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Surface-grafted, environmentally sensitive polymers for biofilm release.

Controlling bacterial biofouling is desirable for almost every human enterprise in which solid surfaces are introduced into nonsterile aqueous environments. One approach that is used to decrease contamination of manufactured devices by microorganisms is using materials that easily slough off accumulated material (i.e., fouling release surfaces). The compounds currently used for this purpose rely on low surface energy to inhibit strong attachment of organisms. In this study, we examined the possible use of environmentally responsive (or "smart") polymers as a new class of fouling release agents; a surface-grafted thermally responsive polymer, poly(N-isopropylacrylamide) (PNIPAAM), was used as a model compound. PNIPAAM is known to have a lower critical solubility temperature of approximately 32 degrees C (i.e., it is insoluble in water at temperatures above 32 degrees C and is soluble at temperatures below 32 degrees C). Under experimental conditions, >90% of cultured microorganisms (Staphylococcus epidermidis, Halomonas marina) and naturally occurring marine microorganisms that attached to grafted PNIPAAM surfaces during 2-, 18-, 36-, and 72-h incubations were removed when the hydration state of the polymer was changed from a wettability that was favorable for attachment to a wettability that was less favorable. Of particular significance is the observation that an organism known to attach in the greatest numbers to hydrophobic substrata (i.e., H. marina) was removed when transition of PNIPAAM to a more hydrated state occurred, whereas an organism that attaches in the greatest numbers to hydrophilic substrata (i.e., S. epidermidis) was removed when the opposite transition occurred. Neither solvated nor desolvated PNIPAAM exhibited intrinsic fouling release properties, indicating that the phase transition was the important factor in removal of organisms. Based on our observations of the behavior of this model system, we suggest that environmentally responsive polymers represent a new approach for controlling biofouling release.

Acrylamides↗

N-acetyl-L-cysteine affects growth, extracellular polysaccharide production, and bacterial biofilm formation on solid surfaces.

N-Acetyl-L-cysteine (NAC) is used in medical treatment of patients with chronic bronchitis. The positive effects of NAC treatment have primarily been attributed to the mucus-dissolving properties of NAC, as well as its ability to decrease biofilm formation, which reduces bacterial infections. Our results suggest that NAC also may be an interesting candidate for use as an agent to reduce and prevent biofilm formation on stainless steel surfaces in environments typical of paper mill plants. Using 10 different bacterial strains isolated from a paper mill, we found that the mode of action of NAC is chemical, as well as biological, in the case of bacterial adhesion to stainless steel surfaces. The initial adhesion of bacteria is dependent on the wettability of the substratum. NAC was shown to bind to stainless steel, increasing the wettability of the surface. Moreover, NAC decreased bacterial adhesion and even detached bacteria that were adhering to stainless steel surfaces. Growth of various bacteria, as monocultures or in a multispecies community, was inhibited at different concentrations of NAC. We also found that there was no detectable degradation of extracellular polysaccharides (EPS) by NAC, indicating that NAC reduced the production of EPS, in most bacteria tested, even at concentrations at which growth was not affected. Altogether, the presence of NAC changes the texture of the biofilm formed and makes NAC an interesting candidate for use as a general inhibitor of formation of bacterial biofilms on stainless steel surfaces.

Acetylcysteine↗

Bacterial adhesion to hydroxyl- and methyl-terminated alkanethiol self-assembled monolayers.

The attachment of bacteria to solid surfaces is influenced by substratum chemistry, but to determine the mechanistic basis of this relationship, homogeneous, well-defined substrata are required. Self-assembled monolayers (SAMs) were constructed from alkanethiols to produce a range of substrata with different exposed functional groups, i.e., methyl and hydroxyl groups and a series of mixtures of the two. Percentages of hydroxyl groups in the SAMs and substratum wettability were measured by X-ray photoelectron spectroscopy and contact angles of water and hexadecane, respectively. SAMs exhibited various substratum compositions and wettabilities, ranging from hydrophilic, hydroxyl-terminated monolayers to hydrophobic, methyl-terminated monolayers. The kinetics of attachment of an estuarine bacterium to these surfaces in a laminar flow chamber were measured over periods of 120 min. The initial rate of net adhesion, the number of cells attached after 120 min, the percentage of attached cells that adsorbed or desorbed between successive measurements, and the residence times of attached cells were quantified by phase-contrast microscopy and digital image processing. The greatest numbers of attached cells occurred on hydrophobic surfaces, because (i) the initial rates of adhesion and the mean numbers of cells that attached after 120 min increased with the methyl content of the SAM and the contact angle of water and (ii) the percentage of cells that desorbed between successive measurements (ca. 2 min) decreased with increasing substratum hydrophobicity. With all surfaces, 60 to 80% of the cells that desorbed during the 120-min exposure period had residence times of less than 10 min, suggesting that establishment of firm adhesion occurred quickly on all of the test surfaces.

