Star-shaped Block Copolymers Research Articles

Doxorubicin-loaded micelles based on multiarm star-shaped PLGA-PEG block copolymers: influence of arm numbers on drug delivery.

Star-shaped block copolymers based on poly(D,L-lactide-co-glycolide) (PLGA) and poly(ethylene glycol) (PEG) (st-PLGA-PEG) were synthesized with structural variation on arm numbers in order to investigate the relationship between the arm numbers of st-PLGA-PEG copolymers and their micelle properties. st-PLGA-PEG copolymers with arm numbers 3, 4 and 6 were synthesized by using different cores such as trimethylolpropane, pentaerythritol and dipentaerythritol, and were characterized by nuclear magnetic resonance and gel permeation chromatography. The critical micelle concentration decreased with increasing arm numbers in st-PLGA-PEG copolymers. The doxorubicin-loaded st-PLGA-PEG micelles were prepared by a modified nanoprecipitation method. Micellar properties such as particle size, drug loading content and in vitro drug release behavior were investigated as a function of the number of arms and compared with each other. The doxorubicin-loaded 4-arm PLGA-PEG micelles were found to have the highest cellular uptake efficiency and cytotoxicity compared with 3-arm PLGA-PEG micelles and 6-arm PLGA-PEG micelles. The results suggest that structural tailoring of arm numbers from st-PLGA-PEG copolymers could provide a new strategy for designing drug carriers of high efficiency. Structural tailoring of arm numbers from star shaped-PLGA-PEG copolymers (3-arm/4-arm/6-arm-PLGA-PEG) could provide a new strategy for designing drug carriers of high efficiency.

Application of Linear and Branched Poly(Ethylene Glycol)-Poly(Lactide) Block Copolymers for the Preparation of Films and Solution Electrospun Meshes.

Poly(ethylene glycol)-poly(lactide) (PEG-PLA) block copolymers are processed to solvent cast films and solution electrospun meshes. The effect of polymer composition, architecture, and number of anchoring points for the plasticizer on swelling, degradation, and mechanical properties of these films and meshes is investigated as potential barrier device for the prevention of peritoneal adhesions. As a result, adequate properties are achieved for the massive films with a longer retention of the plasticizer PEG for star-shaped block copolymers than for the linear triblock copolymers and consequently more endurable mechanical properties during degradation. For electrospun meshes fabricated using the same polymers, similar trends are observed, but with an earlier start of fragmentation and lower tensile strengths. To overcome the poor mechanical strengths and an occurring shrinkage during incubation, which may impair the coverage of the wound, further adaptions of the meshes and the fabrication process are necessary.

Proton Exchange Membrane Based on the Star Shaped Block Copolymer with Well Connected Ionic Domain and Conductivity

Star shaped block copolymer POSS-(PMMA- b- PS)8was synthesized by a two step process of atom transfer radical polymerization(ATRP) with eight functionalized polyhedral oligomeric silisesquioxane POSS-(Cl)8as core and poly(methyl methacrylate-b-polystyrene) as arm. The POSS-(PMMA-bPS)8was then sulfonation treated to produce hybrid polymer POSS-(PMMA- b- SPS)8, which was finally used as the polymer matrix for making proton exchange membranes(PEMs). The examination of conductivity as function of relative humidity for PEMs of high and low hydration status respectively indicated that with longer SPS block length exhibited higher proton conductivity for the PEMs of low hydration status with the same λ i.e. the number of water molecular coupled to sulfonic acid groups. TGA analysis showed that two kinds of PEM all exhibited higher water retention capacity and higher initial decomposition temperature. A well-connected ionic domains in PEM with longer SPS block could be observed by transmission electron microscopy(TEM) and atomic force microscopy(AFM). The features of molecules motion of chain segments and spins relaxation time T2 for the PEMs of low hydration status were analyzed by low field nuclear magnetic resonance, and it is found that the well connected ionic domains could be observed also in the PEMs with longer SPS block, which exhibited higher proton spin- diffusion coefficient,therewith higher proton conductivity by low relative humidity.

