Core Cross-linked Star Polymers Research Articles

Nanoparticle (star polymer) delivery of nitric oxide effectively negates Pseudomonas aeruginosa biofilm formation.

Biofilms are increasingly recognized as playing a major role in human infectious diseases, as they can form on both living tissues and abiotic surfaces, with serious implications for applications that rely on prolonged exposure to the body such as implantable biomedical devices or catheters. Therefore, there is an urgent need to develop improved therapeutics to effectively eradicate unwanted biofilms. Recently, the biological signaling molecule nitric oxide (NO) was identified as a key regulator of dispersal events in biofilms. In this paper, we report a new class of core cross-linked star polymers designed to store and release nitric oxide, in a controlled way, for the dispersion of biofilms. First, core cross-linked star polymers were prepared by reversible addition-fragmentation chain transfer polymerization (RAFT) via an arm first approach. Poly(oligoethylene methoxy acrylate) chains were synthesized by RAFT polymerization, and then chain extended in the presence of 2-vinyl-4,4-dimethyl-5-oxazolone monomer (VDM) with N,N-methylenebis(acrylamide) employed as a cross-linker to yield functional core cross-linked star polymers. Spermine was successfully attached to the star core by reaction with VDM. Finally, the secondary amine groups were reacted with NO gas to yield NO-core cross-linked star polymers. The core cross-linked star polymers were found to release NO in a controlled, slow delivery in bacterial cultures showing great efficacy in preventing both cell attachment and biofilm formation in Pseudomonas aeruginosa over time via a nontoxic mechanism, confining bacterial growth to the suspended liquid.

PH‐Induced Inversion of Water‐in‐Oil Emulsions to Oil‐in‐Water High Internal Phase Emulsions (HIPEs) Using Core Cross‐Linked Star (CCS) Polymer as Interfacial Stabilizer

A pH-responsive core cross-linked star (CCS) polymer containing poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) arms was used as an interfacial stabilizer for emulsions containing toluene (80 v%) and water (20 v%). In the pH range of 12.1-9.3, ordinary water-in-oil emulsions were formed. Intermediate multiple emulsions of oil-in-water-in-oil and water-in-oil-in-water were formed at pH 8.6 and 7.5, respectively. Further lowering the pH resulted in the formation of gelled high internal phase emulsions of oil-in-water type in the pH range of 6.4-0.6. The emulsion behavior was correlated with interfacial tension, conductivity and configuration of the CCS polymer at different pH.

A highly efficient macromonomer approach to core cross-linked star (CCS) polymers via one-step RAFT emulsion polymerization

We have developed a highly efficient, one-step approach for the synthesis of core cross-linked star (CCS) polymers using commercial macromonomers (polyethylene glycol methyl ether methacrylates) as the arms via RAFT-mediated emulsion polymerization in aqueous media. This approach employs a small molecular chain transfer agent (CTA), commercial macromonomer, hydrophobic cross-linker, and optional hydrophobic spacing monomer as the polymerization recipe to synthesize CCS polymers via direct one-step polymerization in aqueous buffer solution. Various polymerization parameters, including buffer concentration and molar ratio of macromonomer/cross-linker/spacing monomer relative to CTA, were investigated. CCS polymers of high yield and low dispersity were obtained within 4 h under a wide range of conditions. Analysis of polymerization kinetics and macromolecular parameters of the generated polymeric species during the polymerization process led to insights into the mechanistic aspects of the CCS formation process, which was proposed to involve three stages, i.e., polymer chain growth, cross-linking to form CCS, and CCS growth. Finally, synthesis of CCS polymers using macromonomers of different molecular weights pointed to the necessity for optimization of the polymerization conditions for each macromonomer, possibly due to different polymerization rates and steric hindrance.

