Photoreactive polymers bearing zwitterionic phosphorylcholine and benzophenone groups on the side chain were synthesized and used as surface modification reagents for biomaterials. A photoreactive ...methacrylate containing the benzophenone group, 3-methacryloyloxy-2-hydroxypropyl-4-oxybenzophenone (MHPBP), was synthesized via a ring-opening and addition reaction between glycidyl methacrylate and 4-hydroxybenzophenone. Then, water-soluble, amphiphilic polymers poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-MHPBP) (PMH) and poly(MPC-co-n-butyl methacrylate-co-MHPBP), with different monomer unit compositions, were synthesized through radical polymerization. Ultraviolet–visible (UV/vis) absorption spectra of these polymer solutions showed that these polymers have maximum absorption peaks at 254 and 289 nm that can be attributed to the benzophenone unit. The intensity of UV adsorption at 289 nm was decreased with increased UV irradiation time, and it was saturated within a few minutes, indicating that the polymers are highly sensitive to UV irradiation. A commercial material (i.e., cyclic polyolefin) was simply modified by a UV irradiation for 1.0 min. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy analysis results indicated that the stability of the polymer on the surface was dramatically enhanced because of the photochemical reaction of the benzophenone moiety. The air contact angles of PMH surfaces measured in water were up to 160°. Thus, highly hydrophilic surfaces were obtained. The critical surface tension of the PMH-modified surface was 45.7 mN/m. By evaluating the biological reactivity of the treated surface, protein adsorption and cell adhesion were completely inhibited on the surface, which was prepared using a photopatterning procedure using PMH. In conclusion, photoreactive MPC polymers with a benzophenone moiety could be used as a novel and effective surface modifier.
Mussel-inspired dopamine chemistry has increasingly been used for surface modification due to its simplicity, versatility, and strong reactivity for secondary functionalization with amine or thiol ...containing molecules. In this work, we demonstrate a facile surface modification technique using dopamine chemistry to prepare a zwitterionic polymer coating with both antifouling and antimicrobial property. Catechol containing adhesive monomer dopamine methacrylamide (DMA) was copolymerized with bioinspired zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) monomer, and the synthesized copolymers were covalently grafted onto the amino (−NH2) rich polyethylenimine (PEI)/polydopamine (PDA) codeposited surface to obtain a stable antifouling surface. The resulting surface was later used for in situ deposition of antimicrobial silver nanoparticles (AgNPs), facilitated by the presence of catechol groups of the coating. The modified surface was characterized using X-ray photoelectron spectroscopy (XPS), water contact angle measurements, and atomic force microscopy (AFM). This dual functional coating significantly reduced the adhesion of both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria and showed excellent resistance to bovine serum albumin (BSA) adsorption. This bioinspired and efficient surface modification strategy with dual functional coating promises its potential application in implantable biomedical devices.
To overcome the thrombogenic reactions of hydrocarbon-based biomaterials in clinical blood treatment, we introduce a model study of surface zwitterionization of a polypropylene (PP) substrate using a ...set of well-defined copolymers for controlling the adhesion of blood cells in vitro. Random and block copolymers containing zwitterionic units of 2-methacryloyloxyethyl phosphorylcholine (MPC), 3-(methacryloylamino)propyldimethyl(3-sulfopropyl)ammonium hydroxide inner salt (SBAA), or nonionic units of 2-hydroxyethyl methacrylate (HEMA) with a controlled hydrophobic segment of 70% n-butyl methacrylate (BMA) units in these polymers were synthesized through reversible addition–fragmentation chain transfer polymerization. A systematic study of how zwitterionic and nonionic copolymer architectures associated with controlled chain orientation via hydration processes affect blood compatibility is reported. The surface wettability of PP substrates coated with the block copolymer with poly(MPC) (PMPC) segments was higher than that of the random copolymer poly(MPC-random-BMA). However, only the random copolymers with SBAA units demonstrate a higher surface wettability. The PP substrate coated with nonionic copolymers containing HEMA units showed relatively lower hydration capability associated with higher protein adsorption, platelet adhesion, and leukocyte attachment than those with zwitterionic copolymers. The random copolymer poly(SBAA-random-BMA) coated on the PP substrates exhibited resistance to cell adhesion in human whole blood at a level comparable to that of MPC copolymers. An ideal zwitterionic PP substrate could be obtained by coating it with a block copolymer composed of PMPC and poly(BMA) (PBMA) segments, PMPC-block-PBMA. The water contact angle decreased dramatically from approximately 100° on the original PP substrate to 11° within 30 s. The number of blood cells attached on PMPC-block-PBMA decreased significantly to less than 2.5% of that on original PP. These results prove that the rational design of zwitterionic polymers incorporated with a hydrophobic anchoring portion provides a promising approach to reduce blood cell adhesion and protein adsorption of hydrocarbon-based biomaterials applied in direct contact with human whole blood.