Sulfonated polymers containing polyhedral oligomeric silsesquioxane (POSS) core for high performance proton exchange membranes

A series of POSS containing star-shaped block copolymers were synthesized by atom transfer radical polymerization (ATRP), with POSS-(Cl)8 as initiator, polymethyl methacrylate as the first building block, and polystyrene as the second building block. Sulfonation of the polystyrene block yielded star-shaped ionic polymers POSS-(PMMA-b-SPS)8 that were evaluated as proton exchange membranes (PEMs) subsequently. Under low relative humidities (RHs), the PEM with longer SPS block exhibited higher proton conductivity than the PEM with shorter SPS block when compared at same hydration number (λ) conditions, which was attributed to the better connected hydrophilic domains of the former as evidenced by electron microscopes. However, this conductivity trend for the two PEMs was reversed at 100% RHs. Low field nuclear magnetic resonance analysis revealed that the PEM with shorter SPS block had more loosely bonded water than the PEM with longer SPS block at 100% RH, giving an explanation of why the conductivity trend was reversed. This study suggested that both ionic domain structure and water–polymer interaction are important parameters for achieving high proton conductivities.

Structure-directing star-shaped block copolymers: Supramolecular vesicles for the delivery of anticancer drugs

Amphiphilic polycarbonate/PEG copolymer with a star-like architecture was designed to facilitate a unique supramolecular transformation of micelles to vesicles in aqueous solution for the efficient delivery of anticancer drugs. The star-shaped amphipilic block copolymer was synthesized by initiating the ring-opening polymerization of trimethylene carbonate (TMC) from methyl cholate through a combination of metal-free organo-catalytic living ring-opening polymerization and post-polymerization chain-end derivatization strategies. Subsequently, the self-assembly of the star-like polymer in aqueous solution into nanosized vesicles for anti-cancer drug delivery was studied. DOX was physically encapsulated into vesicles by dialysis and drug loading level was significant (22.5% in weight) for DOX. Importantly, DOX-loaded nanoparticles self-assembled from the star-like copolymer exhibited greater kinetic stability and higher DOX loading capacity than micelles prepared from cholesterol-initiated diblock analogue. The advantageous disparity is believed to be due to the transformation of micelles (diblock copolymer) to vesicles (star-like block copolymer) that possess greater core space for drug loading as well as the ability of such supramolecular structures to encapsulate DOX. DOX-loaded vesicles effectively inhibited the proliferation of 4T1, MDA-MB-231 and BT-474 cells, with IC50 values of 10, 1.5 and 1.0mg/L, respectively. DOX-loaded vesicles injected into 4T1 tumor-bearing mice exhibited enhanced accumulation in tumor tissue due to the enhanced permeation and retention (EPR) effect. Importantly, DOX-loaded vesicles demonstrated greater tumor growth inhibition than free DOX without causing significant body weight loss or cardiotoxicity. The unique ability of the star-like copolymer emanating from the methyl cholate core provided the requisite modification in the block copolymer interfacial curvature to generate vesicles of high loading capacity for DOX with significant kinetic stability that have potential for use as an anti-cancer drug delivery carrier for cancer therapy.

Synthesis and self-assembly of a triarm star-shaped rod-rod block copolymer

We designed and synthesized a triarm star-shaped rod-rod block copolymer (BCP), (poly{2,5-bis[(4-methoxyphenyl)-oxycarbonyl]styrene}-block-poly(γ-benzyl-l-glutamate))3, (PMPCS-b-PBLG)3. The triarm core with three PMPCS-N3 segments was prepared by copper-mediated atom transfer radical polymerization of 2,5-bis[(4-methoxyphenyl)-oxycarbonyl]styrene initiated by a trifunctional initiator and a subsequent azide reaction. And the PBLG block with alkyne functionality was synthesized through ring-opening polymerization of γ-benzyl-l-glutamate N-carboxyanhydride initiated by propargylamine. Finally, Huisgen’s 1,3-dipolar cycloaddition was employed to combine the triarm (PMPCS-N3)3 and PBLG segments. The chemical structure of the BCP was confirmed by 1H-NMR spectroscopy, Fourier-transform infrared spectroscopy, and gel permeation chromatographic analysis. Results from differential scanning calorimetry, polarized light microscopy, one-dimensional and two-dimensional wide-angle X-ray diffraction, and transmission electron microscopy techniques demonstrate that the triarm star-shaped rod-rod BCP self-assembles into a hexagon-in-lamella morphology, with the PMPCS block in the columnar nematic phase and the PBLG block in the hexagonal columnar arrangement packed in bilayers due to the rigid nature of the two blocks and the covalent connections in the star-shaped BCP.

