Sample records for enteric bead formulation

  1. Drug particle size influence on enteric beads produced by a droplet extrusion/precipitation method.

    PubMed

    Cerdeira, A M; Gouveia, L F; Goucha, P; Almeida, A J

    2000-01-01

    The influence of drug particle size on the production of enteric beads by a polymer precipitation technique was investigated. Drug particle dimensions are known to play an important role in most microencapsulation techniques. Bead morphology was greatly influenced by drug particle size, and spherical shaped beads could only be obtained after size reduction of nimesulide crystals. This is confirmed by the angle of repose measurements, which show a significant decrease in theta values when beads are formulated with smaller drug particles. Furthermore, results show that drug encapsulation efficiency and in vitro drug release rates are also greatly dependent on both drug particle size and drug/polymer ratio in the initial suspension. Preparations containing 10.2 microm drug particles show a two-fold increase in the release rates when compared to those prepared with 40 microm particles.

  2. Development of enteric-coated fixed dose combinations of amorphous solid dispersions of ezetimibe and lovastatin: Investigation of formulation and process parameters.

    PubMed

    Riekes, Manoela K; Dereymaker, Aswin; Berben, Philippe; Augustijns, Patrick; Stulzer, Hellen K; Van den Mooter, Guy

    2017-03-30

    Enteric-coated fixed-dose combinations of ezetimibe and lovastatin were prepared by fluid bed coating aiming to avoid the acidic conversion of lovastatin to its hydroxyacid derivative. In a two-step process, sucrose beads were layered with a glass solution of ezetimibe, lovastatin and Soluplus ® , top-coated with an enteric layer. The impact of different bead size, enteric polymers (Eudragit L100 ® and Eudragit L100-55 ® ) and coating time was investigated. Samples were evaluated by X-ray diffraction, scanning electron microscopy, laser diffraction and in vitro studies in 0.1M HCl and phosphate buffer pH 6.8. Results showed that smaller beads tend to agglomerate and release was jeopardized in acidic conditions, most likely due to irregular coating layer. Eudragit L100-55 ® required longer processing, but thinner coating layers provided lower drug release. Both polymers showed low drug release in acidic environment and fast release at pH 6.8. The off-line measurement of the coating thickness determined the ideal coating time as 15 and 30min for Eudragit L100-55 ® and Eudragit L100 ® -based samples, respectively. Both compounds were molecularly dispersed in Soluplus ® , and Eudragit L100 ® formulations showed concave pores on the surface, presenting higher drug release in acidic conditions. Stability studies after 6 months showed unaltered physical properties and drug release. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. A Multiparticulate Delivery System for Potential Colonic Targeting Using Bovine Serum Albumin as a Model Protein : Theme: Formulation and Manufacturing of Solid Dosage Forms Guest Editors: Tony Zhou and Tonglei Li.

    PubMed

    Jiang, Bowen; Yu, Hua; Zhang, Yongrong; Feng, Hanping; Hoag, Stephen W

    2017-12-01

    There are many important diseases whose treatment could be improved by delivering a therapeutic protein to the colon, for example, Clostridium difficile infection, ulcerative colitis and Crohn's Disease. The goal of this project was to investigate the feasibility of colonic delivery of proteins using multiparticulate beads. In this work, bovine serum albumin (BSA) was adopted as a model protein. BSA was spray layered onto beads, followed by coating of an enteric polymer EUDRAGIT® FS 30 D to develop a colonic delivery system. The secondary and tertiary structure change and aggregation of BSA during spray layering process was examined. The BSA layered beads were then challenged in an accelerated stability study using International Council for Harmonization (ICH) conditions. The in vitro release of BSA from enteric coated beads was examined using United States Pharmacopeia (USP) dissolution apparatus 1. No significant changes in the secondary and tertiary structure or aggregation profile of BSA were observed after the spray layering process. Degradation of BSA to different extents was detected after storing at 25°C and 40°C for 38 days. Enteric coated BSA beads were intact in acidic media while released BSA in pH 7.4 phosphate buffer. We showed the feasibility of delivering proteins to colon in vitro using multiparticulate system.

  4. Formulation and optimization of zinc-pectinate beads for the controlled delivery of resveratrol.

    PubMed

    Das, Surajit; Ng, Ka-Yun; Ho, Paul C

    2010-06-01

    Preventive and therapeutic efficacies of resveratrol on several lower gastrointestinal (GI) diseases (e.g., colorectal cancer, colitis) are well documented. To overcome the problems due to its rapid absorption and metabolism at the upper GI tract, a delayed release formulation of resveratrol was designed to treat these lower GI diseases. The current study aimed to develop a delayed release formulation of resveratrol as multiparticulate pectinate beads by varying different formulation parameters. Zinc-pectinate (Zn-pectinate) beads exhibited better delayed drug release pattern than calcium-pectinate (Ca-pectinate) beads. The effects of the formulation parameters were investigated on shape, size, Zn content, moisture content, drug encapsulation efficiency, swelling-erosion, and resveratrol retention pattern of the formulated beads. Upon optimization of the formulation parameters in relative to the drug release profiles, the optimized beads were further subjected to morphological, chemical interaction, enzymatic degradation, and stability studies. Almost all prepared beads were spherical with approximately 1 mm diameter and efficiently encapsulated resveratrol. The formulation parameters revealed great influence on resveratrol retention and swelling-erosion behavior. In most of the cases, the drug release data more appropriately fitted with zero-order equation. This study demonstrates that the optimized Zn-pectinate beads can encapsulate very high amount of resveratrol and can be used as delayed release formulation of resveratrol.

  5. EFFICACY OF THAI NEEM OIL AGAINST AEDES AEGYPTI (L.) LARVAE.

    PubMed

    Silapanuntakul, Suthep; Keanjoom, Romnalin; Pandii, Wongdyan; Boonchuen, Supawadee; Sombatsiri, Kwanchai

    2016-05-01

    Trees with larvicidal activity may be found in Thailand. We conducted this study to evaluate the efficacy and length of efficacy of Thai neem (Azadirachta siamensis) oil emulsion and an alginate bead of Thai neem oil formulation against early fourth stage Aedes aegypti larvae using a dipping test. The Thai neem oil emulsion had significantly greater larvicidal activity than the alginate bead formulation at 12 to 60 hours post-exposure (p < 0.01). The Thai neem oil formulation resulted in 100% mortality among the early fourth stage Aedes aegypti larvae at 48 hours, while the alginate bead formulation resulted in 98% larval mortality at 84 hours and 100% mortality at 96 hours. The mean larval mortality using the Thai neem oil emulsion dropped to < 25% by 12 days and with the alginate beads dropped to < 25% by 15 days of exposure.

  6. Skin permeation and retention of topical bead formulation containing tranexamic acid.

    PubMed

    Vijayakumar, Ajay; Baskaran, Rengarajan; Yoo, Bong Kyu

    2017-02-01

    The objective of this study is to develop a topical bead formulation of tranexamic acid (TA) which can be used concomitantly with laser treatment. The bead formulation of TA (TAB) was successfully prepared by fluidized bed drying method. Physicochemical properties of the TAB were evaluated in terms of chemical stability of TA and differential scanning calorimetry. TA in the bead was stable up to six months at 25°C and existed as amorphous state. In vitro skin permeation and in vivo skin retention of TA in the beads were significantly higher compared to a commercial product. When the bead was dissolved into distilled water and applied concomitantly with laser treatment, the amount of TA retained in the skin in the in vivo study was inversely proportional to the energy levels of laser treatment, indicating absorption into subcutaneous tissue and drainage to systemic circulation. Therefore, when laser treatment is used concomitantly with TAB, energy level should be very carefully monitored to avoid possible adverse events associated with systemic side effects of TA.

  7. Sulindac loaded alginate beads for a mucoprotective and controlled drug release.

    PubMed

    Yegin, Betül Arica; Moulari, Brice; Durlu-Kandilci, N Tugba; Korkusuz, Petek; Pellequer, Yann; Lamprecht, Alf

    2007-06-01

    Ionotropic gelation was used to entrap sulindac into calcium alginate beads as a potential drug carrier for the oral delivery of this anti-inflammatory drug. Beads were investigated in vitro for a possible sustained drug release and their use in vivo as a gastroprotective system for sulindac. Process parameters such as the polymer concentration, polymer/drug ratio, and different needle diameter were analysed for their influences on the bead properties. Size augmented with increasing needle diameter (0.9 mm needle: 1.28 to 1.44 mm; 0.45 mm needle: 1.04 to 1.07 mm) due to changes in droplet size as well as droplet viscosity. Yields varied between 87% and 98% while sulindac encapsulation efficiencies of about 88% and 94% were slightly increasing with higher alginate concentrations. Drug release profiles exhibited a complete release for all formulations within 4 hours with a faster release for smaller beads. Sulindac loaded alginate beads led to a significant reduction of macroscopic histological damage in the stomach and duodenum in mice. Similarly, microscopic analyses of the mucosal damage demonstrated a significant mucoprotective effect of all bead formulation compared to the free drug. The present alginate formulations exhibit promising properties of a controlled release form for sulindac; meanwhile they provide a distinct tissue protection in the stomach and duodenum.

  8. Formulation and characterization of a compacted multiparticulate system for modified release of water-soluble drugs--part 1--acetaminophen.

    PubMed

    Cantor, Stuart L; Hoag, Stephen W; Augsburger, Larry L

    2009-03-01

    The aim of this study was to characterize and evaluate a modified release, multiparticulate tablet formulation consisting of placebo beads and drug-loaded beads. Acetaminophen (APAP) bead formulations containing ethylcellulose (EC) from 40-60% and placebo beads containing 30% calcium silicate and prepared using 0-20% alcohol were developed using extrusion-spheronization and studied using a central composite experimental design. Particle size and true density of beads were measured. Segregation testing was performed using the novel ASTM D6940-04 method on a 50:50 blend of uncoated APAP beads (60%EC) : calcium silicate placebo beads (10% alcohol). Tablets were prepared using an instrumented Stokes-B2 rotary tablet press and evaluated for crushing strength and dissolution rate. Compared with drug beads (60%EC), placebo beads (10% alcohol) were smaller but had higher true densities: 864.8 mum and 1.27 g/cm(3), and 787.1 mum and 1.73 g/cm(3), respectively. Segregation testing revealed that there was approximately a 20% difference in drug content (as measured by the coefficient of variation) between initial and final blend samples. Although calcium silicate-based placebo beads were shown to be ineffective cushioning agents in blends with Surelease(R)-coated APAP beads, they were found to be very compactibile when used alone and gave tablet crushing strength values between 14 and 17 kP. The EC in the APAP bead matrix minimally suppressed the drug release from uncoated beads (t(100%) = 2 h). However, while tablets containing placebo beads reformulated with glycerol monostearate (GMS) showed a slower release rate (t(60%)= 5 h) compared with calcium silicate-based placebos, some coating damage ( approximately 30%) still occurred on compression as release was faster than coated APAP beads alone. While tablets containing coated drug beads can be produced with practical crushing strengths (>8 kP) and low compression pressures (10-35 MPa), dissolution studies revealed that calcium silicate-based placebos are ineffective as cushioning agents. Blend segregation was likely observed due to the particle size and the density differences between APAP beads and calcium silicate-based placebo beads; placebo bead percolation can perhaps be minimized by increasing their size during the extrusion-spheronization process. The GMS- based placebos offer greater promise as cushioning agents for compacted, coated drug beads; however, this requires an optimized compression pressure range and drug bead : placebo bead ratio (i.e., 50:50).

  9. Tapioca starch blended alginate mucoadhesive-floating beads for intragastric delivery of Metoprolol Tartrate.

    PubMed

    Biswas, Nikhil; Sahoo, Ranjan Kumar

    2016-02-01

    The objective of the study was to develop tapioca starch blended alginate mucoadhesive-floating beads for the intragastric delivery of Metoprolol Tartrate (MT). The beads were prepared by ionotropic gelation method using calcium chloride as crosslinker and gas forming calcium carbonate (CaCO3) as floating inducer. The alginate gel beads having 51-58% entrapped MT showed 90% release within 45 min in gastric medium (pH 1.2). Tapioca starch blending markedly improved the entrapment efficiency (88%) and sustained the release for 3-4 h. A 12% w/w HPMC coating on these beads extended the release upto 9-11 h. In vitro wash off and buoyancy test in gastric media revealed that the beads containing CaCO3 has gastric residence of more than 12 h. In vitro optimized multi-unit formulation consisting of immediate and sustained release mucoadhesive-floating beads (40:60) showed good initial release of 42% MT within 1h followed by a sustained release of over 90% for 11 h. Pharmacokinetic study performed in rabbit model showed that the relative oral bioavailability of MT after administration of oral solution, sustain release and optimized formulation was 51%, 67% and 87%, respectively. Optimized formulation showed a higher percent inhibition of isoprenaline induced heart rate in rabbits for almost 12 h. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Formulation optimization and evaluation of jackfruit seed starch-alginate mucoadhesive beads of metformin HCl.

