Functional coatings for anti-biofouling applications by surface segregation of block copolymer additives

Temperature responsive or bactericidal coatings with poly(n-butyl methacrylate) (PBMA) as bulk material and surface segregated poly(n-butyl acrylate)-block-poly-(N-isopropylacrylamide) (PBA-b-PNIPAAm) or poly(n-butyl acrylate)-block-quaternized poly(2-(dimethylamino)ethyl methacrylate) (PBA-b-PDMAEMAq) as additive were prepared via sequential solvent evaporation of polymer solutions in a solvent mixture. The degree of enrichment at the air surface of the coating and the functionality were examined for different molecular weight additives with different block ratios obtained via Atom Transfer Radical Polymerization (ATRP). The design of the block copolymers with an anchor block (PBA) which is compatible with the bulk polymer (PBMA) and water-compatible functional blocks (PNIPAAm and PDMAEMAq) along with the selection of suited solvent mixtures based on pre-estimation of the selective solubility and sequential evaporation via the Hansen solubility parameters and vapor pressures, respectively, were found to work very well. A small fraction of water in the solvent mixture had been crucial to obtain surface segregation of the functional block, e.g., a PNIPAAm surface with temperature-switchable wettability. Reversible temperature dependent wettability and long term stability of the functionalization, based on contact angle data, were obtained for an optimized PBA-b-PNIPAAm additive. Surface charge density, estimated from dye binding and zeta potential measurements, and killing efficiency against Staphylococcus aureus were investigated for PBA-b-PDMAEMAq as additive. Both block copolymer additives were found to dominate the surface properties and the functionality of the PBMA coating.     

Synthesis and Self-Assembly of β-Cyclodextrin Terminated DMA/NIPAM Diblock Copolymers

A series of β-cyclodextrin (β-CD) terminated diblock copolymers has been prepared via click reaction. The Huisgen cycloaddition between alkyne decorated copolymer and azide functionalized β-CD was performed in organic solvent in the presence of a Cu(I) catalyst, resulting in the formation of β-CD terminated diblock copolymers, which contain thermally responsive poly(N-isopropylacrylamide) (PNIPAM) block and hydrophilic poly(N,N-dimethylacrylamide) (PDMA) block. Using dynamic light scattering and fluorescence spectroscopy measurements, it is demonstrated that these β-CD functionalized block copolymers are capable of reversibly forming micelles in response to changes in solution temperature and that the critical micelle concentration, micellar size, and transition temperature are dependent on both the NIPAM block length and the polymer functionalization.     

Functionalization of poly(ester‐urethane) surface by radiation‐induced grafting of N‐isopropylacrylamide using conventional and reversible addition–fragmentation chain transfer‐mediated methods

The functionalization of poly(ester‐urethane) (PUR) surface was conducted using radiation‐induced grafting. A thermosensitive layer constructed from N‐isopropylacrylamide (NIPAAm) was introduced onto a polyurethane film and characterized using attenuated total reflection Fourier transform infrared and X‐ray photoelectron spectroscopies and contact angle measurements. Size exclusion chromatography was used to analyse the PUR‐graft‐PNIPAAm copolymers and homopolymers formed in solution. Additionally, reversible addition–fragmentation chain transfer (RAFT) polymerization was performed in order to obtain PNIPAAm‐grafted surfaces with well‐defined properties. Atomic force microscopy was used to evaluate the surfaces synthesized via conventional and RAFT‐mediated grafting methods. The results of various techniques confirmed the successful grafting of NIPAAm from PUR film. © 2015 Society of Chemical Industry     

Novel triblock copolymers synthesized via radical telomerization of N-isopropylacrylamide in the presence of polypseudorotaxanes made from thiolated PEG and α-CDs

A protocol for the preparation of novel triblock copolymers comprising a polyrotaxane center block and outer blocks of poly(N-isopropylacrylamide) (PNIPAAm) as bulky stoppers was developed, in which N-isopropylacrylamide was allowed to telomerize in the presence of polypseudorotaxanes made from the self-assembly of thiol end-capped PEG with a varying amount of α-CDs under UV irradiation in aqueous solution. The molecular structure of the resulting copolymers was characterized in detail by ¹H NMR, FTIR, XRD, TG and DSC analyses. It was demonstrated that the PNIPAAm blocks are successfully attached to the two terminals of the polypseudorotaxanes and each block having the minimum 7 NIPAAm units seems long and bulky enough to efficiently impede the dethreading of α-CDs from the PEG axle to give rise to the triblock polyrotaxane-containing copolymers.     

