Mussel-Inspired Polymer-Based Coating Technology for Antifouling and Antibacterial Properties.

Zwitterionic coatings provide a promising antifouling strategy against biofouling adhesion. Quaternary ammonium cationic polymers can effectively kill bacteria on the surface, owing to their positive charges. This strategy can avoid the release of toxic biocides, which is highly desirable for constructing coatings for biomedical devices. The present work aims to develop a facile method by covalently grafting zwitterionic and cationic copolymers containing aldehydes to the remaining amine groups of self-polymerized dopamine. Reversible addition-fragmentation chain transfer polymerization was used to copolymerize either zwitterionic 2-methacryloyloxyethyl phosphorylcholine monomer (MPC) or cationic 2-(methacryloyloxy)ethyl trimethylammonium monomer (META) with 4-formyl phenyl methacrylate monomer (FPMA), and the formed copolymers poly(MPC-st-FPMA) and poly(META-st-FPMA) are denoted as MPF and MTF, respectively. MPF and MTF copolymers were then covalently grafted onto the amino groups of polydopamine-coated surfaces. PDA/MPF/MTF-coated surfaces exhibited antibacterial and antifouling properties against S. aureus, E. coli, and bovine serum albumin protein. In addition, they showed excellent viability of normal human lung fibroblast cells MRC-5. We expect the facile surface modification strategy discussed here to be applicable to medical device manufacturing.

Embedding Thiols into Choline Phosphate Polymer Zwitterions.

The compositional scope of polymer zwitterions has grown significantly in recent years and now offers designer synthetic materials that are broadly applicable across numerous areas, including supracolloidal structures, electronic materials interfaces, and macromolecular therapeutics. Among recent developments in polymer zwitterion syntheses are those that allow insertion of reactive functionality directly into the zwitterionic moiety, yielding new monomer and polymer structures that hold potential for maximizing the impact of zwitterions on the macromolecular materials chemistry field. This manuscript describes the preparation of zwitterionic choline phosphate (CP) methacrylates containing either aromatic or aliphatic thiols embedded directly into the zwitterionic moiety. The polymerization of these functional CP methacrylates by reversible addition-fragmentation chain-transfer methodology yields polymeric zwitterionic thiols containing protected thiol functionality in the zwitterionic units. After polymerization, the protected thiols are liberated to yield thiol-rich polymer zwitterions which serve as precursors to subsequent reactions that produce polymer networks as well as polymer-protein bioconjugates.

Evaluation of the surface characteristics and antibacterial properties of Titanium dioxide nanotube and methacryloyloxyethylphosphorylcholine (MPC) coated orthodontic brackets-a comparative invitro study.

OBJECTIVES: White spot lesions are the most common iatrogenic effect observed during orthodontic treatment. This study aimed to compare the surface characteristics and antibacterial action of uncoated and coated orthodontic brackets. MATERIALS AND METHODS: Sixty commercially available stainless steel brackets were coated with TiO2 nanotubes and methacryloyloxyethylphosphorylcholine. The sample was divided into Group 1: uncoated orthodontic brackets, Group 2: Stainless steel brackets with TiO2 nanotubes coating, Group 3: Stainless steel brackets with methacryloyloxyethylphosphorylcholine coating, and Group 4: Stainless steel brackets with TiO2 nanotubes combined with methacryloyloxyethylphosphorylcholine coating. Surface characterization was assessed using atomic force microscopy and scanning electron microscopy. Streptococcus mutans was selected to test the antibacterial ability of the orthodontic brackets, total bacterial adhesion and bacterial viability were assessed. The brackets were subjected to scanning electron microscopy to detect the presence of biofilm. RESULTS: The surface roughness was the greatest in Group 1 and least in Group 2 followed by Group 4 and Group 3 coated brackets. The optical density values were highest in Group 1 and lowest in Group 4. Comparison of colony counts revealed high counts in Group 1 and low counts in Group 4. A positive correlation between surface roughness and colony counts was obtained, however, was not statistically significant. CONCLUSIONS: The coated orthodontic brackets exhibited less surface roughness than the uncoated orthodontic brackets. Group 4 coated orthodontic brackets showed the best antibacterial properties. CLINICAL RELEVANCE: Coated orthodontic brackets prevent adhesion of streptococcus mutans and reduces plaque accumulation around the brackets thereby preventing formation of white spot lesions during orthodontic treatment.