    PubMed

    Nayak, Amit Kumar; Pal, Dilipkumar

    2013-08-01

    The present study deals with the formulation optimization of jackfruit (Artocarpus heterophyllus Lam., family: Moraceae) seed starch (JFSS)-alginate mucoadhesive beads containing metformin HCl through ionotropic gelation using 3(2) factorial design. The effect of sodium alginate to JFSS ratio and CaCl2 concentration on the drug encapsulation efficiency (DEE, %), and cumulative drug release at 10h (R10h, %) was optimized. The optimized beads containing metformin HCl showed DEE of 97.48±3.92%, R10h of 65.70±2.22%, and mean diameter of 1.16±0.11mm. The in vitro drug release from these beads was followed controlled-release (zero-order) pattern with super case-II transport mechanism. The beads were also characterized by SEM and FTIR. The swelling and degradation of these beads were influenced by pH of the test medium. The optimized beads also exhibited good mucoadhesivity and significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Exploitation of novel gum Prunus cerasoides as mucoadhesive beads for a controlled-release drug delivery.

    PubMed

    Seelan, T Veenus; Kumari, Henry Linda Jeeva; Kishore, Narra; Selvamani, Palanisamy; Lalhlenmawia, H; Thanzami, K; Pachuau, Lalduhsanga; Ruckmani, Kandasamy

    2016-04-01

    The present study deals with the formulation of pH-sensitive mucoadhesive beads using natural gum isolated from Prunus cerasoides (PC) in combination with sodium alginate (SA) for the controlled release of diclofenac sodium (DS). PC and SA composite (PC-SA), DS loaded SA (DS-SA) and DS loaded PC-SA (DS-PC-SA) beads were prepared by ionotropic gelation method. The absence of interaction between DS and PC-SA was shown by FTIR, DSC and TGA analyses. The optimized DS-PC-SA formulation exhibited mucoadhesive property and the controlled release of DS was achieved 68% in 12h. The in vitro release kinetics follows zero order with anomalous diffusion mechanism. Therefore, the formulated mucoadhesive beads with the novel gum are preferable for the controlled release of DS by prolonging the residence time of the drug in the gastrointestinal tract, overcoming the problems associated with the immediate release dosage forms of DS. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. A comparative histological study of alginate beads as a promising controlled release delivery for mefenamic acid.

    PubMed

    Sevgi, Ferhan; Kaynarsoy, Buket; Ozyazici, Mine; Pekcetin, Cetin; Ozyurt, Dogan

    2008-01-01

    The new mefenamic acid-alginate bead formulation prepared by ionotropic gelation method using 3 x 2(2) factorial design has shown adequate controlled release properties in vitro. In the present study, the irritation effects of mefenamic acid (MA), a prominent non-steroidal anti-inflammatory (NSAI) drug, were evaluated on rat gastric and duodenal mucosa when suspended in 0.5% (w/v) sodiumcarboxymethylcellulose (NaCMC) solution and loaded in alginate beads. Wistar albino rats weighing 200 +/- 50 g were used during in vivo animal studies. In this work, biodegradable controlled release MA beads and free MA were evaluated according to the degree of gastric or duodenal damage following oral administration in rats. The gastric and duodenal mucosa was examined for any haemorrhagic changes. Formulation code A10 showing both Case II transport and zero order drug release and t(50) % value of 5.22 h was chosen for in vivo animal studies. For in vivo trials, free MA (100 mgkg(-1)), blank and MA (100 mgkg(-1)) loaded alginate beads (formulation code A10) were suspended in 0.5% (w/v) NaCMC solution and each group was given to six rats orally by gavage. NaCMC solution was used as a control in experimental studies. In vivo data showed that the administration of MA in alginate beads prevented the gastric lesions.

  13. Novel mesalamine-loaded beads in tablets for delayed release of drug to the colon.

    PubMed

    Nguyen, Chien; Christensen, J Mark; Ayres, James W

    2012-01-01

    Novel 'beads-in-a-tablet' formulations (total weight ∼740-780 mg) have been prepared that meet USP 31 requirements for Delayed Release of mesalamine. Several methods are presented that overcome breakage of beads during tablet compaction were explored. Bead formulations comprise a combination of extrusion and spheronization to produce a relatively high drug load (80%), followed by coating (25%) with a colonic-targeted drug release polymer (polymethacrylates, Eudragit(®) S100), overcoated (3%) with hydroxypropyl methylcellulose (Opadry(®)) to improve bead binding and compactability, and using 20% coat of lactose/sodium starch glycolate (Explotab(®)) as binder/disintegrant/cushioning agent, thus allowing a sufficiently thick coating to be uniform and without being broken during tablet compaction. Then, the aforementioned beads were compressed into tablets at 1500 pounds of pressure containing 400 mg of mesalamine, and finally coating the compressed tablets with Surelease(®) (ethylcellulose):Opadry(®) = 1:0.5 ranging from 1.5-2.5% weight gain; the resulting tablets met USP 31 dissolution requirements for delayed release tablets.

  14. Preparation of acetaminophen capsules containing beads prepared by hot-melt direct blend coating.

    PubMed

    Pham, Loan; Christensen, John M

    2014-02-01

    Twelve hydrophobic coating agents were assessed for their effects on drug release after coating sugar cores by a flexible hot-melt coating method using direct blending. Drug-containing pellets were also produced and used as cores. The cores were coated with single or double wax layers containing acetaminophen (APAP). The harder the wax, the slower the resultant drug releases from single-coated beads. Wax coating can be deposited on cores up to 28% of the beads final weight and reaching 58% with wax and drug. Carnauba-coated beads dissolved in approximately 6 h releasing 80% of the loaded drug. Applying another wax layer extended drug release over 20 h, while still delivering 80% of the loaded drug. When drug-containing pellets (33-58% drug loading) were used as cores, double wax-coated pellets exhibited a near zero-order drug release for 16 h, releasing 80% of the loaded drug delivering 18 mg/h. The simple process of hot-melt coating by direct blending of pellet-containing drug-coated formulations provides excellent options for immediate and sustained release formulations when higher lipid coating or drug loading is warranted. Predicted plasma drug concentration time profiles using convolution and in vitro drug release properties of the beads were performed for optimal formulations.

  15. Formulation and characterization of a compacted multiparticulate system for modified release of water-soluble drugs--Part II theophylline and cimetidine.

    PubMed

    Cantor, Stuart L; Hoag, Stephen W; Augsburger, Larry L

    2009-05-01

    The purpose was to investigate the effectiveness of an ethylcellulose (EC) bead matrix and different film-coating polymers in delaying drug release from compacted multiparticulate systems. Formulations containing theophylline or cimetidine granulated with Eudragit RS 30D were developed and beads were produced by extrusion-spheronization. Drug beads were coated using 15% wt/wt Surelease or Eudragit NE 30D and were evaluated for true density, particle size, and sphericity. Lipid-based placebo beads and drug beads were blended together and compacted on an instrumented Stokes B2 rotary tablet press. Although placebo beads were significantly less spherical, their true density of 1.21 g/cm(3) and size of 855 mum were quite close to Surelease-coated drug beads. Curing improved the crushing strength and friability values for theophylline tablets containing Surelease-coated beads; 5.7 +/- 1.0 kP and 0.26 +/- 0.07%, respectively. Dissolution profiles showed that the EC matrix only provided 3 h of drug release. Although tablets containing Surelease-coated theophylline beads released drug fastest overall (t(44.2%) = 8 h), profiles showed that coating damage was still minimal. Size and density differences indicated a minimal segregation potential during tableting for blends containing Surelease-coated drug beads. Although modified release profiles >8 h were achievable in tablets for both drugs using either coating polymer, Surelease-coated theophylline beads released drug fastest overall. This is likely because of the increased solubility of theophylline and the intrinsic properties of the Surelease films. Furthermore, the lipid-based placebos served as effective cushioning agents by protecting coating integrity of drug beads under a number of different conditions while tableting.

  16. Development of an attract-and-kill co-formulation containing Saccharomyces cerevisiae and neem extract attractive towards wireworms.

    PubMed

    Humbert, Pascal; Vemmer, Marina; Mävers, Frauke; Schumann, Mario; Vidal, Stefan; Patel, Anant V

    2018-07-01

    Wireworms (Coleoptera: Elateridae) are major insect pests of worldwide relevance. Owing to the progressive phasing-out of chemical insecticides, there is great demand for innovative control options. This study reports on the development of an attract-and-kill co-formulation based on Ca-alginate beads, which release CO 2 and contain neem extract as a bioinsecticidal compound. The objectives of this study were to discover: (1) whether neem extract can be immobilized efficiently, (2) whether CO 2 -releasing Saccharomyces cerevisiae and neem extract are suitable for co-encapsulation, and (3) whether co-encapsulated neem extract affects the attractiveness of CO 2 -releasing beads towards wireworms. Neem extract was co-encapsulated together with S. cerevisiae, starch and amyloglucosidase with a high encapsulation efficiency of 98.6% (based on measurement of azadirachtin A as the main active ingredient). Even at enhanced concentrations, neem extract allowed growth of S. cerevisiae, and beads containing neem extract exhibited CO 2 -emission comparable with beads without neem extract. When applied to the soil, the beads established a CO 2 gradient of >15 cm. The co-formulation containing neem extract showed no repellent effects and was attractive for wireworms within the first 24 h after exposure. Co-encapsulation of S. cerevisiae and neem extract is a promising approach for the development of attract-and-kill formulations for the control of wireworms. This study offers new options for the application of neem extracts in soil. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  17. Sodium lauryl sulfate impedes drug release from zinc-crosslinked alginate beads: switching from enteric coating release into biphasic profiles.

    PubMed

    Taha, Mutasem O; Nasser, Wissam; Ardakani, Adel; Alkhatib, Hatim S

    2008-02-28

    The aim of this research is to investigate the effects of sodium lauryl sulfate (SLS) on ionotropically cross-linked alginate beads. Different levels of SLS were mixed with sodium alginate and chlorpheniramine maleate (as loaded model drug). The resulting viscous solutions were dropped onto aqueous solutions of zinc or calcium ions for ionotropic curing. The generated beads were assessed by their drug releasing profiles, infrared and differential scanning colorimetery (DSC) traits. SLS was found to exert profound concentration-dependent impacts on the characteristics of zinc-crosslinked alginate beads such that moderate modifications in the levels of SLS switched drug release from enteric coating-like behavior to a biphasic release modifiable to sustained-release by the addition of minute amounts of xanthan gum. Calcium cross-linking failed to reproduce the same behavior, probably due to the mainly ionic nature of calcium-carboxylate bonds compared to the coordinate character of their zinc-carboxylate counterparts. Apparently, moderate levels of SLS repel water penetration into the beads, and therefore minimize chlorpheniramine release. However, higher SLS levels seem to discourage polymeric cross-linking and therefore allow biphasic drug release.

  18. Development of a novel osmotically driven drug delivery system for weakly basic drugs.

    PubMed

    Guthmann, C; Lipp, R; Wagner, T; Kranz, H

    2008-06-01

    The drug substance SAG/ZK has a short biological half-life and because of its weakly basic nature a strong pH-dependent solubility was observed. The aim of this study was to develop a controlled release (cr) multiple unit pellet formulation for SAG/ZK with pH-independent drug release. Pellets with a drug load of 60% were prepared by extrusion/spheronization followed by cr-film coating with an extended release polyvinyl acetate/polyvinyl pyrrolidone dispersion (Kollidon SR 30 D). To overcome the problem of pH-dependent drug release the pellets were then coated with a second layer of an enteric methacrylic acid and ethyl acrylate copolymer (Kollicoat MAE 30 DP). To increase the drug release rates from the double layered cr-pellets different osmotically active ionic (sodium and potassium chloride) and nonionic (sucrose) additives were incorporated into the pellet core. Drug release studies were performed in media of different osmotic pressure to clarify the main release mechanism. Extended release coated pellets of SAG/ZK demonstrated pH-dependent drug release. Applying a second enteric coat on top of the extended release film coat failed in order to achieve pH-independent drug release. Already low enteric polymer levels on top of the extended release coated pellets decreased drug release rates at pH 1 drastically, thus resulting in a reversal of the pH-dependency (faster release at pH 6.8 than in 0.1N HCl). The addition of osmotically active ingredients (sodium and potassium chloride, and sucrose) increased the imbibing of aqueous fluids into the pellet cores thus providing a saturated drug solution inside the beads and increasing drug concentration gradients. In addition, for these pellets increased formation of pores and cracks in the polymer coating was observed. Hence drug release rates from double layered beads increased significantly. Therefore, pH-independent osmotically driven SAG/ZK release was achieved from pellets containing osmotically active ingredients and coated with an extended and enteric polymer. In contrast, with increasing osmotic pressure of the dissolution medium the in vitro drug release rates decreased significantly.

  19. Bioaugmentation potential of free and formulated 2,6-dichlorobenzamide (BAM) degrading Aminobacter sp. MSH1 in soil, sand and water.

