Copolymer Brushes Research Articles

Cytocompatible, soft and thick brush-modified scaffolds with prolonged antibacterial effect to mitigate wound infections.

Biomedical device or implant-associated infections caused by pathogenic bacteria are a major clinical issue, and their prevention and/or treatment remains a challenging task. Infection-resistant antimicrobial coatings with impressive cytocompatibility offer a step towards addressing this problem. Herein, we report a new strategy for constructing highly antibacterial as well as cytocompatible mixed polymer brushes onto the surface of 3D printed scaffold made of biodegradable tartaric acid-based aliphatic polyester blends. The mixed brushes were nothing but a combination of poly(3-dimethyl-(methacryloyloxyethyl) ammonium propane sulfonate) (polyDMAPS) and poly((oligo ethylene glycol) methyl ether methacrylate) (polyPEGMA) with varying chain length (n) of the ethylene glycol unit (n = 1, 6, 11, and 21). Both homo and copolymeric brushes of polyDMAPS with polyPEGMA exhibited antibacterial efficacy against both Gram positive and Gram negative pathogens such as E. coli (Escherichia coli) and S. aureus (Staphylococcus aureus) because of the combined action of bacteriostatic effects originating from strongly hydrated layers present in zwitterionic (polyDMAPS) and hydrophilic (polyPEGMA) copolymer brushes. Interestingly, a mixed polymer brush comprising polyDMAPS and polyPEGMA (ethylene glycol chain unit of 21) at 50/50 ratio provided zero bacterial growth and almost 100% cytocompatibility (tested using L929 mouse fibroblast cells), making the brush-modified biodegradable substrate an excellent choice for an infection-resistant and cytocompatible surface. An attempt was made to understand their extraordinary performance with the help of contact angle, surface charge analysis and nanoindentation study, which revealed the formation of a hydrophilic, almost neutral, very soft surface (99.99% reduction in hardness and modulus) after modification with the mixed brushes. This may completely suppress bacterial adhesion. Animal studies demonstrated that these brush-modified scaffolds are biocompatible and can mitigate wound infections. Overall, this study shows that the fascinating combination of an infection-resistant and cytocompatible surface can be generated on biodegradable polymeric surfaces by modulating the surface hardness, flexibility and hydrophilicity by selecting appropriate functionality of the copolymeric brushes grafted onto them, making them ideal non-leaching, anti-infective, hemocompatible and cytocompatible coatings for biodegradable implants.

Thermoresponsive block copolymer brush for temperature-modulated hepatocyte separation.

Hepatic tissue engineering may be an effective approach for the treatment of liver disease; however, its practical application requires hepatic cell separation technologies that do not involve cell surface modification and maintain cell activity. In this study, we developed hepatocyte cell separation materials using a thermoresponsive polymer and a polymer with high affinity to hepatocytes. A block copolymer of poly(N-p-vinylbenzyl-O-β-D-galactopyranosyl-(1→4)-D-gluconamide) (PVLA) and poly(N-isopropylacrylamide) (PNIPAAm) [PVLA-b-PNIPAAm] was prepared through two steps of atom transfer radical polymerization. On the prepared PVLA-b-PNIPAAm brush, HepG2 cells (model hepatocytes) adhered at 37 °C and detached at 20 °C, attributed to the temperature-modulated affinity between PVLA and HepG2. Cells from the immortalized human hepatic stellate cell line (TWNT-1) did not adhere to the copolymer brush, and RAW264.7 cells (mouse macrophage; model Kupffer cells) adhered to the copolymer brush, regardless of temperature. Using the difference in cell adhesion properties on the copolymer brush, temperature-modulated cell separation was successfully demonstrated. A mixture of HepG2, RAW264.7, and TWNT-1 cells was seeded on the copolymer brush at 37 °C for adherence. By reducing the temperature to 20 °C, adhered HepG2 cells were selectively recovered with a purity of approximately 85% and normal activity. In addition, induced pluripotent stem (iPS) cell-derived hepatocytes adhered on the PVLA-b-PNIPAAm brush at 37 °C and detached from the copolymer brush at 20 °C, whereas the undifferentiated iPS cells did not adhere, indicating that the prepared PVLA-b-PNIPAAm brush could be utilized to separate hepatocyte differentiated and undifferentiated cells. These results indicated that the newly developed PVLA-b-PNIPAAm brush can separate hepatic cells from contaminant cells by temperature modulation, without affecting cell activity or modifying the cell surface. Thus, the copolymer brush is expected to be a useful separation tool for cell therapy and tissue engineering using hepatocytes.

