Uncharged Surface Research Articles

A Positively Charged Surface Triggers Coagulation Activation Through Factor VII Activating Protease (FSAP).

Contact between biomedical materials and blood often initiates undesirable pro-coagulant and pro-inflammatory processes. On negatively charged materials, blood coagulation is known to be triggered through autoactivation of Factor XII, while activation on cationic surfaces follows a distinct and so far enigmatic mechanism. Because Factor VII activating protease (FSAP) is known to be activated on positively and on negatively charged macromolecules in plasma, we have investigated its interaction with charged biomaterials and its consequences for coagulation. Several activation processes in blood and plasma were characterized after contact with material surfaces with varied charge. FSAP was found to be exclusively activated by the positively charged surfaces polyethylenimine (PEI) and poly-l-lysine (PLL), not by the negatively charged glass or self-assembled monolayer with carboxyl group termination (SAM-COOH), as well as uncharged (Teflon AF) surfaces. Whole blood incubation on PEI showed that this activation was concomitant with coagulation as determined by thrombin and fibrin formation, which was high for glass (F1+2, 138 nM) and PEI (F1+2, 44 nM) but low for Teflon AF (F1+2, 3.3 nM) and SAM COOH (F1+2, 5.8 nM). Contact phase inhibitor diminished coagulation to background levels for all surfaces except PEI (F1+2: ^PEI 43 to 25 nM; glass, 58 to 1.5 nM) indicating that coagulation activation is not dependent on FXII activation on the PEI surface. A decisive role of endogenous FSAP for coagulation however was confirmed with the use of FSAP inhibitory antibodies which showed no influence on Teflon AF, glass and SAM COOH but diminished F1+2 on PEI to less than 50%. We propose that FSAP activation could be a novel mechanism of surface-driven coagulation. An inhibition of this protease might improve hemocompatibility of cationic surfaces and therefore facilitate the application of polycationic surfaces in blood.

Genetically tunable M13 phage films utilizing evaporating droplets

This effort utilizes a genetically tunable system of bacteriophage to evaluate the effect of charge, temperature and particle concentration on biomaterial synthesis utilizing the coffee ring (CR) effect. There was a 1.6–3 fold suppression of the CR at higher temperatures while maintaining self-assembled structures of thin films. This suppression was observed in phage with charged and uncharged surface chemistry, which formed ordered and disordered assemblies respectively, indicating CR suppression is not dependent on short-range ordering or surface chemistry. Analysis of the drying process suggests weakened capillary flow at elevated temperatures caused CR suppression and could be further enhanced for controlled assembly for advanced biomaterials.

Structure and Capacitance of Electrical Double Layers at the Graphene–Ionic Liquid Interface

Molecular dynamics simulations are carried out to investigate the structure and capacitance of the electrical double layers (EDLs) at the interface of vertically oriented graphene and ionic liquids [EMIM]+/[BF4]−. The distribution and migration of the ions in the EDL on the rough and non-rough electrode surfaces with different charge densities are compared and analyzed, and the effect of the electrode surface morphology on the capacitance of the EDL is clarified. The results suggest that alternate distributions of anions and cations in several consecutive layers are formed in the EDL on the electrode surface. When the electrode is charged, the layers of [BF4]− anions experience more significant migration than those of [EMIM]+ cations. These ion layers can be extended deeper into the bulk electrolyte solution by the stronger interaction of the rough electrode, compared to those on the non-rough electrode surface. The potential energy valley of ions on the neutral electrode surface establishes a potential energy difference to compensate the energy cost of the ion accumulation, and is capable of producing a potential drop across the EDL on the uncharged electrode surface. Due to the greater effective contact area between the ions and electrode, the rough electrode possesses a larger capacitance than the non-rough one. In addition, it is harder for the larger-sized [EMIM]+ cations to accumulate in the narrow grooves on the rough electrode, when compared with the smaller [BF4]−. Consequently, the double-hump-shaped C–V curve (which demonstrates the relationship between differential capacitance and potential drop across the EDL) for the rough electrode is asymmetric, where the capacitance increases more significantly when the electrode is positively charged.

