MPC Polymer Research Articles

Surface characterization of a silicone hydrogel contact lens having bioinspired 2-methacryloyloxyethyl phosphorylcholine polymer layer in hydrated state

A silicone hydrogel contact lens material, with a unique chemical and physical structure has been designed for long-term ocular performance. Enhancement of this silicone hydrogel contact lens material was achieved through surface modification using a cross-linkable bioinspired 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer, which creates a soft surface gel layer on the silicone hydrogel base material. The surface properties of this MPC polymer-modified lens were characterized under hydrated condition revealing, inter alia, its unique polymer structure, excellent hydrophilicity, lubricity, and flexibility. Analysis of the MPC polymer layer in a hydrated state was performed using a combination of a high-resolution environmental scanning electron microscopy and atomic force microscopy. Compared to the silicone hydrogel base material, this surface had a higher captive bubble contact angle, which corresponds to higher hydrophilicity of the surface. In addition, the hydrated MPC polymer layer exhibited an extremely soft surface and reduced the coefficient of friction by more than 80 %. These characteristics were attributed to the hydration state of the MPC polymer layer on the surface of the silicone hydrogel base material. Also, interaction force of protein deposition was lowered on the surface. Such superior surface properties are anticipated to contribute to excellent ocular performance.

Biomimetic phospholipid polymers for suppressing adsorption of saliva proteins on dental hydroxyapatite substrate

AbstractTo 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.

Water-Soluble and Cytocompatible Phospholipid Polymers for Molecular Complexation to Enhance Biomolecule Transportation to Cells in Vitro.

Water-soluble and cytocompatible polymers were investigated to enhance a transporting efficiency of biomolecules into cells in vitro. The polymers composed of a 2-methacryloyloxyethyl phosphorylcholine (MPC) unit, a hydrophobic monomer unit, and a cationic monomer unit bearing an amino group were synthesized for complexation with model biomolecules, siRNA. The cationic MPC polymer was shown to interact with both siRNA and the cell membrane and was successively transported siRNA into cells. When introducing 20–50 mol% hydrophobic units into the cationic MPC polymer, transport of siRNA into cells. The MPC units (10–20 mol%) in the cationic MPC polymer were able to impart cytocompatibility, while maintaining interaction with siRNA and the cell membrane. The level of gene suppression of the siRNA/MPC polymer complex was evaluated in vitro and it was as the same level as that of a conventional siRNA transfection reagent, whereas its cytotoxicity was significantly lower. We concluded that these cytocompatible MPC polymers may be promising complexation reagent for introducing biomolecules into cells, with the potential to contribute to future fields of biotechnology, such as in vitro evaluation of gene functionality, and the production of engineered cells with biological functions.

Effects of inner polarity and viscosity of amphiphilic phospholipid polymer aggregates on the solubility enhancement of poorly water-soluble drugs

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.

Vacuum microcasting of 2-methacryloyloxyethyl phosphorylcholine polymer for stable cell patterning.

This study demonstrates the rapid fabrication and utility of 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer film for cell patterning. The film was obtained on a cell culture surface by microcasting MPC polymer ethanol solution into a degassed polydimethylsiloxane mold with a desired pattern. After removal of the mold, 293AD cells were cultured on the surface of the polymer film with the patterned microstructures. Patterned cell adhesion restricted by the film was successfully maintained during at least a 168-h cultivation. The microcast MPC polymer film can be prepared rapidly and used for efficient long-term cell confinement.

Characterization of the Hydration Process of Phospholipid-Mimetic Polymers Using Air-Injection-Mediated Liquid Exclusion Methods

2-Methacryloyloxyethyl phosphorylcholine (MPC) polymers including hydrophobic units such as poly(MPC-co-butyl methacrylate) (PMB) and poly(MPC-co-dodecyl methacrylate) (PMD) are used as coating agents for medical devices because of their antifouling effects. In this study, the whole hydration process of MPC polymer-coated surfaces was investigated using air-injection-mediated liquid exclusion (AILE) methods in which the liquid exclusion diameter during air injection was correlated to the water-repelling property. The prejetted and standard AILE methods showed the initial change from a dry to a wet state and the swelling behaviors of the MPC polymers, respectively. The liquid exclusion diameter of the MPC polymer-coated surfaces increased with an increase in the immersion time in various aqueous solutions such as deionized water, phosphate-buffered saline (PBS), and cell culture media. Moreover, the liquid exclusion diameter of the PMD-coated surface was larger than that of the PMB-coated one. Ellipsometry directly indicated the polymer layers swollen in water. Scanning probe microscopy (SPM) revealed that nanosized protuberances were formed in water, especially at the PMD-coated surface. The different swelling behaviors of these MPC polymer-coated surfaces affected the liquid exclusion diameters. Thus, the AILE methods are a powerful tool to elucidate the hydration process in various liquid media.