Effect of barium silicate on mechanical properties, transmittance, and protein adsorption of resin for additive manufacturing containing zwitterionic polymer.

STATEMENT OF PROBLEM: Studies on the effect of barium silicate on the material properties of additively manufactured (AM) resins containing 2-methacryloyloxyethyl phosphorylcholine (MPC) for dental applications are lacking. PURPOSE: The purpose of this in vitro study was to evaluate the mechanical properties, transmittance, and protein adsorption of MPC-containing AM resin incorporated with different barium silicate contents and to compare these findings with those of a commercially available unfilled AM resin marketed for definitive restorations. MATERIAL AND METHODS: Resins incorporating 6 wt% MPC and 4 different concentrations of barium silicate (10 wt%, MB10; 20 wt%, MB20; 30 wt%, MB30; and 40 wt%, MB40) were prepared. An MPC-containing resin with no filler was also prepared (0 wt%, MBN). Surface roughness (n=15), Vickers hardness (n=15), flexural strength and modulus (n=15), fracture toughness (n=15), transmittance (n=15), and protein adsorption (n=3) of the filled resin specimens were measured and compared with those of commercially available unfilled resin specimens. All data were analyzed using the Kruskal-Wallis and Dunn tests (α=.05). RESULTS: All experimental resins had higher surface roughness than the unfilled resin (P≤.048). MB40 had higher hardness, flexural strength, flexural modulus, and fracture toughness than most other groups (P≤.047). MB10 had higher transmittance than most other groups (P≤.012). All experimental resins had lower protein adsorption than the unfilled resin, regardless of the barium silicate content (P≤.023). CONCLUSIONS: The experimental resin containing 6 wt% MPC and 40 wt% barium silicate showed better mechanical properties and lower protein adsorption than the resin with no MPC or ceramic fillers. Transmittance decreased with the increase of barium silicate in the resins.

Lipid packing is disrupted in copolymeric nanodiscs compared with intact membranes.

Discoidal lipid-protein nanoparticles known as nanodiscs are widely used tools in structural and membrane biology. Amphipathic, synthetic copolymers have recently become an attractive alternative to membrane scaffold proteins for the formation of nanodiscs. Such copolymers can directly intercalate into, and form nanodiscs from, intact membranes without detergents. Although these copolymer nanodiscs can extract native membrane lipids, it remains unclear whether native membrane properties are also retained. To determine the extent to which bilayer lipid packing is retained in nanodiscs, we measured the behavior of packing-sensitive fluorescent dyes in various nanodisc preparations compared with intact lipid bilayers. We analyzed styrene-maleic acid (SMA), diisobutylene-maleic acid (DIBMA), and polymethacrylate (PMA) as nanodisc scaffolds at various copolymer-to-lipid ratios and temperatures. Measurements of Laurdan spectral shifts revealed that dimyristoyl-phosphatidylcholine (DMPC) nanodiscs had increased lipid headgroup packing compared with large unilamellar vesicles (LUVs) above the lipid melting temperature for all three copolymers. Similar effects were observed for DMPC nanodiscs stabilized by membrane scaffolding protein MSP1E1. Increased lipid headgroup packing was also observed when comparing nanodiscs with intact membranes composed of binary mixtures of 1-palmitoyl-2-oleoyl-phosphocholine (POPC) and di-palmitoyl-phosphocholine (DPPC), which show fluid-gel-phase coexistence. Similarly, Laurdan reported increased headgroup packing in nanodiscs for biomimetic mixtures containing cholesterol, most notable for relatively disordered membranes. The magnitudes of these ordering effects were not identical for the various copolymers, with SMA being the most and DIBMA being the least perturbing. Finally, nanodiscs derived from mammalian cell membranes showed similarly increased lipid headgroup packing. We conclude that nanodiscs generally do not completely retain the physical properties of intact membranes.

