Cyclic Brush Research Articles

A cyclic brush zwitterionic polymer based pH-responsive nanocarrier-mediated dual drug delivery system with lubrication maintenance for osteoarthritis treatment.

Enhanced joint synergistic lubrication combined with anti-inflammatory therapy is an effective strategy to delay the progression of early osteoarthritis (OA) but has been rarely reported. The hydration lubrication of zwitterions and inherent super-lubrication properties of the cyclic brush, as well as the enhancement of the steric stability of the cyclic topology, can effectively improve the drug loading and utilization; herein we report a pH-responsive cyclic brush zwitterionic polymer (CB) with SBMA and DMAEMA as brushes and a cyclic polymer (c-P(HEMA)) as the core template, possessing a low coefficient of friction (0.017). After loading with hydrophobic curcumin and hydrophilic loxoprofen sodium it demonstrates high drug-loading efficiency. In vitro and in vivo experiments confirmed the triple function of the CB on superlubrication, sequence controlled release and anti-inflammatory effects demonstrated by Micro CT, histological analysis and qRT-PCR. Overall, the CB is a promising long-acting lubricating therapeutic agent, with potential for OA treatment or other diseases.

Aqueous Self-Assembly of Amphiphilic Cyclic Brush Block Copolymers as Asymmetry-Tunable Building Blocks

Cyclic brush (cb) copolymers that are composed of a cyclic core densely grafted with radiating polymer brushes have emerged recently as innovative materials for both fundamental and practical inves...

Fabrication of Cyclic Brush Copolymers with Heterogeneous Amphiphilic Polymer Brushes for Controlled Drug Release

Cyclic brush (cb) copolymers that are composed of a cyclic core densely grafted with radiating polymer brushes have emerged recently as innovative materials for both fundamental and practical investigations due to their capability to form unimolecular micelles with greater stability relative to the analogues self-assembled by the bottlebrush (bb) copolymers with an identical molecular weight (MW). However, compared to the extensive and intensive studies on cb copolymers with homogeneous polymer brushes, the preparation and application of cb copolymers with heterogeneous polymer grafts remains unexplored likely due to the synthetic challenge. For this purpose, we reported in this study the first preparation of cb copolymers with heterogeneous polymer brushes using a diblock copolymer-based cyclic core template. An amphiphilic cb copolymer with both hydrophilic oligo (ethylene glycol) (OEG) and hydrophobic oligo (e-caprolactone) (OCL) brushes grafting from a cyclic core was designed and synthesized by a com...

Fabrication of Reduction-Sensitive Amphiphilic Cyclic Brush Copolymer for Controlled Drug Release.

The cyclic brush polymers, due to the unique topological structure, have shown in the previous studies higher delivery efficacy than the bottlebrush analogues as carriers for drug and gene transfer. However, to the best of knowledge, the preparation of reduction-sensitive cyclic brush polymers for drug delivery applications remains unexplored. For this purpose, a reduction-sensitive amphiphilic cyclic brush copolymer, poly(2-hydroxyethyl methacrylate-g-poly(ε-caprolactone)-disulfide link-poly(oligoethyleneglycol methacrylate)) (P(HEMA-g-PCL-SS-POEGMA)) with reducible block junctions bridging the hydrophobic PCL middle layer and the hydrophilic POEGMA outer corona is designed and synthesized successfully in this study via a "grafting from" approach using sequential ring-opening polymerization (ROP) and atom transfer free radical polymerization (ATRP) from a cyclic multimacroinitiator PHEMA. The resulting self-assembled unimolecular core-shell-corona (CSC) micelles show sufficient salt stability and efficient destabilization in the intracellular reducing environment for a promoted drug release toward a greater therapeutic efficacy relative to the reduction-insensitive analogues. The overall results demonstrate the reducible cyclic brush copolymers developed herein provides an elegant solution to the tradeoff between extracellular stability and intracellular high therapeutic efficacy toward efficient anticancer drug delivery.

Fabrication of Thermosensitive Cyclic Brush Copolymer with Enhanced Therapeutic Efficacy for Anticancer Drug Delivery.

Adaptation of cyclic brush polymer for drug delivery applications remains largely unexplored. Herein, cyclic brush copolymer of poly(2-hydroxyethyl methacrylate-g-poly(N-isopropylacrylamide-st-N-hydroxyethylacrylamide)) (cb-P(HEMA-g-P(NIPAAm-st-HEAAm))), comprising a cyclic core of PHEMA and thermosensitive brushes of statistical copolymer of P(NIPAAm-st-HEAAm), is designed and synthesized successfully via a graft-from approach using atom transfer free radical polymerization from a cyclic multimacroinitiator. The composition of the brush is optimized to endow the resulting cyclic brush copolymer with a lower critical solution temperature (LCST) slightly above the physiological temperature, but lower than the localized temperature of tumor tissue, which is suitable for the hyperthermia-triggered anticancer drug delivery. Critical aggregation concentration determination reveals better stability for the unimolecular nanoparticle formed by the cyclic brush copolymer than that formed by the bottlebrush analogue. The dramatically increased size with elevated temperatures from below to above the LCST confirms hyperthermia-induced aggregation for both formulations. Such structural destabilization promotes significantly the drug release at 40 °C. Most importantly, the drug-loaded cyclic brush copolymer shows enhanced in vitro cytotoxicity against HeLa cells than the bottlebrush counterpart. The better stability and higher therapeutic efficacy demonstrates that the thermosensitive cyclic brush copolymer is a better formulation than bottle brush copolymer for controlled drug release applications.