Multilayer Two-Dimensional Water Structure Confined in MoS2

The conflicting interpretations (square vs rhomboidal) of the recent experimental visualization of the two-dimensional (2D) water confined in between two graphene sheets by transmission electron microscopy measurements, make it important to clarify how the structure of two-dimensional water depends on the constraining medium. Toward this end, we report here molecular dynamics (MD) simulations to characterize the structure of water confined in between two MoS2 sheets. Unlike graphene, water spontaneously fills the region sandwiched by two MoS2 sheets in ambient conditions to form planar multilayered water structures with up to four layer. These 2D water molecules form a specific pattern in which the square ring structure is formed by four diamonds via H-bonds, while each diamond shares a corner in a perpendicular manner, yielding an intriguing isogonal tiling structure. Comparison of the water structure confined in graphene (flat uncharged surface) vs MoS2 (ratchet-profiled charged surface) demonstrates that the polarity (charges) of the surface can tailor the density of confined water, which in turn can directly determine the planar ordering of the multilayered water molecules in graphene or MoS2. On the other hand, the intrinsic surface profile (flat vs ratchet-profiled) plays a minor role in determining the 2D water configuration.

Complex interaction of subsequent surface streamers via deposited charge: a high-resolution experimental study

The coplanar barrier discharge in synthetic air at 30 kPa pressure was studied by time-correlated single photon counting enhanced optical emission spectroscopy, far-field microscopy enhanced intensified CCD camera and sensitive current measurements. The discharge operated in a regime where two subsequent microdischarges appeared within the same voltage half-period. The electrical analysis of the barrier discharge setup enabled us to quantify charge transfer and the effective electric field development. During the second microdischarge the positive surface streamers follow the interface (triple-line) between the area of deposited charge from the previous one and the area of uncharged dielectric surface. It is shown that additional branching and flashes of surface streamers are responsible for the increased spatial complexity of the deposited surface charges at high overvoltage. A suppressed streamer propagating over the area of deposited surface charge was tracked and the evidence of surface streamer reconnection is presented. A spatiotemporal distribution (resolution of 120 ps and 100 μm) of the reduced electric field strength was obtained for both microdischarges from the recorded luminosities of the molecular nitrogen. The reduced electric field of positive streamers in the first microdischarge reached 1200 Td. For the second one, the electric field values for the streamer at the triple-line are slightly lower than that, while for the suppressed streamers are even higher.

Liposomes coated with hydrophobically modified hydroxyethyl cellulose: Influence of hydrophobic chain length and degree of modification

Nanoparticulate systems with an uncharged hydrophilic surface may have a great potential in mucosal drug delivery. In the present study liposomes were coated with hydrophobically modified hydroxyethyl cellulose (HM-HEC) to create a sterically stabilized liposomal system with an uncharged surface. The aim was to clarify the influence of the amount of hydrophobic modification of HEC and the length of the hydrophobic moiety, on the stability of the system and on the release properties. HM-HEC with different degrees of hydrophobic modification (1 and 2mol%) and hydrophobic groups with different chain lengths (C8, C12, C16) were included in the study, as well as fluid phase and gel phase liposomes. Both types of liposomes were successfully coated with HM-HEC containing 1mol% of hydrophobic groups, while 2mol% did not work for the intended pharmaceutical applications. The polymer coated gel phase liposomes were stable (size, zeta potential, leakage) for 24 weeks at 4°C, with no differences between the C8 and C16 HM-HEC coating. For the fluid phase liposomes a size increase was observed after 24 weeks at 4°C for all formulations; the C8 HM-HEC coated liposomes increased the most. No differences in the leakage during storage at 4°C or in the release at 35°C were observed between the fluid phase formulations. To conclude; HM-HEC with a shorter hydrophobic chain length resulted in a less stable product for the fluid phase liposomes, while no influence of the chain length was observed for the gel phase liposomes (1mol% HM).

Lipids regulate the hydrolysis of membrane bound glucosylceramide by lysosomal β-glucocerebrosidase