Water-soluble star-shaped brush-like block copolymers: synthesis and application as multicompartment nanoreactors for fabrication of quantum dot colloidal nanocrystal clusters

Water-soluble multi-arm star-shaped brush-like block copolymers of (PEO-g-PAA)-b-PEO were synthesized and exploited as polymeric nanoreactors to structure-direct in situ fabrication of CdSe QD colloidal nanocrystal clusters.

Correction: Synthesis and properties of clickable A(B-b-C)20 miktoarm star-shaped block copolymers with a terminal alkyne group

Correction for ‘Synthesis and properties of clickable A(B-b-C)20 miktoarm star-shaped block copolymers with a terminal alkyne group’ by Bing Huang et al., Polym. Chem., 2015, DOI: 10.1039/c5py00338e.

Synthesis and properties of clickable A(B-b-C)20 miktoarm star-shaped block copolymers with a terminal alkyne group

A novel and reactive A(B-b-C)20 miktoarm star-shaped block copolymer has been successfully synthesized through ATRP reaction combined with click reactions.

Novel Approaches in Designing Natural/Synthetic Materials for Environmental Applications

This is one of a series of special issues published in this journal, focusing on the latest advances of designing natural or synthetic materials for using them in environmental applications. The designing of materials is one of the most developing sectors of environmental science. Novel materials can be synthesized having the ultimate goal of an environmental application. In this field many parameters play an important role as biodegradability, reuse/regeneration, cost, and environmental-friendly disposal. Other standards will be also taken into account as conditions of synthesis, possible use in columns, and so forth. This issue includes novel approaches in designing either natural or synthetic materials which will have direct application to environmental targets (dyes, heavy metals/ions, phenols, pesticides/insecticides, nuclear pollutants, etc.).Thematerials described can be used either for gas or liquid use (i.e., adsorption). Extra attention and priority will be given to real samples of environmental pollutants (industrial effluents). Various types of works were selected to be published with wide topics. The technique of molecular imprinting was introduced by G. Z. Kyzas et al. for selectively binding of high-added value metals. Yang et al. reported material developments regarding geotechnical engineering, while Y. Zhang et al. extensively describe the synthesis and characterization of star-shaped block copolymer sPCL-bPEG-GA. S.-W.Myoung et al. investigated the thermal barrier coatings in cyclic thermal exposure as well as the effect of plasma pretreatment on their thermal durability, while some other related topics have been also published, such as the unstable temperature distribution in friction stir welding (by S. Aziz et al.), the designing and simulated characteristics of nanosized InSb based heterostructure devices (by T. D. Subash et al.), and the synthesis of raw materials originated from industrial effluents for bioremediation and phytomining (by S. B. Karman et al.). Under the direction of the editorial team, we showcase advances of organic and inorganic based smart materials and their applications in areas of specific interest such as energy, environment, and health. A total of 7 articles are published in this special issue.

Star-shaped polyhedral oligomeric silsesquioxane-polycaprolactone-polyurethane as biomaterials for tissue engineering application