Inhibitory effects of 2-methacryloyloxyethyl phosphorylcholine polymer on the adherence of bacteria causing upper respiratory tract infection

ABSTRACT Objective We aimed to investigate the inhibitory effect of 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer on the adherence of Streptococcus pneumoniae (Spn) and nontypeable Haemophilus influenzae (NTHi) in vitro and in vivo. Materials and Methods Phosphorylcholine (PC) expression of 21 strains each of Spn and NTHi was evaluated using fluorescence-activated cell sorting; the adherence of bacteria to Detroit 562 cells and to the nasal mucosa of BALB/c mice was determined. MPC polymer-mediated inhibitory effects were compared with PC-keyhole limpet hemocyanin (PC-KLH)-mediated inhibitory effects. Results In vitro experiments showed that pretreatment with MPC polymer markedly inhibited the adherence of Spn and NTHi in a concentration dose–dependent manner independently of PC expression. No correlation was observed between PC expression and MPC polymer-mediated inhibitory effects. Contrarily, there was a significant negative correlation between PC-KLH-mediated inhibitory effects and PC expression in Spn and NTHi. The same results were obtained via in vivo experiments. The MPC polymer did not affect the histology of the nasal mucosa. Conclusions MPC polymer might be effective to reduce the occurrence of upper respiratory tract infection caused by Spn and NTHi and could be applied for the development of local treatments, such as topical gargles and nebulizer medications.

Coating of MPC polymer to improve hemocompatibility of implantable artificial kidney

Coating of MPC polymer to improve hemocompatibility of implantable artificial kidney

Macroscale superlubricity achieved between zwitterionic copolymer hydrogel and sapphire in water

Achievement of macroscale superlubricity from the hydration effect could provide a potential application for artificial articular cartilage. In this work, two zwitterionic polymers, 2-methacryloyloxyethyl phosphorylcholine (MPC) and sulfobetaine methacrylate (SBMA), were used to synthesize a P(MPC-co-SBMA) copolymer hydrogel through the additional polymerization of the alkane carbon-carbon double bond. The incorporation of MPC promoted the water-binding property of copolymer hydrogels as well as improved their anti-compression capability. A superlubricity state with a friction coefficient of approximately 0.002 was achieved when a P(MPC-co-SBMA) copolymer hydrogel hemisphere slid on a sapphire in water, which demonstrated its dependence on sliding velocity, load, and aqueous lubricants. The superlubricity mechanism was mainly attributed to the hydration effect from zwitterionic MPC and SBMA polymer chains, which led to the formation of a uniform hydration layer on the hydrogel surface and the strong adsorption of water molecules on the sapphire surface, which provided additional stabilized hydration layers. These findings might provide insight into the superlubricity mechanism of zwitterionic hydrogels based on the hydration effect, thereby broadening their extensive applications.

Synthesis and characterizations of zwitterionic copolymer hydrogels with excellent lubrication behavior

Abstract Various studies on hydrogel applications as cartilage substitutes and artificial joints have been previously conducted. In this study, a copolymer hydrogel comprising zwitterionic sulfobetaine methacrylate (SBMA) and 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers is synthesized in an aqueous system via free-radical polymerization. A P(MPC-co-SBMA) copolymer hydrogel network is formed via the additional polymerization of the alkane carbon–carbon double bond from the combination of MPC and SBMA polymer chains using ethylene glycol dimethacrylate (EGDMA) as the crosslinker. Introduction of MPC in the PSBMA hydrogel under water lubrication improved the compressive stress by almost double and considerably lowered the coefficient of friction (COF) to approximately 0.011. This phenomenon was attributed to the fact that MPC could intertwine with SBMA to increase the crosslink density of the hydrogel and preferentially adhere to the water to reduce the adhesion of the contact between hydrogels, leading to an intertwined copolymer network structure with excellent load-bearing capacity and superior hydration lubrication capability. This study might provide potentially useful information relating to cartilage replacement applications requiring high mechanical strength and excellent friction behavior.