    PubMed

    Schultz-Jensen, Nadja; Aamand, Jens; Sørensen, Sebastian R

    2016-12-01

    Pesticides are used extensively worldwide, which has led to the unwanted contamination of soil and water resources. Former use of the herbicide 2,6-dichlorobenzonitrile (dichlobenil) has caused pollution of ground and surface water resources by the stable degradation product 2,6-dichlorobenzamide (BAM) in several parts of Europe, which has resulted in the costly closure of several drinking water wells. One strategy for preventing this in future is bioaugmentation using bacterial degraders. BAM-degrading Aminobacter sp. MSH1 was therefore formulated into dried beads and tests undertaken to establish their potential for use in the remediation of polluted soil, sand and water. The formulation procedure included freeze drying, combined with trehalose addition for cell wall protection, thus ensuring a high amount of viable cells following prolonged storage at room temperature. The beads were round-shaped pellets with a diameter of about 1.25 mm, a dry matter content of approximately 95 % and an average viable cell content of 4.4 × 10(9) cells/g bead. Formulated MSH1 cells led to a similar, and frequently even faster, BAM mineralisation (20-65 % (14)CO2 produced from (14)C-labelled BAM) in batch tests conducted with sand, water and different soil moisture contents compared to adding free cells. Furthermore, the beads were easy to handle and had a shelf life of several months.

  20. Pharmacokinetics and analgesic effect of ketorolac floating delivery system.

    PubMed

    Radwan, Mahasen A; Abou El Ela, Amal El Sayeh F; Hassan, Maha A; El-Maraghy, Dalia A

    2015-05-01

    The efficacy of ketorolac tromethamine (KT) floating alginate beads as a drug delivery system for better control of KT release was investigated. The formulation with the highest drug loading, entrapment efficiency, swelling, buoyancy, and in vitro release would be selected for further in vivo analgesic effect in the mice and pharmacokinetics study in rats compared to the tablet dosage form. KT floating alginate beads were prepared by extrusion congealing technique. KT in plasma samples was analyzed using a UPLC MS/MS assay. The percentage yield, drug loading and encapsulation efficiency were increased proportionally with the hydroxypropylmethyl cellulose (HPMC) polymer amount in the KT floating beads. A reverse relationship was observed between HPMC amount in the beads and the KT in vitro release rate. F3-floating beads were selected, due to its better in vitro results (continued floating for >8 h) than others. A longer analgesic effect was observed for F3 in fed mice as compared to the tablets. After F3 administration to rats, the Cmax (2.2 ± 0.3 µg/ml) was achieved at ∼2 h and the decline in KT concentration was slower. F3 showed a significant increase in the AUC (1.89 fold) in rats as compared to the tablets. KT was successfully formulated as floating beads with prolonged in vitro release extended to a better in vivo characteristic with higher bioavailability in rats. KT in floating beads shows a superior analgesic effect over tablets, especially in fed mice.

  1. Incorporation of beads into oral films for buccal and oral delivery of bioactive molecules.

    PubMed

    Castro, Pedro M; Sousa, Flávia; Magalhães, Rui; Ruiz-Henestrosa, Victor Manuel Pizones; Pilosof, Ana M R; Madureira, Ana Raquel; Sarmento, Bruno; Pintado, Manuela E

    2018-08-15

    The association of alginate beads and guar-gum films in a single delivery system was idealized to promote a more effective buccal and oral delivery of bioactive molecules. A response surface method (experimental design approach) was performed to obtain optimal formulations of alginate beads to be incorporated into guar gum oral films as combined buccal and oral delivery systems for caffeine delivery. The combined formulation was further characterized regarding physicochemical properties, drug release, cell viability and buccal permeability. Beads average size, determined by dynamic light scattering (DLS), was of 3.37 ± 6.36 μm. Film thickness was set to 62 μm. Scanning electron microscopy micrographs revealed that beads were evenly distributed onto the film matrix and beads size was in accordance to data obtained from DLS analysis. Evaluation of Fourier-transform infrared spectra did not indicate the formation of new covalent bonds between the matrix of guar-gum films, alginate beads and caffeine. In vitro release assays by dialysis membrane allowed understanding that the combination of guar-gum films and alginate beads assure a slower release of caffeine when compared with the delivery profile of free caffeine from alginate beads or guar-gum films alone. MTT assay, performed on human buccal carcinoma TR146 cell line, allowed concluding that neither guar-gum film, alginate beads nor guar-gum film incorporated into alginate beads significantly compromised cell viability after 12 h of exposure. As demonstrated by in vitro permeability assay using TR146 human buccal carcinoma cell lines, combination of guar-gum films and alginate beads also promoted a slower release and, thus, lower apparent permeability (1.15E-05 ± 3.50E-06) than for caffeine solution (2.68E-05 ± 7.30E-06), guar-gum film (3.12E-05 ± 4.70E-06) or alginate beads (2.01E-05 ± 3.90E-06). The conjugation of alginate beads within an orodispersible film matrix represents an effective oral/buccal delivery system that induces a controlled release along with an enhanced intimate contact with cell layers that may promote higher in vivo bioavailability of carried drugs. Copyright © 2018. Published by Elsevier Ltd.

  2. Study of the physical properties of calcium alginate hydrogel beads containing vineyard pruning waste for dye removal.

    PubMed

    Vecino, X; Devesa-Rey, R; Cruz, J M; Moldes, A B

    2015-01-22

    In this work the morphological and surface properties of a biocomposite formulated with vineyard pruning waste entrapped in calcium alginate hydrogel beads were studied. The formulation of the calcium alginate hydrogel beads, containing vineyard pruning waste, was based on the capacity of this green adsorbent to remove dye compounds from wastewater, observing that in the optimum condition (1.25% of cellulosic residue, 2.2% of sodium alginate and 0.475 mol L(-1) CaCl2) the percentage of dyes was reduced up to 74.6%. At lower concentration of CaCl2, high-resolution optical images show that the elongation of the vineyard-alginate biocomposite decreased, whereas the compactness increased. Moreover, higher concentrations of cellulosic residue increased the biocomposite roundness in comparison with biocomposite without the cellulosic residue. Interferometric perfilometry analysis (Ra, Rq, Rz and Rt) revealed that high concentrations of CaCl2 increased the roughness of the of the calcium alginate hydrogel beads observing vesicles in the external surface. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Development of Wax-Incorporated Emulsion Gel Beads for the Encapsulation and Intragastric Floating Delivery of the Active Antioxidant from Tamarindus indica L.

    PubMed

    Soradech, Sitthiphong; Petchtubtim, Intira; Thongdon-A, Jeerayu; Muangman, Thanchanok

    2016-03-22

    In this study, tamarind (Tamarindus indica L.) seed extracts with potential antioxidant activity and toxicity to cancer cells were developed as functional foods and nutraceutical ingredients in the form of emulsion gel beads. Three extracts were obtained from ethanol and water: TSCH50, TSCH95 and TSCH. All extracts exhibited high potential for superoxide anion scavenging activity over the IC50 range < 5-11 µg/mL and had no toxic effects on normal cells, however, the water extract (TSCH) was the most effective due to its free radical scavenging activity and toxicity in mitochondrial membranes of cancer cells. Next a study was designed to develop a new formulation for encapsulation and intragastric floating delivery of tamarind seed extract (TSCH) using wax-incorporated emulsion gel beads, which were prepared using a modified ionotropic gelation technique. Tamarind seed extract at 1% (w/w) was used as the active ingredient in all formulations. The effect of the types and amounts of wax on the encapsulation efficiency and percentage of the active release of alginate gel beads was also investigated. The results demonstrated that the incorporation of both waxes into the gel beads had an effect on the percentage of encapsulation efficiency (%) and the percentage of the active ingredient release. Furthermore, the addition of water insoluble waxes (carnauba and bee wax) significantly retarded the release of the active ingredient. The addition of both waxes had a slight effect on drug release behavior. Nevertheless, the increase in incorporated waxes in all formulations could sustain the percentage of active ingredient release. In conclusion, wax-incorporated emulsion gel beads using a modified ionotropic gelation technique could be applied for the intragastric floating delivery and controlled release of functional food and nutraceutical products for their antioxidant and anticancer capacity.

  4. Synthesis of zinc-crosslinked thiolated alginic acid beads and their in vitro evaluation as potential enteric delivery system with folic acid as model drug.

    PubMed

    Taha, M O; Aiedeh, K M; Al-Hiari, Y; Al-Khatib, H

    2005-10-01

    The aim of this study is to explore the potential of synthetic modifications of alginic acid as a method to enhance the stability of its complexes with divalent cations under physiological conditions. A fraction of algin's carboxylic acid moieties was substituted with thiol groups to different substitution degrees through conjugating alginate to cysteine to produce alginate-cysteine (AC) conjugates. Infrared spectrophotometry and iodometry were used to characterize the resulting polymeric conjugates in terms of structure and degree of substitution. Moreover, zinc ions were used to crosslink the resulting AC polymers. Folic acid loaded beads were prepared from Zinc-crosslinked AC polymers (AC-Zn) of different cysteine substitution degrees. The generated beads were then investigated in vitro for their capacity to modify folic acid release. AC-Zn polymeric beads resisted drug release under acidic conditions (pH 1.0). However, upon transfer to a phosphate buffer solution (pH 7.0) they released most of their contents almost immediately. This change in drug release behavior is most probably due to the sequestering of zinc cations by phosphate ions within the buffer solution to form insoluble chelates and, to a lesser extent, the ionization of the carboxylic acid and thiol moieties. Removal of zinc ions from the polymeric matrix seems to promote polymeric disintegration and subsequent drug release. A similar behavior is expected in vivo due to the presence of natural zinc sequestering agents in the intestinal fluids. AC-Zn polymers provided a novel approach for enteric drug delivery as drug release from these matrices complied with the USP specifications for enteric dosage forms.

  5. Immobilization of Aspergillus niger xylanase on magnetic latex beads.

    PubMed

    Tyagi, R; Gupta, M N

    1995-04-01

    Xylanase from Pectinex 3XL was purified 70-fold by precipitation with an enteric polymer, Eudragit S-100. The purified xylanase was immobilized on magnetic latex beads via carbodi-imide coupling. The immobilized preparation showed 80% of the total activity bound to the beads. The pH optimum remained unchanged at 6.0 and the Km increased from 0.25 g/100 ml (free enzyme) to 0.39 g/100 ml on immobilization. Immobilization resulted in significant thermal stability at 60 degrees C. The time course of hydrolysis of xylan at 60 degrees C by free enzyme as well as immobilized enzyme was also studied.

  6. Wax-incorporated emulsion gel beads of calcium pectinate for intragastric floating drug delivery.

    PubMed

    Sriamornsak, Pornsak; Asavapichayont, Panida; Nunthanid, Jurairat; Luangtana-Anan, Manee; Limmatvapirat, Sontaya; Piriyaprasarth, Suchada

    2008-01-01

    The purpose of this study was to prepare wax-incorporated pectin-based emulsion gel beads using a modified emulsion-gelation method. The waxes in pectin-olive oil mixtures containing a model drug, metronidazole, were hot-melted, homogenized and then extruded into calcium chloride solution. The beads formed were separated, washed with distilled water and dried for 12 h. The influence of various types and amounts of wax on floating and drug release behavior of emulsion gel beads of calcium pectinate was investigated. The drug-loaded gel beads were found to float on simulated gastric fluid if the sufficient amount of oil was used. Incorporation of wax into the emulsion gel beads affected the drug release. Water-soluble wax (i.e. polyethylene glycol) increased the drug release while other water-insoluble waxes (i.e. glyceryl monostearate, stearyl alcohol, carnauba wax, spermaceti wax and white wax) significantly retarded the drug release. Different waxes had a slight effect on the drug release. However, the increased amount of incorporated wax in the formulations significantly sustained the drug release while the beads remained floating. The results suggest that wax-incorporated emulsion gel beads could be used as a carrier for intragastric floating drug delivery.

  7. Clinical utility of topiramate extended-release capsules (USL255): Bioequivalence of USL255 sprinkled and intact capsule in healthy adults and an in vitro evaluation of sprinkle delivery via enteral feeding tubes.