Glucosylceramide (GlcCer) is the primary storage lipid in the lysosomes of Gaucher patients and a secondary one in Niemann-Pick disease types A, B, and C. The regulatory roles of lipids on the hydrolysis of membrane bound GlcCer by lysosomal β-glucocerebrosidase (GBA1) was probed using a detergent-free liposomal assay. The degradation rarely occurs at uncharged liposomal surfaces in the absence of saposin (Sap) C. However, anionic lipids stimulate GlcCer hydrolysis at low pH by up to 1,000-fold depending on the nature and position of the negative charges in their head groups while cationic lipids inhibit the degradation, thus showing the importance of electrostatic interactions between the polycationic GBA1 and the negatively charged vesicle surfaces at low pH. Ceramide, fatty acids, monoacylglycerol, and diacylglycerol also stimulate GlcCer hydrolysis while SM, sphingosine, and sphinganine play strong inhibitory roles, thereby explaining the secondary storage of GlcCer in Niemann-Pick diseases. Surprisingly, cholesterol stimulates GlcCer degradation in the presence of bis(monoacylglycero)phosphate (BMP). Sap C strongly stimulates GlcCer hydrolysis even in the absence of BMP and the regulatory roles of the intraendolysosomal lipids on its activity is discussed. Our data suggest that these strong modifiers of GlcCer hydrolysis affect the genotype-phenotype correlation in several cases of Gaucher patients independent of the types.

Further understanding of the biased diffusion for peptide adsorption on uncharged solid surfaces that strongly interact with water molecules

Molecular-level understanding of protein adsorption on uncharged solid surfaces has been a challenge due to experimental limitations. Recent computational efforts have demonstrated that the adsorption process starts from a biased diffusion phase, where the peptide or protein tends to move towards the solid surface from a position beyond the interaction range that the surface can reach. The strong interactions between the solid surface and the water molecules adjacent or near it would establish well-oriented water molecular ‘layers’, which are said to bring the ‘net’ electrostatic interactions hence exhibiting longer distance attractions. In this work, the peptide adsorption process has been investigated by resorting to a unique mesoscale modeling approach. Here, quantitative analyses on the adsorption of an A3 peptide on uncharged solid surfaces that strongly interact with water have revealed that, different from previous reports, the biased diffusion could be mainly attributed to the Lennard-Jones (LJ) forces, whose ‘net’ value could reach one order of magnitude bigger than the ‘net’ electrostatic force originated from the aggregated water ‘layers’ close to the surface. In addition to offering the new understanding of the adsorption mechanisms, promising applications of the current method for large systems beyond a single peptide are also discussed.

Glucose dithiocarbamate derivatives as capping ligands of water-soluble CdSeS/ZnS quantum dots

In the framework of presented study selected glucose analogues: 1-thio-β-d-glucose (βDG-SH), D-glucosamine dithiocarbamate (DG-DTC) and N-methyl-d-glucamine dithiocarbamate (NMDG-DTC) were used to modify CdSexS1-x/ZnS quantum dots via ligand exchange. The special emphasis was put on the careful optimization of DTC synthesis in an aqueous media. Properties of primary and secondary dithiocarbamates, such as stability in solutions of various pH and capability to form complexes with the divalent ions, which are crucial for their applications as surface ligands of QDs, were thoroughly compared. Due to the facility of DTCs preparation as well as colloidal stability and good optical properties of obtained hydrophilic QDs, DTC-derivatives turn out to be an alternative to most commonly used thiolated ligands. Examination of biological activity of DTC-modified QDs on A549 cell line revealed that DTC-ligands exhibit negligible intrinsic cytotoxicity. Biomimetic character of anchored ligands (similar to glucose) combined with satisfactory physicochemical properties of obtained QDs, such as high hydrophilicity and uncharged surface, indicate the potential of so modified QDs for cellular imaging and biosensing.

Activation of blood clotting on cationic biomaterials via factor VII activating protease (FSAP)