Adsorption↗

Suppression of cell attachment and protein adsorption onto amphiphilic polylactide-grafted dextran films.

To develop novel biodegradable biomedical materials, polylactide-grafted dextrans (Dex-g-PLA)s having various lengths, numbers of graft chains and sugar units were synthesized using the trimethylsilyl (TMS) protection method. To explore the possibility of using Dex-g-PLA as a biomedical soft-material, the contact angle, cell attachment and protein adsorption properties of the films prepared from these biodegradable and amphiphilic graft co-polymers were investigated. The poly-L-lactide (PLLA) film did not absorb water at all because of its high hydrophobicity, while the graft co-polymer films started immediately to swell after immersion in PBS. The percentage of water absorption at equilibrium increased with increasing sugar unit content. The receding contact angle of the Dex-g-PLA films against water was smaller than that of the PLLA film. The receding contact angle of Dex-g-PLA films against water decreased with increasing the sugar unit content. The top surface of the Dex-g-PLA film was suggested to be covered with hydrophilic Dex segments by means of annealing in water and to afford the wettable surface. Such a wettable surface led to the suppression of cell attachment and protein adsorption onto the film.

Adsorption↗

Immobilization of functionalized alkyl-poly(ethylene oxide) surfactants on poly(ethylene) surfaces by means of an argon plasma treatment.

Alkyl-poly(ethylene oxide) (PEO) surfactants containing a terminal hydroxyl, sulfate, or carboxylate group were grafted at the surface of poly(ethylene) (PE) samples to improve their blood compatibility. Grafting was achieved by immobilizing PEO surfactants on PE using an argon plasma treatment. The sulfate group containing PEO surfactant was synthesized by sulfating polyoxyethylene(20)stearylether (Brij78; B) with chlorosulfonic acid. A carboxylate-terminated surfactant was synthesized by a substitution reaction of the sodium alkoxide form of B with sodium iodoacetate. XPS analysis of the modified PE samples showed that at short plasma treatment times of up to 5 s the structure of the immobilized surfactants is largely retained. When plasma treatment times longer than 30 s were applied, the PEO chains of the surfactants were degraded. The wettability of the modified PE samples was improved compared to the unmodified PE samples. The wettability of the modified samples did not change when they were stored in air at room temperature for at least 12 weeks.

Alkylation↗

Nanoparticle multilayers: surface modification of photosensitive drug microparticles for increased stability and in vitro bioavailability.

The results of this study report the novel use of electrostatic layer-by-layer nanoassembly of biocompatible nanoparticulate TiO2 multilayers to coat irregular nifedipine (NF) microcrystals to increase the photostability of the drug when exposed to simulated sunlight and to increase the dissolution rate and possibly the bioavailability of the drug after oral administration. The photostability of NF microcrystals (35 microm) coated with multiple bilayers of positively charged PDDA and negatively charged nanosized TiO2 particles (20-25 nm) was measured when exposed to an illuminance of 12 W/m2 corresponding to a light dose of 30 k lux or 25 W/m2 corresponding to light dose of 60 k lux. The dissolution rate of nifedipine from the coated microcrystals was measured in simulated gastric fluid containing 0.05% w/v polysorbate 80. Coating with one TiO2 layer increased the shelf life of nifedipine by 30 hours independent of the intensity of the light exposure. With an increase in the number of TiO2 layers; the photostability of the drug was enhanced even more. A TiO2 monolayer decreased the contact angle by 20 degrees for water and 33 degrees for the dissolution medium as compared with uncoated NF surfaces. This increase in wettability due to a decrease in contact angle increased the dissolution rate of nifedipine microcrystals coated with 1 PDDA/TiO2 bilayer 13-fold after 10 minutes, 5-fold after 1 hour, and 2-fold after 12 hours when compared to uncoated microcrystals. It is assumed that TiO2 increased the photostability because the nanoparticulate multilayers acts as a potential filter protecting the drug from damaging light rays reaching the drug crystals. The dissolution rate was increased because the hydrophilic TiO2 nanoparticles increased the aqueous wettability of the drug crystals thereby preventing aggregation in the dissolution medium. This ensured that the maximum drug surface area was exposed to the dissolution medium.