Bottlebrush copolymers for gene delivery: influence of architecture, charge density, and backbone length on transfection efficiency.

The influence of polymer architecture of polycations on their ability to transfect mammalian cells is probed. Polymer bottle brushes with grafts made from partially hydrolysed poly(2-ethyl-2-oxazoline) are used while varying the length of the polymer backbone as well as the degree of hydrolysis (cationic charge content). Polyplex formation is investigated via gel electrophoresis, dye-displacement and dynamic light scattering. Bottle brushes show a superior ability to complex pDNA when compared to linear copolymers. Also, nucleic acid release was found to be improved by a graft architecture. Polyplexes based on bottle brush copolymers showed an elongated shape in transmission electron microscopy images. The cytotoxicity against mammalian cells is drastically reduced when a graft architecture is used instead of linear copolymers. Moreover, the best-performing bottle brush copolymer showed a transfection ability comparable with that of linear poly(ethylenimine), the gold standard of polymeric transfection agents, which is used as positive control. In combination with their markedly lowered cytotoxicity, cationic bottle brush copolymers are therefore shown to be a highly promising class of gene delivery vectors.

Diblock and Random Antifouling Bioactive Polymer Brushes on Gold Surfaces by Visible‐Light‐Induced Polymerization (SI‐PET‐RAFT) in Water

AbstractSurface‐initiated photoinduced electron‐transfer‐reversible addition–fragmentation chain transfer (SI‐PET‐RAFT) is, for the first time, used for the creation of antifouling polymer brushes on gold surfaces based on three monomers: oligo(ethylene glycol) methyl ether methacrylate (MeOEGMA), N‐(2‐hydroxypropyl) methacrylamide (HPMA), and carboxybetaine methacrylamide (CBMA). These coatings are subsequently characterized by X‐ray photoelectron spectroscopy (XPS) and ellipsometry. The living nature of this polymerization allows for the creation of random and diblock copolymer brushes, which are based on HPMA (superb antifouling) and CBMA (good antifouling and functionalizable via activated ester chemistry). The polymer brushes demonstrate good antifouling properties against undiluted human serum, as monitored by quartz crystal microbalance with dissipation (QCM‐D) and surface plasmon resonance (SPR) spectroscopy in real time. The amount of immobilization of bioactive moieties, here an antibody immobilized using N‐succinimidyl ester–1‐ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide hydrochloride (NHS–EDC) coupling, in the diblock and random copolymer brushes is monitored by SPR, and is analyzed with respect to the brush structure, and is shown to be superior in the diblock copolymer brush. This approach represents a scalable, robust, mild, oxygen‐tolerant, and heavy‐metal‐free route toward the production of antifouling and functional copolymer brushes (on gold surfaces) that open up applications in biosensing and tissue engineering.

One-Shot synthesis of heterografted brush copolymers through orthogonal Ring-Opening polymerization and atom transfer radical polymerization

• One-shot heterografted brush copolymers synthesis based on simultaneously orthogonal ring-opeing polymerization (ROP) and atom transfer radical polymerization (ATRP). • The dule role of DBU as the catalyst of ROP and the ligand of ATRP. • Brush copolymers with biodegradable polycarbonates or polyesters and poly(meth)acrylates or polystyrenes heterografts. • The self-assemble of the amphiphilic brush copolymer prepared with the one-shot method. The characteristics of brush copolymers enable them applicable materials in catalysis, pharmaceutical and compatibilizer, and the scope of the application could be greatly expanded through the regulating of grafted branches. In this manuscript, the one-shot orthogonal preparation of heterografted brush copolymers has been achieved successfully with 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) as the catalyst of ring-opening polymerization (ROP) and ligand of atom transfer radical polymerization (ATRP), avoiding the tedious purification processes in the two-step procedure for the synthesis of heterografted brush copolymers. Well-defined brush copolymers with various contents of poly(trimethylene carbonate) (PTMC) and poly( tert -butyl methacrylate) (P t BMA) graftings have been successfully prepared and the range of this method was further evaluated with a variety of cyclic and vinyl monomers in one-shot. Amphiphilic brush copolymer has also been successfully prepared allowing for the formation of micelles in water through self-assembling.