Polyhedral oligomeric silsesquioxane (POSS) is a unique molecule that is composed of an inorganic silica core with eight organic functional arms, which can be used as a nucleus for covalent bonding to create star-shaped block copolymers with improved mechanical and biological properties. In this work, highly porous star-shaped POSS-polycaprolactone-polyurethane (POSS-PCL-PU) films were synthesized as scaffold biomaterials for tissue engineering. These films have an interesting morphology consisting of rough spherulites with filamentous structures spreading out from their centers; the unique nanotopography was shown to be suitable for cell growth. In vitro degradation was monitored for 52 weeks in terms of the weight loss and morphology changes of the films. The degradation profile exhibited a slow initial weight loss of <1% during the first 24 weeks, followed by a rapid weight loss of ~18% in the following 28 weeks. The films demonstrated excellent biocompatibility and cell-substrate affinity, with a high cell viability of >95% and rapid cell proliferation. The high porosity, unique surface nanotopography and excellent biocompatibility of the star-shaped POSS-PCL-PU film make it a great candidate as a tissue engineering scaffold biomaterial. Researchers in Singapore have prepared highly porous films that are very promising as scaffold biomaterials for tissue engineering. They synthesized the films by using star-shaped polyhedral oligomeric silsesquioxane as the starting inorganic core and incorporating polycaprolactone (PCL) and polyurethane (PU). The researchers, who are from the Institute of Materials Research and Engineering and the National University of Singapore, demonstrate that the inorganic-organic nanocomposite films satisfy all the key criteria for a biodegradable scaffold biomaterial — they have an excellent biocompatibility, a high porosity and a controlled and slow degradability. In addition, the scientists show that the material's unique nanotopography, which is produced by filamentous structures branching out from the centres of rough spherulites, promotes cell growth. The combination of organic and inorganic functionalities makes these films superior to conventional PCL-PU films. Highly porous star-shaped polyhedral oligomeric silsesquioxane (POSS) hybrid films were synthesized using POSS as the starting core followed by polycaprolactone (PCL) extension and polyurethane (PU) cross-linking. The unique three-dimensional nanotopography of these films is conducive for cell growth. The combination of favorable factors such as high porosity, reactive surface topography, excellent biocompatibility and biphasic degradation makes the star-shaped POSS-PCL-PU film a great candidate as a tissue engineering scaffold biomaterial.

Synthesis and self-assembly in bulk of star-shaped block copolymers based on helical polypeptides

A series of star-shaped copolymers containing poly (styrene) (PS) and poly(γ-benzyl-l-glutamate) (PBLG) were synthesized by click reaction from alkyne- and azide-functionalized homopolymers. The α-azide PS star-shaped homopolymer was synthesized by copper-mediated atom transfer radical polymerization from a bromine-containing star-shaped initiator, and α-alkyne PBLG homopolymers were synthesized by ring-opening polymerization of γ-benzyl-l-glutamate N-carboxyanhydride with an amino-containing α-alkyne initiator. The molecular structures of the homopolymers and star-shaped block copolymers were confirmed by 1H nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy (FTIR), and gel permeation chromatography analysis. The self-assembling behavior of the star-shaped block copolymers in bulk was investigated using wide-angle X-ray diffraction, and small-angle X-ray scattering. For star-shaped block copolymer at lower f PS of ~0.27, PBLG segment was assigned to a hexagonally packed-cylinder structure (Φ H) based on the rod-like α-helix conformation as shown in FTIR spectra. By increasing f PS to ~0.42, a proposed microphase-separated double-hexagonal morphology was observed, in which PBLG rods formed the core of the columns by interdigitated packing in Φ H phase with PS domain as the matrix in a larger hexagonal columnar structure. The proposed structure was based on calculation from the simulated molecular length of each block of the copolymer and experimental analyses.

Synthesis and Characterization of Star-Shaped Block Copolymer sPCL-b-PEG-GA

Compared to linear polymers with the same molecular weight, star-shaped polymers have the superiority of drug loading and delivery. The glycyrrhetinic acid (GA) from licorice is remarkably characteristic of liver distribution and liver cells targetability. In this paper, four-armed star-shaped polycaprolactone was synthesized and amino polyethylene glycol was modified by glycyrrhetinic acid (NH2-PEG-GA). Then the condensation reaction between the two above polymers finally produced four-armed star-shaped poly(ethylene glycol)-b-poly(ε-caprolactone) block copolymer (sPCL-b-PEG-GA). The structures of the intermediates and product were characterized by1H NMR. The results indicated that the structure and molecular weight of sPCL-b-PEG-GA can be controlled by the varied ratios of pentaerythritol (PTOL) toε-caprolactone (ε-CL) in the presence of stannous octoate (Sn(Oct)2), and the amphiphilic copolymer sPCL-b-PEG-GA consists of PTOL as core, PCL as inner hydrophobic segments, PEG as external hydrophilic segments, and terminal glycyrrhetic acid as targeting ligand. The work explored a new synthesis route of star poly(ethylene glycol)-b-poly(ε-caprolactone) copolymer with liver targetability. The star-shaped polymer is expected to be an efficient drug carrier.

