Multiarm Star Research Articles

Transparent thermo-responsive poly(N-isopropylacrylamide)-l-poly(ethylene glycol)acrylamide conetwork hydrogels with rapid deswelling response

Transparent thermo-responsive poly(N-isopropylacrylamide)-l-poly(ethylene glycol)acrylamide conetwork hydrogels with rapid deswelling response are developed with multi-arm star poly(ethylene glycol)acrylamide as a cross-linker.

Synthesis of star thermoresponsive amphiphilic block copolymer nano-assemblies and the effect of topology on their thermoresponse

Well-defined multi-arm star thermoresponsive block copolymer nano-assemblies of [poly(N-isopropylacrylamide)-block-polystyrene]n [(PNIPAM-b-PS)n] with n = 1, 2, 3 and 4 arms were synthesized by RAFT dispersion polymerization via polymerization-induced self-assembly.

Synthesis of Multiarm Star Polymer Based on Hyperbranched Polyester Core and Poly(ε-caprolactone) Arms and Its Application in UV-Curable Coating.

Hyperbranched polymers have attracted much attention in the field of UV-curable coatings because of its low viscosity, highly branched structure, and rich functional moieties. However, hyperbranched polymers also have some limitations. For example, the spherical structure increases the crosslinking hindrance, resulting in surplus functional moieties. In this study, a multiarm star polymer with hyperbranched polyester core and linear polymer arms was synthesized and used as UV-curable coating. H40, the fourth generation of the hyperbranched polyester, was chosen as the core owing to its low viscosity and high chemical reactivity. Poly(ε-caprolactone) (PCL) arms were introduced to increase the content of flexible segments and reduce the cross-linking hindrance. The terminal hydroxyls were then replaced with methacrylate groups to endow the star polymer with UV curable ability, yielding HPCLn-M. This multiarm star polymer was considered as a promising candidate to make up for the shortcomings of UV-curable coating made from the hyperbranched polymer. The properties, such as hardness, adhesion, acid resistance, and alkali resistance of cured films were enhanced obviously after the grafting of PCL. Moreover, to further explore the effect of the length of PCL grafts on the coating, star polymers with different degree of polymerization (DP) were synthesized. Through the performance tests of cured films, it was found that the multiarm star polymer HPCLn-M could make up for the limitations of the hyperbranched polymer when the DP of PCL was suitable, and the comprehensive performance of cured film reached the best when the DP of PCL was 20. Overall, this multiarm star polymer could combine the advantages of the hyperbranched polymer and linear polymer and has the potential to be the next environmentally friendly UV-curable coating.

Synthesis of a novel tunable lignin-based star copolymer and its flocculation performance in the treatment of kaolin suspension

Abstract In current work, lignin-based multi-arm star copolymer phenolated kraft lignin-graft-poly (2-methacryloyloxyethyl) trimethyl ammonium chloride (PKL-g-PDMC) was designed and synthesized as a new kind of cationic flocculant via Steglich esterification of PKL and subsequent RAFT polymerization with DMC, and its flocculation performance in the removal of kaolin particles from simulated wastewater was evaluated. The star PKL-g-PDMCs with varying graft density and arm length of PDMCs chains were characterized by 1H NMR, 31P NMR, GPC and TGA. The effects of graft density and arm length, PKL-g-PDMC dosage, suspension pH and settling time on flocculating performance were investigated by measuring residual turbidity of the settled suspension. The treatment was effective, as demonstrated by 96.4% efficiency of turbidity removal. Above all, the chemical structure of the copolymers, including graft density and the arm length, can be designable and tunable by simply changing feeding ratios of Steglich esterification and subsequent RAFT polymerization, and thus the best flocculation performance can be obtained. This work provides a blueprint for the design, synthesis and use of novel lignin-based multi-arm star copolymers for wastewater treatment with tunable properties.

Synthesis of multi-arm star thermo-responsive polymers and topology effects on phase transition

Linear and star thermo-responsive polymers of poly(N-acryloylsarcosine methyl ester) [(PNASME)n] and poly(N-isopropylacrylamide) [(PNIPAM)n] with arm number n = 1, 2, 3 and 4 were synthesized following a core-first method via solution RAFT polymerization employing a series of mono- and multi-functional chain transfer agents.