In situ polarity functionalization and properties of styrenic triblock copolymers synthesized via RAFT emulsion polymerization

The in situ polarity functionalization of the styrenic triblock copolymers was accomplished via the block introduction of polar monomer, n‐butyl acrylate, with the help of reversible addition‐fragmentation chain transfer (RAFT) emulsion polymerization. The polarity functionalization, microphase separation, static and dynamic mechanical properties, water resistance, transparency, and thermal stability of the synthesized polarity‐functionalized triblock copolymers, polystyrene‐block‐poly(n‐butyl acrylate)‐block‐polystyrene (SAS), were extensively studied. The poly(n‐butyl acrylate) (PBA) middle block higher than 10 wt % has the favorable toughening effect on polystyrene (PSt) two‐end block due to the microphase separation in SAS. The glass transition of the continuous plastic phase (mainly composed of PSt block) has a much greater influence on the storage modulus than that of the dispersed rubber phase (mainly composed of PBA block). The polarity‐functionalized SAS has good water resistance, high transparency, and robust thermal stability. The polarity‐functionalized SAS will have such a potential application broadening as polar adhesive. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44603.     

Temperature-sensitive and highly water-soluble titanate nanotubes

Water-soluble titanate nanotubes (TNTs) with temperature-responsive shells were synthesized by grafting poly(N-isopropylacrylamide) (PNIPAAm) from TNTs via surface atom transfer radical polymerization (ATRP) using ATRP agent functionalized TNTs as macroinitiator. Proton Nuclear magnetic resonance spectroscopy (¹H NMR), Fourier-transform infrared (FT-IR) and thermogravimetric analyses (TGA) results prove the successful graft of PNIPAAm chains from TNTs. TGA shows that the amount of PNIPAAm grown from the TNTs increased with the increase of monomer/initiator ratio. Transmission electron microscope (TEM) measurements displays the obtained TNTs-g-PNIPAAm nanohybrids have a core-shell structure of TNT cores and PNIPAAm shells. In addition, the functional nanotubes demonstrate a reversible low critical solution temperature (LCST) transition with the increase of solution temperature. The synthetic method presented here can also be extended to graft other stimuli responsive polymers from TNTs.     

Fabrication of star-shaped, thermo-sensitive poly(N-isopropylacrylamide)-cholic acid-poly(?-caprolactone) copolymers and their self-assembled micelles as drug carriers

Novel star-shaped copolymers, comprised of a thermo-sensitive poly(N-isopropylacrylamide) (PNIPAAm) segment and three hydrophobic poly(?-caprolactone) (PCL) arms were fabricated. The copolymers were prepared by stannous octoate (Sn(Oct)₂) catalyzed ring-opening polymerization of ?-caprolactone (CL) using cholic acid functionalized PNIPAAm as the macroinitiator. The lower critical solution temperatures (LCST) of the copolymer solutions are attractively close to the nominal physiologic temperature at around 37 °C. The in vitro cytotoxicity test indicated no apparent cytotoxicity. The amphiphilic star-shaped copolymers were capable of self-assembling into spherical micelles in water at room temperature, and they possessed low critical micelle concentrations (CMCs) of 3 ∼ 8 mg/L in aqueous solution determined by fluorescence spectroscopy using pyrene as a probe. Transmission electron microscopy (TEM) measurement showed that the micelles exhibited a spherical shape with a size range of 30 ∼ 75 nm in diameter. In addition, the anticancer drug, methotrexate (MTX) can be loaded effectively in the polymeric micelles and its release was temperature-stimulated, which suggests that these materials have good potential as “intelligent” drug carriers.     