    PubMed

    Clark, Annie M; Pellock, John M; Holmay, Mary; Anders, Bob; Cloyd, James

    2016-04-01

    The objectives of these two studies were to determine if beads from extended-release topiramate capsules sprinkled onto soft food are bioequivalent to the intact capsule and if beads from the capsule can be passed through enteral gastrostomy (G-) and jejunostomy (J-) feeding tubes. Bioequivalence of 200-mg USL255 (Qudexy XR [topiramate] extended-release capsules) sprinkled onto soft food (applesauce) versus the intact capsule was evaluated in a phase 1, randomized, single-dose, crossover study (N=36). Pharmacokinetic evaluations included area under the curve (AUC), maximum plasma concentration (Cmax), time to Cmax (Tmax), and terminal elimination half-life (t1/2). If 90% confidence intervals (CI) of the ratio of geometric least-squares means were between 0.80 and 1.25, AUC and Cmax were considered bioequivalent. In separate in vitro experiments, 100-mg USL255 beads were passed through feeding tubes using gentle syringe pressure to develop a clog-free bead-delivery method. Multiple tube sizes (14- to 18-French [Fr] tubes), dilutions (5 mg/15 mL-25 mg/15 mL), and diluents (deionized water, apple juice, Ketocal, sparkling water) were tested. Area under the curve and Cmax for USL255 beads sprinkled onto applesauce were bioequivalent to the intact capsule (GLSM [90% CI]: AUC0-t 1.01 [0.97-1.04], AUC0-∞ 1.02 [0.98-1.05]; Cmax 1.09 [1.03-1.14]). Median Tmax was 4h earlier for USL255 sprinkled versus the intact capsule (10 vs 14 h; p=0.0018), and t1/2 was similar (84 vs 82 h, respectively). In 14-Fr G-tubes, USL255 beads diluted in Ketocal minimized bead clogging versus deionized water. Recovery of USL255 beads diluted in deionized water was nearly 100% in 16-Fr G-, 18-Fr G-, and 18-Fr J-tubes. For patients with difficulty swallowing pills, USL255 sprinkled onto applesauce offers a useful once-daily option for taking topiramate. USL255 beads were also successfully delivered in vitro through ≥14-Fr G- or J-tubes, with tube clogging minimized by portioning the dose and using glidant diluents for smaller tubes. Copyright © 2016 Upsher-Smith Laboratories, Inc. Published by Elsevier Inc. All rights reserved.

  8. In vivo cleansing efficacy of biodegradable exfoliating beads assessed by skin bioengineering techniques.

    PubMed

    Kitsongsermthon, J; Duangweang, K; Kreepoke, J; Tansirikongkol, A

    2017-11-01

    The plastic microbeads, used in many cleansers, will be banned in cosmetic and personal care products within 2017 since they are non-degradable and can disturb the living organisms in water reservoirs. Various choices of biodegradable beads are commercially available, but their efficacy has not been proven yet. This study aimed to compare the cleansing efficacy in dirt and sebum removal aspects of three types of exfoliating beads. The gel scrubs with polyethylene (PE) beads, mannan beads or wax beads, were formulated and evaluated for their stability. The in vivo evaluation was done in 38 healthy volunteers and the skin irritation, efficacy for dirt and sebum removal were measured by Mexameter ® , Colorimeter ® , and Sebumeter ® , respectively. The selected gel scrubs did not cause an irritation in any volunteers. The differences in dirt residues between before and after scrubbing were not statistically significant among three gel scrubs and the similar result was also reported in the sebum removal study. All gel scrubs demonstrated the comparable cleansing efficacy in term of dirt and sebum removal. Thus, mannan beads and wax beads may be replaced non-biodegradable PE beads to achieve the similar cleansing effect. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Immobilization of alginate-encapsulated Bacillus thuringiensis var. israelensis containing different multivalent counterions for mosquito control.

    PubMed

    Prabakaran, G; Hoti, S L

    2008-08-01

    Immobilized techniques have been used widely for the controlled release formulation of mosquitoes. Among the microbial formulations, polymeric matrices play an important role in the controlled release of microbial pesticide at rates sufficiently effective to kill mosquitoes in the field. The advantage of these matrices is that they enhance the stability of both spores and toxin against pH, temperature variations, and UV irradiation. The disadvantage of using calcium alginate beads is that they are unstable upon contact with phosphate of potassium or sodium ions rich in the mosquito habitats. To overcome these problems, attempts were made to encapsulate Bacillus thuringiensis var. israelensis within alginate by using different multivalent counterions, namely, calcium chloride, zinc sulfate, copper sulfate, cobalt chloride, and ferric chloride, and the beads formed were tested for its mosquito larvicidal activity. Among all the beads tested, zinc alginate beads resulted in maximum larvicidal activity of 98% (+/-1.40 SE) against Culex quinquefasciatus IIIrd instar larvae and maximum spore count of 3.36 x 10(5) (+/-5291.50 SE) CFU/ml. Zinc alginate beads maintained their structure for up to 48 h when shaken vigorously on a rotary shaker at 180 rpm in the presence of 10 mM potassium phosphate buffer (pH 6.8 +/- 0.1). In conclusion, our results suggest that the use of zinc sulfate as counterions to encapsulate B. thuringiensis var. israelensis within alginate may be a potent mosquito control program in the habitats where more phosphate ions are present.

  10. Development and in vitro evaluation of mesalamine delayed release pellets and tableted reservoir-type pellets.

    PubMed

    Bendas, Ehab R; Christensen, J Mark; Ayres, James W

    2010-04-01

    The basic objective of this study was to develop a novel technique that aids in compaction of coated pellets into tablets and obtain a release pattern from compressed pellets resembling the same pattern before compression. Multi-unit dosage forms of mesalamine targeted to the colon were formulated by extrusion-spheronization, and then coated with Eudragit S (30%). These pellets were filled into gelatin capsules or further formulated and compressed into tablets. Tablets for colonic delivery of mesalamine were prepared by mixing the coated beads with cushioning agents like stearic acid and Explotab, or by applying an additional coat of gelatin (4% weight gain) onto the Eudragit S coated pellets, and then compressing into tablets (tableted reservoir-type pellets). Then additional coating of the tablets prepared by the coating technique was applied utilizing Eudragit L 100-55 (5% weight gain). This technique provides additive protection for the coated beads to withstand the compression force during tableting. Excellent in vitro dissolution results were obtained, which were comparable to the results of the release of mesalamine from uncompressed beads filled in capsules. Mesalamine release from the capsules was 0.3% after 2 hours in gastric pH, 0.37% was released after an additional 1 hour in pH 6, and 89% was released after 1.5 hours in colonic pH 7.2. Various formulation and process parameters have to be optimized in order to obtain tableted reservoir-type pellets having the same release properties as the uncompressed pellets. The coating technique delays the release of mesalamine until the beads reach the terminal ileum and colon. Once released in the colon, mesalamine is minimally absorbed and can act locally to treat ulcerative colitis.

  11. Porous polystyrene beads as carriers for self-emulsifying system containing loratadine.

    PubMed

    Patil, Pradeep; Paradkar, Anant

    2006-03-01

    The aim of this study was to formulate a self-emulsifying system (SES) containing a lipophilic drug, loratadine, and to explore the potential of preformed porous polystyrene beads (PPB) to act as carriers for such SES. Isotropic SES was formulated, which comprised Captex 200 (63% wt/wt), Cremophore EL (16% wt/wt), Capmul MCM (16% wt/wt), and loratadine (5% wt/wt). SES was evaluated for droplet size, drug content, and in vitro drug release. SES was loaded into preformed and characterized PPB using solvent evaporation method. SES-loaded PPB were evaluated using scanning electron microscopy (SEM) for density, specific surface area (S BET ), loading efficiency, drug content, and in vitro drug release. After SES loading, specific surface area reduced drastically, indicating filling of PPB micropores with SES. Loading efficiency was least for small size (SS) and comparable for medium size (MS) and large size (LS) PPB fractions. In vitro drug release was rapid in case of SS beads due to the presence of SES near to surface. LS fraction showed inadequate drug release owing to presence of deeper micropores that resisted outward diffusion of entrapped SES. Leaching of SES from micropores was the rate-limiting step for drug release. Geometrical features such as bead size and pore architecture of PPB were found to govern the loading efficiency and in vitro drug release from SES-loaded PPB.

  12. Porous polystyrene beads as carriers for self-emulsifying system containing loratadine.

    PubMed

    Patil, Pradeep; Paradkar, Anant

    2006-03-24

    The aim of this study was to formulate a self-emulsifying system (SES) containing a lipophilic drug, loratadine, and to explore the potential of preformed porous polystyrene beads (PPB) to act as carriers for such SES. Isotropic SES was formulated, which comprised Captex 200 (63% wt/wt), Cremophore EL (16% wt/wt), Capmul MCM (16% wt/wt), and loratadine (5% wt/wt). SES was evaluated for droplet size, drug content, and in vitro drug release. SES was loaded into preformed and characterized PPB using solvent evaporation method. SES-loaded PPB were evaluated using scanning electron microscopy (SEM) for density, specific surface area (S(BET)), loading efficiency, drug content, and in vitro drug release. After SES loading, specific surface area reduced drastically, indicating filling of PPB micropores with SES. Loading efficiency was least for small size (SS) and comparable for medium size (MS) and large size (LS) PPB fractions. In vitro drug release was rapid in case of SS beads due to the presence of SES near to surface. LS fraction showed inadequate drug release owing to presence of deeper micropores that resisted outward diffusion of entrapped SES. Leaching of SES from micropores was the rate-limiting step for drug release. Geometrical features such as bead size and pore architecture of PPB were found to govern the loading efficiency and in vitro drug release from SES-loaded PPB.

  13. Formulation and statistical optimization of gastric floating alginate/oil/chitosan capsules loading procyanidins: in vitro and in vivo evaluations.

    PubMed

    Chen, Rencai; Guo, Xiaomin; Liu, Xuecong; Cui, Haiming; Wang, Rui; Han, Jing

    2018-03-01

    The aim of the present work was to develop gastric floating capsules containing oil-entrapped beads loading procyanidins. The floating beads were prepared by ionotropic gelation method using sodium alginate, CaCl 2 and chitosan. The effect of three independent parameters (concentration of sodium alginate, CaCl 2 and chitosan) on entrapment efficiency were analyzed by Box-Behnken design. The floating beads were evaluated for surface morphology, particle size, density, entrapment efficiency, buoyancy, release behavior in vitro and floating ability in vivo. The prepared beads were grossly spherical in shape and the mean size was approximately 1.54±0.17mm. The density was 0.97g/cm 3 . And the optimal conditions were as follows: concentration of sodium alginate, CaCl 2 and chitosan were 33.75mg/mL, 9.84mg/mL and 9.05mg/mL, respectively. The optimized formulation showed entrapment efficiency of 88.84±1.04% within small error-value (0.65). The release mechanism of floating capsules followed Korsmeyer-Peppas model (r 2 =0.9902) with non-Fickian release. The gastric floating capsules exhibited 100% floating percentage in vitro and they could float on the top of gastric juice for 5h in vivo. Therefore, the floating capsules are able to prolong the gastroretentive delivery of procyanidins. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Development of orally disintegrating tablets comprising controlled-release multiparticulate beads

    PubMed Central

    2012-01-01

    Melperone is an atypical antipsychotic agent that has shown a wide spectrum of neuroleptic properties, particularly effective in the treatment of senile dementia and Parkinson’s-associated psychosis, and is marketed in Europe as an immediate-release (IR) tablet and syrup. An orally disintegrating tablet (ODT) dosage form would be advantageous for patients who experience difficulty in swallowing large tablets or capsules or those who experience dysphagia. Controlled-release (CR) capsule and ODT formulations containing melperone HCl were developed with target in vitro release profiles suitable for a once-daily dosing regimen. Both dosage forms allow for the convenient production of dose-proportional multiple strengths. Two ODT formulations exhibiting fast and medium release profiles and one medium release profile capsule formulation (each 50 mg) were tested in vivo using IR syrup as the reference. The two medium release formulations were shown to be bioequivalent to each other and are suitable for once-daily dosing. Based on the analytical and organoleptic test results, as well as the blend uniformity and in-process compression data at various compression forces using coated beads produced at one-tenth (1/10) commercial scale, both formulations in the form of CR capsules and CR ODTs have shown suitability for progression into further clinical development. PMID:22356215

  15. Pharmaceutical acrylic beads obtained by suspension polymerization containing cellulose nanowhiskers as excipient for drug delivery.