A powerful tool for preparing peripherally post-functionalized multiarm star block copolymer

A facile synthetic approach for the design of peripherally post-functionalized multiarm star block copolymer has been established by nucleophilic aromatic substitution reaction of pentafluorophenyl periphery functional multiarm star polymer with alcohol moieties of poly(ethylene glycol) (PEG-OH) under mild reaction conditions. For this purpose, α-fluoro-functionalized PS (α-fluoro-PS) was prepared by atom transfer radical polymerization (ATRP) of styrene (St) and was allowed to react with divinyl benzene (DVB) as a linking agent yielding (fluoro-PS)n–polyDVB multiarm star polymer. Then, (PEG)m–(PS)n–polyDVB multiarm star block copolymer was synthesized via nucleophilic addition of PEG-OH precursor with (fluoro-PS)n–polyDVB multiarm star polymer in the presence of sodium hydride in tetrahydrofuran at reflux for 3 h. Multiarm star polymers were characterized using triple detection gel permeation chromatography (TD-GPC), FT-IR, 1H NMR, 19F NMR and 13C NMR.

A sequence of physical processes quantified in LAOS by continuous local measures

The response to large amplitude oscillatory shear of a soft colloidal glass formed by a suspension of multiarm star polymers is investigated by means of well-defined continuous local measures. The local measures provide information regarding the transient elastic and viscous response of the material, as well as elastic extension via a shifting equilibrium position. It is shown that even when the amplitude of the strain is very large, cages reform and break twice per period and exhibit maximum elasticity around the point of zero stress. It is also shown that around the point of zero stress, the cages are extended by a nearly constant amount of approximately 5% at 1 rad/s and 7% at 10 rad/s, even when the total strain is as large as 420%. The results of this study provide a blueprint for a generic approach to elucidating the complex dynamics exhibited by soft materials under flow.

Multiarm Polycarbonate Star Polymers with a Hyperbranched Polyether Core from CO2 and Common Epoxides

Multiarm star copolymers, consisting of hyperbranched poly(ethylene oxide) (hbPEO) or poly(butylene oxide) (hbPBO) polyether copolymers with glycerol branching points as a core, and linear aliphatic polycarbonate arms generated from carbon dioxide (CO2) and epoxide monomers, were synthesized via a “core-first” approach in two steps. First, hyperbranched polyether polyols were prepared by anionic copolymerization of ethylene oxide or 1,2-butylene oxide with 8–35% glycidol with molecular weights between 800 and 389,000 g·mol–1. Second, multiple arms were grown via immortal copolymerization of CO2 with propylene oxide or 1,2-butylene oxide using the polyether polyols as macroinitiators and (R,R)-(salcy)-CoCl as a catalyst in a solvent-free procedure. Molecular weights up to 812,000 g·mol–1 were obtained for the resulting multiarm polycarbonates, determined by online viscometry with universal calibration and 1H NMR. Comparing the synthesis of different multiarm star polycarbonates, a combination of a highly r...

Bidirectional metal‐free ROMP from difunctional organic initiators

Bidirectional metal‐free ROMP from difunctional organic initiators

Dendrons and Multiarm Polymers with Thiol-Exchangeable Cores: A Reversible Conjugation Platform for Delivery.

Disulfide exchange reaction has emerged as a powerful tool for reversible conjugation of proteins, peptides and thiol containing molecules to polymeric supports. In particular, the pyridyl disulfide group provides an efficient handle for the site-specific conjugation of therapeutic peptides and proteins bearing cysteine moieties. In this study, novel biodegradable dendritic platforms containing a pyridyl disulfide unit at their focal point were designed. Presence of hydroxyl groups at the periphery of these dendrons allows their elaboration to multivalent initiators that yield poly(ethylene glycol) based multiarm star polymers via controlled radical polymerization. The pyridyl disulfide unit at the core of these star polymers undergoes efficient reaction with thiol functional group containing molecules such as a hydrophobic dye, namely, Bodipy-SH, glutathione, and KLAK sequence containing peptide. While conjugation of the hydrophobic fluorescent dye to the PEG-based multiarm polymer renders it water-soluble, it can be cleaved off the construct through thiol-disulfide exchange in the presence of an external thiol such as dithiothreitol. The multiarm polymer was conjugated with a thiol group containing apoptotic peptide to increase its solubility and cellular transport. In vitro cytotoxicity and apoptosis assays demonstrated that the resultant peptide-polymer conjugate had almost five times more apoptotic potential primarily through triggering apoptosis by disrupting mitochondrial membranes of human breast cancer cell line (MDA-MB-231) compared to naked peptide. The novel dendritic platform disclosed here offers an attractive template that can be modified to multiarm polymeric constructs bearing a "tag and release" characteristic.