Event Abstract Back to Event Activation of blood clotting on cationic biomaterials via factor VII activating protease (FSAP) Claudia Sperling1*, Marion Fischer1, Manfred F. Maitz1*, Simona Grasso2*, Carsten Werner1* and Sandip M. Kanse2 1 Leibniz-Institut fuer Polymerforschung Dresden e.V., Institute Biofunctional Polymer Materials, Max Bergmann Center of Biomaterials, Germany 2 University of Oslo, Department of Biochemistry, Institute of Basic Medical Sciences, Norway Introduction: Factor VII activating protease (FSAP), a serine protease involved in coagulation[1], fibrinolysis and inflammatory processes[2] is known to be auto-activated on charged macromolecules. It is highly homologous to Factor XII, a main initiator of coagulation on negatively charged biomaterials. We hypothesize similar activation processes for FSAP on material surfaces with impact on biomaterial related thrombogenicity. Materials and Methods: Materials with varied surface charge were prepared, characterized and incubated with either fresh human whole blood or plasma to detect activation of FSAP as well as blood activation processes: 1. PEI (Poly(ethyleneimine) spin-coated on argon-plasma treated teflon AF, cationic); 2. SAM-COOH (self assembled monolayers with terminal carboxylic groups, anionic); 3. Glass (anionic); 4. Teflon-AF (spincoated on glass, no ionizable groups on surface). Blood from healthy donors was heparinized and incubated in a customized set-up for 3 hours. For additional FSAP inhibition experiments the inhibitory antibody mab570 was used. Subsequently blood and surfaces were analyzed for FSAP activity as well as for specific blood activation parameters: thrombin and fibrin formation (F1+2, FPA), platelet activation (PF4, cell adhesion) and immunologic reactions (CD11b, C5a, cell adhesion). Results and Discussion: Different activation processes on negatively and positively charged surfaces were observed: FSAP was exclusively activated on cationic PEI surfaces, not on anionic or hydrophobic, uncharged surfaces (Table 1) while contact activation was only detectable on anionic surfaces (glass, SAM-COOH). Table 1: FSAP activity in blood after 3 h incubation detected using a direct activity assay as well as FSAP inhibitor complexes [arb. units] Substantial coagulation activation (thrombin/fibrin formation) occurred on FSAP activating PEI and on FXII activating glass but not on Teflon-AF or SAM-COOH (Figure 1) due to a missing coagulation initiation on Teflon and missing platelet supported coagulation amplification on SAM-COOH[3]. The strong coagulation propagation on PEI was confirmed to be FSAP dependent with the implementation of an FSAP inhibitory antibody that diminished thrombin formation. Figure 1: Coagulation activation and fibrin formation on surfaces. Coagulation activation measured as TAT (Thrombin-antithrombin-complex, grey bars) and fibrin formation measured as FPA (fibrinopeptide A, white bars) Statistics: *: significantly different to all other samples. Insets: SEM photographs of surfaces (magnification 4000x; ESEM XL 30 FEG, FEI-Philips, Eindhoven, The Netherlands) Conclusion: We present a new hypothesis on blood activation claiming that on cationic surfaces FSAP gets activated and mediates thrombin amplification. Our experiments are relevant for the interaction of blood with surfaces but also for the role of FSAP in coagulation and immunology.

Interaction of functionalized PEG-PLA/PLGA nanoparticles with serum proteins and impact on nanoparticle stability and cell toxicity

Event Abstract Back to Event Interaction of functionalized PEG-PLA/PLGA nanoparticles with serum proteins and impact on nanoparticle stability and cell toxicity Kathrin Abstiens1 and Achim M. Goepferich1* 1 University of Regensburg, Department of Pharmaceutical Technology, Germany Introduction: Formation of a nanoparticle (NP) protein corona upon administration into the bloodstream plays a pivotal role concerning safety and efficacy of nanoparticle formulations. As a result of the complex interplay between chemical and physical factors, it is particularly challenging to forecast the extent and composition of protein adsorption onto different nanomaterials. Therefore, the aim of this study was to characterize the interaction of serum proteins with poly(lactic-co-glycolic acid) blended poly(ethylene glycol)-polylactid acid (PEG-PLA/PLGA) NPs depending on particle charge and net charge density. Moreover, impact on NP stability and cell toxicity in vitro was assessed. For this purpose methoxy- (m), carboxy- (C) and amino-functionalized (N) PEG-PLA copolymers were used to prepare NPs with a negative (NP510C), positive (NP510N) or uncharged (NP510m) surface as well as dual charged particles (NP510CN). Materials and Methods: PEG-PLA copolymers were synthesized by ring-opening polymerization and NPs were prepared by nanoprecipitation as previously described [1]. Size and zeta potential was measured on a Zetasizer Nano ZS. Serum protein adsorption was evaluated by incubation of functionalized nanoparticles with fetal calf serum (FCS) at 37 °C. Composition of the hard protein corona was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and total protein amount was determined using Micro BCA Assay. The involvement of bovine serum albumin (BSA) in the soft and hard protein corona was assessed by DLS upon incubation with NP at 37 °C. NP stability was evaluated with a fluorescence resonance energy transfer (FRET) experiment as previously described [2]. Influence on cell toxicity was investigated by MTT assay. Results and Discussion: NP surface charge has been shown to influence protein corona formation [3]. As depicted in Fig. 1 A, positively charged NP adsorbed significantly more serum proteins than negatively charged. Furthermore, interaction with serum proteins was even more decreased when particle surface was dual charged (NP510CN) compared to uncharged nanoparticles (NP510m). A FRET experiment revealed that NP stability in serum is directly correlated with the extent of protein adsorption. This may be due to the fact that formation of a protein corona has a strong impact on NP integrity. As a consequence thereof an escape of the lipophilic cargo was facilitated which led to a decrease of the FRET ratio over time [Fig. 1 B]. As interactions with serum proteins are likely to influence cell-NP interactions, cytotoxicity of NPs was assessed by MTT assay. It could be observed that cytotoxicity of NPs was significantly decreased when cell media was supplemented with FCS which indicates that unspecific cellular uptake was interfered by formation of a protein corona. Figure 1: A) Quantification of the hard protein corona of different NP formulations determined by BCA assay B) FRET stability of NP formulations in PBS pH 7.4 and FCS as a function of time Conclusion: The electrostatic interaction of polymeric NP with serum proteins can be regulated by combining differently functionalized PEG-PLA copolymers. Such tailored NPs can be used to control the extent of protein adsorption onto NP surface and thus NP stability and toxicity in vitro.