Grafting copolymer brushes on polyhedral oligomeric silsesquioxanes silsesquioxane-decorated silica stationary phase for hydrophilic interaction liquid chromatography

A strategy is proposed to develop a stationary phase for hydrophilic interaction liquid chromatography (HILIC) using the synergistic effect of polyhedral oligomeric silsesquioxane (POSS) and copolymer brushes. Octahedral octa-aminopropylsisesquioxane (8NH2-POSS) was first bound to silica gel, followed by bromination to form a cubic initiator. Then, using acrylamide (AM) and dihydroxypropyl methacrylate (DPMA) as mixed monomers, surface initiated-atom transfer radical polymerization was conducted to prepare a stationary phase comprising cubic copolymer brushes with amide and diol groups. The characterization of the stationary phase confirmed the successful synthesis of Sil-NH2-POSS/Poly(AM-co-DPMA). The chromatographic properties were investigated using nucleosides, organic acids and β-agonists to find that our designed column has superior hydrophilic property, better separation performance compared with classical HILIC columns consisting of diol- or amino-modified silica. The systematic investigation of the retention mechanism and separation selectivity using various types of polar compounds revealed that Sil-NH2-POSS/Poly(AM-co-DPMA) follows a mixed-mode retention composed of HILIC and electrostatic interactions. Besides, it exhibits good column efficiency and stability. The role of 8NH2-POSS in the separation was evaluated by comparing the performance of Sil-NH2-POSS/Poly(AM-co-DPMA) and poly(AM-co-DPMA)-modified silica without 8NH2-POSS. In conclusion, our designed based on POSS and hydrophilic copolymer brushes can contribute to the development of HILIC separation materials with enhanced performance.

On‐Surface RAFT Polymerization using Oxygen to form Triblock Copolymer Brushes

AbstractSurface‐initiated polymerization of various monomers (methacrylic acid, methacrylate, acrylate, acrylamide, and zwitterionic monomer) is conducted to form triblock copolymer brushes using oxygen‐initiated reversible addition−fragmentation chain‐transfer polymerization in the presence of air. An ellipsometry analysis, water contact angle analysis, X‐ray photoelectron spectroscopy, and atomic force microscopy confirm the successful formation of polymer brushes with complex architectures on a silicon substrate.

Dual-Functional Surfaces Based on an Antifouling Polymer and a Natural Antibiofilm Molecule: Prevention of Biofilm Formation without Using Biocides.

Pathogenic biofilms formed on the surfaces of implantable medical devices and materials pose an urgent global healthcare problem. Although conventional antibacterial surfaces based on bacteria-repelling or bacteria-killing strategies can delay biofilm formation to some extent, they usually fail in long-term applications, and it remains challenging to eradicate recalcitrant biofilms once they are established and mature. From the viewpoint of microbiology, a promising strategy may be to target the middle stage of biofilm formation including the main biological processes involved in biofilm development. In this work, a dual-functional antibiofilm surface is developed based on copolymer brushes of 2-hydroxyethyl methacrylate (HEMA) and 3-(acrylamido)phenylboronic acid (APBA), with quercetin (Qe, a natural antibiofilm molecule) incorporated via acid-responsive boronate ester bonds. Due to the antifouling properties of the hydrophilic poly(HEMA) component, the resulting surface is able to suppress bacterial adhesion and aggregation in the early stages of contact. A few bacteria are eventually able to break through the protection of the anti-adhesion layer leading to bacterial colonization. In response to the resulting decrease in the pH of the microenvironment, the surface could then release Qe to interfere with the microbiological processes related to biofilm formation. Compared to bactericidal and anti-adhesive surfaces, this dual-functional surface showed significantly improved antibiofilm performance to prevent biofilm formation involving both Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus for up to 3 days. In addition, both the copolymer and Qe are negligibly cytotoxic, thereby avoiding possible harmful effects on adjacent normal cells and the risk of bacterial resistance. This dual-functional design approach addresses the different stages of biofilm formation, and (in accordance with the growth process of the biofilm) allows sequential activation of the functions without compromising the viability of adjacent normal cells. A simple and reliable solution may thus be provided to the problems associated with biofilms on surfaces in various biomedical applications.