Thermoresponsive poly(ϵ‐caprolactone)‐graft‐poly(N‐isopropylacrylamide) graft copolymers prepared by a combination of ring‐opening polymerization and sequential azide–alkyne click chemistry

A straightforward strategy is described to synthesize poly(?‐caprolactone)‐graft‐poly(N‐isopropylacrylamide) (PCL‐g‐PNIPAAm) amphiphilic graft copolymers consisting of potentially biodegradable polyester backbones and thermoresponsive grafting chains. PCL with pendent chlorides was prepared by ring‐opening polymerization, followed by conversion of the pendent chlorides to azides. Alkyne‐terminated PNIPAAm was synthesized by atom transfer radial polymerization. Then, the alkyne end‐functionalized PNIPAAm was grafted onto the PCL backbone by a copper‐catalyzed azide–alkyne cycloaddition. PCL‐g‐PNIPAAm graft copolymers self‐assembled into spherical micelles comprised of PCL cores and PNIPAAm coronas. The critical micelle concentrations of the graft copolymers were in the range 7.8–18.2 mg L^?1, depending on copolymer composition. Mean hydrodynamic diameters of micelles were in the range 65–135 nm, which increased as the length of grafting chains grew. PCL‐g‐PNIPAAm micelles were thermosensitive and aggregated upon heating. © 2014 Society of Chemical Industry     

Thermosensitive poly(allylamine)-g-poly(N-isopropylacrylamide): synthesis, phase separation and particle formation

Grafting of poly(N-isopropylacrylamide) (PNIPAAm) having carboxylic groups at one end onto poly(allylamine) (PAH) in the presence of water soluble carbodiimide has yielded PAH-g-PNIPAAm copolymers with grafting ratios of 50, 29 and 18, respectively. These thermosensitive copolymers exhibit a lower critical solution temperature (LCST) at 34 °C at a temperature increase cycle regardless of their grafting ratios, a temperature identical to that of PNIPAAm-COOH oligomers. Temperature cycling reveals completely reversible polymer aggregation and dissolution above and below the LCST, respectively. Much smaller particle sizes are observed by scanning force microscopy and transmission electron microscopy compared to dynamic light scattering. A porous sphere model is suggested to depict the structure of the particles formed above the LCST, by which the dependence of the particle sizes on their grafting ratios is interpreted taking into account the surface tension and the spatial aggregation distance. Finally, to demonstrate the capability of the copolymers being used as thermosensitive polyelectrolytes, assembly onto multilayers is conducted and the increase of layer thickness is confirmed by small angle X-ray scattering and ellipsometry characterizations.     

Thermoresponsive sodium alginate‐g‐poly(N‐isopropylacrylamide) copolymers III. Solution properties

Stimuli‐responsive biocompatible and biodegradable materials can be obtained by combining polysaccharides with polymers exhibiting lower critical solution temperature (LCST) phase behavior, such as poly(N‐isopropylacrylamide) (PNIPAAm). The behavior of aqueous solutions of sodium alginate (NaAl) grafted with PNIPAAm (NaAl‐g‐PNIPAAm) copolymers as a function of composition and temperature is presented. The products obtained exhibit a remarkable thermothickening behavior in aqueous solutions if the degree of grafting, the concentration, and the temperature are higher than some critical values. The sol–gel‐phase transition temperatures have been determined. It was found that at temperatures below LCST the systems behave like a solution, whereas at temperatures above LCST, the solutions behave like a stiff gel, because of PNIPAAm segregation. This behavior is reversible and could find applications in tissue engineering and drug delivery systems. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Preparation and swelling properties of homopolymeric alginic acid fractions/poly(N‐isopropyl acrylamide) graft copolymers