In situ surface modification on dental composite resin using 2-methacryloyloxyethyl phosphorylcholine polymer for controlling plaque formation.

Composite resins (CRs) are widely used as dental restorative materials for caries treatment. They cause problems of secondary caries since Streptococcus mutans stays in the dental plaque, which the surface exists and produces acidic compounds during metabolism. The dental plaque depositions are induced by the protein adsorption on the surface. Therefore, suppression of protein adsorption on the surface of the CRs is important for inhibiting the formation of plaque and secondary caries. In this study we developed a surface treatment to provide an antibiofouling nature to the CRs by chemical reaction with 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers in the oral cavity during dental treatment. To carry out the photochemical reaction on the remaining polymerizable groups of CRs, we synthesized the MPC polymer with a polymerizable group in the side chain. The MPC polymer could bind on the surfaces of the CRs chemically under dental treatment procedures. The treated surface showed significant resistance to oral protein adsorption and bacterial adhesion even when the surface was brushed with a toothbrush. Thus, we concluded that the photochemical reaction of the MPC polymer with the CRs in the oral cavity was good for making an antibiofouling surface and preventing secondary caries.

Formation of Hydrophobic Domains on the poly(MPC-co-Dodecyl Methacrylate)-Coated Surface Recognized by Macrophage-like Cells

Copolymers comprising 2-methacryloyloxyethyl phosphorylcholine (MPC) and hydrophobic methacrylic esters were used as biomembrane-mimetic polymers to provide blood compatibility. In the present study, we compared the surfaces coated with two MPC polymers with different alkyl groups, namely, poly(MPC-co-butyl methacrylate) (PMB) and poly(MPC-co-dodecyl methacrylate) (PMD), to clarify the effect of their hydrophobic units. Various substrates, such as poly(ethylene terephthalate), polycarbonate, polypropylene, acrylonitrile-butadiene-styrene copolymer, and stainless steel, were coated with ethanol solutions containing various concentrations ofPMD or PMB. The solubility of PMD in ethanol changed depending on the water content. Scanning probe microscopy and rhodamine 6G staining revealed heterogeneous microstructures on the PMD-coated surface but not on the PMB-coated surface. Adhesion of various cells was efficiently suppressed by the PMD coating at lower concentration than the PMB coating, except regarding the adhesion of macrophage-like RAW264.7 cells. Our results suggest that the dodecyl groups in PMD increased its affinity for the substrates and simultaneously induced the formation of hydrophobic domains recognized by RAW264.7 cells.

Novel anti-biofouling bioactive calcium silicate-based cement containing 2-methacryloyloxyethyl phosphorylcholine.

Calcium silicate-based cements (CSCs) are commonly used for endodontic procedures; however, their antibacterial effects are limited. The objective of this study was to develop a 2-methacryloyloxyethyl phosphorylcholine (MPC)-incorporated CSC with improved antibacterial properties, while maintaining the original advantageous features of CSC. MPC was incorporated into a commercial CSC (Endocem MTA) at 0 wt% (control), 1.5%, 3.0 wt%, 5.0 wt%, 7.5 wt%, and 10 wt%. The setting time, compressive strength, water sorption, and glycerol contact angle were measured. Protein absorption was measured and bacterial adhesion on the surface was evaluated using Enterococcus faecalis. The bactericidal effect was examined by the disc diffusion test. Mineralization ability was assessed based on calcium ion deposition, as assessed by alizarin red staining, after immersion into Hank’s balanced salt solution for 7 days. High concentrations of MPC in CSC (7.5 wt% and 10 wt%) increased the setting time, reduced compressive strength, and reduced wettability. MPC (3 wt%) had greater protein repellent and anti-biofouling effects than those of control and test materials (P < 0.001). However, no bactericidal effect was observed for any control or test materials. There was greater calcium ion deposition on the surface of MPC-supplemented CSC than on the control (P < 0.001). The addition of 3 wt% MPC polymer to CSC confers protein-repellent properties and reduced bacterial attachment, with the potential for improved mineralization.