    PubMed

    Villanova, J C O; Ayres, E; Carvalho, S M; Patrício, P S; Pereira, F V; Oréfice, R L

    2011-03-18

    Direct compression is one of the most popular techniques to prepare tablets but only a few commercial excipients are well adapted for this process into controlled release formulations. In the last years, the introduction of new materials for drug delivery matrix tablets has become more important. This paper evaluated the physicochemical and flow properties of new polymeric excipient of ethyl acrylate, methyl methacrylate and butyl metacrylate, synthesized by suspension polymerization using cellulose nanowhiskers as co-stabilizer, to be used as direct compression for modified release tablets. Infrared spectroscopy (FTIR) confirmed the success of the copolymerization reaction. Scanning electron microscopy (SEM) showed that excipient was obtained how spherical beads. Thermal properties of the beads were characterized by thermogravimetric (TG) analysis. Particle size analysis of the beads with cellulose nanowhiskers (CNWB) indicated that the presence of the nanowhiskers led to a reduction of particle size and to a narrower size distribution. In vitro test showed that the nanowhiskers and beads produced are nontoxic. Parameters such as Hausner ratio, Carr's index and cotangent of angle α were employed to characterize the flow properties of CNWB beads. Furthermore, the beads are used to produce tablets by direct compression contained propranolol hydrochloride as model drug. Dissolution tests performed suggested that beads could be used as excipient in matrix tablets with a potential use in drug controlled release. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Reverse Osmosis Water Purification Unit: Efficacy of Cartridge Filters for Removal of Bacteria and Protozoan Cysts when Ro Elements are Bypassed

    DTIC Science & Technology

    1993-04-01

    were Klebsiella terrigena, Cryptosporidium parvum oocysts, Rhodotorula rubra, and 3.7 pm latex beads. Challenge waters were dechlorinated tap water and...The morphological and size characteristics of Rhodotorula rubra (ATCC 36053) made the yeast suitable as a protozoan cyst simulant. The yeast cells...representative enteric bacterium), Cryptosporidium parvum (an enteric protozoan pathogen) oocysts, Rhodotorula rubra (a yeast, used to test prefilters only

  17. Field Trial of Attenuated Salmonella Typhi Live Oral Vaccine TY21A in Liquid and Enteric-Coated Formulations and Epidemiological Survey for Incidence of Diarrhea due to Shigella Species

    DTIC Science & Technology

    1989-03-01

    and absolute efficacy of three doses of Ty2la vaccine given in enteric-coated capsule or liquid formulation. Intensive clinical and bacteriologic...TABLES Table 1. Evaluation of the efficacy of three doses of the enteric-coated capsule formulation of Ty2la live oral vaccine given within one week in...November, 1986 thzough February, 1989 of a field trial in Area Sur Oriente and Area Norte assessing the efficacy of Ty21a vaccine in liquid or enteric

  18. Adsorption of ochratoxin A from grape juice by yeast cells immobilised in calcium alginate beads.

    PubMed

    Farbo, Maria Grazia; Urgeghe, Pietro Paolo; Fiori, Stefano; Marceddu, Salvatore; Jaoua, Samir; Migheli, Quirico

    2016-01-18

    Grape juice can be easily contaminated with ochratoxin A (OTA), one of the known mycotoxins with the greatest public health significance. Among the different approaches to decontaminate juice from this mycotoxin, microbiological methods proved efficient, inexpensive and safe, particularly the use of yeast or yeast products. To ascertain whether immobilisation of the yeast biomass would lead to successful decontamination, alginate beads encapsulating Candida intermedia yeast cells were used in our experiments to evaluate their OTA-biosorption efficacy. Magnetic calcium alginate beads were also prepared by adding magnetite in the formulation to allow fast removal from the aqueous solution with a magnet. Calcium alginate beads were added to commercial grape juice spiked with 20 μg/kg OTA and after 48 h of incubation a significant reduction (>80%), of the total OTA content was achieved, while in the subsequent phases (72-120 h) OTA was slowly released into the grape juice by alginate beads. Biosorption properties of alginate-yeast beads were tested in a prototype bioreactor consisting in a glass chromatography column packed with beads, where juice amended with OTA was slowly flowed downstream. The adoption of an interconnected scaled-up bioreactor as an efficient and safe tool to remove traces of OTA from liquid matrices is discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Construction of hydrodynamic bead models from high-resolution X-ray crystallographic or nuclear magnetic resonance data.

    PubMed Central

    Byron, O

    1997-01-01

    Computer software such as HYDRO, based upon a comprehensive body of theoretical work, permits the hydrodynamic modeling of macromolecules in solution, which are represented to the computer interface as an assembly of spheres. The uniqueness of any satisfactory resultant model is optimized by incorporating into the modeling procedure the maximal possible number of criteria to which the bead model must conform. An algorithm (AtoB, for atoms to beads) that permits the direct construction of bead models from high resolution x-ray crystallographic or nuclear magnetic resonance data has now been formulated and tested. Models so generated then act as informed starting estimates for the subsequent iterative modeling procedure, thereby hastening the convergence to reasonable representations of solution conformation. Successful application of this algorithm to several proteins shows that predictions of hydrodynamic parameters, including those concerning solvation, can be confirmed. PMID:8994627

  20. Tamarind seed gum-hydrolyzed polymethacrylamide-g-gellan beads for extended release of diclofenac sodium using 32 full factorial design.

    PubMed

    Nandi, Gouranga; Nandi, Amit Kumar; Khan, Najim Sarif; Pal, Souvik; Dey, Sibasish

    2018-07-15

    Development of tamarind seed gum (TSG)-hydrolyzed polymethacrylamide-g-gellan (h-Pmaa-g-GG) composite beads for extended release of diclofenac sodium using 3 2 full factorial design is the main purpose of this study. The ratio of h-Pmaa-g-GG and TSG and concentration of cross-linker CaCl 2 were taken as independent factors with three different levels of each. Effects of polymer ratio and CaCl 2 on drug entrapment efficiency (DEE), drug release, bead size and swelling were investigated. Responses such as DEE and different drug release parameters were statistically analyzed by 3 2 full factorial design using Design-Expert software and finally the formulation factors were optimized to obtain USP-reference release profile. Drug release rate was found to decrease with decrease in the ratio of h-Pmaa-g-GG:TSG and increase in the concentration of Ca 2+ ions in cross-linking medium. The optimized formulation showed DEE of 93.25% and an extended drug release profile over a period of 10h with f 2 =80.13. Kinetic modeling unveiled case-I-Fickian diffusion based drug release mechanism. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Inorganic optical taggant and method of making

    DOEpatents

    Lauf, Robert J.; Anderson, Kimberly K.; Montgomery, Frederick C.

    2005-05-31

    Sintered, translucent ceramic microbeads, preferably alumina, titania, zirconia, yttria, zirconium phosphate, or yttrium aluminum garnet (YAG) are doped with one or more optically active species. The beads may be added to substances such as explosives in order to create a distinctive optical signature that identifies a manufacturer, lot number, etc. in the event of the need for forensic analysis. Because the beads have a generally spherical surface, the radius of curvature provides an additional distinguishing characteristic by which a particular sample may be identified. The beads could also be formulated into paints if needed to create distinctive optical signatures for camouflage, decoys, or other countermeasures and could also be applied as a dust to track the movement of personnel, vehicles, etc.

  2. Floating capsules containing alginate-based beads of salbutamol sulfate: In vitro-in vivo evaluations.

    PubMed

    Malakar, Jadupati; Datta, Prabir Kumar; Purakayastha, Saikat Das; Dey, Sanjay; Nayak, Amit Kumar

    2014-03-01

    The present study deals with the development and evaluations of stomach-specific floating capsules containing salbutamol sulfate-loaded oil-entrapped alginate-based beads. Salbutamol sulfate-loaded oil-entrapped beads were prepared and capsulated within hard gelatin capsules (size 1). The effects of HPMC K4M and potato starch weight masses on drug encapsulation efficiency (DEE) of beads and cumulative drug release at 10h (R10 h) from capsules was analyzed by 3(2) factorial design. The optimization results indicate increasing of DEE in the oil-entrapped beads and decreasing R10 h from capsules with increment of HPMC K4M and potato starch weight masses. The optimized formulation showed DEE of 70.02 ± 3.16% and R10 h of 56.96 ± 2.92%. These capsules showed floatation over 6h and sustained drug release over 10h in gastric pH (1.2). In vivo X-ray imaging study of optimized floating capsules in rabbits showed stomach-specific gastroretention over a prolonged period. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Expression of single-chain Fv gene specific for gamma-seminoprotein by RTS and its biological activity identification.

    PubMed

    Han, Yuedong; Haun, Yi; Deng, Jinlan; Gao, Feng; Pan, Bifeng; Cui, Daxiang

    2006-01-01

    Fabricating a single-chain variable fragment specific for human seminoprotein is very important in antibody-directed enzyme prodrug therapy and NMR imaging for prostate cancer. Here a single-chain Fv specific for gamma-seminoprotein was expressed by RTS. Its activity and the efficiency of entry into prostate cancer cells are investigated by immunoprecipitation and Western blotting and immunofluorescent staining, as well as entry of conjugated magnetic beads into cells. Results showed that ScFv peptides specific for gamma-seminoprotein were successfully prepared, which can bind with the prostate cells specifically and can bring magnetic beads into prostate cancer cells within 15 min, the amount of magnetic beads inside prostate cancer cells increased as the culture time prolonged. ScFv-conjugated magnetic beads did not enter into control cells. In conclusion, the ScFv peptide against human gamma-seminoprotein with biological activity was successfully fabricated, which can take magnetic beads to prostate cancer cells specifically and not to the control cells. This ScFv peptide against human gamma-seminoprotein should be useful in improving the detection and therapy of prostate cancer at early stages and NMR imaging.

  4. Development of the rectal dosage form with silver-coated glass beads for local-action applications in lower sections of the gastrointestinal tract.

    PubMed

    Siczek, Krzysztof; Fichna, Jakub; Zatorski, Hubert; Karolewicz, Bożena; Klimek, Leszek; Owczarek, Artur

    2018-03-01

    Recent findings indicating the anti-inflammatory action of silver preparations through modulation of the gut microbiota and apoptosis of inflammatory cells predestine silver use in inflammatory bowel disease (IBD). The aim of our study was to validate the possibility of effective silver release from silver-coated glass beads for anti-inflammatory local application in the lower sections of the gastrointestinal (GI) tract. Silver-coated glass beads were prepared using magnetron method. Release of silver from the silver-coated glass bead surface was carried out in BIO-DIS reciprocating cylinder apparatus. Erosion of silver coating and indirect estimation of the silver release dynamics was assessed using scanning electron microscope. Rectal suppositories containing silver-coated glass beads were prepared using five different methods (M1-M5) and X-ray scanned for their composition. The XR microanalysis and the chemical composition analysis evidenced for a rapid (within 30 min) release of nearly 50% of silver from the coating of the glass beads, which remained stable up to 24 h of incubation. The most homogeneous distribution of beads in the entire volume of the suppository was obtained for formulation M5, where the molten base was poured into mold placed in an ice bath, and the beads were added after 10 s. Our study is the first to present the concept of enclosing silver-coated glass beads in the lipophilic suppository base to attenuate inflammation in the lower GI tract and promises efficient treatment with reduced side effects.

  5. Granulocytes of the red claw crayfish Cherax quadricarinatus can endocytose beads, E. coli and WSSV, but in different ways.

    PubMed

    Duan, Hu; Jin, Songjun; Zhang, Yan; Li, Fuhua; Xiang, Jianhai

    2014-10-01

    The hemocytes of the red claw crayfish Cherax quadricarinatus are classified by morphologic observation into the following types: hyalinocytes (H), semi-granulocytes (SG) and granulocytes (G). Density gradient centrifugation with Percoll was developed to separate these three subpopulations of hemocytes. Beads, Escherichia coli, and FITC labeling WSSV were used to investigate the characteristics of granulocytes by using scanning electron microscope, transmission electron microscope, and laser scan confocal microscope. Results showed that granulocytes could phagocytose beads and E. coli by endocytic pathways. WSSV could rely on caveolae-mediated endocytosis to mainly enter into granulocytes. These results could elucidate the mechanism of the innate immunity function of granulocytes, and it also showed the mechanism by which WSSV invaded granulocytes in the red claw crayfish. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Formulation of itraconazole nanococrystals and evaluation of their bioavailability in dogs.

    PubMed

    De Smet, Lieselotte; Saerens, Lien; De Beer, Thomas; Carleer, Robert; Adriaensens, Peter; Van Bocxlaer, Jan; Vervaet, Chris; Remon, Jean Paul

    2014-05-01

    The aim of the study is to increase the bioavailability of itraconazole (ITRA) using nanosized cocrystals prepared via wet milling of ITRA in combination with dicarboxylic acids. Wet milling was used in order to create a nanosuspension of ITRA in combination with dicarboxylic acids. After spray-drying and bead layering, solid state was characterized by MDSC, XRD, Raman and FT-IR. The release profiles and bioavailability of the nanococrystalline suspension, the spray-dried and bead layered formulation were evaluated. A monodisperse nanosuspension (549±51nm) of ITRA was developed using adipic acid and Tween®80. Solid state characterization indicated the formation of nanococrystals by hydrogen bounds between the triazole group of ITRA and the carboxyl group of adipic acid. A bioavailability study was performed in dogs. The faster drug release from the nanocrystal-based formulation was reflected in the in vivo results since Tmax of the formulations was obtained 3h after administration, while Tmax of the reference formulation was observed only 6h after administration. This fast release of ITRA was obtained by a dual concept: manufacturing of nanosized cocrystals of ITRA and adipic acid via wet milling. Formation of stable nanosized cocrystals via this approach seems a good alternative for amorphous systems to increase the solubility and obtain a fast drug release of BCS class II drugs. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Development of a CO2 releasing co-formulation 1 based on starch, Saccharomyces cerevisiae and Beauveria bassiana attractive towards western corn rootworm larvae

    USDA-ARS?s Scientific Manuscript database

    CO2 is known as an attractant for many soil-dwelling pests. To implement an attract-and-kill strategy for soil pest control, CO2 emitting formulations need to be developed. This work aimed at the development of a slow release bead system in order to bridge the gap between application and hatching of...