Phosphorylcholine/Heparin Composite Coatings on Artificial Lung Membrane for Enhanced Hemo-compatibility.

As the key component of extracorporeal membrane oxygenation (ECMO), artificial lung membranes have low gas permeability and plasma leakage problems, and the contact between membrane materials and blood can cause coagulation, leading to the blockage of medical equipment and seriously threatening the safety of human life. In our work, poly(4-methyl-1-pentene) hollow fiber membranes (PMP HFMs) were prepared by the thermally induced phase separation (TIPS) method, the redox method was adopted for the surface hydroxylation of PMP HFMs, and then, heparin (Hep) and 2-(methacryloyloxy)ethyl(2-(trimethylammonio)ethyl) phosphate (MPC) were grafted to the surface of PMP HFMs to prepare anticoagulant coatings. The gas permeability and hemo-compatibility of the coatings were investigated by various characterization methods, such as gas flow meter, scanning electron microscope, extracorporeal circulation experiment, etc. The results show that PMP HFMs possess a bicontinuous pore structure with a dense surface layer, which could maintain good gas permeability with an oxygen permeance of 0.8 mL/bar·cm2·min and stable gas selectivity. Furthermore, the whole blood circulation of rabbit indicated that a composite surface of bioactive Hep and biopassive MPC might be used as artificial lung membranes without the formation of thrombosis within 21 days.

Photoassisted Surface Modification with Zwitterionic Phosphorylcholine Polymers for the Fabrication of Ideal Biointerfaces.

Surface modification using zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers is commonly performed to fabricate interfaces that reduce nonspecific fouling by biomolecules and cells. Accordingly, several clinically used devices, such as guide wires, stents, oxygenators, left ventricular assist devices, and microcatheters have been modified using MPC polymers. The specific types of surface modifications vary across substrates and applications. Recently, photoreactions have garnered attention for surface modification due to their stability and tunability. This review highlights various studies that employed photoreactions to modify surfaces using MPC polymers, especially photoinduced graft polymerization of MPC. In addition to antifouling materials, several micromanipulated, long-lasting hydrophilic, and super antiwear surfaces are summarized. Furthermore, several photoreactive MPC polymers that can be used to control interactions between biomolecules and materials are presented along with their potential to form selective recognition surfaces that target biomolecules for biosensors and diagnostic devices.

C-reactive protein interacts with amphotericin B liposomes and its potential clinical consequences.

OBJECTIVES: Amphotericin B (AmB) is the gold standard for treating invasive fungal infections. New liposomal-containing AmB formulations have been developed to improve efficacy and tolerability. Serum/plasma C-reactive protein (CRP) values are widely used for monitoring infections and inflammation. CRP shows a high affinity to phosphocholine and it aggregates structures bearing this ligand, e.g. phosphocholine-containing liposomes. Therefore, we studied the interaction between CRP and phosphocholine-containing liposomal AmB preparations in vivo and in vitro. METHODS: CRP was prepared by affinity chromatography. Liposomal AmB (L-AmB, AmBisome®) was spiked (final concentrations of L-AmB: 150 mg/L) to CRP-containing serum (final CRP concentration: 300 mg/L). Following the addition of L-AmB, complex formation was monitored turbidimetrically. The size of CRP-L-AmB complexes was assessed using gel filtration. CRP was monitored in patients receiving either L-Amb or AmB lipid complex (ABLC). RESULTS: Following addition of L-AmB to CRP-containing plasma, turbidimetry showed an increase in absorbance. These results were confirmed by gel permeation chromatography. Similarly, in vivo effects were observed following intravenous administration of AmBisome®: a decline in CRP values was observed. In patients receiving L-Amb, decline of CRP concentration was faster than in patients receiving ABLC. CONCLUSIONS: In vitro experiments are suggestive of a complexation between CRP and liposomes in plasma. Interpretation of CRP values following administration of AmBisome® might be impaired due to this complexation. In vivo formation of complexes between liposomes and CRP might contribute, or even lead, to intravascular microembolisation. Similar effects have been described following the administration of Intralipid® and other phosphocholine-containing liposomes.

