Miktoarm Star Block Copolymers Research Articles

Discrete Miktoarm Star Block Copolymers with Tailored Molecular Architecture.

Molecular architecture is a critical factor in regulating phase behaviors of the block copolymer and prompting the formation of unconventional nanostructures. This work meticulously designed a library of isomeric miktoarm star polymers with an architectural evolution from the linear-branched block copolymer to the miktoarm star block copolymer and to the star-like block copolymer (i.e., 3AB → 3(AB1)B2 → 3(AB)). All of the polymers have precise chemical composition and uniform chain length, eliminating inherent molecular uncertainties such as chain length distribution or architectural defects. The self-assembly behaviors were systematically studied and compared. Gradually increasing the relative length of the branched B1 block regulates the ratio between the bridge and loop configuration and effectively releases packing frustration in the formation of the spherical or cylindrical structures, leading to a substantial deflection of phase boundaries. Complex structures, such as Frank-Kasper phases, were captured at a surprisingly higher volume fraction. Rationally regulating the molecular architecture offers rich possibilities to tune the packing symmetry of block copolymers.

Synthesis and morphological characterization of linear and miktoarm star poly(solketal methacrylate)-block-polystyrene copolymers

The synthesis, molecular characterization, and morphological evaluation of ABn, (n = 2,3) miktoarm star block copolymers consisting of poly(glycerol monomethacrylate) (PGMA) and polystyrene (PS) with varying molecular weights and compositions is described. The system is known to demonstrate a remarkably high Flory-Huggins interaction parameter. The corresponding linear diblock copolymer analogues, were synthesized as well, and comparisons with regard to feature dimensions and morphologies are provided. Well-ordered nanostructures of various morphologies were formed with domain spacing as low as 7.2 nm. Different morphologies were attained by some of the topological isomers indicating that in miktoarm star block copolymers the phase boundaries were strongly shifted. Additionally, a triblock ABA analogue was studied to investigate the effect of triblock copolymer conformations. Noteworthy is that for copolymers with different macromolecular architecture leading to similar morphology; different domain spacings were obtained. The synthesis of all the samples was carried out by high-vacuum anionic polymerization techniques. Molecular characterization with Size Exclusion Chromatography (SEC) and Proton Nuclear Magnetic Resonance Spectroscopy (1H NMR) confirmed well-defined copolymers obtained. The morphological characterization was accomplished by Small-Angle X-ray Scattering (SAXS). The observations from this study highlight the potential of incorporating macromolecular architecture in the self-assembly of strongly immiscible block copolymers to attain ultra-small nanofeatures with desired morphologies.

Linear and Star Block Copolymer Nanoparticles Prepared by Heterogeneous RAFT Polymerization Using an ω,ω-Heterodifunctional Macro-RAFT Agent.

Herein, an ω,ω-heterodifunctional macromolecular reversible addition-fragmentation chain transfer (macro-RAFT) agent containing two different RAFT end groups was synthesized and employed to mediate aqueous photoinitiated RAFT dispersion polymerization of a methacrylic monomer. Because of the different RAFT controllability of two RAFT end groups toward methacrylic monomers, the RAFT end group with good controllability dominated the polymerization while the other RAFT end group with poor controllability was unreacted, leading to the formation of linear block copolymers. Because of the unique structure of the linear block copolymers, a diverse set of block copolymer nanoparticles with rich RAFT groups at the interface of the hydrophilic corona/the hydrophobic core were successfully prepared. Finally, μ-A(BC)C miktoarm star block copolymer nanoparticles were prepared by RAFT seeded emulsion polymerization of an acrylic monomer, which enables the further morphological control over polymer nanoparticles. We believe that the utilization of an ω,ω-heterodifunctional macro-RAFT agent in heterogeneous RAFT polymerization will offer considerable opportunities for the rational synthesis of well-defined molecular architectures and polymer nanoparticles.

Is the “Bricks-and-Mortar” Mesophase Bicontinuous? Dynamic Simulations of Miktoarm Block Copolymer/Homopolymer Blends