  8. Radial flow nuclear thermal rocket (RFNTR)

    DOEpatents

    Leyse, Carl F.

    1995-11-07

    A radial flow nuclear thermal rocket fuel assembly includes a substantially conical fuel element having an inlet side and an outlet side. An annular channel is disposed in the element for receiving a nuclear propellant, and a second, conical, channel is disposed in the element for discharging the propellant. The first channel is located radially outward from the second channel, and separated from the second channel by an annular fuel bed volume. This fuel bed volume can include a packed bed of loose fuel beads confined by a cold porous inlet frit and a hot porous exit frit. The loose fuel beads include ZrC coated ZrC-UC beads. In this manner, nuclear propellant enters the fuel assembly axially into the first channel at the inlet side of the element, flows axially across the fuel bed volume, and is discharged from the assembly by flowing radially outward from the second channel at the outlet side of the element.

  9. Radial flow nuclear thermal rocket (RFNTR)

    DOEpatents

    Leyse, Carl F.

    1995-01-01

    A radial flow nuclear thermal rocket fuel assembly includes a substantially conical fuel element having an inlet side and an outlet side. An annular channel is disposed in the element for receiving a nuclear propellant, and a second, conical, channel is disposed in the element for discharging the propellant. The first channel is located radially outward from the second channel, and separated from the second channel by an annular fuel bed volume. This fuel bed volume can include a packed bed of loose fuel beads confined by a cold porous inlet frit and a hot porous exit frit. The loose fuel beads include ZrC coated ZrC-UC beads. In this manner, nuclear propellant enters the fuel assembly axially into the first channel at the inlet side of the element, flows axially across the fuel bed volume, and is discharged from the assembly by flowing radially outward from the second channel at the outlet side of the element.

  10. BAF is a cytosolic DNA sensor that leads to exogenous DNA avoiding autophagy

    PubMed Central

    Kobayashi, Shouhei; Koujin, Takako; Kojidani, Tomoko; Osakada, Hiroko; Mori, Chie; Hiraoka, Yasushi; Haraguchi, Tokuko

    2015-01-01

    Knowledge of the mechanisms by which a cell detects exogenous DNA is important for controlling pathogen infection, because most pathogens entail the presence of exogenous DNA in the cytosol, as well as for understanding the cell’s response to artificially transfected DNA. The cellular response to pathogen invasion has been well studied. However, spatiotemporal information of the cellular response immediately after exogenous double-stranded DNA (dsDNA) appears in the cytosol is lacking, in part because of difficulties in monitoring when exogenous dsDNA enters the cytosol of the cell. We have recently developed a method to monitor endosome breakdown around exogenous materials using transfection reagent-coated polystyrene beads incorporated into living human cells as the objective for microscopic observations. In the present study, using dsDNA-coated polystyrene beads (DNA-beads) incorporated into living cells, we show that barrier-to-autointegration factor (BAF) bound to exogenous dsDNA immediately after its appearance in the cytosol at endosome breakdown. The BAF+ DNA-beads then assembled a nuclear envelope (NE)-like membrane and avoided autophagy that targeted the remnants of the endosome membranes. Knockdown of BAF caused a significant decrease in the assembly of NE-like membranes and increased the formation of autophagic membranes around the DNA-beads, suggesting that BAF-mediated assembly of NE-like membranes was required for the DNA-beads to evade autophagy. Importantly, BAF-bound beads without dsDNA also assembled NE-like membranes and avoided autophagy. We propose a new role for BAF: remodeling intracellular membranes upon detection of dsDNA in mammalian cells. PMID:25991860

  11. BAF is a cytosolic DNA sensor that leads to exogenous DNA avoiding autophagy.

    PubMed

    Kobayashi, Shouhei; Koujin, Takako; Kojidani, Tomoko; Osakada, Hiroko; Mori, Chie; Hiraoka, Yasushi; Haraguchi, Tokuko

    2015-06-02

    Knowledge of the mechanisms by which a cell detects exogenous DNA is important for controlling pathogen infection, because most pathogens entail the presence of exogenous DNA in the cytosol, as well as for understanding the cell's response to artificially transfected DNA. The cellular response to pathogen invasion has been well studied. However, spatiotemporal information of the cellular response immediately after exogenous double-stranded DNA (dsDNA) appears in the cytosol is lacking, in part because of difficulties in monitoring when exogenous dsDNA enters the cytosol of the cell. We have recently developed a method to monitor endosome breakdown around exogenous materials using transfection reagent-coated polystyrene beads incorporated into living human cells as the objective for microscopic observations. In the present study, using dsDNA-coated polystyrene beads (DNA-beads) incorporated into living cells, we show that barrier-to-autointegration factor (BAF) bound to exogenous dsDNA immediately after its appearance in the cytosol at endosome breakdown. The BAF(+) DNA-beads then assembled a nuclear envelope (NE)-like membrane and avoided autophagy that targeted the remnants of the endosome membranes. Knockdown of BAF caused a significant decrease in the assembly of NE-like membranes and increased the formation of autophagic membranes around the DNA-beads, suggesting that BAF-mediated assembly of NE-like membranes was required for the DNA-beads to evade autophagy. Importantly, BAF-bound beads without dsDNA also assembled NE-like membranes and avoided autophagy. We propose a new role for BAF: remodeling intracellular membranes upon detection of dsDNA in mammalian cells.

  12. Controlled assembly of nanoparticle structures: spherical and toroidal superlattices and nanoparticle-coated polymeric beads.

    PubMed

    Isojima, Tatsushi; Suh, Su Kyung; Vander Sande, John B; Hatton, T Alan

    2009-07-21

    The emulsion droplet solvent evaporation method has been used to prepare nanoclusters of monodisperse magnetite nanoparticles of varying morphologies depending on the temperature and rate of solvent evaporation and on the composition (solvent, presence of polymer, nanoparticle concentration, etc.) of the emulsion droplets. In the absence of a polymer, and with increasing solvent evaporation temperatures, the nanoparticles formed single- or multidomain crystalline superlattices, amorphous spherical aggregates, or toroidal clusters, as determined by the energetics and dynamics of the solvent evaporation process. When polymers that are incompatible with the nanoparticle coatings were included in the emulsion formulation, monolayer- and multilayer-coated polymer beads and partially coated Janus beads were prepared; the nanoparticles were expelled by the polymer as its concentration increased on evaporation of the solvent and accumulated on the surfaces of the beads in a well-ordered structure. The precise number of nanoparticle layers depended on the polymer/magnetic nanoparticle ratio in the oil droplet phase parent emulsion. The magnetic nanoparticle superstructures responded to the application of a modest magnetic field by forming regular chains with alignment of nonuniform structures (e.g., toroids and Janus beads) that are in accord with theoretical predictions and with observations in other systems.

  13. Physico-chemical state influences in vitro release profile of curcumin from pectin beads.

    PubMed

    Nguyen, An Thi-Binh; Winckler, Pascale; Loison, Pauline; Wache, Yves; Chambin, Odile

    2014-09-01

    Curcumin is a polyphenolic compound with diverse effects interesting to develop health benefit products but its formulation in functional foods or in food supplement is hampered by its poor water solubility and susceptibility to alkaline conditions, light, oxidation and heat. Encapsulation of curcumin could be a mean to overcome these difficulties. In this paper, curcumin was encapsulated by ionotropic gelation method in low methoxyl pectin beads associated with different surfactants: Solutol(®), Transcutol(®) and sodium caseinate. After encapsulation, physico-chemical properties of encapsulated curcumin such as its solubility, physical state, tautomeric forms and encapsulation efficiency as well as encapsulation yield were characterized. In vitro dissolution of curcumin from beads displayed different kinetic profiles according to bead composition due to different matrix network. As Solutol(®) was a good solvent for curcumin, the drug was present into amorphous form in these beads inducing a rapid release of curcumin in the simulated digestive fluids. In contrast, drug release was slower from sodium caseinate beads since curcumin was not totally dissolved during the manufacturing process. Moreover, the FLIM studies showed that a part of curcumin was encapsulated in caseinate micelles and that 34% of this drug was in keto form which may delay the curcumin release. The Transcutol beads showed also a slow drug release because of the low curcumin solubility and the high density of the matrix. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Ketorolac tromethamine floating beads for oral application: Characterization and in vitro/in vivo evaluation

    PubMed Central

    Abou el Ela, Amal El Sayeh F.; Hassan, Maha A.; El- Maraghy, Dalia A.

    2013-01-01

    The floating beads have been employed to make a sustained release of the drug in the stomach and to decrease the dose of the drug and hence overcome its side effects. The common benefits of the floating beads were it is easy preparation, without the need of a high temperature, and high percentage of the drug entrapment. In the present work, the Ketorolac tromethamine (KT) floating beads were prepared by extrusion congealing method utilizing calcium carbonate as a gas forming agent. The physical characters of the produced beads were investigated such as KT yield, KT loading, and entrapment efficiency of the drug. In addition, floating behavior, swelling, particle size, morphology and KT stability were also evaluated. In vitro drug release study was carried out, and the kinetics of the release was evaluated using the linear regression method. Furthermore, the in vivo analgesic effect of KT after oral administration of the selected formula of floating beads (F10) was carried out using hot plate and tail flick methods. Oral commercial KT tablets and KT solution were used for the comparison. The prepared beads remained floated for more than 8 h. The optimized formulation (F10) exhibited prolonged drug release (more than 8 h) and the drug release follows the Higuchi kinetic model, with a Fickian diffusion mechanism according to Korsmeyer-Peppas (n = 0.466). Moreover, F10 showed a sustained analgesic effect as compared to the commercial tablet. PMID:25161380

  15. Pectin-based oral drug delivery to the colon.

    PubMed

    Sande, Sverre Arne

    2005-05-01

    This review presents an overview of studies concerning oral formulations intended for site-specific drug delivery to the colon with pectin as the main excipient. The biological aspects covered include gastrointestinal transit and the enzymatic degradation of pectin. Scintigraphic methods demonstrating the functionality of pectin formulations are discussed. The main focus is on the various formulations reported, including matrix tablets, multiparticulate formulations as pellets and hydrogel beads, and pectin-based coatings. Also included is an evaluation of common excipients employed to improve colon specificity by crosslinking or increasing the hydrophobicity. Finally, properties of the pectin molecules that are important for successful formulations are examined. The conclusion is that the studies found in the literature provide an excellent platform for the development of pectin-based colon delivery systems.

  16. DC bead: in vitro characterization of a drug-delivery device for transarterial chemoembolization.

    PubMed

    Lewis, Andrew L; Gonzalez, M Victoria; Lloyd, Andrew W; Hall, Brenda; Tang, Yiqing; Willis, Sean L; Leppard, Simon W; Wolfenden, Laura C; Palmer, Rosemary R; Stratford, Peter W

    2006-02-01

    The purpose of this investigation is to present the in vitro characterization and detailed drug-loading procedure for DC Bead, a microsphere product that can be loaded with chemotherapeutic agents for embolization. DC Bead is an embolic microsphere product that is capable of being loaded with anthracycline drugs such as doxorubicin just before administration in a transarterial chemoembolization (TACE) procedure. Beads can be loaded from solutions prepared from doxorubicin powder or the doxorubicin HCl formulation. In this evaluation, bead sizes were measured by optical microscopy with video imaging. Gravimetric analysis demonstrated the effect of drug loading on bead water content, and its consequent impact on bead compressibility was determined. The subsequent deliverability of the beads was assessed by mixing the beads with contrast medium and saline solution and passing the beads through an appropriately sized microcatheter. A T-cell apparatus was used to monitor the in vitro elution of the drug from the beads over a period of 24 hours in various elution media. DC Bead spheres could be easily loaded with doxorubicin to a recommended level of 25 mg/mL of hydrated beads by immersion of the beads in the drug solution for 10-120 minutes depending on microsphere size. Other commercial embolic microspheres were shown not to load doxorubicin to the same extent or release it in the same fashion and were considered unsuitable for local drug delivery. Maximum theoretic capacity for DC Bead was approximately 45 mg/mL. Increase in doxorubicin loading resulted in a concomitant decrease in water content and consequential increase in bead resistance to compression force. Drug loading also resulted in a decrease in the average size of the beads, which was dependent on bead size and drug dose. This did not impact bead delivery at any drug loading level to a maximum of 37.5 mg/mL. Beads 100-700 microm in size could be delivered through 2.7-F microcatheters, whereas the 700-900-microm range required 3-F catheters. Modeling of the kinetics of drug elution from the beads in vitro at a loading dose of 25 mg/mL yielded calculated half-lives of 150 hours for the 100-300-microm range to a maximum of 1,730 hours for the 700-900-microm size range, which was dependent on the ionic strength of the elution medium. For comparison, there was a rapid loss of drug from an unstable Lipiodol emulsion with a half-life of approximately 1 hour. DC Bead can be loaded with doxorubicin to provide an accurate dosage of drug per unit volume of beads. Drug elution is dependent on ion exchange with the surrounding environment and is controlled and sustained, unlike the rapid separation of the drug from Lipiodol. Drug loading has no impact on the handling and deliverability of the beads, making them suitable for superselective TACE.