Protein-liposome interactions: the impact of surface charge and fluidisation effect on protein binding.

At the dawn of a new nanotechnological era in the pharmaceutical field, it is very important to examine and understand all the aspects that influence in vivo behaviour of nanoparticles. In this point of view, the interactions between serum proteins and liposomes with incorporated anionic, cationic, and/or PEGylated lipids were investigated to elucidate the role of surface charge and bilayer fluidity in protein corona's formation. 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (DPPC), hydrogenated soybean phosphatidylcholine (HSPC), and 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine (DSPC) liposomes with the presence or absence of 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (sodium salt) (DPPG), 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (chloride salt) (DOTAP), and/or 1,2-dipalmitoylsn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-5000] (DPPE-PEG 5000) lipids were prepared by the thin-film hydration method. The evaluation of their biophysical characteristics was enabled by differential scanning calorimetry and dynamic and electrophoretic light scattering. The physicochemical characteristics of mixed liposomes were compared before and after exposure to foetal bovine serum (FBS) and were correlated to calorimetric data. Our results indicate protein binding to all liposomal formulations. However, it is highlighted the importance of surface charge and fluidisation effect to the extent of protein adsorption. Additionally, considering the extensive use of cationic lipids for innovative delivery platforms, we deem PEGylation a key parameter, because even in a small proportion can reduce protein binding, and thus fast clearance and extreme toxicity without affecting positive charge. This study is a continuation of our previous work about protein-liposome interactions and fraction of stealthiness (Fs) parameter, and hopefully a design road map for drug and gene delivery.

Polymethyl methacrylate resin containing ε-poly-L-lysine and 2-methacryloyloxyethyl phosphorylcholine with antimicrobial effects.

STATEMENT OF PROBLEM: Polymethyl methacrylate (PMMA) is commonly used in dentistry, including as a denture base material. However, the colonization of a PMMA surface by microbial microorganisms could increase the risk of oral diseases such as denture stomatitis and gingivitis. The development of PMMA with antibacterial properties should improve its clinical application, but whether adding ε-poly-L-lysine (ε-PL) and 2-methacryloyloxyethyl phosphorylcholine (MPC) provides antimicrobial effects is unclear. PURPOSE: This in vitro study aimed to develop a novel antibacterial PMMA resin containing the natural nontoxic antibacterial agent ε-PL and the protein repellent agent MPC. The mechanical properties, protein repellency, and antimicrobial activities of the resin were then evaluated. MATERIAL AND METHODS: Different mass fractions of ε-PL and MPC were mixed into PMMA as the experimental groups, with unaltered PMMA as the control group. The flexural strength (n=10) and surface roughness (n=6) of the resulting mixtures were measured to determine their mechanical properties. The antiprotein properties were measured by using the micro bicinchoninic acid method (n=6). The antimicrobial effect of the resin was assessed using live/dead staining (n=6) and methyltransferase (MTT) assays (n=10). According to the variance homogeneity and normal distribution results, 1-way analysis of variance followed by the Tukey honestly significant difference test or the Welch test and the Games-Howell test were used (α=.05 for all tests). RESULTS: No significant differences were found in the flexural strength values and surface roughness of the specimens containing 1.5% MPC and 1.5% ε-PL compared with those of the control (P>.05). The addition of ε-PL to the PMMA resin alone significantly increased its bactericidal properties (P<.05). Adding both ε-PL and MPC further increased the antibacterial activity of the PMMA resin without increasing protein adhesion more than in the control group. CONCLUSIONS: The incorporation of both ε-PL and MPC into PMMA improved its antibacterial capacity without affecting its mechanical properties and did not increase protein adhesion. Therefore, the novel PMMA fabricated in this study shows promise for dental applications.

