA in the presence of Bel-7402 cells. The result suggested that the block copolymers PAGE/cys-b-PLA exhibited better biocompatibility. Therefore, these PLA-based copolymers are expected to find promising applications in drug delivery or tissue engineering.     

Poly(N-tert-butyl acrylamide-b-N-acryloylmorpholine) amphiphilic block copolymers via RAFT polymerization: Synthesis, purification and characterization

Amphiphilic block copolymers consisting of two poly(acrylamide) derivative blocks have been synthesized via the reversible addition fragmentation chain transfer (RAFT) polymerization process with a hydrophobic block, poly(N-tert-butyl acrylamide), poly(TBAm), and a non-ionic hydrophilic one, poly(N-acryloylmorpholine), poly(NAM). Both polymerization orders, poly(TBAm-b-NAM) and poly(NAM-b-TBAm), were compared in terms of conversion and control over molecular weights (MW). Purification of the block copolymers was carried out via several methods in order to optimize their subsequent characterization. ¹H NMR analysis resulted in an accurate determination of the second block MW whereas determination of the CMC by the pendant drop method confirmed the ability of the poly(TBAm-b-NAM) block copolymers to self-assemble into micelles in aqueous phase.     

Adsorption of block copolymers at latex surface and their utilization in emulsion polymerization

Amphiphilic block copolymers have been investigated for their utilization in emulsion polymerization of butyl methacrylate. Special attention has been paid to the adsorption mechanism of the block copolymers from systematic measurements of equilibrium adsorption isotherms. A series of well-defined water-soluble amphiphilic block copolymers, composed of poly(butyl methacrylate) and poly(sodium methacrylate) blocks, were synthesized by anionic polymerization of butyl methacrylate and tert-butyl methacrylate followed by the thermal deprotection of the tert-butyl ester groups and final hydrolysis. The number density of emulsion polymer particles N_P varied as [copolymer]^α, α lying between 0.44 and 0.73 according to the hydrophilic content of the copolymers. In contrast with SDS taken as a reference emulsifier, the adsorption of the copolymers was very strong and this provided quite an efficient stabilization of the polymer particles during emulsion polymerization, even at low concentrations (<10⁻⁴ mol L⁻¹) and low coverages (<10% of the interfacial area).     

One-step synthesis of poly(2-oxazoline)-based amphiphilic block copolymers using a dual initiator for RAFT polymerization and CROP

A range of poly(2-oxazoline) (POx)-based amphiphilic block copolymers were synthesized using 4-cyano-4-(dodecylthiocarbonothioylthio)pentyl-4-methylbenzenesulfonate (CDPS) as a dual initiator for reversible addition-fragmentation chain transfer (RAFT) polymerization and cationic ring-opening polymerization (CROP) in a one-step procedure. Methyl (meth)acrylate, butyl (meth)acrylate, tert-butyl (meth)acrylate, and N-isopropylacrylamide were polymerized for the hydrophobic block, and 2-methyl-2-oxazoline and 2-ethyl-2-oxazoline were used as the hydrophilic block. RAFT polymerization and CROP proceeded independently in a controlled manner and resulted in amphiphilic block copolymers with a narrow molecular weight distribution. CDPS was found to be a useful dual initiator for the one-step synthesis of POx-based amphiphilic block copolymers via a combination of RAFT polymerization and CROP.     

Synthesis and self-assembly behaviors of three-armed amphiphilic block copolymers via RAFT polymerization

The novel trifunctional reversible addition-fragmentation chain transfer (RAFT) agent, tris(1-phenylethyl) 1,3,5-triazine-2,4,6-triyl trithiocarbonate (TTA), was synthesized and used to prepare the three-armed polystyrene (PS₃) via RAFT polymerization of styrene (St) in bulk with thermal initiation. The polymerization kinetic plot was first order and the molecular weights of polymers increased with the monomer conversions with narrow molecular weight distributions (M_w/M_n ≤ 1.23). The number of arms of the star PS was analyzed by gel permeation chromatography (GPC), ultraviolet visible (UV-vis) and fluorescence spectra. Furthermore, poly(styrene-b-N-isopropylacrylamide)₃ (PS-b-PNIPAAM)₃, the three-armed amphiphilic thermosensitive block copolymer, with controlled molecular weight and well-defined structure was also successfully prepared via RAFT chain extension method using the three-armed PS obtained as the macro-RAFT agent and N-isopropylacrylamide as the second monomer. The copolymers obtained were characterized by GPC and ¹H nuclear magnetic resonance (NMR) spectra. The self-assembly behaviors of the three-armed amphiphilic block copolymers (PS-b-PNIPAAM)₃ in mixed solution (DMF/CH₃OH) were also investigated by high performance particle sizer (HPPS) and transmission electron microscopy (TEM). Interestingly, the lower critical solution temperature (LCST) of aqueous solutions of the three-armed amphiphilic block copolymers (PS-b-PNIPAAM)₃ decreased with the increase of relative length of PS in the block copolymers.     

Characterization of aqueous micellar solutions of amphiphilic block copolymers of poly(acrylic acid) and polystyrene prepared via ATRP. Toward the control of the number of particles in emulsion polymerization

A series of diblock, triblock and star-block copolymers composed of polystyrene and poly(acrylic acid) were synthesized by ATRP. The structure of the copolymers, the size of the blocks and the composition were varied, keeping however a short polystyrene block and a poly(acrylic acid) content larger than 60 mol% to allow solubility in alkaline water. Their micellization was studied by static and dynamic light scattering and the influence of their structural characteristics on the aggregation number, N_agg, was examined at low salt concentration and alkaline pH. It was shown that micelles were in thermodynamic equilibrium and that N_agg followed the power law N_agg∼N_A^−0.9N_S² (with N_A, the total number of acrylic acid units in the copolymer and N_S, the total number of styrene units), that is characteristic of amphiphile micelles formed from strongly segregated block copolymers. Moreover, N_agg was independent of salt concentration in the investigated range. The same copolymers were previously used as stabilizers in emulsion polymerization [Macromolecules 34 (2001) 4439]. The final latex particle concentration, N_p, was compared with N_m, the initial micelle concentration. This enabled us to conclude that among the block copolymers studied, those with high acid content behaved like low molar mass surfactants. In contrast, those with low acid content formed stable micelles that could be directly nucleated to create latex particles, allowing a good control over N_p.     

Preparation of pH-responsive membranes with amphiphilic copolymers by surface segregation method☆

Novel pH-responsive membranes were prepared by blending pH-responsive amphiphilic copolymers with pol-yethersulfone (PES) via a nonsolvent-induced phase separation (NIPS) technique. The amphiphilic copolymers bearing Pluronic F127 and poly(methacrylic acid) (PMAA) segments, abbreviated as PMAAn–F127–PMAAn, were synthesized by free radical polymerization. The physical and chemical properties of the blend membranes were evaluated by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectrum, water con-tact angle, Zeta potential and X-ray photoelectron spectroscopy (XPS). The enrichment of hydrophilic PMAA seg-ments on the membrane surfaces was attributed to surface segregation during the membrane preparation process. The blend membranes had significant pH-responsive properties due to the conformational changes of surface-segregated PMAA segments under different pH values of feed solutions. Fluxes of the blend membranes were larger at low pH values of feed solutions than that at high pH values. The pH-responsive ability of the mem-branes was enhanced with the increase of the degree of PMAA near-surface coverage.     

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.