Development of Tissue Adhesives Based on Amphiphilic Isocyanate‐Terminated Trimethylene Carbonate Block Copolymers

SummaryIn this study, novel 3‐armed star‐shaped isocyanate‐terminated block copolymers based on trimethylolpropane ethoxylate (TMPE) and trimethylene carbonate (TMC) varying in composition were designed and synthesized. By reaction with water, networks were formed. The characteristics of these networks were compared with those prepared from analogous linear structures based on polyethylene glycol (PEG) and TMC.Tensile testing of the networks highlighted good mechanical properties. In lap shear adhesion tests to chamois leather, very good bonding strengths of up to 0.6 MPa were obtained. These values compare favorably with those of Dermabond®, which is currently one of the strongest clinically used tissue adhesives.

Comparison of four-arm and six-arm star-shaped mPEG-PLA block copolymer micelles for drug delivery

Comparison of four-arm and six-arm star-shaped mPEG-PLA block copolymer micelles for drug delivery

Paclitaxel-loaded nanoparticles of star-shaped cholic acid-core PLA-TPGS copolymer for breast cancer treatment

A system of novel nanoparticles of star-shaped cholic acid-core polylactide-d-α-tocopheryl polyethylene glycol 1000 succinate (CA-PLA-TPGS) block copolymer was developed for paclitaxel delivery for breast cancer treatment, which demonstrated superior in vitro and in vivo performance in comparison with paclitaxel-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles and linear PLA-TPGS nanoparticles. The paclitaxel- or couramin 6-loaded nanoparticles were fabricated by a modified nanoprecipitation method and then characterized in terms of size, surface charge, surface morphology, drug encapsulation efficiency, and in vitro drug release. The CA-PLA-TPGS nanoparticles were found to be spherical in shape with an average size of around 120 nm. The nanoparticles were found to be stable, showing no change in the particle size and surface charge during 90-day storage of the aqueous solution. The release profiles of the paclitaxel-loaded nanoparticles exhibited typically biphasic release patterns. The results also showed that the CA-PLA-TPGS nanoparticles have higher antitumor efficacy than the PLA-TPGS nanoparticles and PLGA nanoparticles in vitro and in vivo. In conclusion, such nanoparticles of star-shaped cholic acid-core PLA-TPGS block copolymer could be considered as a potentially promising and effective strategy for breast cancer treatment.

Synthesis and Drug Release of Star‐Shaped Poly(benzyl L‐aspartate)‐block‐poly(ethylene glycol) Copolymers with POSS Cores

Star-shaped amphiphilic block copolymers with polyhedral oligomeric silsesquioxanes (POSS) as cores are synthesized using the "arm-first" strategy. First, the block copolymer poly(benzyl L-aspartate)-block-poly(ethylene glycol) (PBLA-b-PEG) is synthesized via ring-opening polymerization of β-benzyl L-aspartate-N-carboxyanhydride (BLA-NCA) with α-methoxy-ω-aminopoly(ethylene glycol) (mPEG-NH2 ) as a macroinitiator. The copolymers are then immobilized on the eight groups of the polyhedral oligomeric silsesquioxanes (POSS-COOH). The star-shaped copolymers (POSS-g-(PBLA-b-PEG)) are characterized by (1) H NMR and FT-IR spectroscopy and gel permeation chromatography. The star-shaped block copolymers self-assemble into micelles in aqueous medium. Quercetin is used as a model drug and the drug loading content and encapsulation efficiency increases with increasing chain length of the PBLA blocks. The drug release behaviors of drug loaded micelles are investigated and the cytotoxicity assay demonstrates that the POSS-g-(PBLA-b-PEG) copolymers are non-toxic. The star-shaped block copolymers are potential carriers for anticancer drug delivery.