Phosphorus-Containing Polymers as Sensitive Biocompatible Probes for 31P Magnetic Resonance.

The visualization of organs and tissues using 31P magnetic resonance (MR) imaging represents an immense challenge. This is largely due to the lack of sensitive biocompatible probes required to deliver a high-intensity MR signal that can be distinguished from the natural biological background. Synthetic water-soluble phosphorus-containing polymers appear to be suitable materials for this purpose due to their adjustable chain architecture, low toxicity, and favorable pharmacokinetics. In this work, we carried out a controlled synthesis, and compared the MR properties, of several probes consisting of highly hydrophilic phosphopolymers differing in composition, structure, and molecular weight. Based on our phantom experiments, all probes with a molecular weight of ~3-400 kg·mol-1, including linear polymers based on poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), poly(ethyl ethylenephosphate) (PEEP), and poly[bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)]phosphazene (PMEEEP) as well as star-shaped copolymers composed of PMPC arms grafted onto poly(amidoamine) dendrimer (PAMAM-g-PMPC) or cyclotriphosphazene-derived cores (CTP-g-PMPC), were readily detected using a 4.7 T MR scanner. The highest signal-to-noise ratio was achieved by the linear polymers PMPC (210) and PMEEEP (62) followed by the star polymers CTP-g-PMPC (56) and PAMAM-g-PMPC (44). The 31P T1 and T2 relaxation times for these phosphopolymers were also favorable, ranging between 1078 and 2368 and 30 and 171 ms, respectively. We contend that select phosphopolymers are suitable for use as sensitive 31P MR probes for biomedical applications.

Ganglioside-Enriched Phospholipid Vesicles Induce Cooperative Aß Oligomerization and Membrane Disruption.

A major hallmark of Alzheimer's disease (AD) is the accumulation of extracellular aggregates of amyloid-ß (Aß). Structural polymorphism observed among Aß fibrils in AD brains seem to correlate with the clinical subtypes suggesting a link between fibril polymorphism and pathology. Since fibrils emerge from a templated growth of low-molecular-weight oligomers, understanding the factors affecting oligomer generation is important. Membrane lipids are key factors to influence early stages of Aß aggregation and oligomer generation, which cause membrane disruption. We have previously demonstrated that conformationally discrete Aß oligomers can be generated by modulating the charge, composition, and chain length of lipids and surfactants. Here, we extend our studies into liposomal models by investigating Aß oligomerization on large unilamellar vesicles (LUVs) of total brain extracts (TBE), reconstituted lipid rafts (LRs), or 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Varying the vesicle composition by specifically increasing the amount of GM1 gangliosides as a constituent, we found that only GM1-enriched liposomes induce the formation of toxic, low-molecular-weight oligomers. Furthermore, we found that the aggregation on liposome surface and membrane disruption are highly cooperative and sensitive to membrane surface characteristics. Numerical simulations confirm such a cooperativity and reveal that GM1-enriched liposomes form twice as many pores as those formed in the absence GM1. Overall, this study uncovers mechanisms of cooperativity between oligomerization and membrane disruption under controlled lipid compositional bias, and refocuses the significance of the early stages of Aß aggregation in polymorphism, propagation, and toxicity in AD.

Bioinspired Phosphorylcholine Coating for Surface Functionalization of Interventional Biomedical Implants with Bacterial Resistance and Anti-Encrustation Properties.