A new mesophase in binary blends of A–b–(BA′)3 miktoarm star block copolymers and A homopolymers has recently been discovered experimentally and explored with field-theoretic simulations. This mesophase has been reported to consist of aperiodic discrete domains of A embedded in a continuous matrix of B up to very high concentrations of A. Because of the material’s potential as a thermoplastic elastomer, a deeper understanding of its structural and dynamic-mechanical properties, including its domain connectivity, linear rheological behavior, response to shear, and response to uniaxial tension, is warranted. These properties are explored here using dissipative particle dynamics in three dimensions, for the first time. These simulations establish that the so-called “bricks-and-mortar” phase, while appearing discrete in two dimensions, is bicontinuous. The simulations focusing on dynamics establish that the role of molecular bridging dominates the mechanical behavior and outweighs the influence of microphase segregation (contributions from the interfacial tension alone) even at the highest homopolymer concentrations we study. Additionally, it appears that the bricks-and-mortar phase is sensitive to the application of sufficiently high shear, leading to nonisotropic mechanical responses, which has ramifications for the processability of such materials. We find that upon application of shear the phase becomes closer in structure to its speculated discrete nature. Molecular simulations on our longest accessible timescales show that the material is unable to relax back to its original structure, suggesting that the morphology observed depends heavily on the material process pathway.

Preparation of Doxorubicin-Loaded Amphiphilic Poly(D,L-Lactide-Co-Glycolide)-b-Poly(N-Acryloylmorpholine) AB2 Miktoarm Star Block Copolymers for Anticancer Drug Delivery.

Owing to their unique topology and physical properties, micelles based on miktoarm amphiphilic star block copolymers play an important role in the biomedical field for drug delivery. Herein, we developed a series of AB2-type poly(D,L-lactide-co-glycolide)-b-poly(N-acryloyl morpholine) (PLGA-b-PNAM2) miktoarm star block copolymers by reversible addition–fragmentation chain–transfer polymerization and ring-opening copolymerization. The resulting miktoarm star polymers were investigated by 1H NMR spectroscopy and gel permeation chromatography. The critical micellar concentration value of the micelles increases with an increase in PNAM block length. As revealed by transmission electron microscopy and dynamic light scattering, the amphiphilic miktoarm star block copolymers can self-assemble to form spherical micellar aggregates in water. The anticancer drug doxorubicin (DOX) was encapsulated by polymeric micelles; the drug-loading efficiency and drug-loading content of the DOX-loaded micelles were 81.7% and 9.1%, respectively. Acidic environments triggered the dissociation of the polymeric micelles, which led to the more release of DOX in pH 6.4 than pH 7.4. The amphiphilic PLGA-b-PNAM2 miktoarm star block copolymers may have broad application as nanocarriers for controlled drug delivery.

Biobased miktoarm star copolymer from soybean oil, isosorbide, and caprolactone

ABSTRACTSoybean oil‐based macroinitiator was prepared from epoxidized soybean oil. A 1H NMR quantitative method was utilized for the characterization of this macroinitiator. A kind of renewable carbohydrate derivate, 1,4: 3,6‐Dianhydro‐D‐glucitol 2‐acrylate 5‐acetate (AAI) was prepared as the substitute monomer of styrene. Series of renewable miktoarm star copolymers initiated by soybean oil macroinitiator were obtained by atom transfer radical polymerization (ATRP) of AAI and ring‐opening polymerization (ROP) of ε‐caprolactone sequentially. The obtained miktoarm star block copolymers were characterized by 1H NMR, FTIR, and DSC. The DSC results show well dependence of the thermal behaviors of these miktoarm star block copolymers on the component of the two kinds of segments. A new strategy of renewable resource utilization has been provided on polymeric materials. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48281.

AB2-type miktoarm poly(l-lactide)-b-poly(N-acryloylmorpholine) amphiphilic star block copolymers as nanocarriers for drug delivery

In this study, a series of amphiphilic AB2-type miktoarm star block copolymers consisting of hydrophobic poly(l-lactide) (PLLA) as a A arm and hydrophilic poly(N-acryloylmorpholine) (PNAM) as two B arms were synthesized via the combination of ring opening polymerization and xanthate-mediated reversible addition-fragmentation chain transfer polymerization. Resultant polymers were analyzed by 1H NMR spectroscopy and gel permeation chromatography. Aggregation properties of the amphiphilic miktoarm star block copolymers were studied by fluorescence spectroscopy, transmission electron microscopy and dynamic light scattering. Doxorubicin (DOX) was successfully loaded into the miktoarm star block copolymer micelles and the DLC and DLE of the DOX-loaded micelles increased (9.4 to 13.6% and 55.6 to 78.7%) with an increase in the hydrophilic PNAM chain length of the miktoarm star block copolymer. The result revealed that DOX release was enhanced as the pH reduced from 7.4 to 6.4 and the rate of release slightly increased with increasing the PNAM hydrophilic chain length of the micelles.