Length of the Stabilizing Zwitterionic Poly(2-methacryloyloxyethyl phosphorycholine) Block Influences the Activity of the Conjugated Arsenic Drug in Drug-Directed Polymerization-Induced Self-Assembly Particles.

We report on the synthesis of poly(2-methacryloyloxyethyl phosphorycholine-co-PENAO)-block-poly(methyl methacrylate) core-shell nanoparticles which carry different chain lengths of zwitterionic 2-methacryloyloxyethyl phosphorycholine (MPC) on a nanoparticle surface. The particles, 30-40 nm in size, were readily obtained by polymerization-induced self-assembly (PISA) of the corresponding arsenic-based MPC polymers as the stabilizer block and methyl methacrylate (MMA) as the core-forming block. Zwitterionic nanoparticles are ideal candidates for protein-repellent materials. Herein, we show how the decrease of zwitterionic chain lengths tunes the reactivity and cytotoxicity of the organoarsenical anticancer drug PENAO (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid). More cytotoxic (5-fold) nanoparticles were obtained when the MPC chain lengths were condensed from 37 to 13 repeating units. To gain a better understanding of the behavior of the drug-directed PISA particles, small-angle neutron scattering (SANS) experiments were conducted, evidencing that having PENAO located in the hydrophilic building block indeed influences the physiochemical micelle structure in terms of core radius (rcore), SLD, shell thickness, and aggregation number.

Examination of 2-methacryloyloxyethyl phosphorylcholine polymer coated acrylic resin denture base material: surface characteristics and Candida albicans adhesion

The aim of this study is to evaluate the effects of 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer coating with various concentrations onto acrylic resin denture base material on surface characteristics such as contact angle and surface roughness and on Candida albicans adhesion which is the major factor of denture stomatitis. Specimens, prepared from heat-polymerized acrylic denture base material, were divided into control and three test groups, randomly. Surfaces of the specimens in test groups were coated with poly(MPC) (PMPC) by graft polymerization of MPC in different concentrations (0.25 mol/L; 0.50 mol/L and 0.75 mol/L), while no surface treatment was applied to the control group. Contact angles and surface roughness were examined, and chemical composition of the surfaces was analyzed by Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (FTIR) to verify the presence of PMPC coatings. Then, specimens were incubated with C. albicans for 18 h and the number of adhered cells was determined. Upon PMPC coating, the contact angle values statistically decreased, but no difference was found in surface roughness values. A statistically significant decrease was observed in C. albicans adhesion in parallel with the increase in the MPC polymer concentration. There was no significant difference between 0.50 mol/L and 0.75 mol/L groups in terms of adhesion. These findings indicated that graft polymerization of MPC on acrylic denture base material reduces the adhesion of C. albicans, and may be evaluated as a coating for prevention of denture stomatitis.

Photoinduced Surface Zwitterionization for Antifouling of Porous Polymer Substrates

Surface functionalization of polymeric porous substrates is one of the most important requirements to enhance their applications in the biomedical field. In this study, we achieved photoinduced surface modification using a highly efficient reaction of hydrophilic polymers bearing phosphorylcholine groups. Polymers composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) units and 2-( N-ethylanilino)ethyl methacrylate units were synthesized with attention to the polymer architectures. The surface modification of the porous polyethylene (PE) substrates was carried out by the coating of the MPC polymers with a photochemical radical generator, followed by photoirradiation for a few minutes. Surface analysis by attenuated total reflectance Fourier transform IR spectroscopy and X-ray photoelectron spectroscopy indicated that the MPC polymer layer was generated on the PE surface. Cross-sectional confocal microscopy images showed that the MPC polymers were coated on the polymer surface, even inside the porous structure of the PE substrate. After modification, the porous PE substrates showed a significant increase in hydrophilicity and the water-penetration rate through the pores. Furthermore, the amount of protein adsorbed on the PE substrate was reduced significantly by the surface modification. These functionalities were dependent on the MPC polymer architectures. Thus, we concluded that the photoreactive polymer system developed furnished the porous substrates with antifouling properties.