  17. X-ray radiographic measurements of falling beads in thermally heated Comp B

    NASA Astrophysics Data System (ADS)

    Suvorova, Natalya; Remelius, Dennis; Oschwald, David; Smilowitz, Laura; Henson, Bryan; Davis, Stephen; Zerkle, David

    2017-06-01

    We have studied the behavior of Composition B under thermal heating conditions. Comp B formulation has complex thermal behavior due to the combination of 40% low melting point TNT and 60% RDX. At temperatures above the TNT melt, the mechanical behavior of Comp B is complex and sensitive to handling conditions (for instance, stirred versus stationary). In this presentation, we will discuss our experiments studying the motion of embedded beads of various densities different from Comp B density as the system is heated above the TNT melt temperature and before the onset of significant gas generation in the Comp B which acts to mix the RDX and molten TNT. X-ray radiography was used to directly observe the motion of the embedded bead in the Comp B as it is slowly and uniformly heated.

  18. Statistical field theory description of inhomogeneous polarizable soft matter

    NASA Astrophysics Data System (ADS)

    Martin, Jonathan M.; Li, Wei; Delaney, Kris T.; Fredrickson, Glenn H.

    2016-10-01

    We present a new molecularly informed statistical field theory model of inhomogeneous polarizable soft matter. The model is based on fluid elements, referred to as beads, that can carry a net monopole of charge at their center of mass and a fixed or induced dipole through a Drude-type distributed charge approach. The beads are thus polarizable and naturally manifest attractive van der Waals interactions. Beyond electrostatic interactions, beads can be given soft repulsions to sustain fluid phases at arbitrary densities. Beads of different types can be mixed or linked into polymers with arbitrary chain models and sequences of charged and uncharged beads. By such an approach, it is possible to construct models suitable for describing a vast range of soft-matter systems including electrolyte and polyelectrolyte solutions, ionic liquids, polymerized ionic liquids, polymer blends, ionomers, and block copolymers, among others. These bead models can be constructed in virtually any ensemble and converted to complex-valued statistical field theories by Hubbard-Stratonovich transforms. One of the fields entering the resulting theories is a fluctuating electrostatic potential; other fields are necessary to decouple non-electrostatic interactions. We elucidate the structure of these field theories, their consistency with macroscopic electrostatic theory in the absence and presence of external electric fields, and the way in which they embed van der Waals interactions and non-uniform dielectric properties. Their suitability as a framework for computational studies of heterogeneous soft matter systems using field-theoretic simulation techniques is discussed.

  19. Statistical field theory description of inhomogeneous polarizable soft matter.

    PubMed

    Martin, Jonathan M; Li, Wei; Delaney, Kris T; Fredrickson, Glenn H

    2016-10-21

    We present a new molecularly informed statistical field theory model of inhomogeneous polarizable soft matter. The model is based on fluid elements, referred to as beads, that can carry a net monopole of charge at their center of mass and a fixed or induced dipole through a Drude-type distributed charge approach. The beads are thus polarizable and naturally manifest attractive van der Waals interactions. Beyond electrostatic interactions, beads can be given soft repulsions to sustain fluid phases at arbitrary densities. Beads of different types can be mixed or linked into polymers with arbitrary chain models and sequences of charged and uncharged beads. By such an approach, it is possible to construct models suitable for describing a vast range of soft-matter systems including electrolyte and polyelectrolyte solutions, ionic liquids, polymerized ionic liquids, polymer blends, ionomers, and block copolymers, among others. These bead models can be constructed in virtually any ensemble and converted to complex-valued statistical field theories by Hubbard-Stratonovich transforms. One of the fields entering the resulting theories is a fluctuating electrostatic potential; other fields are necessary to decouple non-electrostatic interactions. We elucidate the structure of these field theories, their consistency with macroscopic electrostatic theory in the absence and presence of external electric fields, and the way in which they embed van der Waals interactions and non-uniform dielectric properties. Their suitability as a framework for computational studies of heterogeneous soft matter systems using field-theoretic simulation techniques is discussed.

  20. Development of a CO2 -releasing coformulation based on starch, Saccharomyces cerevisiae and Beauveria bassiana attractive towards western corn rootworm larvae.

    PubMed

    Vemmer, Marina; Schumann, Mario; Beitzen-Heineke, Wilhelm; French, Bryan W; Vidal, Stefan; Patel, Anant V

    2016-11-01

    CO 2 is known as an attractant for many soil-dwelling pests. To implement an attract-and-kill strategy for soil pest control, CO 2 -emitting formulations need to be developed. The aim of the present work was to develop a slow-release bead system in order to bridge the gap between application and hatching of western corn rootworm larvae. We compared different Ca-alginate beads containing Saccharomyces cerevisiae for their potential to release CO 2 over a period of several weeks. The addition of starch improved CO 2 release, resulting in significantly higher CO 2 concentrations in soil for at least 4 weeks. The missing amylase activity was compensated for either by microorganisms present in the soil or by coencapsulation of Beauveria bassiana. Formulations containing S. cerevisiae, starch and B. bassiana were attractive for western corn rootworm larvae within the first 4 h following exposure; however, when considering the whole testing period, the maize root systems remained more attractive for the larvae. Coencapsulation of S. cerevisiae, starch and B. bassiana is a promising approach for the development of attractive formulations for soil applications. For biological control strategies, the attractiveness needs to be increased by phagostimuli to extend contact between larvae and the entomopathogenic fungus growing out of these formulations. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  1. Development of novel gastroretentive floating particulate drug delivery system of gliclazide.

    PubMed

    Awasthi, Rajendra; Kulkarni, Giriraj T

    2012-09-01

    The objective of present project was to improve the dissolution profile of gliclazide by developing floating alginate beads using various biodegradable polymers like gelatin, pectin and hydroxypropylmethylcellulose (HPMC). The floating beads were prepared by a simple ionotropic gelatin method using calcium carbonate as gas generating agent. The developed beads were characterized by Fourier transform infrared spectroscopy analysis, differential scanning calorimetry, X-ray diffraction analysis and scanning electron microscopy (SEM). The prepared beads showed good in vitro floatation, which was dependent on the concentration of gas-forming agent. SEM photomicrographs confirmed that the developed beads were spherical in shape and had particle size in the range of 730 to 890 μm. The incorporation efficiency was found to be in the range of 59.96 to 85.1%. The cumulative percent drug release from the beads after 10 h dissolution study at pH 1.2 and pH 5.8 was in the range of 33 to 46% and 82 to 95% respectively. The concentration of the gas generating agent was found to influence the release rate. The mechanism of drug release was Fickian diffusion with swelling. The in vivo sub-acute hypoglycemic study in high fat diet induced diabetic C57BL/6J mice demonstrated significant (p < 0.05) hypoglycemic effect over a period of 12 h and 24 h, respectively, with HPMC and pectin beads. A significant (p & 0.05) reduction in fasting and non-fasting blood glucose levels, reduction in fasting plasma insulin level and a significant improvement in glucose tolerance were observed in animals treated with formulations. The developed beads were suitable carriers for improving the systemic absorption of gliclazide and maintaining reduced blood glucose levels.

  2. Prednisolone Delivery Platforms: Capsules and Beads Combination for a Right Timing Therapy

    PubMed Central

    Cerciello, Andrea; Auriemma, Giulia; Morello, Silvana; Aquino, Rita P.; Del Gaudio, Pasquale

    2016-01-01

    In this work, a platform of alginate beads loaded with Prednisolone in hypromellose/gellan gum capsules (F6/Cps) able to delay steroidal anti-inflammatory drug (SAID) release as needed for chronotherapy of rheumatoid arthritis is proposed. Rheumatoid arthritis, showing a worsening in symptoms in the morning upon waking, is a pathology that can benefit from chronotherapy. With the aim to maximize prednisolone therapeutic action allowing the right timing of glucocorticoid therapy, different engineered microparticles (gel-beads) were manufactured using prilling (laminar jet break-up) as micro-encapsulation technique and Zn-alginate as gastroresistant carrier. Starting from various feed solutions and process parameters, the effect of the variables on particles size, morphology, solid state properties and drug release was studied. The optimization of operative and prilling/ionotropic gelation variables led to microspheres with almost spherical shape and a narrow dimensional range. The feed solution with the highest alginate (2.5% w/v) amount and drug/polymer ratio (1:5 w/w) gave rise to the highest encapsulation efficiency (78.5%) as in F6 formulation. As to drug release, F6 exhibited an interesting dissolution profile, releasing about 24% of the drug in simulated gastric fluid followed by a more sustained profile in simulated intestinal fluid. #F6, acting as a gastro-resistant and delayed release formulation, was selected for in vivo studies on male Wistar rats by means of a carrageenan-induced oedema model. Finally, this efficacious formulation was used as core material for the development of a final dosage form: F6/Cps allowed to significantly reduce prednisolone release in simulated gastric fluid (12.6%) and delayed drug release up to about 390 minutes. PMID:27472446

  3. Trophic pathways supporting Arctic grayling in a small stream on the Arctic Coastal Plain, Alaska

    USGS Publications Warehouse

    McFarland, Jason J.; Wipfli, Mark S.; Whitman, Matthew S.

    2018-01-01

    Beaded streams are prominent across the Arctic Coastal Plain (ACP) of Alaska, yet prey flow and food web dynamics supporting fish inhabiting these streams are poorly understood. Arctic grayling (Thymallus arcticus) are a widely distributed upper-level consumer on the ACP and migrate into beaded streams to forage during the short 3-month open-water season. We investigated energy pathways and key prey resources that support grayling in a representative beaded stream, Crea Creek. We measured terrestrial invertebrates entering the stream from predominant riparian vegetation types, prey types supporting a range of fish size classes, and how riparian plants and fish size influenced foraging habits. We found that riparian plants influenced the quantity of terrestrial invertebrates entering Crea Creek; however, these differences were not reflected in fish diets. Prey type and size ingested varied with grayling size and season. Small grayling (<15 cm fork length (FL)) consumed mostly aquatic invertebrates early in the summer, and terrestrial invertebrates later in summer, while larger fish (>15 cm FL) foraged most heavily on ninespine stickleback (Pungitius pungitius) throughout the summer, indicating that grayling can be insectivorous and piscivorous, depending on size. These findings underscore the potential importance of small streams in Arctic ecosystems as key summer foraging habitats for fish. Understanding trophic pathways supporting stream fishes in these systems will help interpret whether and how petroleum development and climate change may affect energy flow and stream productivity, terrestrial–aquatic linkages and fishes in Arctic ecosystems.

  4. Hot spot-derived shock initiation phenomena in heterogeneous nitromethane

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dattelbaum, Dana M; Sheffield, Stephen A; Stahl, David B

    2009-01-01

    The addition of solid silica particles to gelled nitromethane offers a tractable model system for interrogating the role of impedance mismatches as one type of hot spot 'seed' on the initiation behaviors of explosive formulations. Gas gun-driven plate impact experiments are used to produce well-defined shock inputs into nitromethane-silica mixtures containing size-selected silica beads at 6 wt%. The Pop-plots or relationships between shock input pressure and rundistance (or time)-to-detonation for mixtures containing small (1-4 {micro}m) and large (40 {micro}m) beads are presented. Overall, the addition of beads was found to influence the shock sensitivity of the mixtures, with the smallermore » beads being more sensitizing than the larger beads, lowering the shock initiation threshold for the same run distance to detonation compared with neat nitromethane. In addition, the use of embedded electromagnetic gauges provides detailed information pertaining to the mechanism of the build-up to detonation and associated reactive flow. Of note, an initiation mechanism characteristic of homogeneous liquid explosives, such as nitromethane, was observed in the nitromethane-40 {micro}m diameter silica samples at high shock input pressures, indicating that the influence of hot spots on the initiation process was minimal under these conditions.« less

  5. Improving the Stability of Astaxanthin by Microencapsulation in Calcium Alginate Beads.

    PubMed

    Lin, Shen-Fu; Chen, Ying-Chen; Chen, Ray-Neng; Chen, Ling-Chun; Ho, Hsiu-O; Tsung, Yu-Han; Sheu, Ming-Thau; Liu, Der-Zen

    2016-01-01

    There has been considerable interest in the biological functions of astaxanthin and its potential applications in the nutraceutical, cosmetics, food, and feed industries in recent years. However, the unstable structure of astaxanthin considerably limits its application. Therefore, this study reports the encapsulation of astaxanthin in calcium alginate beads using the extrusion method to improve its stability. This study also evaluates the stability of the encapsulated astaxanthin under different storage conditions. The evaluation of astaxanthin stability under various environmental factors reveals that temperature is the most influential environmental factor in astaxanthin degradation. Stability analysis shows that, regardless of the formulation used, the content of astaxanthin encapsulated in alginate beads remains above 90% of the original amount after 21 days of storage at 25°C. These results suggest that the proposed technique is a promising way to enhance the stability of other sensitive compounds.