Synthesis of soluble core cross-linked polystyrene star polymer by application of acrylate-nitrile oxide ‘click chemistry’ using metal-free reagents

In the present work, we have established a novel and environmentally benign method, whereby a 1,3-dipolar cycloaddition reaction has been applied using a non-toxic reagent, iodosobenzenediacetate [PhI(OAc)2], instead of the conventional copper-based reagents for the development of star-branched polymers. Here we have demonstrated the synthesis of core cross-linked star (CCS) polymers via the formation of isoxazoline ring using ‘click reaction’ between acrylate functionalities in a polymer chain and in situ generated nitrile oxide groups from a cross-linker added externally. In the initial step, a well-defined styrenic block copolymer with acrylate-functionalized middle-block was synthesized by controlled radical polymerization (RAFT) using α,α′-xylyl-bis(dithiobenzoate) as a chain transfer agent using 4-vinyl benzyl chloride and styrene as comonomers. Thereafter, the chlorobenzyl groups were converted into acrylate by reaction with acrylic acid. In the following step, core cross-linked star (CCS) polymers were synthesized by reacting the above block copolymer and oxime-functionalized cross-linkers (bi- and tetra-functional) using PhI(OAc)2 ‘click chemistry’. Formation of CCS polymers was confirmed from NMR, FTIR, GPC and DLS studies.

Core cross-linked star (CCS) polymers with temperature and salt dual responsiveness: synthesis, formation of high internal phase emulsions (HIPEs) and triggered demulsification

Temperature and salt dually responsive core cross-linked star (CCS) polymers can effectively stabilize high internal phase emulsions (HIPEs) that show temperature and salt dual responsiveness.

Biodegradable core crosslinked star polymer nanoparticles as19F MRI contrast agents for selective imaging

With the aim of developing stimuli-responsive imaging agents, we report here the synthesis of core crosslinked star (CCS) polymers and their evaluation as pH-sensitive 19F magnetic resonance imaging (19F MRI) contrast agents. Block copolymers consisting of poly(ethylene glycol)methyl ether methacrylate (PPEGMA) as the first block and a copolymer of 2-(dimethylamino)ethyl methacrylate (DMAEMA) and 2,2,2-trifluoroethyl methacrylate (TFEMA) as the second block were synthesised using RAFT polymerisation. The polymerisation kinetics were studied in detail. The block copolymers were then used as arm precursors for the arm-first synthesis of CCS polymers through RAFT dispersion polymerisation. The synthetic conditions were investigated and optimised. CCS polymers with a degradable core were also synthesised and evaluated as 19F MRI contrast agents. The degradation of the core was confirmed by treatment with various reducing agents. The particle size, 19F NMR signal and relaxation times as well as 19F MRI imaging performance of the CCS polymers were studied at a range of value of solution pH. Significant enhancement of the image intensity was observed when the pH was decreased from 8 to 5, indicating that the CCS nanoparticles could be used as 19F MRI contrast agents for the detection of the acidic environment within tumour tissue.

Synthesis of core cross-linked star polystyrene with functional end groups and self-assemblies templated by breath figures

We report the synthesis of core cross-linked star (CCS) polymers with functional end groups for self-assembled films, which show mono-layer and multi-layer transition, depending on arm numbers, arm length, and end groups.

Development of amphiphilic multi-star polymers with highly grafted pyrene connectors as unimolecular encapsulation devices

Complex and hierarchically structured unimolecular polymeric architectures provide unique opportunities for self-assembly, encapsulation, segregation and recognition. Herein, we report the synthesis of unimolecular anisotropic and amphiphilic multi-star architectures consisting of multiple discrete core cross-linked star (CCS) polymers covalently tethered together through highly grafted polymeric connectors. These multi-star architectures, referred to as di-star and tri-star polymers, were prepared via a combination of atom transfer radical polymerisation (ATRP) and a copper-catalysed azide-alkyne cycloaddition (CuAAC) grafting-to approach. Initially, poly(tert-butyl methacrylate) (PtBMA)-based multi-star polymers with polyalkyne linear connectors were prepared via ATRP and the arm-first approach. Following isolation of the individual di-star and tri-star polymers, an azido-pyrene derivative was grafted onto the connectors via click chemistry with grafting efficiencies of 88 and 84%, respectively. Subsequently, hydrolysis of the PtBMA star arms provided amphiphilic poly(methacrylic acid) (PMAA)-based multi-stars with pyrene grafted connectors. The ability of the unimolecular di-star polymer to sequester and stabilise hydrophobic guests in aqueous solutions via π–π stacking interactions was investigated through the encapsulation of the anticancer drug pirarubicin. UV measurements provided loading capabilities of ca. 135 molecules of pirarubicin per di-star polymer (ca. 12 wt%).