Ultrafast organocatalytic ring‐opening polymerization of N‐sulfonyl aziridine in the melt

AbstractAn ultrafast approach for controlled synthesis of well‐defined polysulfonamides is established through organocatalytic anionic ring‐opening polymerization (ROP) of N‐sulfonyl aziridine in the melt. Several different organobases are investigated, and it is found that N,N,N′,N″,N″‐pentamethyldiethylenetriamine (PMDETA) catalyzed ROP of 2‐methyl‐N‐tosylaziridine (TsMAz) gives the desired polymer, while 1,4‐diazabicyclo[2.2.2]octane (DABCO) and 1,8‐diazabicyclo[5.4.0]‐undec‐7‐ene (DBU) initiate the polymerization along with initiator to produce uncontrolled polymers. Using PMDETA as the catalyst, poly(2‐methyl‐N‐tosylaziridine) with molecular weight over 100 kg/mol can be synthesized in less than 90 s. Various initiators, including carboxylic acid, N‐sulfonyl amide, unactivated amine, phenol, and thiol, are applicable for this protocol to give the molecular weight and end‐group controlled polymers under the open‐flask condition. Combining this ultrafast ROP with ring‐opening metathesis polymerization (ROMP), a brush copolymer is facile synthesized. This approach allows the ultrafast metal‐free synthesis of polysulfonamide and expands the scope of initiators for the ROP of N‐sulfonyl aziridines.

A general and robust strategy for in-situ templated synthesis of patterned inorganic nanoparticle assemblies

Precisely controlling the spatial organization of inorganic nanoparticles is essential for many applications, such as sensing, catalytic, and optical/electronic systems. Here, we describe a general and robust strategy to fabricate arbitrary quasi-two-dimensional (quasi-2D) nanoparticle assembly structures with tunable size and thickness on a substrate by using block copolymer brushes as the templates. To achieve this, patterned amphiphilic block copolymer brushes were first grown via light-mediated surface-initiated atom transfer radical polymerization. The hydrophilic polymer blocks could interact and enrich the inorganic precursors, and thus accelerate the in-situ growth of nanoparticles within the patterned hydrophilic polymer domains. In our method, the block copolymer template could strictly limit the vertical growth of quasi-2D nanoparticle assemblies to achieve thickness control in the nanometer scale. By changing the design of the photomask and experimental conditions for the light-mediated polymerization, quasi-2D inorganic nanoparticle assemblies with controllable shape and dimension can be feasibly obtained. Moreover, this method is also generally applicable to prepare various patterned inorganic nanoparticle assemblies with different compositions.

Enhanced Sulfite-Selective Sensing and Cell Imaging with Fluorescent Nanoreactors Containing a Ratiometric Lipid Peroxidation Sensor.

The detection of SO2 and its derivatives is indispensable for monitoring atmospheric, water quality, and biological fluctuation of oxidative stress and metabolism of biothiols within native cellular contexts. In this article, the brush copolymer nanoreactors containing amine-terminated PDMS were used to encapsulate the fluorescent indicator C11-BDP, forming sulfite-sensitive nanoreactors (ssNRs). Surprisingly, the ssNRs were found to be highly selective to sulfite over a range of reactive oxygen/nitrogen/sulfur species and anions, which was not observed with freely dissolved indicators. The ssNRs showed a rapid response (t95 = 65 s), an excellent detection limit (0.7 μM), and a very high sensitivity (ca. 1000-fold ratiometric intensity change) to sulfite. For cellular studies, the ssNRs exhibited negligible toxicity and could be endocytosed into endosomes and lysosomes. Finally, the ssNRs allowed us to visualize the different responses of three different types of cells (pre-adipocytes, RAW264.7, and HeLa cells) to external stimuli in the culture media with sulfites and lipopolysaccharides.