Field-Theoretic Simulations of Fluctuation-Stabilized Aperiodic “Bricks-and-Mortar” Mesophase in Miktoarm Star Block Copolymer/Homopolymer Blends

A new class of thermoplastic elastomers possessing unusual mechanical properties has recently been discovered in binary blends of A-b-(B-b-A′)n miktoarm star block copolymers and A homopolymers that spontaneously form an unusual, thermodynamically stable, aperiodic “bricks-and-mortar” (B&M) mesophase morphology. The B&M mesophase is believed to be stabilized by thermal fluctuations as in the well-known case of the bicontinuous microemulsion phase. Here, two-dimensional field-theoretic simulations are used to study the equilibrium self-assembly of such miktoarm polymer binary blends. As expected, the B&M mesophase is not present in the mean-field phase diagram obtained with self-consistent field theory, but complex Langevin (CL) simulations, which fully incorporate thermal fluctuation effects, reveal dramatic changes to the phase diagram. A region of strong fluctuations results in the emergent stabilization of the B&M mesophase in a broad composition channel positioned between microphase separation and mac...

Preparation of pH-sensitive micelles from miktoarm star block copolymers by ATRP and their application as drug nanocarriers

In this study, novel pH-sensitive micelles were prepared from miktoarm star block copolymer, mPEG-b-P(MMA-co-MAA)2, by the atom transfer radical polymerization (ATRP) technique and dialysis method. Molecular structures and characteristics of the micelles were confirmed by 1H nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) spectroscopy, gel permeation chromatography (GPC), dynamic light scattering (DLS), and transmission electron microscopy (TEM). The self-assembled micelles have a very low critical micelle concentration, indicating a high colloidal stability in aqueous solution. Methotrexate (MTX) was selected as the model drug of poor solubility. A relatively high drug loading capacity was found, and the in vitro release studies revealed that about 26% of the drug was released in simulated gastric fluid (SGF, pH1.2) over 48h compared to the maximum drug release of about 98% in simulated intestinal fluid (SIF, pH7.4). Thus, the pH-sensitive micelles might serve as promising carriers for oral drug delivery of hydrophobic drugs with controlled release behavior.

Temperature‐Sensitive (BA)(AC)2 Miktoarm Star Diblock Copolymer Based on PMMA, PPEGMA, and PNIPAm

A well‐defined (BA)(AC)2 miktoarm star diblock copolymer, (PPEGMA32‐b‐PMMA41)‐b‐(PMMA45‐b‐PNIPAm19)2, is synthesized by the combination of ATRP and click reaction. The miktoarm star block copolymer and its precursors are characterized by means of NMR and SEC/MALLS measurements. The copolymer exhibits a low critical aggregation concentration in aqueous solution. Micelles that self‐assemble from the copolymer are prepared in aqueous solution below 15 °C by a sonication method. The micelles have a PMMA core and a PPEGMA/PNIPAm corona and exhibit temperature sensitivity. Using celecoxib as a guest molecule, it is found that the loading capacity of the star copolymer is 8.8 wt% and the celecoxib release from the loaded self‐assembly is temperature tunable. image

Mechanics of an Asymmetric Hard-Soft Lamellar Nanomaterial.

Nanolayered lamellae are common structures in nanoscience and nanotechnology, but most are nearly symmetric in layer thickness. Here, we report on the structure and mechanics of highly asymmetric and thermodynamically stable soft-hard lamellar structures self-assembled from optimally designed PS1-(PI-b-PS2)3 miktoarm star block copolymers. The remarkable mechanical properties of these strong and ductile PS (polystyrene)-based nanomaterials can be tuned over a broad range by varying the hard layer thickness while maintaining the soft layer thickness constant at 13 nm. Upon deformation, thin PS lamellae (<100 nm) exhibited kinks and predamaged/damaged grains, as well as cavitation in the soft layers. In contrast, deformation of thick lamellae (>100 nm) manifests cavitation in both soft and hard nanolayers. In situ tensile-SAXS experiments revealed the evolution of cavities during deformation and confirmed that the damage in such systems reflects both plastic deformation by shear and residual cavities. The aspects of the mechanics should point to universal deformation behavior in broader classes of asymmetric hard-soft lamellar materials, whose properties are just being revealed for versatile applications.