The precise molecular location of gadolinium atoms has a significant influence on the efficacy of nanoparticulate MRI positive contrast agents

In this work, we studied the influence of the structure of macromolecular ligands on the relaxivity of gadolinium contrast agents constructed as nanoparticle systems. Macromolecular ligands were assembled as single-molecule nanoparticles in the form of either discrete core cross-linked star polymers or hyperbranched polymers. 1-(5-Amino-3-aza-2-oxypentyl)-4,7,10-tris(tert-butoxycarbonylmethyl)-1,4,7,10-tetraaza-cyclododecane (DO3A–tBu–NH2) chelate was incorporated into different parts (arms, cores, and end-groups) of the polymeric structures using activated ester/amine nucleophilic substitutions, deprotected and complexed with Gd3+. The relaxivity properties of the ligated Gd3+ agents were then studied to evaluate the effect of macromolecular architecture and Gd3+ placement on their behavior as discrete nanoparticle magnetic resonance imaging (MRI) contrast agents. The precise placement of Gd3+ in the polymeric structures (and therefore in the nanoparticles) proved to be critical in optimizing the performance of the nanoparticles as MRI contrast agents. The relaxivity was measured to vary from 11 to 22 mM−1 s−1, 2–5 times higher than that of a commercial DOTA–Gd contrast agent when using a magnetic field strength of 0.47 T. The relaxivity of these nanoparticles was examined at different magnetic fields from 0.47 T to 9.4 T. Finally, the residence time of the coordinated water (τM) and the rotational correlation time of the final molecule (τR) were evaluated for these different nanostructures and correlated with the polymeric architecture.

Azobenzene-Functionalised Core Cross-Linked Star Polymers and their Host–Guest Interactions

Water-soluble poly(2-hydroxyethyl acrylate) (PHEA)-based core cross-linked star polymers were efficiently synthesised with high macroinitiator-to-star-conversion (>95 %) in a one-pot system via single electron transfer-living radical polymerisation. The star polymers display excellent water solubility and the pendant hydroxyl groups provide a platform for facile post-functionalisation with various molecules. In demonstrating this, a photo-isomerisable molecule, 4-(phenylazo)benzoic acid was conjugated onto the preformed stars through partial esterification of the available hydroxyl groups (5–20 %). The azobenzene functionalised stars were subsequently employed to form reversible inclusion complexes with α-cyclodextrin.

Synthesis of Anisotropic, Amphiphilic Grafted Multi-Star Polymers and Investigation of their Self-Assembling Characteristics

Herein, we report the synthesis of amphiphilic multi-star architectures consisting of discrete poly(methacrylic acid)-based core cross-linked star polymers joined together by polystyrene-grafted linear connectors by a combination of atom transfer radical polymerisation of protected macroinitiator precursors and a copper-catalysed azide-alkyne cycloaddition grafting-to approach. The anisotropic multi-star architectures, which were obtained as individual di- and tri-star polymers with segregated hydrophobic and hydrophilic domains, undergo aggregation in apolar solvents resulting in the formation of large nanometre-scale vesicles. The self-assembling behaviour of these large amphiphilic multi-star polymers (Mw = 869–1097 kDa) was studied using dynamic light scattering, transmission electron microscopy, and atomic force microscopy.

Emerging Synthetic Strategies for Core Cross‐Linked Star (CCS) Polymers and Applications as Interfacial Stabilizers: Bridging Linear Polymers and Nanoparticles

Core cross-linked star (CCS) polymers become increasingly important in polymer science and are evaluated in many value-added applications. However, limitations exist to varied degrees for different synthetic methods. It is clear that improvement in synthetic efficiency is fundamental in driving this field moving even further. Here, the most recent advances are highlighted in synthetic strategies, including cross-linking with cross-linkers of low solubility, polymerization-induced self-assembly in aqueous-based heterogeneous media, and cross-linking via dynamic covalent bonds. The understanding of CCS polymers is also further refined to advocate their role as an intermediate between linear polymers and polymeric nanoparticles, and their use as interfacial stabilizers is rationalized within this context.