Membrane lipids regulate ganglioside GM2 catabolism and GM2 activator protein activity

Ganglioside GM2 is the major lysosomal storage compound of Tay-Sachs disease. It also accumulates in Niemann-Pick disease types A and B with primary storage of SM and with cholesterol in type C. Reconstitution of GM2 catabolism with β-hexosaminidase A and GM2 activator protein (GM2AP) at uncharged liposomal surfaces carrying GM2 as substrate generated only a physiologically irrelevant catabolic rate, even at pH 4.2. However, incorporation of anionic phospholipids into the GM2 carrying liposomes stimulated GM2 hydrolysis more than 10-fold, while the incorporation of plasma membrane stabilizing lipids (SM and cholesterol) generated a strong inhibition of GM2 hydrolysis, even in the presence of anionic phospholipids. Mobilization of membrane lipids by GM2AP was also inhibited in the presence of cholesterol or SM, as revealed by surface plasmon resonance studies. These lipids also reduced the interliposomal transfer rate of 2-NBD-GM1 by GM2AP, as observed in assays using Förster resonance energy transfer. Our data raise major concerns about the usage of recombinant His-tagged GM2AP compared with untagged protein. The former binds more strongly to anionic GM2-carrying liposomal surfaces, increases GM2 hydrolysis, and accelerates intermembrane transfer of 2-NBD-GM1, but does not mobilize membrane lipids.

Molecular Dynamics Study of the Gold/Ionic Liquids Interface.

The results of a systematic molecular dynamics study of the interfacial structure between the gold (100) surface and two room-temperature ionic liquids, namely, 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIm][PF6]) and 1-butyl-3-methylimadazolium bis(trifluoromethylsulfonyl)imide ([BMIm][NTf2]), are herein reported. It is found that near an uncharged surface the IL structure differs from its bulk, having an enhanced density extended until the two first layers. Interfacial layering is clearly observed at the gold surface, with a higher effect for the [BMIm][NTf2] IL but a higher packing for [BMIm][PF6]. In both ILs the alkyl side chains are oriented parallel to the interface while the imidazolium rings tend to be parallel to the interface in about 60% of the cases. The presence of the interface has a higher impact on the orientation of the cations than on the chemical properties of the counterion. The surface potential drop across the interface is more pronounced toward a negative value for ([BMIm][PF6]) than for ([BMIm][NTf2]), due to relatively larger local density of the anions for ([BMIm][PF6]) near the gold surface.

Electroneutrality breakdown and specific ion effects in nanoconfined aqueous electrolytes observed by NMR

Ion distribution in aqueous electrolytes near the interface plays a critical role in electrochemical, biological and colloidal systems, and is expected to be particularly significant inside nanoconfined regions. Electroneutrality of the total charge inside nanoconfined regions is commonly assumed a priori in solving ion distribution of aqueous electrolytes nanoconfined by uncharged hydrophobic surfaces with no direct experimental validation. Here, we use a quantitative nuclear magnetic resonance approach to investigate the properties of aqueous electrolytes nanoconfined in graphitic-like nanoporous carbon. Substantial electroneutrality breakdown in nanoconfined regions and very asymmetric responses of cations and anions to the charging of nanoconfining surfaces are observed. The electroneutrality breakdown is shown to depend strongly on the propensity of anions towards the water-carbon interface and such ion-specific response follows, generally, the anion ranking of the Hofmeister series. The experimental observations are further supported by numerical evaluation using the generalized Poisson-Boltzmann equation.