Graft copolymers of crosslinked poly(N‐isopropyl acrylamide) (PNIPAAm) and homopolyguluronic acid (GG) and homopolymannuronic acid (MM) fractions of alginic acid were synthesized. MM and GG block fractions were obtained by partial acid hydrolysis of the alkaline extract from the brown seaweed Macrocystis pyrifera. The conjugation of these block fractions with the synthetic polymer was achieved by amidation with crosslinked PNIPAAm functionalized with an amino group at the end of the polymer chain. The structure of conjugates was determined by Fourier transform infrared and NMR spectroscopy. Atomic force microscopy of the graft copolymer GG‐g‐PNIPAAm showed a regular porous pattern, whereas the MM‐g‐PNIPAAm graft copolymer showed a regular netlike structure. Aqueous solutions of the synthesized graft copolymers afforded hydrogels by stirring with 0.1M CaCl₂. The hydrogels showed a well‐defined stimulus–response to temperature and pH. The swelling, thermal, and pH characterizations demonstrated the superior properties of the GG‐g‐PNIPAAm hydrogel over the MM‐g‐PNIPAAm hydrogel. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42398.     

Structural effect of a series of block copolymers consisting of poly(N-isopropylacrylamide) and poly(N-hydroxyethylacrylamide) on thermoresponsive behavior

Well-defined diblock and triblock copolymers consisting of poly(N-isopropylacrylamide) (PNIPAM) and poly(N-hydroxyethylacrylamide) (PHEAA) were prepared using the atom transfer radical polymerization (ATRP) method. The number-average molecular weight and fraction of each segment were precisely controllable by adjusting the monomer/initiator ratio in feed. The lower critical solution temperature (LCST) of a series of block copolymers with different compositions was examined using a turbidimetry analysis. The copolymers with a relatively lower molar fraction of HEAA units in the polymer chain exhibited phase transition phenomenon, in which the LCST depended on the fraction in the copolymer. On the other hand, the LCST disappeared for the copolymers with higher HEAA unit molar fractions. The ¹H NMR measurement clarified that the disappearance of the LCST was attributed to the formation of the water-soluble micelle. Furthermore, the thermoresponsive property of the series of block copolymers was elucidated on the basis of the structural effect of the copolymer, which includes the order and length of the block segments.     

Effect of hydrophobic polystyrene microphases on temperature-responsive behavior of poly(N-isopropylacrylamide) hydrogels

Reversible addition-fragmentation chain transfer polymerization was employed to prepare the crosslinked poly(N-isopropylacrylamide)-graft-polystyrene networks (PNIPAAm-g-PS). Due to the immiscibility of PNIPAAm with PS, the crosslinked PNIPAAm-g-PS copolymers displayed the microphase-separated morphology. While the PNIPAAm-g-PS copolymer networks were subjected to the swelling experiments, it is found that the PS block-containing PNIPAAm hydrogels significantly exhibited faster response to the external temperature changes according to swelling, deswelling, and reswelling experiments than the conventional PNIPAAm hydrogels. The improved thermo-responsive properties of hydrogels have been interpreted on the basis of the formation of the specific microphase-separated morphology in the hydrogels, i.e., the PS blocks pendent from the crosslinked PNIPAAm networks were self-assembled into the highly hydrophobic nanodomains, which behave as the microporogens and thus promote the contact of PNIPAAm chains and water. The self-organized morphology in the hydrogels was further confirmed by photon correlation spectroscopy (PCS). The PCS shows that the linear model block copolymers of PNIPAAm-g-PS networks were self-organized into micelle structures, i.e., the PS domains constitute the hydrophobic nanodomains in PNIPAAm-g-PS networks.     

RAFT synthesis of poly(N‐isopropylacrylamide) and poly(methacrylic acid) homopolymers and block copolymers: Kinetics and characterization