Unimolecular Micelle-Based Hybrid System for Perivascular Drug Delivery Produces Long-Term Efficacy for Neointima Attenuation in Rats.

At present, there are no clinical options for preventing neointima-caused (re)stenosis after open surgery such as bypass surgery for treating flow-limiting vascular disease. Perivascular drug delivery is a promising strategy, but in translational research, it remains a major challenge to achieve long-term (e.g., > 3 months) anti(re)stenotic efficacy. In this study, we engineered a unique drug delivery system consisting of durable unimolecular micelles, formed by single multiarm star amphiphilic block copolymers with only covalent bonds, and a thermosensitive hydrogel formed by a poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) triblock copolymer (abbreviated as triblock gel) that is stable for about 4 weeks in vitro. The drug-containing unimolecular micelles (UMs) suspended in Triblock gel were able to sustain rapamycin release for over 4 months. Remarkably, even 3 months after perivascular application of the rapamycin-loaded micelles in Triblock gel in the rat model, the intimal/medial area ratio (a restenosis measure) was still 80% inhibited compared to the control treated with empty micelle/gel (no drug). This could not be achieved by applying rapamycin in Triblock gel alone, which reduced the intimal/medial ratio only by 27%. In summary, we created a new UM/Triblock gel hybrid system for perivascular drug delivery, which produced a rare feat of 3-month restenosis inhibition in animal tests. This system exhibits a real potential for further translation into an anti(re)stenotic application with open surgery.

Using block copolymer architecture to achieve sub-10 nm periods

Using salt-doped polystyrene-b-poly(2-vinylpyridine) star shaped block copolymer as a model, we show that the architecture of (A-b-B)n type multi-arm star block copolymers enhances the ordering of the block copolymers, enabling the generation of nanostructures with microdomain periods less than 10 nm. The influence of the arm number on the order-to-disorder transition temperature and molecular weight was systematically studied using small angle X-ray scattering. The configurational constraints placed on the chains by anchoring each block copolymer to a central junction point have a significant effect on the disorder-to-order transition behavior. In addition to an increase in the Flory-Huggins parameter (χ), block copolymers with multi-arm star shape chain architecture have a critical segregation strength (χN)C that decreases with arm number, opening a simple route to generate ordered nanostructures with periods below 10 nm.

Core Cross-Linked Multiarm Star Polymers with Aggregation-Induced Emission and Temperature Responsive Fluorescence Characteristics

Aggregation-induced emission (AIE) active core cross-linked multiarm star polymers, carrying polystyrene (PS), polyethylene (PE), or polyethylene-b-polycaprolactone (PE-b-PCL) arms, have been synthesized through an “arm-first” strategy, by atom transfer radical copolymerization (ATRP) of a double styrene-functionalized tetraphenylethene (TPE-2St) used as a cross-linker with linear arm precursors possessing terminal ATRP initiating moieties. Polyethylene macroinitiator (PE–Br) was prepared via the polyhomologation of dimethylsulfoxonium methylide with triethylborane followed by oxidation/hydrolysis and esterification of the produced PE–OH with 2-bromoisobutyryl bromide; polyethylene-block-poly(e-caprolactone) diblock macroinitiator was derived by combining polyhomologation with ring-opening polymerization (ROP). All synthesized star polymers showed AIE-behavior either in solution or in bulk. At high concentration in good solvents (e.g., THF, or toluene) they exhibited low photoluminescence (PL) intensity d...

Synthesis and properties of multiarm star hydroxyl-terminated polyesters for two-component polyurethane coatings

A series of multiarm star hydroxyl-terminated polyesters (MHPs) were synthesized through a “one-pot” method with di-trimethylolpropane as the core molecule, 2,2-dimethylolpropionic acid as the AB2-type monomer, e-caprolactone, and monocarboxylic acids as modifiers. The influence of different monocarboxylic acids on the viscosities of polyesters and their 2K-PU films hardness was studied and it was found that MHPs prepared from lauric acid displayed the higher films hardness and lower viscosities. IR spectra of MHPs disclosed the ring-opening reaction between e-caprolactone and hydroxyl groups occurred. 1H NMR spectra demonstrated that the molecular structures of MHPs were irregular due to the multiplicity of reaction processes. The measured number-average molecular weights (M n) of MHPs were around 715–1854 g/mol with the PDI of 1.45–2.05. MHPs exhibited lower viscosities in the range of 3304–9060 mPa s at 100% solid contents and possessed lower intrinsic viscosities compared with linear polymers of similar molecular weight. The cured films of MHPs exhibited excellent impact resistance, adhesion, flexibility, and high hardness and displayed good thermal stability with 5% weight loss at 280°C. The solution viscosities of MHPs were less than 450 mPa s at 80% solid contents, and the VOC contents of 2K-PU coatings obtained from MHPs were low to 300 g/L.