Sulfate radicals induced from peroxymonosulfate by magnetic ferrospinel MFe2O4 (M = Co, Cu, Mn, and Zn) as heterogeneous catalysts in the water

Magnetic ferrospinel MFe2O4 (M=Co, Cu, Mn, and Zn) prepared in a sol–gel process was introduced as catalyst to generate powerful radicals from peroxymonosulfate (PMS) for refractory di-n-butyl phthalate (DBP) degradation in the water. Various catalysts were described and characterized, and the catalytic activities in PMS oxidation system were investigated. Most important of all, the mechanism of different catalysts in the catalytic PMS solution was illustrated. The results showed that the incorporation of CoFe2O4 had the highest catalytic performance in PMS oxidation for DBP degradation. All catalysts presented favorable recycling and stability in the repeated batch experiment. The catalytic process showed a dependence on initial pH, and an uncharged surface of the catalyst was more profitable for sulfate radical generation. H2-TPR and CVs analysis indicated that the sequence of the catalyst's reducibility in PMS solution was CoFe2O4>CuFe2O4>MnFe2O4>ZnFe2O4, which had a close connection with the activity of metal ion in A site of the catalysts. The surface hydroxyl sites played an important role in the catalytic process, and its quantity determined the degradation of DBP. Moreover, the reactive species in PMS/MFe2O4 system were identified as sulfate radical and hydroxyl radical. The promotion of these radical's reaction was due to the fact that a balance action in the process of M2+/M3+, O2−/O2, occurred, and at the same time, PMS was catalyzed.

Explicit interrelationship between Donnan and surface potentials and explicit quantification of capacitance of charged soft interfaces with pH-dependent charge density

A charged soft interface is characterized by a charged polyelectrolyte layer (PEL) sandwiched between an uncharged rigid surface and an electrolyte solution. The PEL harbors or consists of a particular kind of ion (henceforth denoted as PEL ion), different from the electrolyte ions. The PEL ions remain excluded from locations outside the PEL. This gives rise to a Donnan potential (ψD) deep within the PEL, with the PEL-electrolyte interface (having an electrostatic potential, also called the surface potential, ψ0) behaving as a possible ion-selective permeable membrane. In this paper, we provide closed-form explicit analytical expressions for the interrelationship between ψD and ψ0 for both positively and negatively charged PEL with pH-dependent charge densities. We demonstrate that for a given magnitude of ψD, magnitude of ψ0 is identical for both positively and negatively charged PEL, dictated only by a parameter α, which depends on the difference between pH and pKa values for negatively charged PEL or the difference between pKb and pOH values for positively charged PEL. Most importantly, derivation of explicit form of interrelationship between ψD and ψ0, hitherto missing in the existing literature, allows us to provide substantially new insights into the relative variation of ψD and ψ0 and at the same time helps us to rectify several earlier misconceptions. Further, using this explicit relationship, it becomes possible to quantify the capacitance of a soft interface as explicit functions of α and the Donnan potential, with relevance for development of possible soft-interface-based energy storage system.

Nanoparticle penetration of human cervicovaginal mucus: the effect of polyvinyl alcohol.

Therapeutic nanoparticles must rapidly penetrate the mucus secretions lining the surfaces of the respiratory, gastrointestinal and cervicovaginal tracts to efficiently reach the underlying tissues. Whereas most polymeric nanoparticles are highly mucoadhesive, we previously discovered that a dense layer of low MW polyethylene glycol (PEG) conferred a sufficiently hydrophilic and uncharged surface to effectively minimize mucin-nanoparticle adhesive interactions, allowing well-coated particles to rapidly diffuse through human mucus. Here, we sought to investigate the influence of surface coating by polyvinyl alcohol (PVA), a relatively hydrophilic and uncharged polymer routinely used as a surfactant to formulate drug carriers, on the transport of nanoparticles in fresh human cervicovaginal mucus. We found that PVA-coated polystyrene (PS) particles were immobilized, with speeds at least 4000-fold lower in mucus than in water, regardless of the PVA molecular weight or incubation concentration tested. Nanoparticles composed of poly(lactide-co-glycolide) (PLGA) or diblock copolymers of PEG-PLGA were similarly immobilized when coated with PVA (slowed 29,000- and 2500-fold, respectively). PVA coatings could not be adequately removed upon washing, and the residual PVA prevented sufficient coating with Pluronic F127 capable of reducing particle mucoadhesion. In contrast to PVA-coated particles, the similar sized PEG-coated formulations were slowed only ~6- to 10-fold in mucus compared to in water. Our results suggest that incorporating PVA in the particle formulation process may lead to the formation of mucoadhesive particles for many nanoparticulate systems. Thus, alternative methods for particle formulation, based on novel surfactants or changes in the formulation process, should be identified and developed in order to produce mucus-penetrating particles for mucosal applications.