Enhancing the lubrication property and bacterial resistance is extremely important for interventional biomedical implants to avoid soft tissue damage and biofilm formation. In this study, a zwitterionic phosphorylcholine coating (PMPC) was successfully developed to achieve surface functionalization of a polyurethane (PU)-based ureteral stent via subsurface "grafting from" photopolymerization. Typical surface characterizations such as Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and surface wettability and morphology analyses examined by scanning electron microscopy, atomic force microscopy, and transmission electron microscopy demonstrated that the phosphorylcholine polymer was grafted on the substrate with a thickness of 180 nm. Additionally, the tribological experiment performed by a universal material tester showed that the lubrication performance of PU-PMPC was significantly improved compared with that of PU. The in vitro experiments indicated that the PMPC coating was biocompatible and stably modified on the surface of the substrate with an excellent bacterial resistance rate of >90%. Furthermore, the result of the in vivo experiment showed that the anti-encrustation performance of the surface-functionalized ureteral stent was better than that of the bare ureteral stent. The great enhancement in the lubrication, bacterial resistance, and anti-encrustation properties of the phosphorylcholine coating was thought to be due to the hydration effects of the zwitterionic charges. In summary, the bioinspired zwitterionic phosphorylcholine coating developed herein achieved significantly improved lubrication, bacterial resistance, and anti-encrustation performances and could be used as a convenient approach for surface functionalization of interventional biomedical implants.

Preparation of Biocompatible Poly(2-(methacryloyloxy)ethyl phosphorylcholine) Hollow Particles Using Silica Particles as a Template.

Hydrophilic poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC) shows biocompatibility because the pendant phosphorylcholine group has the same chemical structure as the hydrophilic part of phospholipids that form cell membranes. Hollow particles can be used in various fields, such as a carrier in drug delivery systems because they can encapsulate hydrophilic drugs. In this study, vinyl group-decorated silica particles with a radius of 150 nm were covered with cross-linked PMPC based on the graft-through method. The radius of PMPC-coated silica particles increased compared to that of the original silica particles. The PMPC-coated silica particles were immersed in a hydrogen fluoride aqueous solution to remove template silica particles to prepare the hollow particles. The PMPC hollow particles were characterized by dynamic light scattering, infrared spectroscopy, thermogravimetric analysis, and transmission electron microscopy observations. The thickness of the hollow particle shell can be controlled by the polymerization solvent quality. When a poor solvent for PMPC was used for the polymerization, PMPC hollow particles with thick shells can be obtained. The PMPC hollow particles can encapsulate hydrophilic guest molecules by immersing the hollow particles in a high-concentration guest molecule solution. The biocompatible PMPC hollow particles can be used in a drug carrier.

pH-Responsive Association Behavior of Biocompatible Random Copolymers Containing Pendent Phosphorylcholine and Fatty Acid.

Well-defined pH-responsive biocompatible random copolymers composed of 2-(methacryloyloxy)ethyl phosphorylcholine and varying quantities of sodium 11-(acrylamido)undecanoate (AaU) (fAaU = 0-58 mol %) were synthesized via reversible addition-fragmentation chain transfer radical polymerization. The pH-responsive association and dissociation behavior of the random copolymers was studied via turbidity, 1H nuclear magnetic resonance relaxation time, dynamic light scattering, static light scattering (SLS), and fluorescence measurements. At basic pH levels, the random copolymers dissolved in water in a unimer state because the AaU units behaved in a hydrophilic manner as a result of the ionization of the pendent fatty acids. The random copolymers with fAaU < 52 mol % associated intramolecularly within a single polymer chain to form unimer micelles at pH 3 because of the protonation of the pendent fatty acids. On the other hand, the random copolymer with fAaU ≥ 52 mol % formed intermolecular aggregates composed of four polymer chains at pH 3, as established by the SLS measurements. The random copolymers displayed the ability to solubilize hydrophobic guest molecules, such as N-phenyl-1-naphthylamine, into the hydrophobic microdomain formed by the pendent dehydrated fatty acids at acidic pHs. At pH 4, 1-pyrememethanol is captured by the random copolymer with fAaU = 52 mol %, and it is released from the random copolymer above pH 9. Furthermore, the mucoadhesive properties of the random copolymer with fAaU = 9 mol % were studied using a surface plasmon resonance technique. The copolymer was adsorbed onto mucin at pH 3; however, the adsorption decreased at pH 7.4.