Reversible addition‐fragmentation chain transfer (RAFT) polymerization was used successfully to synthesize temperature‐responsive poly(N‐isopropylacrylamide) (PNIPAAm), poly(methacrylic acid) (PMAA), and their temperature‐responsive block copolymers. Detailed RAFT polymerization kinetics of the homopolymers was studied. PNIPAAm and PMAA homopolymerization showed living characteristics that include a linear relationship between M _n and conversion, controlled molecular weights, and relatively narrow molecular weight distribution (PDI < 1.3). Furthermore, the homopolymers can be reactivated to produce block copolymers. The RAFT agent, carboxymethyl dithiobenzoate (CMDB), proved to control molecular weight and PDI. As the RAFT agent concentration increases, molecular weight and PDI decreased. However, CMDB showed evidence of having a relatively low chain transfer constant as well as degradation during polymerization. Solution of the block copolymers in phosphate buffered saline displayed temperature reversible characteristics at a lower critical solution temperature (LCST) transition of 31°C. A 5 wt % solution of the block copolymers form thermoreversible gels by a self‐assembly mechanism above the LCST. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 1191–1201, 2006     

Synthesis and self-assembly of a new amphiphilic thermosensitive poly(N-vinylcaprolactam)/poly(ε-caprolactone) block copolymer

New amphiphilic thermosensitive poly(N-vinylcaprolactam)/poly(ε-caprolactone) (PNVCL-b-PCL) block copolymers were synthesized by ring-opening polymerization of ε-caprolactone with hydroxy-terminated poly(N-vinylcaprolactam) (PNVCL-OH) as a macroinitiator. The structures of the polymers were confirmed by IR, ¹H NMR and GPC. The critical micelle concentrations of copolymer in aqueous solution measured by the fluorescence probe technique reduced with the increasing of the proportion of hydrophobic parts, so did the diameter and distribution of the micelles determined by dynamic light scattering. The shape observed by transmission electron microscopy (TEM) demonstrated that the micelles are spherical. On the other hand, the UV–vis measurement showed that polymers exhibit a reproducible temperature-responsive behavior with a lower critical solution temperature (LCST). The LCST of PNVCL-OH can be adjusted by controlling the molecular weights, and that of copolymers can be adjusted by controlling the compositions and the concentration. Variable temperature TEM measurements demonstrated that LCST transition was the result of transition of individual micelles to larger aggregates.     

Thermosensitive poly(N-isopropylacrylamide)-b-poly(ε-caprolactone) nanoparticles for efficient drug delivery system

To investigate thermosensitive polymeric nanoparticle, amphiphilic block copolymers of poly(N-isopropylacrylamice)-b-poly(ε-caprolactone) (PNPCL) with different PCL block lengths were synthesized by hydroxy-terminated poly(N-isopropyoacrylamide) (PNiPAAm) initiated ring opening polymerization of ε-caprolactone. Owing to their amphiphilic characteristics, the block copolymers formed self-assembled polymeric nanoparticles in aqueous milieus with thermosensitive PNiPAAm shell compartment. The characterizations of the nanoparticles revealed that the PNPCL nanoparticles showed PCL block length dependent physicochemical characters such as particle sizes, critical aggregation concentrations, and core hydrophobicities. Moreover, the thermosensitive PNiPAAm shells conferred unique temperature responsive properties such as phase transitions with temperature elevation over its lower critical solution temperature (LCST). The temperature induced phase transition resulted in the formation of PNiPAAm hydrogel layer on the PNPCL nanoparticle surface. The drug release tests revealed that the formation of thermosensitive hydrogel layer resulted in the enhanced sustained drug release patterns by acting as an additional diffusion barriers. Therefore, the introduction of thermosensitive polymers on polymeric nanoparticles might be a potential approaches to modulate drug release behaviors.     

Miscibility of polysulfone and poly(ether sulfone) with tertiary amide polymers

The miscibility of polysulfone (PSf) and poly(ether sulfone) (PES) with three tertiary amide polymers has been studied. PES is miscible with poly(N-methyl-N-vinylacetamide) (PMVAc) and with poly(N,N-dimethylacrylamide) (PDMA) but not with poly(2-methyl-2-oxazoline) (PMOx). Miscible PES/PDMA blends show lower critical solution temperature behavior. However, PSf is immiscible with all the three tertiary amide polymers. Previous studies have shown that both PES and PSf are miscible with poly(N-vinyl-2-pyrrolidone). PES is also miscible with poly(2-ethyl-2-oxazoline) but PSf is not. Therefore, PES is more readily miscible with tertiary amide polymers as compared to PSf. Received: 23 October 1996/Revised: 11 November 1996/Accepted: 12 November 1996     