Covalent grafting of functional oligo-isoprenes onto silica-based surfaces to achieve robust elastomeric monolayers, thin films and coatings

A new methodology is presented to covalently graft polyisoprene from natural or recycled rubber on hydroxylated and silicon-containing surfaces. For this purpose, we first synthesized novel functional telechelic oligomers from natural rubber, bearing a hydroxyl group at one chain end and a silane group at the other, which allowed their direct tethering on silicon-based and other materials. As alternative approach, we also synthesized bi-functional telechelic oligomers with a ketone and an aldehyde end-moieties and they reacted selectively with surface amino groups, introduced via a pre-functionalization step using commercial amino-alkoxysilanes. A high glass surface coverage density was reached and the oligoisoprenes free chain-ends were converted to acrylate functions, to possibly grow more polymer or to engage a photopolymerization process with other bio-based acrylate-terminated telechelic oligoisoprenes, in order to obtain thick films. In this way, ultra-thin oligomer layers, copolymer brushes, as well as grafted films and bulk materials were formed and characterized at sub-nanometer resolution using X-rays Reflectivity. A strong covalent grafting of polyisoprene coatings was achieved and resisted to long immersions in water and aggressive organic solvents under strong mechanical agitation. The robust molecular, thin films, and bulk sheathings are versatile polymeric constituents and represent a new family of sustainable coatings.

Understanding Design Rules for Optimizing the Interface between Immobilized Enzymes and Random Copolymer Brushes.

A long-standing goal in the field of biotechnology is to develop and understand design rules for the stabilization of enzymes upon immobilization to materials. While immobilization has sometimes been successful as a strategy to stabilize enzymes, the design of synthetic materials that stabilize enzymes remains largely empirical. We sought to overcome this challenge by investigating the mechanistic basis for the stabilization of immobilized lipases on random copolymer brush surfaces comprised of poly(ethylene glycol) methacrylate (PEGMA) and sulfobetaine methacrylate (SBMA), which represent novel heterogeneous supports for immobilized enzymes. Using several related but structurally diverse lipases, including Bacillus subtilis lipase A (LipA), Rhizomucor miehei lipase, Candida rugosa lipase, and Candida antarctica lipase B (CALB), we showed that the stability of each lipase at elevated temperatures was strongly dependent on the fraction of PEGMA in the brush layer. This dependence was explained by developing and applying a new algorithm to quantify protein surface hydrophobicity, which involved using unsupervised cluster analysis to identify clusters of hydrophobic atoms. Characterization of the lipases showed that the optimal brush composition correlated with the free energy of solvation per enzyme surface area, which ranged from -17.1 kJ/mol·nm2 for LipA to -11.8 kJ/mol·nm2 for CALB. Additionally, using this algorithm, we found that hydrophobic patches consisting of aliphatic residues had a higher free energy than patches consisting of aromatic residues. By providing the basis for rationally tuning the interface between enzymes and materials, this understanding will transform the use of materials to reliably ruggedize enzymes under extreme conditions.

Ultrathin Yet Robust Single Lithium-Ion Conducting Quasi-Solid-State Polymer-Brush Electrolytes Enable Ultralong-Life and Dendrite-Free Lithium-Metal Batteries.

Quasi-solid-state polymer electrolytes are one of the most promising candidates for long-life lithium-metal batteries. However, introduction of plasticizers for high ion conductivity at room temperature inevitably gives rise to poor mechanical strength and requires a very thick electrolyte membrane, which is detrimental to safety and energy density of the batteries. Herein, inspired by tube brushes coupling hardness with softness, a novel superstructured polymer bottlebrush BC-g-PLiSTFSI-b-PEGM (BC = bacterial cellulose; PLiSTFSI = poly(lithium 4-styrenesulfonyl-(trifluoromethylsulfonyl) imide); PEGM = poly(diethylene glycol monomethyl ether methacrylate)) with a hard nanofibril backbone and soft functional polymer side-chains is reported as an effective strategy to well balance the mechanical strength and ion conductivity of quasi-solid-state polymer electrolytes. The resulting single lithium-ion conducting quasi-solid-state polymer-brush electrolytes (SLIC-QSPBEs) integrate the features of the ultrathin membrane thickness (10µm), the nanofibril backbone-strengthened porous nanonetwork (Young's modulus = 1.9GPa), and the high-rate single lithium-ion conducting diblock copolymer brushes. As a result, the ultrathin yet robust SLIC-QSPBEs enable ultralong-term (over 3300 h) reversible and stable lithium plating/stripping in Li/Li symmetrical cell at a current density of 1mA cm-2 for lithium anode. This work affords a promising strategy to develop advanced electrolytes for solid-state lithium-metal batteries.