Formation of Water-Soluble Complexes from Fullerene with Biocompatible Block Copolymers Bearing Pendant Glucose and Phosphorylcholine.

Double-hydrophilic diblock copolymers, PMPC100-block-PGEMAn (M100Gn), were synthesized via reversible addition-fragmentation chain transfer radical polymerization using glycosyloxyethyl methacrylate and 2-(methacryloyloxy)ethyl phosphorylcholine. The degree of polymerization (DP) of the poly(2-(methacryloyloxy) ethylphosphorylcholine) (PMPC) block was 100, whereas the DPs (n) of the poly(glycosyloxyethyl methacrylate) PGEMA block were 18, 48, and 90. Water-soluble complexes of C70/M100Gn and fullerene (C70) were prepared by grinding M100Gn and C70 powders in a mortar and adding phosphate-buffered saline (PBS) solution. PMPC can form a water-soluble complex with hydrophobic C70 using the same method. Therefore, the C70/M100Gn complexes have a core-shell micelle-like particle structure possessing a C70/PMPC core and PGEMA shells. The maximum amounts of solubilization of C70 in PBS solutions using 2 g/L each of M100G18, M100G48, and M100G90 were 0.518, 0.358, and 0.257 g/L, respectively. The hydrodynamic radius (Rh) of C70/M100Gn in PBS solutions was 55-75 nm. Spherical aggregates with a similar size to the Rh were observed by transmission electron microscopy. When the C70/M100Gn PBS solutions were irradiated with visible light, singlet oxygen was generated from C70 in the core. It is expected that the C70/M100Gn complexes can be applied to photosensitizers for photodynamic therapy treatments.

Characterization of Hydration Water Bound to Choline Phosphate-Containing Polymers.

Zwitterionic methacrylate polymers with either choline phosphate (CP) (poly(MCP)) or phosphorylcholine (PC) (poly(MPC)) side groups were analyzed to characterize the bound hydration water molecules as nonfreezing water (NFW), intermediate water (IW), or free water (FW). This characterization was carried out by differential scanning calorimetry (DSC) of polymer/water systems, and the enthalpy changes of cold crystallization and melting were determined. The electron pair orientation of CP is opposite to that of PC, and the former binds the alkyl terminal groups at the phosphate esters. The numbers of NFW and IW molecules per monomer unit of poly(MCP) with an isopropyl terminal group were estimated to be 10.7 and 11.3 mol/mol, respectively, which were slightly greater than those of the poly(MCP) bearing an ethyl terminal group. More NFW and IW molecules hydrated the phosphobetaine polyzwitterions, poly(MCP) and poly(MPC), compared with carboxybetaine and sulfobetaine polymers. Moreover, the hydration states of polyelectrolytes were compared with the zwitterionic polymers. Finally, we discuss the relationship between the amount of hydration water and bio-inert properties.

Synthesis and Characterization of Palmitoyl-block-poly(methacryloyloxyethyl phosphorylcholine) Polymer Micelles for Anticancer Drug Delivery.