Highly hydrophilic and antibiofouling surface of zwitterionic polymer immobilized on polydimethylsiloxane by initiator-free atmospheric plasma-induced polymerization

In this study, we have successfully grafted zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer brushes (5–8 nm) on the silicone (polydimethylsiloxane, PDMS)-based contact lenses using “initiator-free” and atmospheric plasma-induced polymerization. Varied atmospheric plasmas (O2, N2 and Ar gas) were employed in the process of the polymerization of the zwitterionic polymer brushes on the silicone surfaces without the addition of any initiators. The morphology and characterization of the zwitterionic MPC-immobilized films were investigated using atomic force microscopy, contact angle (CA) measurements and X-ray photoelectron spectroscopy. MPC immobilizations will significantly improve the hydrophilicity of silicone contact lenses, and the CA of the MPC modified-silicone contact lenses will decrease to 50°–60°, compared with that of the pristine ones (CA: ~90°). Furthermore, the MPC modifications exhibit an anti-fouling capability (25–30% decrease of protein adsorption), which can avoid protein (fibrinogen and human serum bovine) adhesion that would contaminate the contact lenses. It maintains the great oxygen permeability (103 ± 5 Dk) and transmittance (T%) is still transparent and colorless after MPC grafted on the PDMS contact lens. Therefore, the immobilization of the MPC polymer brushes by atmospheric plasma-induced polymerization would be a rapid method to improve the hydrophilicity and enhance the anti-fouling capability of silicone based-contact lenses.

Preferential capture of EpCAM-expressing extracellular vesicles on solid surfaces coated with an aptamer-conjugated zwitterionic polymer.

Extracellular vesicles (EVs) collectively represent small vesicles that are secreted from cells and carry biomolecules (e.g., miRNA, lncRNA, mRNA, proteins, lipids, metabolites, etc.) that originate in those cells. Body fluids, such as blood and saliva, include large numbers of EVs, making them potentially a rich source of diagnostic information. However, these EVs are mixtures of vesicles released from diseased tissues as well as from normal cells. This heterogeneous nature therefore blurs the clinical information obtainable from EV-based diagnosis. Here, we synthesized an EpCAM-affinity coating agent, which consists of a peptide aptamer for EpCAM and a zwitterionic MPC polymer, and have shown that this conjugate endowed the surfaces of inorganic materials with the preferential affinity to EpCAM-expressing EVs. This coating agent, designated as EpiVeta, could be useful as a coating for various diagnostic devices to allow concentration of cancer-related EVs from heterogeneous EV mixtures.

Surface modifications and oxidative degradation in MPC-grafted highly cross-linked polyethylene liners retrieved from short-term total hip arthroplasty.

Several studies reported that highly crosslinked polyethylene (HXLPE) have resulted in reduced wear in total hip arthroplasty. Beyond those studies, HXLPE hip liners grafted with 2-methacryloyloxyethyl phosphorylcholine (MPC) on their bearing surface were extensively studied in vitro and then commercialized as a new generation of artificial hip joints. The present study reports for the first time results about the evaluation of surface modification and oxidative degradation in retrieved the MPC grafted liners. The findings of this investigation clearly show that the MPC layer has been peeled off on the bearing surface of the liner main wear zone although the MPC layer remained on the surface of the rim zones. Furthermore, we assessed the microstructural modifications and the oxidation drifts that occurred in vivo in the hip joints despite the presence of the MPC layer.

Solubilization of poorly water-soluble compounds using amphiphilic phospholipid polymers with different molecular architectures

To achieve stable and effective solubilization of poorly water-soluble bioactive compounds, water-soluble and amphiphilic polymers composed of hydrophilic 2-methacryloyloxyethyl phosphorylcholine (MPC) units and hydrophobic n-butyl methacrylate (BMA) units were prepared. MPC polymers having different molecular architectures, such as random-type monomer unit sequences and block-type sequences, formed polymer aggregates when they were dissolved in aqueous media. The structure of the random-type polymer aggregate was loose and flexible. On the other hand, the block-type polymer formed polymeric micelles, which were composed of very stable hydrophobic poly(BMA) cores and hydrophilic poly(MPC) shells. The solubilization of a poorly water-soluble bioactive compound, paclitaxel (PTX), in the polymer aggregates was observed, however, solubilizing efficiency and stability were strongly depended on the polymer architecture; in other words, PTX stayed in the poly(BMA) core of the polymer micelle formed by the block-type polymer even when plasma protein was present in the aqueous medium. On the other hand, when the random-type polymer was used, PTX was transferred from the polymer aggregate to the protein. We conclude that water-soluble and amphiphilic MPC polymers are good candidates as solubilizers for poorly water-soluble bioactive compounds.