Biodegradable micelles self-assembled from miktoarm star block copolymers for MTX delivery

Biodegradable micelles based on disulfide-linked monomethoxy poly(ethylene glycol)-b-poly(methyl methacrylate)2 (mPEG-SS-PMMA2) miktoarm star block copolymers were synthesized through atom transfer radical polymerization procedure and applied to solubilization and delivery of methotrexate (MTX). The synthesized miktoarm star block copolymers were characterized by 1H nuclear magnetic resonance, Fourier transform infrared spectra, and gel permeation chromatography. The block copolymers were able to self-assemble into spherical micelles in water with an average diameter up to 130 nm by transmission electron microscopy observation and dynamic light scattering measurements and have a critical micelle concentration of 0.91 mg/L. When MTX was incorporated into obtained micelles, high drug loading capacity was found attributed to the designed miktoarm star-shaped nanostructure. Interestingly, in presence of dithiothreitol, the micelles could be degraded into polymer chains by cleavage of the disulfide linkages. The in vitro release studies revealed that these micelles released over 95 % of MTX within 48 h under a reductive environment analogous to that of the cell comparing to minimal drug release (<22 %) under nonreductive conditions. Cell cytoxicity experiments showed that the obtained micelles exhibited nontoxic, and the drug-loaded micelles exhibited high anticancer efficacy and better biocompatibility as compared to free MTX. All of these results showed that mPEG-SS-PMMA2 micelles are promising carriers for delivery of hydrophobic antitumor drugs.

Creating Extremely Asymmetric Lamellar Structures via Fluctuation-Assisted Unbinding of Miktoarm Star Block Copolymer Alloys.

We report the creation of highly asymmetric lamellar structures with a well-designed miktoarm star block copolymer of the S(IS')3 type, where S and S' are polystyrenes of different lengths and I is poly(isoprene). The domain spacing can be tuned continuously from 37 nm to over 300 nm when the miktoarm star block copolymer is blended with suitable molecular weight polystyrene homopolymers. Beyond the unbinding transition of the lamellar phase, extremely asymmetric lamellar structures were obtained with up to 97 wt % polystyrene, remarkably leaving the poly(isoprene) layers intact at only 3 wt %!

Nanocapsules Based on Linear and Y-Shaped 3-Miktoarm Star-Block PEO-PCL Copolymers as Sustained Delivery System for Hydrophilic Molecules

Well-defined amphiphilic Y-shaped miktoarm star-block copolymers of PEO and PCL were synthesized by ring-opening polymerization of ε-caprolactone initiated by a PEO-bound lysine macroinitiator. The copolymers were characterized by (1)H NMR, SEC, DSC, and WAXD techniques. Separate PCL and PEO crystalline phases occur in melt-crystallized copolymers when their segmental lengths were comparable and the PCL content was ≤80 wt %. Self-assembling of these copolymers in aqueous medium led to nanoaggregates with low critical aggregation concentration values (0.35 to 1.6 mg·L(-1)) and size depending on composition. Despite the fact that copolymers were not prone to self-organize in vesicles, once processed by a novel w/o emulsion-melting-sonication technique, they gave nanocapsules with a water core and a hydrophilic surface. A macromolecular fluorescent dye was effectively loaded and released at sustained rate by optimizing nanocapsule formulation. The results demonstrate that amphiphilic block copolymers can be assembled in different kinds of nanomorphologies independently of their hydrophilic/hydrophobic balance and architecture through specifically designed preparation techniques.

Synthesis and self‐assembly of amphiphilic macrocyclic block copolymer topologies

AbstractWe demonstrated the synthesis of miktoarm star block copolymers of AB, AB2, and A2B, in which block A consisted of linear poly(tert‐butyl acrylate) (PtBA) and block B consisted of cyclic polystyrene. These structures were produced using the atom transfer radical polymerization to make telechelic polymers that, after modification, were further coupled together by copper‐catalyzed “click” reactions with high coupling efficiency. Deprotection of PtBA to poly(acrylic acid) (PAA) afforded amphiphilic miktoarm structures that when micellized in water gave vesicle morphologies when the block length of PAA was 21 units. Increasing the PAA block length to 46 units produced spherical core‐shell micelles. AB2 miktoarm stars packed more densely into the core compared to its linear counterpart (i.e., a four times greater aggregation number with approximately the same hydrodynamic diameter), resulting in the PAA arms being more compressed in the corona and extending into the water phase beyond its normal Gaussian chain conformation. These results show that the cyclic structure attached to an amphiphilic block has a significant influence on increasing the aggregation number through a greater packing density. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011.

Synthesis of A2B2 miktoarm star copolymers from a new heterobifunctional initiator by combination of ROP and ATRP

A new heterobifunctional initiator, 2,3-bis(2-bromo-2-methylpropionyloxy) succinic acid, was synthesized and used in preparation of A2B2 miktoarm star copolymers, (polystyrene)2(poly(e-caprolactone))2, by combination of atom transfer radical polymerization (ATRP) and Controlled ring-opening polymerization (ROP). The structures of products were confirmed by the 1H NMR, 13C NMR, FT–IR, elemental analysis, differential scanning calorimetry (DSC), and gel permeation chromatography (GPC). GPC traces show that the obtained polymers have a relatively narrow molecular weight distribution. The compositions of resulting miktoarm star copolymers were very close to theoretical. A new heterobifunctional initiator was synthesized and successfully used in the preparation of miktoarm star block copolymers via a combination of Controlled ring-opening polymerization and atom transfer radical polymerization, in a sequential process.