Biological Availability↗

Adhesion and function of rat liver cells adherent to silk fibroin/collagen blend films.

Collagen is often used in bioartificial livers as a biomimetic coating to promote liver cell adhesion and differentiation. Animal proteins are expensive and expose the host to risks of cross-species infection due to contamination with prions. Silk fibroin (SF) is a biocompatible protein produced by Bombyx mori silk worms and possibly an alternative to collagen. We prepared SF-collagen blend films with different SF content adherent to the bottom of standard tissue culture dishes, and characterized their surface morphology by SEM, their wettability and examined them for their capacity to support rat liver cell adhesion and metabolism. Cell metabolism was characterized by estimating the rate at which cells eliminated ammonia and synthesized urea for up to 48h of culture. SF-containing films were smooth, clear and more wettable than collagen. Cells readily adhered, formed junctions and small size aggregates on all films. As many cells adhered on SF as on collagen films. Cell adhesion to high collagen content blend films could not be reliably estimated because cells dwelt in the large cavities in the film. The effect of SF on cell metabolism differed with the investigated metabolic pathway. However, cells on SF-containing films eliminated ammonia and synthesized urea at rates generally comparable to, for urea synthesis at times higher than, that of cells on collagen. These results suggest that silk fibroin is a suitable substratum for liver cell attachment and culture, and a potential alternative to collagen as a biomimetic coating.

Animals↗

Adhesion of L1210 cells to modified styrene copolymer surfaces in the presence of serum.

The static adhesion of living L1210 cells (in serum-containing medium) to the surface of (styrene/methylmethacrylate) copolymers differing in styrene content (from 5% to 50% of styrene units) was investigated. The examination of wettability of the copolymer surfaces showed that the contact angle of water on the hydrophobic surfaces is an increasing linear function of styrene content in the copolymer. Cell adhesion to the unwettable surfaces is low (within 2-4%). A novel method of modification of the styrene copolymer surfaces was used to render these surfaces suitable for cell attachment. The modification consists of sulfonation of the surfaces with sulfur trioxide at the gas/solid interface. The contact angle of sulfonated copolymer surfaces is a decreasing linear function of styrene content in the copolymer. The contact angle decreases due to the increased number of highly hydrophilic sulfonic groups bonded to styrene. By acetylation of the sulfonated surfaces it was shown that cell adhesion to acetylated surfaces is not diminished and is at the same level as cell adhesion to sulfonated copolymer surfaces. Thus, it can be concluded that sulfonation of copolymer surfaces does not form hydroxyl groups. Cell adhesion to substrata of high wettability stabilizes after 30s. The relative number of cells adhering to the sulfonated copolymer surfaces is a decreasing linear function of the contact angle. For the copolymer surfaces containing 50% of styrene units the contact angle decreases sevenfold, due to sulfonation, and the number of adhering cells increases 40-fold. The results obtained show that for cell-substratum adhesive interaction the presence of sulfonic groups at the substratum surface is important.