We report the synthesis and characterization of an amphiphilic polymer comprising a hydrophobic palmitoyl (Pal) group and a zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC) block, which is capable of forming micelles as a drug carrier system for delivering hydrophobic anticancer drugs such as doxorubicin (DOX). We hypothesize that the sharp polarity contrast between the Pal domain and the pMPC block would strengthen the micelles and improve the drug loading capacity, while the pMPC shells improve the micelle stability and cellular uptake efficiency. In this study, the Pal-pMPC polymer was characterized and compared with a Pal-poly(ethylene glycol) (Pal-PEG) polymer in terms of their micelle formation, cytotoxicity, and drug loading of DOX. The DOX-loaded Pal-pMPC micelles were further evaluated for the cellular uptake and anticancer activities in cell culture systems including the non-multidrug-resistance HeLa cell line and the multidrug-resistance AT3B-1 cell line. The results showed that the Pal-pMPC polymer had a minimal toxicity. The Pal-pMPC micelles exhibited higher drug loading capacity and enhanced cellular internalization efficiency compared to micelles formed by the Pal-PEG polymer. It was also found that DOX-loaded Pal-pMPC micelles exhibited a more efficient anticancer effect than Pal-PEG micelles in multidrug-resistance cancer cells in an environment with fetal bovine serum.

Preclinical In Vivo Safety of Poly-Phosphorylated Superlubrication Vectors for the Treatment of Osteoarthritis.

Osteoarthritis (OA) can lead to a significant functional disability. Poly[2-(methacryloyloxy)ethyl phosphorylcholine] (pMPC) liposomes are a novel treatment modality for OA, intended to restore the natural lubrication properties of articular cartilage. Here, we report on two studies aimed to assess the local and systemic safety and toxicity of pMPCylated liposomes in comparison with physiological saline, in Sprague-Dawley (SD) rats and in sheep after a single intra-articular (IA) injection. The animals were sacrificed after 1 and 6 weeks (rats) and 3 and 6 weeks (sheep). No signs of toxicity or abnormal clinical findings were observed. Histopathological evaluation revealed no signs of reactivity or abnormal findings in the injected joints or in any other organs. In conclusion, a single IA injection of the pMPCylated liposomes demonstrated an excellent safety profile and did not result in local reactivity or systemic toxicity, thus supporting its further development for use in humans.

Acute exposure to microplastics induces metabolic disturbances and gut dysbiosis in adult zebrafish (Danio rerio).

There is limited knowledge of the ecotoxicological impacts of MPs at the environmentally relevant concentration on freshwater animals, even though numerous studies have demonstrated the toxic effects of MPs on living organisms. In this study, zebrafish (Danio rerio) was used as a model organism to investigate the ecotoxicological effects of acute exposure of virgin MPs on changes in metabolome and gut microbiota. High-throughput untargeted metabolomics using liquid chromatography with tandem mass spectrometry (LC-MS/MS) provided comprehensive insights into the metabolic responses of zebrafish exposed to PE (polyethylene) and PES (polyester) MPs. Statistical analysis of metabolomics data indicated that 39 and 27 metabolites, such as lysophosphatidylcholine, phosphocholine, phosphatidylserine, triglyceride, glycosphingolipid, psychosine, 8-amino-7-oxononanoate, cholesterol fatty acid ester, phosphatidylinositol, n-Triacontanol, were significantly altered in PE- and PES-exposed zebrafish, respectively. Furthermore, the enrichment pathway analysis unveiled the synthesis of the structural and functional lipids, signaling molecules, fatty alcohol metabolism, and amino acid metabolism, which was considerably perturbated in MPs-exposed zebrafish. In addition, high-throughput DNA sequencing was conducted to examine changes in gut microbiota in the MPs-treated zebrafish. The MPs exposure increased in the relative abundance of Fusobacteria and Proteobacteria, while the relative abundance of Firmicutes declined in MPs-treated zebrafish. Also, microbial diversity and linear discriminant analyses indicated microbiota dysbiosis, metabolomic dysregulation, and oxidative stress. Taken together, the acute exposure of MPs at environmentally relevant concentrations could disrupt the metabolic interaction via the microbiota-gut-liver-brain relationship, implying gastrointestinal and neurological/immune disorders in zebrafish.