Sustainable poly(ε-decalactone)−poly(l-lactide) multiarm star copolymer architectures for thermoplastic elastomers with fixed molar mass and block ratio

To improve the thermal and mechanical properties of thermoplastic elastomers derived from plant-based monomers, a series of well-defined multiarm star block copolymers was investigated. Controlled bulk ring-opening polymerization of ε-decalactone (DL) with multiarm initiators yielded hydroxyl-terminated (PDL−OH)n, which were subsequently converted to (PDL−PLLA)n using l-lactide (LLA) through a one-pot, two-step process. The multiarm copolymers were designed for targeting on Mn,NMR and fPLLA of 180 kg mol−1 and 0.27, respectively. Structural analysis proved that PLLA hard domains were thinner, and thus, more compact microphase-separated structures with hexagonally packed cylinders were induced by increasing n. Thermal and tensile property measurement demonstrated that, although the copolymers had a lower crystallinity in PLLA due to the shorter chain length, the thermal degradation stability and mechanical strength were enhanced, which was caused by to an amplified pinning effect caused by the more closed packed PLLA domains, in addition to chemical crosslinking of the PDL strands.

Study of the Molecular Dynamics of Multiarm Star Polymers with a Poly(ethyleneimine) Core and Poly(lactide) Multiarms.

Multiarm star polymers, denoted PEIx-PLAy and containing a hyperbranched poly(ethyleneimine) (PEI) core of different molecular weights x and poly(lactide) (PLA) arms with y ratio of lactide repeat units to N links were used in this work. Samples were preconditioned to remove the moisture content and then characterized by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and dielectric relaxation spectroscopy (DRS). The glass transition temperature, Tg, is between 48 and 50 °C for all the PEIx-PLAy samples. The dielectric curves show four dipolar relaxations: γ, β, α, and α′ in order of increasing temperature. The temperatures at which these relaxations appear, together with their dependence on the frequency, allows relaxation maps to be drawn, from which the activation energies of the sub-Tg γ- and β-relaxations and the Vogel–Fulcher–Tammann parameters of the α-relaxation glass transition are obtained. The dependence of the characteristic features of these relaxations on the molecular weight of the PEI core and on the ratio of lactide repeat units to N links permits the assignation of molecular motions to each relaxation. The γ-relaxation is associated with local motions of the –OH groups of the poly(lactide) chains, the β-relaxation with motions of the main chain of poly(lactide), the α-relaxation with global motions of the complete assembly of PEI core and PLA arms, and the α′-relaxation is related to the normal mode relaxation due to fluctuations of the end-to-end vector in the PLA arms, without excluding the possibility that it could be a Maxwell–Wagner–Sillars type ionic peak because the material may have nano-regions of different conductivity.

An intraocular drug delivery system using targeted nanocarriers attenuates retinal ganglion cell degeneration

Glaucoma is a common blinding disease characterized by loss of retinal ganglion cells (RGCs). To date, there is no clinically available treatment directly targeting RGCs. We aim to develop an RGC-targeted intraocular drug delivery system using unimolecular micelle nanoparticles (unimNPs) to prevent RGC loss. The unimNPs were formed by single/individual multi-arm star amphiphilic block copolymer poly(amidoamine)–polyvalerolactone–poly(ethylene glycol) (PAMAM–PVL–PEG). While the hydrophobic PAMAM–PVL core can encapsulate hydrophobic drugs, the hydrophilic PEG shell provides excellent water dispersity. We conjugated unimNPs with the cholera toxin B domain (CTB) for RGC-targeting and with Cy5.5 for unimNP-tracing. To exploit RGC-protective sigma-1 receptor (S1R), we loaded unimNPs with an endogenous S1R agonist dehydroepiandrosterone (DHEA) as an FDA-approved model drug. These unimNPs produced a steady DHEA release in vitro for over two months at pH7.4. We then co-injected (mice, intraocular) unimNPs with the glutamate analog N-methyl-d-aspartate (NMDA), which is excito-toxic and induces RGC death. The CTB-conjugated unimNPs (i.e., targeted NPs) accumulated at the RGC layer and effectively preserved RGCs at least for 14days, whereas the unimNPs without CTB (i.e., non-targeted NPs) showed neither accumulation at nor protection of NMDA-treated RGCs. Consistent with S1R functions, targeted NPs relative to non-targeted NPs showed markedly better inhibitory effects on apoptosis and oxidative/inflammatory stresses in the RGC layer. Hence, the DHEA-loaded, CTB-conjugated unimNPs represent an RGC/S1R dual-targeted nanoplatform that generates an efficacious template for further development of a sustainable intraocular drug delivery system to protect RGCs, which may be applicable to treatments directed at glaucomatous pathology.