Animals↗

Cephalopod sucker design and the physical limits to negative pressure

Two factors determine the strength of pressure-based adhesive mechanisms such as suction: the magnitude of the pressure differential that their musculature and mechanics can produce and the pressure differential that water can sustain. This paper compares the adhesive strength of the primary cephalopod sucker types: the stalked suckers of decapods (cuttlefish and squid) and the unstalked suckers of octopods. These results are compared with the physical limits imposed by cavitation, the failure of water under negative pressure. The maximum pressure differentials that suckers can produce were measured using a wettable pressure transducer or by measuring their force of attachment on a wettable surface and dividing by the area exposed to reduced pressure. The maximum pressure differentials that water can sustain on a typical marine surface were measured in a Z-tube. Fifteen cephalopod species representing three orders were studied. At sea level, cavitation limits all suckers to the same range of pressure differentials (100-200 kPa), regardless of their morphology. As ambient pressure increases with depth, cavitation ceases to be limiting. In this case, stalked decapod suckers produce greater pressure differentials than unstalked octopod suckers. In addition, small suckers produce greater pressure differentials than large suckers. Suckers larger than 7.5 mm2, both decapod and octopod, typically achieve pressure differentials of 100 kPa. As their size decreases below 7.5 mm2, octopod suckers get slightly stronger, sometimes producing pressure differentials of 250-300 kPa, while decapod suckers get exponentially stronger, sometimes producing pressure differentials near 800 kPa. There were no differences in sucker strength among the four octopod species, but seven of the ten decapod species differed from the overall decapod regression curve. The strongest suckers belonged to the fast-swimming, open-water species in the decapod sub-order Oegopsida.

Journal Article↗

Preparation, characterization and in vitro dissolution studies of solid dispersion of meloxicam with PEG 6000.

The poor solubility and wettability of meloxicam leads to poor dissolution and hence showing variations in bioavailability. The present study is aimed to increase solubility and dissolution of the drug using solid dispersion techniques. The solid binary systems were prepared at various drug concentrations (5-40%) with polyethylene glycol 6000 by different techniques (physical mixing, solvent evaporation). The formulations were characterized by solubility studies, differential scanning calorimetry, fourier transform infrared spectroscopy and in vitro dissolution rate studies. The solubility of drug increased linearly with increase in polymer concentration showing A(L) type solubility diagrams. Infrared spectroscopy studies indicated the possibility of hydrogen bonding with polymer. The differential scanning calorimetry and powder X ray diffraction demonstrated the presence of polymer as eutectica or monotectica in solid dispersion along with the physical characteristics of the drug (crystalline, amorphous or a mixture of both). The solid dispersions of the drug demonstrated higher drug dissolution rates than physical mixtures and pure meloxicam, as a result of increased wettability and dispersibility of drug in a solid dispersion system.

Adjuvants, Pharmaceutic↗

An in vitro comparison of the mucoactive properties of guaifenesin, iodinated glycerol, surfactant, and albuterol.

STUDY OBJECTIVE: The mechanism of action of potential mucoactive agents could relate to effects on the mucociliary apparatus or to direct effects on the secretions. The purpose of this study was to determine the in vitro effects of several agents on the properties of mucus simulants and sputum collected from 30 adults with stable chronic bronchitis. DESIGN: Sputum or simulants were analyzed untreated and after the addition of the test agent at 1:5 volume to volume ratio for a contact period of 60 s. The concentrations of the agents were as follows: guaifenesin, 20 mg/mL; iodinated glycerol, 3 mg/mL; surfactant (Exosurf; Glaxo Wellcome; Research Triangle Park, NC) containing 13.5 mg of phospholipid per milliliter; albuterol, 5 mg/mL; and amphibian Ringer's solution (ARS) as a control. Dynamic viscoelasticity and surface mechanical impedance were measured in a magnetic microrheometer. Cohesiveness was measured using a filancemeter. The wettability of a hydrophilic surface was measured using an image processing system. The mucociliary transportability of sputum was timed on the frog palate, and cough transportability (CTR) was measured in a cough machine. RESULTS: When compared to sputum that had no test agent or ARS added, all agents reduced sputum elasticity G', with surfactant, albuterol, and guaifenesin significant at p < 0.001. As well, guaifenesin (p = 0.006), albuterol (p = 0.003), and surfactant (p = 0.02) decreased surface mechanical impedance (frictional adhesiveness) compared to untreated sputum. However, there were no significant changes in wettability, hydration, cohesiveness, or CTR with any agent, and there were no significant changes in the properties of sputum or simulants treated with test agents when compared to those treated with ARS. Guaifenesin irreversibly disrupted mucociliary transport when applied directly to the frog palate. CONCLUSIONS: These agents appear to have a minimal direct action on sputum in vitro, suggesting that at the concentrations studied, these agents do not have a significant beneficial effect on either the mucociliary transportability or CTR of chronic bronchitis sputum. However, there could be an effect of some of these agents after oral administration, especially if there is a secondary effect of the agent on an effector cell.