Stimuli‐responsive star polymers

ABSTRACTStimuli‐responsive star polymers gain more and more interest over the last decades due to their unique properties compared to their linear counterparts. The branched structure for instance has influence on the responsive behavior of these polymers. This review offers an overview of stimuli‐responsive star polymers generated by different polymerization techniques, e.g. anionic and controlled radical polymerization (CRP). Beside conventional branched homopolymers different other types like block copolymers, miktoarm star copolymers, core crosslinked star polymers (CCS) and comb polymers are also presented. Furthermore their responsive behavior in solution or immobilized on a substrate, and their applications are outlined. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2980–2994

Nanoprecipitation of PMMA Stabilized by Core Cross‐Linked Star Polymers

AbstractNanoprecipitation of poly(methyl methacrylate) (PMMA) in the presence of water‐soluble core cross‐linked star (CCS) polymers is investigated. Slowly dropping water into DMF solutions containing PMMA and CCS polymers of varying compositions produces colloidally stable particles with CCS polymers being effectively incorporated. During the solvent‐shifting process, CCS polymers migrate to and concentrate at the particle surface to stabilize the formed particles, which is confirmed by X‐ray photoelectron spectroscopy, transmission electron microscopy, and contact angle measurements. This stabilizing effect is realized via the steric effect of the CCS polymers adsorbed at the particle surface. magnified image

PH-responsive high internal phase emulsions stabilized by core cross-linked star (CCS) polymers

Well-defined core cross-linked star (CCS) polymers of poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) were prepared via cross-linking copolymerization in an aqueous-based dispersion polymerization system, mediated by reversible addition–fragmentation chain transfer (RAFT) polymerization. The synthesized CCS polymers were characterized by nuclear magnetic resonance (NMR) spectroscopy, gel permeation chromatography (GPC), dynamic light scattering (DLS), and conductivity and zeta potential measurements. The use of PDMAEMA CCS polymers as effective emulsifiers for oil-in-water emulsions was investigated. Interfacial tension measurements showed that the CCS polymer reduced the interfacial tension between water and oil in a pH-dependent manner. Gelled high internal phase emulsions (HIPEs) were formed at high oil fractions (80–89 vol%) and over a wide range of pH values (2–12). The HIPEs were characterized by conductivity, confocal laser scanning microscopy (CLSM) and rheology. The emulsion properties in terms of oil droplet size, long-term stability and rheology were pH-dependent. Complete demulsification of HIPEs was easily realized 2 min after the addition of base. The CCS-stabilized HIPEs were used as templates to prepare porous hydrophilic polymers by polymerizing the monomers in the continuous aqueous phase. The study presented herein reveals that responsive CCS polymers can be used as effective stabilizers for the formation of responsive HIPEs, which have a wide range of applications.

Core cross-linked star (CCS) polymers with tunable polarity: synthesis by RAFT dispersion polymerization, self-assembly and emulsification

Homoarm and heteroarm core cross-linked star (CCS) polymers based on poly(N,N-dimethylacrylamide) (PDMA) as the high-polarity arm and poly(2-methoxyethylacrylate) (PMEA) as the low-polarity arm were efficiently prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization in a dispersion polymerization system. PDMA and PMEA arm polymers exhibited similar conversion rates, such that their composition in the heteroarm CCS polymers was easily controlled by the feed ratio in the synthesis. The ability to control the arm composition allowed facile tuning of the polarity of the CCS polymers. Heteroarm CCS polymers self-assembled in water to form aggregates and their size was related to the composition and polarity of the CCS polymers. The composition and polarity of the CCS polymers significantly affected the emulsifying behaviour of the CCS polymers as emulsifiers. Oil-in-water (o/w) emulsions were favoured for CCS polymers with relatively high polarity and lowering the polarity of CCS polymers to a certain degree enhanced the stability of the emulsions. Multiple emulsions, both o/w and water-in-oil (w/o), were gradually produced when the polarity of CCS polymers was gradually lowered and the oil fraction in the emulsion samples was gradually increased, and at the same time the emulsions also became increasingly less stable.