Synthesis and Phase Transition of Poly(N-isopropylacrylamide)-Based Thermo-Sensitive Cyclic Brush Polymer.

Polymers with advanced topological architectures are promising materials for wide applications due to their structure-generated unique properties different from that of the linear analogues. The elegant integration of stimuli-responsive polymers with such advanced architectures can create novel materials with virtues from both moieties, are thus a hot subject of research for both fundamental and practical investigations. To fabricate cyclic brush polymer-based intelligent materials for biomedical applications, herein, we designed and synthesized thermo-sensitive cyclic brush polymers with poly(N-isopropylacrylamide) (PNIPAAm) brushes by controlled living radical polymerization using cyclic multimacroinitiator. The thermo-induced phase transition behaviors of the resultant cyclic brush polymers with different compositions were investigated in detail by temperature-dependent optical transmittance measurements, and compared with the properties of bottlebrush and linear counterparts. Interestingly, the cloud point transition temperature (Tcp) of cyclic brush PNIPAAm could be regulated by the chain length of PNIPAAm brush. Although the bottlebrush polymers with the same composition exhibited similarly structurally dependent Tcps behaviors to the cyclic brush polymers, the cyclic brush PNIPAAm did show higher critical aggregation concentration (CAC) and enhanced stability against dilution than the bottlebrush counterpart. The readily tailorable Tcps together with the ability to form highly stable nanoparticles makes thermo-sensitive cyclic brush PNIPAAm a promising candidate for controlled drug delivery.

Cyclic polymers as a building block for cyclic brush polymers and gels

Cyclic polymers, as one of the oldest topological polymers, are undergoing resurgence. This is largely ascribed to the significant achievements in modern polymer chemistry. The novel ring-expansion techniques have conveniently produced varied cyclic polymers with highly topological purity and on large scales, which should facilitate their use in the near future. Beyond the monocyclic molecular conformations, the combination of controlled polymerization techniques and click chemistry have established a robust strategy for preparing cyclic polymers with more complex architectures, such as theta, eight, and tadpole shapes. This diversification in cyclic polymer composition and conformation significantly broadens interest in the cyclic polymers. However, compared to the synthesis achievements, the exploration of cyclic polymer property and application are lagging behind. Recently, we explored the ring-expansion metathesis polymerization on various functional ring-strained olefin monomers to produce cyclic functional polymers, which were then used as the building blocks to fabricate cyclic brush polymers and cyclic gel materials and will be discussed here.

Metallo-Supramolecular Cyclic Polymers

Cyclic brush polymers represent an exciting new macromolecular topology. For the first time, this new topology has been combined with metallo-supramolecular interactions to construct novel cyclic brush polymers. Here, ring-expansion metathesis polymerization was used to synthesize a universal cyclic template with a polynorbornene backbone, which was further modified with the metal-chelating synthon terpyridine. The terpyridine side chains served as the key supramolecular unit for the creation of cyclic polymer brushes and gels. This metallo-supramolecular functionality allowed direct visualization of the cyclic brush polymers by transmission electron microscopy for the first time. This demonstration should open a new area in which supramolecular interactions are used to build an array of novel cyclic brush copolymers as well as other cyclic-polymer-based architectures generating new materials.

Cyclic Brush Polymers by Combining Ring-Expansion Metathesis Polymerization and the "Grafting from" Technique.

A novel synthetic route to cyclic brush polymers was developed by combining ring-expansion metathesis polymerization (REMP) and the "grafting from" technique. In this approach, ultrahigh molecular weight cyclic polymers with hydroxyl side groups were synthesized first by REMP to form the cyclic macroinitiators. Polyester side chains were then grown from these cyclic macroinitiators by virtue of a triazabicyclodecene-catalyzed cyclic ester ring-opening polymerization to produce the cyclic brush polymers.

Synthesis and Direct Imaging of Ultrahigh Molecular Weight Cyclic Brush Polymers

Convenient route to cyclic polymers: Ultrahigh molecular weight cyclic brush polymers were synthesized through ring-expansion metathesis polymerization of various macromonomers. Atomic force microscopy was used to visualize toroidal shapes and large opening pores, along with linear chains, which may result from high sensitivity of brush polymers to mechanical degradation.

Synthesis and Direct Imaging of Ultrahigh Molecular Weight Cyclic Brush Polymers

Bequemer Zugang zu cyclischen Polymeren: Cyclische Bürstenpolymere mit sehr hohem Molekulargewicht wurden durch Ringerweiterungsmetathese-Polymerisation verschiedenster Makromonomere synthetisiert. Mithilfe von Rasterkraftmikroskopie wurden toroidale Formen und große Porenöffnungen sichtbar gemacht. Die ebenfalls beobachtete Bildung von linearen Polymeren kann der Anfälligkeit von Bürstenpolymeren gegen mechanischen Abbau zugeschrieben werden. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.