Adult↗

Soft contact lens biomaterials from bioinspired phospholipid polymers.

Soft contact lens (SCL) biomaterials originated from the discovery of a poly(2-hydroxyethyl methacrylate) (poly[HEMA])-based hydrogel in 1960. Incorporation of hydrophilic polymers into poly(HEMA) hydrogels was performed in the 1970-1980s, which brought an increase in the equilibrium water content, leading to an enhancement of the oxygen permeability. Nowadays, the poly(HEMA)-based hydrogels have been applied in disposable SCL. At the same time, high oxygen-permeable silicone hydrogels were produced, which made it possible to continually wear SCL. Recently, numerous trials for improving the water wettability of silicone hydrogels have been performed. However, little attention has been paid to improving their anti-biofouling properties and biocompatibility. Since biomimetic phospholipid polymers possess excellent anti-biofouling properties and biocompatibility they have the potential to play a valuable role in the surface modification of the silicone hydrogel. The representative phospholipid polymers containing a 2-methacryloyloxyethyl phosphorylcholine (MPC) unit suppressed nonspecific protein adsorption, increased cell compatibility and contributed to blood compatible biomaterials. The MPC polymer coating on the silicone hydrogel improved its water wettability and biocompatibility, while maintaining high oxygen permeability compared with the original silicone hydrogel. Furthermore, the newly prepared phospholipid-type intermolecular crosslinker made it possible to synthesize a 100% phospholipid polymer hydrogel that can enhance the anti-biofouling properties and biocompatibility. In this review, the authors discuss how polymer hydrogels should be designed in order to obtain a biocompatible SCL and future perspectives.

Biocompatible Materials↗

Fipronil insecticide: novel application against triatomine insect vectors of Chagas disease.

We investigated the efficacy and the residual effect of fipronil(R) against two species of triatomine bugs, Triatoma infestans and Rhodnius neglectus, in laboratory conditions measuring concentration-response and residual activity on different surfaces (dried mud and lime coated mud). Lethal concentrations (LC50,90) were determined on filter paper. The higher insecticide efficacy against R. neglectus when compared to T. infestans may be partially attributed to the differences in their biological cycles and genetic structures. Comparison with lambdacyhalothrin wettable powder showed that fipronil mortality rates (above 50%) were observed on mud blocks and lime-coated mud blocks up to 3 months when fipronil was sprayed at 100 and 200 mg a.i./m2. Residual effect deeply decayed after 3 months; and at 6 months post treatment mortality was not observed. In contrast, lambdacyhalothrin showed a long lasting residual effect on both surfaces up to 6 months. Also, it should be mentioned that fipronil had a slow, but lethal activity on the triatomine bugs when wettable formulations were used on porous surfaces.

Animals↗

The role of mucus sol phase in clearance by simulated cough.

Using a simulated cough machine, we analyzed the effect of adding tensio-active liquids as sol phase simulant on the clearance of gel mucus simulant by cough. Polysaccharides crosslinked with sodium tetraborate were used at different concentration as gel mucus simulant. A drop of gel mucus simulant was deposited either directly on the model trachea or on a sol phase layer simulant (2% sodium dodecyl sulfate in water). The clearance of the mucus simulants was quantified by observing the movement of marker particles in the gel layer. The viscoelastic properties of gel mucus simulants were determined by using a viscoelastometer (SEFAM). The adhesive properties were analyzed by means of the platinum ring technique. The wettability of the mucus simulants was quantified by the automatic measurement of the contact angle of the drop of gel on the model trachea. We found that the addition of a sol phase significantly decreased by about 50% the adhesivity and wettability of the gel mucus simulants. This decrease was associated with a marked enhancement of cough clearance, whatever the viscoelastic properties of the gel mucus simulants. These results suggest that the sol phase is essential in bronchial respiratory mucus clearance by the cough mechanism.

Adhesiveness↗

Residues of stirofos (rabon) in eggs of laying hens treated for northern fowl mite control by dipping.