Associative properties of perfluorooctyl end‐functionalized polystyrene–poly(ethylene oxide) diblock copolymers

The synthesis of 2,2,3,3‐tetrahydro‐perfluoroundecanoyl end‐functionalized polystyrene–poly(ethylene oxide) block (PS‐block‐PEO‐R_F) copolymers and their matching PS‐block‐PEO diblock copolymers was carried out by sequential anionic polymerization. Viscometry and ¹⁹F NMR studies show that the PS‐block‐PEO copolymers, in contrast to their matching PS‐block‐PEO‐R_F copolymers, exhibit a micellar rather than the associative behavior seen for the latter. However, the presence of an excess of fluorinated acid, used for end‐functionalization, produces a reduction of the associative behavior above the overlap concentration, with the fluorinated acid acting like a surfactant. A competition may also occur between PS—and R_F—mediated micellization. Copyright © 2004 Society of Chemical Industry     

Functionalization of amphiphilic coil-rod-coil triblock copolymer poly(2-vinylpyridine)-b-poly(n-hexyl isocyanate)-b-poly(2-vinylpyridine) with florescence moiety and C60

We recently achieved quantitative synthesis of an amphiphilic coil-rod-coil triblock copolymer, poly(2-vinylpyridine)-b-poly(n-hexyl isocyanate)-b-poly(2-vinylpyridine), by coupling in situ living diblock copolymer poly(2-vinylpyridine)-b-poly(n-hexyl isocyanate) (P2VP-b-PHIC) using malonyl chloride in the presence of pyridine. This led to the introduction of an active methylene group that is a site for further functionalization in the rod block. The Michael addition reaction of the triblock copolymer with 7-(4-trifluoromethyl) coumarin acrylamide led to copolymer bearing a fluorescent pendent in the rod block. The fluorescent labeled copolymers were isolated in ∼94% yields. Similarly C₆₀ pendent was introduced to the rod block by the Bingel reaction. The yields of C₆₀ functionalized copolymers were ∼54%. The precursor and functionalized amphiphilic coil-rod-coil copolymer show diverse morphologies, such as micelles and vesicles by simply changing the solvent. For the C₆₀ functionalized block copolymer, structural constraints in micelles and vesicles prevented C₆₀ pendents to aggregate.     

One-pot synthesis of poly(N-vinylcaprolactam)-based biocompatible block copolymers using a dual initiator for ROP and RAFT polymerization

Thermosensitive, biocompatible poly(ε-caprolactone)-b-poly(N-vinylcaprolactam) (PCL-b-PVCL), poly(δ-valerolactone)-b-PVCL, and poly(trimethylene carbonate)-b-PVCL block copolymers were synthesized at 30 °C using a hydroxyl-functionalized xanthate reversible addition-fragmentation chain transfer (RAFT) agent, 2-hydroxyethyl 2-(ethoxycarbonothioylthio)propanoate (HECP), as a dual initiator for ring-opening polymerization (ROP) and RAFT polymerization in a one-pot procedure. The hydrophobic blocks were first synthesized by the ROP of cyclic monomers using diphenyl phosphate (DPP) as a catalyst and the RAFT polymerization of the PVCL block was followed by adding N-vinylcaprolactam (VCL) and 2,2′-azobis(4-methoxy-2,4-dimethyl valeronitrile) (V-70) as an initiator to the reaction mixture. This novel one-pot process is convenient and powerful method for the synthesis of the PVCL-based biocompatible block copolymers. The lower critical solution temperature (LCST) of the PVCL-based biocompatible block copolymer can be readily tuned by controlling the hydrophobicity of the block copolymers. By copolymerizing a hydrophilic N-vinylpyrrolidone moiety to the PVCL blocks by RAFT copolymerization, the LCST of the copolymer was matched with the body temperature for its future biomedical applications.