Polymer Coupling via Hetero-Disulfide Exchange and Its Applications to Rewritable Polymer Brushes.

An iodide-terminated polymer (Polymer-I) is converted to a thiol-terminated polymer (Polymer-SH) using HSCH2CH2SH in a remarkably short time (10 min). Polymer-SH is further converted to a pyridyl disulfide-terminated polymer (Polymer-SS-Py). The hetero-coupling of Polymer-SH and Polymer-SS-Py is successfully achieved to quantitatively generate a polymer disulfide (Polymer-SS-Polymer). Exploiting this efficient hetero-coupling technique, Polymer-SH is attached (grafted) on a Py-SS-immobilized surface to generate a polymer brush via a disulfide (-SS-) linkage (writing process). The -SS- linkage is cleaved by the treatment with dithiothreitol (DTT) to detach the polymer from the surface (erasing process). Subsequently, another Polymer-SH is attached on the surface to generate another polymer brush (rewriting process). Thus, a writable, erasable, and rewritable polymer brush surface is achieved. Hydrophilic, hydrophobic, and super-hydrophobic polymers (Polymer-SH) are attached on the surface, tailoring the surface wettability in the writing-erasing-rewriting cycles. Polymer-SH is also attached on a chain-end Py-SS-functionalized polymer brush surface, generating a rewritable block copolymer brush surface. A patterned block copolymer brush surface is also obtained using photo-irradiation and a photo-mask in the erasing process. The metal-free synthetic procedure, accessibility to patterned brushes, and switchable surface properties via the writing-erasing-rewriting process are attractive features of the present approach.

Tailor-made magnetic nanocomposite with pH and thermo-dual responsive copolymer brush for bacterial separation

Rapid detection of pathogenic bacteria particularly in food samples demands efficient separation and enrichment strategies. Here, hydrophilic temperature-responsive boronate affinity magnetic nanocomposites were established for selective enrichment of bacteria. The thermo-responsive polymer brushes were developed by surface-initiated atom transfer radical polymerization of N-isopropylacrylamide (NIPAm) and allyl glycidyl ether (AGE), followed by a reaction of epoxy groups, and incorporation of fluorophenylboronic acid. The physical and chemical characteristics of the magnetic nanocomposites were analyzed systematically. After optimization, S. aureus and Salmonella spp. showed high binding capacities of 32.14 × 106 CFU/mg and 50.98 × 106 CFU/mg in 0.01 M PBS (pH 7.4) without bacteria death. Bacterial bindings can be controlled by altering temperature and the application of competing monosaccharides. The nanocomposite was then utilized to enrich S. aureus and Salmonella spp. from the spiked tap water, 25% milk, and turbot extraction samples followed by multiplex polymerase chain reaction (mPCR), which resulted in high bacteria enrichment, and demonstrated great potential in separation of bacteria from food samples.

Mixed-charge pseudo-zwitterionic copolymer brush as broad spectrum antibiofilm coating

Zwitterionic polymers are classical antifouling polymers but they require specialized monomers that have cationic and anionic charges integrated into a single monomer. Herein, we show that pseudo-zwitterionic copolymers synthesized from a mixture of 2 monomers each having a single opposite polarity has excellent antibiofilm efficacy. We have discovered a new mixed-charge copolymer brush (#1-A) synthesized from 2 oppositely charged monomers, the anionic SPM (3-Sulfopropyl methacrylate) and the cationic AMPTMA ((3-Acrylamidopropyl) trimethylammonium chloride), that achieves broad spectrum in vitro antibiofilm effect of greater than 99% reductions against all six Gram-positive and Gram-negative bacteria tested. In the murine subcutaneous wound catheter infection models, the #1-A has good long-term anti-biofilm efficacy against MRSA and Pseudomonas aeruginosa of 3.41 and 3.19 orders respectively, outperforming previous mixed-charge copolymer coatings. We discovered a new method to choose the cationic/anionic pair combination to form the best antibiofilm copolymer brush coating by exploiting the solution polymerization kinetics disparity between the cationic and anionic monomers. We also showed that #1-A is softer and has higher hydration than the classical zwitterionic polymer. This study shows the possibility of achieving potent antibiofilm efficacy by combining readily available opposite singly charged monomers.