Laying hens were treated with a wettable powder formulation of stirofos [Rabon, 2-chloro-1-(2,4,5-trichlorophenyl) vinyl dimethylphosphate] by dipping in a .5 or 1.0% actual ingredient (AI) water suspension of a 50% wettable powder (WP) stirfos formulation. Stirofos residues were detected in eggs within 1 day after treatment and reached maximum levels 3 days after dipping (.021 and .035 ppm in the low- and high-dose birds, respectively). After that time, levels of residues in eggs declined rapidly and no sample contained detectable quantities (less than .004 ppm) of stirofos after 21 days. Dipping may be a practical control method for the northern fowl mite on chickens, because stirofos dips effectively control this mite on laying hens for at least 6 weeks and because resulting residues in eggs are well below established tolerances.

Administration, Topical↗

[Influence of tendencies toward depression, neurosis and psychosomatic disorders on oral symptoms].

This study revealed that the tendencies towards depression, neurosis, and psychosomatic disorders have effects on oral symptoms. The total number of subjects was 102. The subjects were divided into two groups using the SDS (Self-rating Depression Scale): a control group of 66 subjects with an SDS value of less than 40, and a group of 36 subjects having depression tendencies with an SDS value of over 50. Most of the subjects in the depression tendency group showed symptoms of neurosis and psychosomatic disorders as well. The two groups were compared on the basis of their psychological characteristics, dosages of medicine taken, esthesis of mouth dryness, glossalgia, salivary flow rate, oral wettability, existence of dental cavities, and condition of the oral mucosa. No xerostomia at the mucobuccal fold was observed in the depression tendency group. However, there was an evident decrease of the resting salivary flow rate and the wettability of proglossis. It is considered that such a decrease resulted in an increase in the symptoms derived from xerostomia or esthesis of mouth dryness. The number of conservable but untreated dental cavities in the depression tendency group was larger than that in the control group with a significant difference, suggesting that both oral self-care and dental care management tended to be inadequate in the depression tendency group.

Adult↗

Primary bacterial colonization of implant surfaces.

The purpose of this study was to assess the effects of modifying titanium surfaces, in terms of wettability, roughness, and mode of sterilization, on the ability of the oral bacterium Streptococcus sanguis to colonize. An in vitro model system was developed. All surfaces were colonized by the bacteria, but to significantly different levels. Titanium samples that exhibited rough or hydrophobic (low wettability) surfaces, along with all autoclaved surfaces, were preferentially colonized (P < .01). Titanium surfaces that had been repeatedly autoclaved were colonized with the levels of bacteria 3 to 4 orders of magnitude higher than other modes of sterilization. This may have implications relative to the commonly used method of autoclaving titanium implants, which may ultimately enhance bacterial biofilm formation on these surfaces.

Bacterial Adhesion↗

[Solubility and dissolution rate of digoxin from Digitalis lanata drug extracts] .

The influence on solubility and dissolution rate was investigated for digoxin as a model drug with a very low solubility in water. The investigations were carried out with different fractions of extracts from leaves of Digitalis lanata. These fractions differ in the composition of concomitant compounds. The solubility of digoxin from the extract fractions is increased up to 42 times, with considerable differences between the fractions. The solubility depends on the weight of the extract fraction; a limit of solubility exists. Even after separation of the solved extract components the solubility of digoxin in the residues is larger than that of the pure digoxin. The dissolution rate of digoxin of "Vorgereinigter Gesamtglykosidextrakt (VE)" and the glycosid fraction G 1 is influenced significantly, whereas digoxin in the glycosid fraction G 4 has such a degree of purity that the solubility properties are not influenced by the small amount of concomitant compounds. After 10 min already 50.4% of the digoxin in the extract fraction G 1 are dissolved, while only 21.7% of the pure digoxin are dissolved in that interval. The extract fractions exhibit different wettability properties, so that the increased dissolution rate could be attributed to improved wettability of the extract fractions. Physical mixtures of crystal-line digoxin and compounds of the extracts of the almost digoxin free fraction G 2 did not exert an influence on the dissolution behavior. Different batches of the extract fractions showed different solubility in spite of comparable digoxin content.

Cardiotonic Agents↗