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•A thick phospholipid polymer brush with a defined polymer density could be prepared.•The maximum thickness of polymer layer in an aqueous medium was more than ...100nm.•Thickness-independent high resistance to protein adsorption was realized.
The purpose of this study was to prepare a thick polymer brush layer composed of poly(2-methacryloyloxyethyl phosphorylcholine (MPC)) and assess its resistance to protein adsorption from the dissolved state of poly(MPC) chains in an aqueous condition. The thick poly(MPC) brush layer was prepared through the surface-initiated atom transfer radical polymerization (SI-ATRP) of MPC with a free initiator from an initiator-immobilized substrate at given Monomer/Free initiator ratios. The ellipsometric thickness of the poly(MPC) brush layers could be controlled by the polymerization degree of the poly(MPC) chains. The thickness of the poly(MPC) brush layer in an aqueous medium was larger than that in air, and this tendency became clearer when the polymerization degree of the poly(MPC) increased. The maximum thickness of the poly(MPC) brush layer in an aqueous medium was around 110nm. The static air contact angle of the poly(MPC) brush layer in water indicated a reasonably hydrophilic nature, which was independent of the thickness of the poly(MPC) brush layer at the surface. This result occurred because the hydrated state of the poly(MPC) chains is not influenced by the environment surrounding them. Finally, as measured with a quartz crystal microbalance, the amount of protein adsorbed from a fetal bovine serum solution (10% in phosphate-buffered saline) on the original substrate was 420ng/cm2. However, the poly(MPC) brush layer reduced this value dramatically to less than 50ng/cm2. This effect was independent of the thickness of the poly(MPC) brush layer for thicknesses between 20nm and about 110nm. These results indicated that the surface covered with a poly(MPC) brush layer is a promising platform to avoid biofouling and could also be applied to analyze the reactions of biological molecules with a high signal/noise ratio.
The molecular interaction forces generated during the adsorption of proteins to surfaces were examined by the force-versus-distance (f–d) curve measurements of atomic force microscopy using probes ...modified with appropriate molecules. Various substrates with polymer brush layers bearing zwitterionic, cationic, anionic, and hydrophobic groups were systematically prepared by surface-initiated atom transfer radical polymerization. Surface interaction forces on these substrates were analyzed by the f–d curve measurements using probes with the same polymer brush layer as the substrate. Repulsive forces, which decreased depending on the ionic strength, were generated between cationic or anionic polyelectrolyte brush layers; these were considered to be electrostatic interaction forces. A strong adhesive force was detected between hydrophobic polymer brush layers during retraction; this corresponded to the hydrophobic interaction between two hydrophobic polymer layers. In contrast, no significant interaction forces were detected between zwitterionic polymer brush layers. Direct interaction forces between proteins and polymer brush layers were then quantitatively evaluated by the f–d curve measurements using protein-immobilized probes consisting of negatively charged albumin and positively charged lysozyme under physiological conditions. In addition, the amount of protein adsorbed on the polymer brush layer was quantified by surface plasmon resonance measurements. Relatively large amounts of protein adsorbed to the polyelectrolyte brush layers with opposite charges. It was considered that the detachment of the protein after contact with the polymer brush layer hardly occurred due to salt formation at the interface. Both proteins adsorbed significantly on the hydrophobic polymer brush layer, which was due to hydrophobic interactions at the interface. In contrast, the zwitterionic polymer brush layer exhibited no significant interaction force with proteins and suppressed protein adsorption. Taken together, our results suggest that to obtain the protein-repellent surfaces, the surface should not induce direct interaction forces with proteins after contact with them.