Multiarm star polymers with a thermally cleavable core: A “grafting‐from” approach paves the way

ABSTRACTThermally cleavable multiarm star polymers containing thermo‐reversible furan–maleimide cycloadduct‐based core were synthesized using dendritic macroinitiators. Peripheries of dendritic macroinitiators were modified with bromine containing free radical initiators to obtain multiarm polymers by utilizing atom transfer radical polymerization (ATRP). Cleavage of thus obtained multiarm polymers was achieved via the retro Diels–Alder cycloreversion reaction of the furan–maleimide core at elevated temperatures. As an alternative approach, combination of multiarm polymers containing a furan and maleimide functional group at their core was attempted to realize that the steric bulk does not allow their formation. Hence the “grafting‐from” route using a thermally fragmentable trigger containing multiarm initiators provides a plausible methodology for fabrication of such thermally cleavable multiarm polymeric materials. Syntheses of dendritic initiators, formation of star polymers as well as their fragmentation were followed by proton nuclear magnetic resonance spectroscopy and size exclusion chromatography. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 885–893

Fabrication of injectable high strength hydrogel based on 4-arm star PEG for cartilage tissue engineering.

Hydrogels prepared from poly(ethylene glycol) (PEG) are widely applied in tissue engineering, especially those derived from a combination of functional multi-arm star PEG and linear crosslinker, with an expectation to form a structurally ideal network. However, the poor mechanical strength still renders their further applications. Here we examined the relationship between the dynamics of the pre-gel solution and the mechanical property of the resultant hydrogel in a system consisting of 4-arm star PEG functionalized with vinyl sulfone and short dithiol crosslinker. A method to prepare mechanically strong hydrogel for cartilage tissue engineering is proposed. It is found that when gelation takes place at the overlap concentration, at which a slow relaxation mode just appears in dynamic light scattering (DLS), the resultant hydrogel has a local maximum compressive strength ∼20MPa, while still keeps ultralow mass concentration and Young's modulus. Chondrocyte-laden hydrogel constructed under this condition was transplanted into the subcutaneous pocket and an osteochondral defect model in SCID mice. The invivo results show that chondrocytes can proliferate and maintain their phenotypes in the hydrogel, with the production of abundant extracellular matrix (ECM) components, formation of typical chondrocyte lacunae structure and increase in Young's modulus over 12 weeks, as indicated by histological, immunohistochemistry, gene expression analyses and mechanical test. Moreover, newly formed hyaline cartilage was observed to be integrated with the host articular cartilage tissue in the defects injected with chondrocytes/hydrogel constructs. The results suggest that this hydrogel is a promising candidate scaffold for cartilage tissue engineering.

Synthesis of multiarm star block copolymers via simplified electrochemically mediated ATRP

Star-shaped polymers were received using β-cyclodextrin (β-CD) as core, and methyl methacrylate (MMA) arms via a simplified electrochemically mediated ATRP (seATRP). To demonstrate the living nature of the seATRP, star multiblock copolymers were successfully prepared by chain extension of the ω-functional PMMA arms with a tert-butyl acrylate (tBA), and respectively, n-butyl acrylate (BA). Novelty of this work is that the β-CD-PMMA-b-PtBA-b-PBA multiarm star block copolymers were synthesized for the first time via seATRP procedure, utilizing 4 × 10−6 mol% of CuII complex. The results from 1H NMR spectral studies support the formation of 21-arm star (co)polymers. Furthermore, the GPC traces of the arms detached from synthesized star-like (co)polymers confirms the absence of star–star coupling reactions during seATRP. It was shown as an advantage over other ATRP methods–low catalyst concentrations and narrow molecular mass distributions, while maintaining well-defined composition.