Mesogen-controlled ion channel of star-shaped hard-soft block copolymers for solid-state lithium-ion battery

Novel star-shaped hard–soft triblock copolymers, 4-arm poly(styrene)-block-poly [poly(ethylene glycol) methyl ethyl methacrylate]-block-poly{x-[(4-cyano-4′-biphenyl) oxy] alkyl methacrylate} (4PS-PPEGMA-PMAxLC) (x = 3, 10), with different mesogen spacer length are prepared by atom-transfer radical polymerization. The star copolymers comprised three different parts: a hard polystyrene (PS) core to ensure the good mechanical property of the solid-state polymer, and a soft, mobile poly[poly(ethylene glycol) methyl ethyl methacrylate] (PPEGMA) middle sphere responsible for the high ionic conductivity of the solid polyelectrolytes, and a poly{x-[(4-cyano-4′-biphenyl)oxy]alkyl methacrylate} with a birefringent mesogens at the end of each arm to tuning the electrolytes morphology. The star-shaped hard–soft block copolymers fusing hard PS core with soft PPEGMA segment can form a flexible and transparent film with dimensional stability. Thermal annealing from the liquid crystalline states allows the cyanobiphenyl mesogens to induce a good assembly of hard and soft blocks, consequently obtaining uniform nanoscale microphase separation morphology, and the longer spacer is more helpful than the shorter one. There the ionic conductivity has been improved greatly by the orderly continuous channel for efficient ion transportation, especially at the elevated temperature. The copolymer 4PS-PPEGMA-PMA10LC shows ionic conductivity value of 1.3 × 10−4 S cm−1 (25 °C) after annealed from liquid crystal state, which is higher than that of 4PS-PPEGMA electrolyte without mesogen groups. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4341–4350

Formation of Nanophases in Epoxy Thermosets Containing Amphiphilic Block Copolymers with Linear and Star-like Topologies

In this work, we investigated the effect of topological structures of block copolymers on the formation of the nanophase in epoxy thermosets containing amphiphilic block copolymers. Two block copolymers composed of poly(ε-caprolactone) (PCL) and poly(2,2,2-trifluoroethyl acrylate) (PTFEA) blocks were synthesized to possess linear and star-shaped topologies. The star-shaped block copolymer composed a polyhedral oligomeric silsesquioxane (POSS) core and eight poly(ε-caprolactone)-block-poly(2,2,2-trifluoroethyl acrylate) (PCL-b-PTFEA) diblock copolymer arms. Both block copolymers were synthesized via the combination of ring-opening polymerization and reversible addition-fragmentation chain transfer/macromolecular design via the interchange of xanthate (RAFT/MADIX) process; they were controlled to have identical compositions of copolymerization and lengths of blocks. Upon incorporating both block copolymers into epoxy thermosets, the spherical PTFEA nanophases were formed in all the cases. However, the sizes of PTFEA nanophases from the star-like block copolymer were significantly lower than those from the linear diblock copolymer. The difference in the nanostructures gave rise to the different glass transition behavior of the nanostructured thermosets. The dependence of PTFEA nanophases on the topologies of block copolymers is interpreted in terms of the conformation of the miscible subchain (viz. PCL) at the surface of PTFEA microdomains and the restriction of POSS cages on the demixing of the thermoset-philic block (viz. PCL).

Functional star block copolymers with a cholane core: Thermo-responsiveness and aggregation behavior

Star block copolymers composed of hydrophilic poly(ethylene glycol) (PEG) as an inner block and tuneable poly(allyl glycidyl ether) (PAGE) as an outer block were made by sequential anionic polymerization on a cholane core. The 4-armed CA(EGn-b-AGEm)4 star block copolymers show dual thermo-responsive behavior in aqueous solutions, where the two cloud points (CPs) vary in the range of 10–34 °C for the first CP and 16−39 °C for the second CP, depending on the length of the PEG and PAGE segments. 1H NMR spectroscopy, dynamic light scattering and atomic force microscopy all indicate a two-step aggregation process of flower-like micelles, where the micelles form through the association of the hydrophobic PAGE blocks and the bile acid core. The allyl groups of the star copolymers were further functionalized by radical thiol-ene coupling to introduce NH2 or COOH groups in the outer block. As a result, star-shaped block copolymers with dual pH- and thermo-sensitivity were obtained with different aggregation characteristics corresponding to the pKa of the functionalized blocks. Interestingly, the deprotonated NH2-bearing polymers showed dual thermo-responsive characteristics different from their allyl group-bearing precursor.