To prevent infectious diseases induced by the adhesion of microorganisms and their metabolic products to dental implants, saliva protein adsorption, which induces the plaque deposition to the ...intraoral substrates should be inhibited. We used a water‐soluble 2‐methacryloyloxyethyl phosphorylcholine (MPC) polymer to modify the surface of hydroxyapatite (HAp) substrate, the main component of dental implant surface. The MPC polymer containing a catechol group at the terminal of polymer chain and amino groups in the side chain was synthesized by mimicking the mussel adhesive protein. The MPC polymer containing 2% of the primary amino groups showed effective adhesion to the HAp substrate. Mucin, the dental plaque protein, adsorbs on the HAp surface; however, the MPC polymer modification could reduce this adsorption amount by more than 98% compared to the original HAp substrate surface. Thus, the treatment of the MPC polymer has potential to reduce oral infection due to plaque deposition.
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•Water-soluble amphiphilic polymers with various hydrophobic units were synthesized.•Viscosity and polarity inside the polymer aggregate were quantitatively evaluated.•Solubility of ...water-insoluble drugs improved in the polymer solution.•High viscosity inside of aggregate influenced maintaining of drug molecules.
We quantitatively evaluated the properties of aggregates of amphiphilic polymers formed in an aqueous medium and clarified the effect of the inside polarity and viscosity of the polymer aggregate on the solubilization of poorly water-soluble drugs. Three water-soluble amphiphilic 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers with various hydrophobic monomer units, namely, n-butyl methacrylate (BMA), 2-methacryloyloxyethyl butylurethane (MEBU), and 2-methacryloyloxyethyl benzylurethane (MEBZU), were synthesized. The different molecular interactions between the hydrophobic monomer units, such as hydrophobic interactions, hydrogen bonding, and dispersion force between the aromatic rings, were considered. Fluorescence spectroscopic measurements revealed that every polymer aggregate had almost the same polarity as that of ethanol. Also, the polymers with urethane bonds, poly(MPC-co-MEBU) and poly(MPC-co-MEBZU) had slightly higher polarity and viscosity inside the polymer aggregate than that of poly(MPC-co-BMA). The water solubility of nifedipine and indomethacin was clearly enhanced in the MPC polymer aqueous solution depending on the polymer structure. As indomethacin is less soluble in polar solvents than is nifedipine, it needed to be transferred deeper into the polymer aggregates for stable solubilization. It is plausible that the high viscosity inside the polymer aggregate prevented the diffusion of drug molecules. We concluded that not only the polarity inside the polymer aggregates and the strength of the interaction force between the polymer and drug, but also the viscosity inside the polymer aggregates were responsible for enhancing the solubilization of poorly water-soluble drugs.
We report on a cost-effective synthesis method for copolymers containing bioinspired phenolic and phosphorylcholine groups in the side chain. Adsorption of the gallol group bearing polymers onto ...surfaces was compared with reference polymers containing catechol, phenol, phenyl or n -butyl groups. We found that the gallol group was the most effective functional group among those tested to immobilize the low-fouling phospholipid polymer on surfaces. The adlayer exhibited the same degree of low-fouling properties as the commercially available phospholipid polymer (LIPIDURE®-PMB), while exhibiting better solvent resistance, especially in water and alcohol. Thus we expect that the reported method may be advantageous in biomedical applications that often involve an alcohol sterilization process.
We summarize the development and evaluation of new type of phospholipid polymers as a solubilizer for poorly water-soluble compounds. That is, a water-soluble and amphiphilic ...poly(2-methacryloyloxyethyl phosphorylcholine-random-n-butyl methacrylate) contains 30 mol% hydrophilic 2-methacryloyloxyethyl phosphorylcholine units and its weight-averaged molecular weight is around 5.0 × 10
4
. When the polymer is dissolved in an aqueous medium, a large portion of hydrophobic n-butyl methacrylate units assemble, forming polymer aggregates. To avoid severe biological reactions caused by conventional solubilizers, the phospholipid polymer can be applied for the solubilization of poorly water-soluble bioactive compounds. The polarity inside these polymer aggregate is the same as that of ethanol and n-butanol. Therefore, bioactive compounds, whose solubility is poor in water but good in these alcohols, can be entrapped in the polymer aggregate. The phospholipid polymer can penetrate the cell membrane by molecular diffusion, carrying inside the cell the bioactive compound, without exhibiting significant cytotoxicity. Several animal experiments have revealed that the pharmacological performance of various bioactive compound/phospholipid polymer complexes is excellent. Furthermore, functionalization of the polymer aggregate with biomolecules, such as antibodies and oligonucleotides, can be done, leading to selective capturing of the target molecules. These examples clearly indicate that water-soluble and amphiphilic phospholipid polymer is a candidate for preparing safer formulations and more effective pharmaceutical treatment with several bioactive compounds.
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BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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