Synthesis and Aggregation Behaviors of Nonlinear Multiresponsive, Multihydrophilic Block Copolymers

The well-defined nonlinear multiresponsive, multihydrophilic block copolymers (MHBCs), poly(N-isopropylacrylamide)2−[poly(N-vinylpyrrolidone)-b-poly(acrylic acid)]2 ((PNIPAAM)2(PNVP-b-PAA)2) and poly[N-isopropylacrylamide-b-(acrylic acid)]2−poly(N-vinylpyrrolidone)2 ((PNIPAAM-b-PAA)2(PNVP)2), were successfully synthesized via a combination of single-electron transfer living radical polymerization (SET-LRP) and reversible addition−fragmentation chain transfer (RAFT) polymerization techniques. All the final miktoarm star block copolymers were characterized by GPC and 1H NMR spectra. Interestingly, the hydrogen bonding interactions have a great effect on the water solubility of PAA chains, and the nonlinear MHBCs solutions showed sharp phase separation at pH = 7.0. The novel water-soluble nonlinear MHBCs consisting of pH-responsive PAA segments, thermoresponsive PNIPAAM segments, and hydrophilic, noncharged and biocompatible PNVP segments tend to self-assemble into three different types of micellar aggregates and umimers, which can be reversibly controlled by pH value and temperature of aqueous solution of these copolymers.

Star and miktoarm star block (co)polymers viaself-assembly of ATRP generated polymer segments featuring Hamilton wedge and cyanuric acid binding motifs

The self-assembly of well-defined ATRP prepared polymers with terminal and mid-chain Hamilton wedge as well as cyanuric acid binding motifs is demonstrated to be an efficient avenue to star and miktoarm star block copolymers.

Preparation of miktoarm star-block copolymers PSn-b-PVAc4-n via combination of ATRP and RAFT polymerization

Three tetrafunctional bromoxanthate agents (Xanthate3-Br, Xanthate2-Br2, and Xanthate-Br3) were synthesized. Initiative atom transfer radical polymerizations (ATRP) of styrene (St) or reversible addition fragmentation chain transfer (RAFT) polymerizations of vinyl acetate (VAc) proceeded in a controlled manner in the presence of Xanthate3-Br, Xanthate2-Br2, or Xanthate-Br3, respectively. The miktoarm star-block copolymers containing polystyrene (PS) and poly(vinyl acetate) (PVAc) chains, PSn-b-PVAc4-n (n = 1, 2, and 3), with controlled structures were successfully prepared by successive RAFT and ATRP chain-extension experiments using VAc and St as the second monomers, respectively. The architecture of the miktoarm star-block copolymers PSn-b-PVAc4-n (n = 1, 2, and 3) were characterized by gel permeation chromatography and 1H NMR spectra. Furthermore, the results of the cleavage of PS3-b-PVAc and PVAc2-b-PS2 confirmed the structures of the obtained miktoarm star-block copolymers. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010

Design of Soft and Strong Thermoplastic Elastomers Based on Nonlinear Block Copolymer Architectures Using Self-Consistent-Field Theory

Thermoplastic elastomers (TPEs) that are soft at low extension yet strong at large extension are of great importance in a variety of technological applications. In ABA-triblock architectures, both the overall molecular weight and the composition of the glassy A-blocks correlate with TPE strength. The design space of current TPEs based on linear ABA triblock copolymers (e.g., polystyrene-b-polybutadiene-b-polystyrene) is restricted by the accessibility of the order−disorder transition temperature, limiting the molecular weight, and restricted by the maximum volume fraction for which glassy A-blocks will form discrete domains. Using self-consistent-field theory (SCFT), we designed in silico two new, nonlinear TPE architectures that significantly relax the composition restriction: radial (ABA′)n and A(BA′)n miktoarm star-block copolymers with chemically identical, but unequal, molecular weight A-blocks. Through a balance of end-block bidispersity, block extraction from the interface, and architectural asymmetry, these molecular architectures are able to stabilize phases with discrete A-rich domains at remarkably high overall A-monomer compositions (fA). In some cases the maximum fA achieved for phases with discrete A-rich domains surpasses twice that of conventional linear ABA TPEs.