Injectable hydrogels of newly designed brush biopolymers as sustained drug-delivery vehicle for melanoma treatment

Novel biocompatible and brush copolymers have been developed for cancer treatment using its controlled drug-release potential. Polyurethane graft on linear dextrin has been synthesized to control the hydrophilic–hydrophobic balance for regulated drug delivery. The properties of the graft copolymers have been tuned through graft density. The prepared grafts are thermally stable and mechanically strong. An injectable hydrogel has been developed by embedding the drug-loaded brush copolymers in methyl cellulose to better control the release for a prolonged period, importantly by keeping the drug release at a constant rate. Cellular studies indicate the biocompatible nature of the brush copolymers whose controlled and slow release of drug exhibit significant cytotoxic effects on cancer cells. Endocytosis of drug tagged contrast agent indicates greater transport of biologically active material inside cell as observed through cellular uptake studies. In vivo studies on melanoma mice exhibit the real efficacy of the controlled drug release from the injectable hydrogel with significant melanoma suppression without any side effects as opposed to severe toxic effects observed in conventional chemotherapy. Special application method of drug-loaded hydrogel just beneath the tumor makes this system incredibly effective through confinement. Thus, brush copolymer injectable hydrogel is a promising vehicle for control release of drug for cancer treatment in future.

Synthesis and Properties of Cationic Gradient Brush Copolymers Carrying PEO Side Chains and Catechol Moieties

AbstractSynthesis and study of brush copolymers carrying long PEO side chains and catechol moieties are reported. Kinetics of reversible‐addition‐fragmentation chain‐transfer copolymerization of 2‐(dimethylamino) ethyl methacrylate (DMAEMA) and poly(ethylene glycol) methyl ether methacrylate (PEOMEMA) is studied by size exclusion chromatography (SEC) and 1H NMR spectroscopy, which allow calculating not only copolymerization rate but also the evolution of copolymer composition during copolymerization. Molecular weight Mn and dispersity Ð of the copolymers are determined by SEC with triple detection. Well defined gradient copolymers p(DMAEMA‐co‐PEOMEMA) of various composition with degree of polymerization close to 100 and Ð less than 1.18 are synthesized. For attachment of catechol moieties and introduction of positive charge, DMAEMA units are quaternized with 2‐chloro‐3,4‐dihydroxyacetophenone. The use of tetrahydrofuran as a solvent for that reaction allows obtaining the degree of quaternization close to 100%. Positively charged catechol brush copolymers and their solutions are characterized by 1H NMR, fourier‐transform infrared spectroscopy), and ultraviolet–visible spectroscopy, potentiometric titration, and water contact angle measurements, and their properties are compared with those of similar neutral catechol brush copolymers.

The direction of influence of specific ion effects on a pH and temperature responsive copolymer brush is dependent on polymer charge

The effect of electrolyte identity on the conformation of homopolymer brushes of poly(2-(2-methoxyethoxy) ethyl methacrylate) (PMEO2MA) and poly(2-(diethylamino)ethyl methacrylate) (PDEA), as well as a P(MEO2MA-co-DEA) copolymer brush of 90:10 mol% composition has been examined. PMEO2MA is a thermoresponsive polymer with a lower critical solution temperature of ~28 °C, PDEA a weak polybase with an apparent pKa of ~7.5, while the copolymer brush exhibits both pH and temperature responsive behaviour. Brushes were synthesised using surface initiated ARGET ATRP. The effect of temperature at low and high pH in the presence of different electrolytes on the thickness of the P(MEO2MA-co-DEA) 90:10 mol% brush was tracked with ellipsometry and the polymer volume fraction profile was elucidated with neutron reflectometry. The effect of each electrolyte on the copolymer brush conformation as the temperature changes could be switched by changing the pH from low (charged DEA segments) to high (uncharged DEA segments). The overall behaviour of the copolymer in each salt was PDEA-like at low pH, and MEO2MA-like at high pH. At low pH a reverse Hofmeister effect was observed, while at high pH a direct Hofmeister effect was observed.