RAFT emulsion polymerization of styrene mediated by core cross-linked star (CCS) polymers

Core cross-linked star (CCS) polymers of poly(N,N-dimethylacrylamide) (PDMA) were prepared and explored as macromolecular chain transfer agents (Macro-CTAs) in the emulsion polymerization of styrene. The mass ratio of styrene : CCS and the solid content were systematically varied to elucidate their effect on the size and morphology of the particles. Control experiments using linear PDMA as a Macro-CTA were also performed in order to understand the mechanistic difference in CCS-mediated emulsion polymerization. While a two-phase process was typical of emulsion polymerization using linear Macro-CTAs, the CCS polymers functioned as “seeds” for the emulsion polymerization of styrene and exhibited a much higher polymerization rate. Significant clustering of spherical particles was observed when the mass ratio of styrene : CCS was increased while maintaining the solid content. On the other hand, linear and branched fibers were observed when the solid content was increased while maintaining the mass ratio of styrene : CCS. This morphology transformation is unique to CCS-mediated emulsion polymerization, and a protrusion mechanism caused by the cross-links in the core of the CCS was proposed to account for the aggregation of spherical particles into clusters or fibers.

Quantitative formation of core cross-linked star polymers via a one-pot two-step single electron transfer-living radical polymerization

A novel and highly efficient one-pot two-step strategy towards core cross-linked star polymers based on single electron transfer-living radical polymerization (SET-LRP) is described. Macroinitiators with high end-group fidelity were generated at high monomer conversions prior to the addition of cross-linkable monomers in the same pot to induce the formation of star polymers. Quantitative (>99%) star formation is achieved without the purification of unreacted monomers or macroinitiators.

A novel cyclodextrin-containing pH-responsive star polymer for nanostructure fabrication and drug delivery

A novel cyclodextrin-containing star polymer was synthesized by atom transfer radical polymerization using the arm-first approach. Copolymerization of a mixture of mono- and multi-methacrylate substituted cyclodextrin and 2-(dimethylamino) ethyl methacrylate initiated by poly(ethylene glycol) macroinitiator produced a core cross-linked star polymer. The star polymer could self-assemble into nanostructures via host–guest interactions between the cyclodextrin polymer and hydrophobic guest molecules. The morphologies of these nanostructures showed regular transitions by altering the type of guest molecule, the ratio of star polymer to guest, and the pH of the solution. Furthermore, doxorubicin (DOX) was entrapped into the star polymer for the purpose of drug delivery. In vitro experiments demonstrated that the DOX-loaded nanoparticles could release their payload in response to the endosomal-pH after being internalized by HeLa cell via endocytosis. At high DOX concentration, DOX-loaded nanoparticles showed significantly higher cell cytotoxicity compared to the free drug. The results indicate that the star polymer has great promise for potential anticancer treatment.

Synthesis of Novel Core Cross‐Linked Star‐Based Polyrotaxane End‐Capped via “CuAAC” Click Chemistry

The first example of core cross-linked star (CCS) polyrotaxane was prepared using the poly(ϵ-caprolactone) (PCL) CCS three-dimensional (3D) scaffold. The 3D CCS polymer was firstly prepared through the "arm-first" approach. Then, the "arms" of the resultant PCL CCS polymer were threaded with α-cyclodextrins (α-CDs). The threaded α-CDs were permanently locked by the "click" reaction of terminal alkyne functionalities of the star polymers with the azide-functionalized end caps to afford the CCS polyrotaxanes. All analytical results confirm the formation of the CCS polyrotaxanes and reveal their characteristics, including fluorescence under UV, a channel-type crystalline structure, a two-step thermal decomposition, and a unique core-shell structure in great contrast to the polymer precursors.