Charging of moving surfaces by corona discharges sustained in air

Atmospheric pressure corona discharges are used in electrophotographic (EP) printing technologies for charging imaging surfaces such as photoconductors. A typical corona discharge consists of a wire (or wire array) biased with a few hundred volts of dc plus a few kV of ac voltage. An electric discharge is produced around the corona wire from which electrons drift towards and charge the underlying dielectric surface. The surface charging reduces the voltage drop across the gap between the corona wire and the dielectric surface, which then terminates the discharge, as in a dielectric barrier discharge. In printing applications, this underlying surface is continuously moving throughout the charging process. For example, previously charged surfaces, which had reduced the local electric field and terminated the local discharge, are translated out of the field of view and are replaced with uncharged surface. The uncharged surface produces a rebound in the electric field in the vicinity of the corona wire which in turn results in re-ignition of the discharge. The discharge, so reignited, is then asymmetric. We found that in the idealized corona charging system we investigated, a negatively dc biased corona blade with a dielectric covered ground electrode, the discharge is initially sustained by electron impact ionization from the bulk plasma and then dominated by ionization from sheath accelerated secondary electrons. Depending on the speed of the underlying surface, the periodic re-ignition of the discharge can produce an oscillatory charging pattern on the moving surface.

The structure and properties of a simple model mixture of amphiphilic molecules and ions at a solid surface.

We investigate microscopic structure, adsorption, and electric properties of a mixture that consists of amphiphilic molecules and charged hard spheres in contact with uncharged or charged solid surfaces. The amphiphilic molecules are modeled as spheres composed of attractive and repulsive parts. The electrolyte component of the mixture is considered in the framework of the restricted primitive model (RPM). The system is studied using a density functional theory that combines fundamental measure theory for hard sphere mixtures, weighted density approach for inhomogeneous charged hard spheres, and a mean-field approximation to describe anisotropic interactions. Our principal focus is in exploring the effects brought by the presence of ions on the distribution of amphiphilic particles at the wall, as well as the effects of amphiphilic molecules on the electric double layer formed at solid surface. In particular, we have found that under certain thermodynamic conditions a long-range translational and orientational order can develop. The presence of amphiphiles produces changes of the shape of the differential capacitance from symmetric or non-symmetric bell-like to camel-like. Moreover, for some systems the value of the potential of the zero charge is non-zero, in contrast to the RPM at a charged surface.

Molecular dynamics study of salt-solution interface: solubility and surface charge of salt in water.

The NaCl salt-solution interface often serves as an example of an uncharged surface. However, recent laser-Doppler electrophoresis has shown some evidence that the NaCl crystal is positively charged in its saturated solution. Using molecular dynamics (MD) simulations, we have investigated the NaCl salt-solution interface system, and calculated the solubility of the salt using the direct method and free energy calculations, which are kinetic and thermodynamic approaches, respectively. The direct method calculation uses a salt-solution combined system. When the system is equilibrated, the concentration in the solution area is the solubility. In the free energy calculation, we separately calculate the chemical potential of NaCl in two systems, the solid and the solution, using thermodynamic integration with MD simulations. When the chemical potential of NaCl in the solution phase is equal to the chemical potential of the solid phase, the concentration of the solution system is the solubility. The advantage of using two different methods is that the computational methods can be mutually verified. We found that a relatively good estimate of the solubility of the system can be obtained through comparison of the two methods. Furthermore, we found using microsecond time-scale MD simulations that the positively charged NaCl surface was induced by a combination of a sodium-rich surface and the orientation of the interfacial water molecules.