  6. Improving the Stability of Astaxanthin by Microencapsulation in Calcium Alginate Beads

    PubMed Central

    Lin, Shen-Fu; Chen, Ying-Chen; Chen, Ray-Neng; Chen, Ling-Chun; Ho, Hsiu-O; Tsung, Yu-Han; Sheu, Ming-Thau; Liu, Der-Zen

    2016-01-01

    There has been considerable interest in the biological functions of astaxanthin and its potential applications in the nutraceutical, cosmetics, food, and feed industries in recent years. However, the unstable structure of astaxanthin considerably limits its application. Therefore, this study reports the encapsulation of astaxanthin in calcium alginate beads using the extrusion method to improve its stability. This study also evaluates the stability of the encapsulated astaxanthin under different storage conditions. The evaluation of astaxanthin stability under various environmental factors reveals that temperature is the most influential environmental factor in astaxanthin degradation. Stability analysis shows that, regardless of the formulation used, the content of astaxanthin encapsulated in alginate beads remains above 90% of the original amount after 21 days of storage at 25°C. These results suggest that the proposed technique is a promising way to enhance the stability of other sensitive compounds. PMID:27093175

  7. Chromium (VI) ion adsorption by grafted cross-linked chitosan beads in aqueous solution - a mathematical and statistical modeling study.

    PubMed

    Igberase, E; Osifo, P; Ofomaja, A

    2017-12-01

    Chitosan outstanding qualities and efficient way of binding metal ions even to near zero concentration is the major reason for special attention. Modification of chitosan allows the polymer to be applied in numerous field of research. Depending on the modification techniques, chitosan possesses increased adsorption capacity. In this study chitosan beads (CS) were formulated from chitosan flakes, the beads were cross-linked with glutaraldehyde and thereafter grafted with ethyldiaminetetraacetic acid. The stability and amine concentration of the beads were determined. The chemical functionalities of the beads were obtained by Fourier transform infrared spectroscopy, X-ray diffraction and thermogravimetric analysis (TGA). However, in the adsorption studies with Cr(VI), the number of runs in the experiment was obtained by response surface methodology (RSM), and the maximum adsorption capacity (Q m ) from each run was determined from the Langmuir model. The results of the experiment showed that the non-modified beads were soluble at pH 1-4 and insoluble at pH 5, while the modified beads were insoluble at pH 1-6. The amine concentration of CS, CCS and grafted cross-linked chitosan beads (GCCS) were 4.4, 3.8 and 5.0 mmol/g, respectively. The point of zero charge (pH PZC ) of GCCS was found to be 4.4. The quadratic model was significant and adequate in describing the experimental data. The difference between experimental and predicted Q m was negligible. From the design matrix and results, increased Q m was achieved at pH 5, contact time 70 min, temperature 45°C, adsorbent dosage 5 g and initial concentration 70 mg/l. The desorption of the beads loaded with Cr(VI) was successful with 0.5 M HCl eluant and contact time of 180 min, leading to cost minimization.

  8. Floating lipid beads for the improvement of bioavailability of poorly soluble basic drugs: in-vitro optimization and in-vivo performance in humans.

    PubMed

    Abouelatta, Samar M; Aboelwafa, Ahmed A; Khalil, Rawia M; ElGazayerly, Omaima N

    2015-01-01

    The challenge in developing oral drug delivery systems of poorly soluble basic drugs is primarily due to their pH dependent solubility. Cinnarizine (CNZ), a model for a poorly soluble basic drug, has pH dependent solubility; where it dissolves readily at low pH in the stomach and exhibits a very low solubility at pH values greater than 4. It is also characterized by a short half life of 3-6h, which requires frequent daily administration resulting in poor patient compliance. In an attempt to solve these problems, extended release floating lipid beads were formulated. A 2(4) full factorial design was utilized for optimization of the effects of various independent variables; lipid:drug ratio, % Pluronic F-127, % Sterotex, and Gelucire 43/01:Gelucire 50/13 ratio, on the loading efficiency and release of CNZ from the lipid beads. In-vivo pharmacokinetic study of the optimized CNZ-lipid beads compared to Stugeron® (reference standard) was performed in healthy human volunteers. A promising approach for enhancing the bioavailability of the poorly soluble basic drug, CNZ, utilizing novel and simple floating lipid beads was successfully developed. Zero order release profile of CNZ was achieved for 12h. Mean AUC0-24 and AUC0-∞ of the optimized CNZ-loaded lipid beads were 4.23 and 6.04 times that of Stugeron® tablets respectively. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Use of bicarbonate buffer systems for dissolution characterization of enteric-coated proton pump inhibitor tablets.

    PubMed

    Shibata, Hiroko; Yoshida, Hiroyuki; Izutsu, Ken-Ichi; Goda, Yukihiro

    2016-04-01

    The aim of this study was to assess the effects of buffer systems (bicarbonate or phosphate at different concentrations) on the in vitro dissolution profiles of commercially available enteric-coated tablets. In vitro dissolution tests were conducted using an USP apparatus II on 12 enteric-coated omeprazole and rabeprazole tablets, including innovator and generic formulations in phosphate buffers, bicarbonate buffers and a media modified Hanks (mHanks) buffer. Both omeprazole and rabeprazole tablets showed similar dissolution profiles among products in the compendial phosphate buffer system. However, there were large differences between products in dissolution lag time in mHanks buffer and bicarbonate buffers. All formulations showed longer dissolution lag times at lower concentrations of bicarbonate or phosphate buffers. The dissolution rank order of each formulation differed between mHanks buffer and bicarbonate buffers. A rabeprazole formulation coated with a methacrylic acid copolymer showed the shortest lag time in the high concentration bicarbonate buffer, suggesting varied responses depending on the coating layer and buffer components. Use of multiple dissolution media during in vitro testing, including high concentration bicarbonate buffer, would contribute to the efficient design of enteric-coated drug formulations. © 2016 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology.

  10. Fabrication of a microfluidic device for studying the in situ drug-loading/release behavior of graphene oxide-encapsulated hydrogel beads.

    PubMed

    Veerla, Sarath Chandra; Kim, Da Reum; Yang, Sung Yun

    2018-01-01

    Controlled drug delivery system is highly important for not only prolonged the efficacy of drug but also cellular development for tissue engineering. A number of biopolymer composites and nanostructured carriers behave been used for the controlled drug delivery of therapeutics. Recently, in vitro microfluidic devices that mimic the human body have been developed for drug-delivery applications. A microfluidic channel was fabricated via a two-step process: (i) polydimethyl siloxane (PDMS) and curing agent were poured with a 10:2 mass ratio onto an acrylic mold with two steel pipes, and (ii) calcium alginate beads were synthesized using sodium alginate and calcium chloride solutions. Different amounts (10, 25, 50 μg) of graphene oxide (GO) were then added by Hummers method, and studies on the encapsulation and release of the model drug, risedronate (Ris), were performed using control hydrogel beads (pH 6.3), GO-containing beads (10GO, 25GO and 50GO), and different pH conditions. MC3T3 osteoblastic cells were cultured in a microchannel with Ris-loaded GO-hydrogel beads, and their proliferation, viability, attachment and spreading were assessed for a week. The spongy and textured morphology of pristine hydrogel beads was converted to flowery and rod-shaped structures in drug-loaded hydrogel beads at reduced pH (6.3) and at a lower concentration (10 μg) of GO. These latter 10GO drug-loaded beads rapidly released their cargo owing to the calcium phosphate deposited on the surface. Notably, beads containing a higher amount of GO (50GO) exhibited an extended drug-release profile. We further found that MC3T3 cells proliferated continuously in vitro in the microfluidic channel containing the GO-hydrogel system. MTT and live/dead assays showed similar proliferative potential of MC3T3 cells. Therefore, a microfluidic device with microchannels containing hydrogel beads formulated with different amounts of GO and tested under various pH conditions could be a promising system for controlled drug release. The GO and drug (risedronate, Rig) were directed loaded into a hydrogel placed in a microchannel. Through interactions such as hydrogen bonding between Go and the Rig-loaded GO-hydrogel beads, the bead-loaded microfluidic device supported MC3T3 proliferation and development as osteoblast without additional osteogenic differentiation supplements.

  11. Study and Understanding Behavior of Alginate-Inulin Synbiotics Beads for Protection and Delivery of Antimicrobial-Producing Probiotics in Colonic Simulated Conditions.

    PubMed

    Atia, Abdelbasset; Gomaa, Ahmed; Fernandez, Benoit; Subirade, Muriel; Fliss, Ismail

    2018-06-01

    According to the World Health Organization (WHO), using antibiotics as growth promoters for livestock-particularly swine-is the principal cause of antibiotic resistance. It is therefore clear that finding an alternative to antibiotics becomes an emergency. Hundreds of recent studies have appointed probiotics as potential candidates to replace or to be used in combination with antibiotics. However, bringing probiotics alive to the colon-their site of action-remains a big challenge because of different physiological barriers encountered in proximal gastrointestinal tract (GIT) such as acidic pH and bile salts that may affect the viability of probiotic cultures. To overcome this problem, in previous studies, we developed and characterize a synbiotic formula consisting of beads of a mixture of alginate and inulin. Three potential probiotics strains namely Pediococcus acidilactici UL5 (UL5), Lactobacillus reuteri (LR), and Lactobacillus salivarius (LS) were encapsulated to study their release and the behavior of this synbiotic formula throughout the GIT using in vitro models. The survival and the release of bacteria from beads were studied by specific PMA-qPCR counting. The microscopic aspects of the beads were studied using scanning electron microscopy (SEM). Moreover, the microbial dynamics inside beads were studied by fluorescence microscopy using the live/dead test. Our results have shown that the beads containing 5% inulin were the most stable in the stomach and throughout the small intestine. However, beads were completely degraded in approximately 3 h of incubation in the fermented medium that mimic the colon. These results were confirmed by SEM and fluorescence microscopy images. Therefore, it can be stated that the AI5 formulation well protected the bacteria in the upper part of the digestive tract and allowed their controlled release in the colon.

  12. Co-delivery of cisplatin and doxorubicin from calcium phosphate beads/matrix scaffolds for osteosarcoma therapy.

    PubMed

    Hess, Ulrike; Shahabi, Shakiba; Treccani, Laura; Streckbein, Philipp; Heiss, Christian; Rezwan, Kurosch

    2017-08-01

    Bone substitute materials with a controlled drug release ability can fill cavities caused by the resection of bone tumours and thereby combat any leftover bone cancer cells. The combined release of different cytostatics seems to enhance their toxicity. In this study, calcium phosphate beads and matrix scaffolds are combined for a long-term co-delivery of cis-diamminedichloroplatinum (cisplatin, CDDP) and doxorubicin hydrochloride (DOX) as clinical relevant model drugs. Tricalcium phosphate/alginate beads as additional drug carrier are produced by droplet extrusion with ionotropic gelation and incorporated in scaffold matrix by freeze gelation without sintering. CDDP shows a short burst release while DOX has a continuous release measurable over the entire study period of 40days. Drug release from matrix is decreased by ~30% compared to release from beads. Nevertheless, all formulations follow the Korsmeyer-Peppas release kinetic model and show Fickian diffusion. Cytotoxic activity was conducted on MG-63 osteosarcoma cells after 1, 4, and 7days with WST-1 cell viability assay. Co-loaded composites enhance activity towards MG-63 cells up to ~75% toxicity while reducing the released drug quantity. The results suggest that co-loaded beads/matrix scaffolds are highly promising for osteosarcoma therapy due to synergistic effects over a long period of more than a month. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Formation of Cucurbit[8]uril-Based Supramolecular Hydrogel Beads Using Droplet-Based Microfluidics.

    PubMed

    Xu, Xuejiao; Appel, Eric A; Liu, Xin; Parker, Richard M; Scherman, Oren A; Abell, Chris

    2015-09-14

    Herein we describe the use of microdroplets as templates for the fabrication of uniform-sized supramolecular hydrogel beads, assembled by supramolecular cross-linking of functional biopolymers with the macrocyclic host molecule, cucurbit[8]uril (CB[8]). The microdroplets were formed containing diluted hydrogel precursors in solution, including the functional polymers and CB[8], in a microfluidic device. Subsequent evaporation of water from collected microdroplets concentrated the contents, driving the formation of the CB[8]-mediated host-guest ternary complex interactions and leading to the assembly of condensed three-dimensional polymeric scaffolds. Rehydration of the dried particles gave monodisperse hydrogel beads. Their equilibrium size was shown to be dependent on both the quantity of material loaded and the dimensions of the microfluidic flow focus. Fluorescein-labeled dextran was used to evaluate the efficacy of the hydrogel beads as a vector for controlled cargo release. Both passive, sustained release (hours) and triggered, fast release (minutes) of the FITC-dextran was observed, with the rate of sustained release dependent on the formulation. The kinetics of release was fitted to the Ritger-Peppas controlled release equation and shown to follow an anomalous (non-Fickian) transport mechanism.

  14. Optical Encoding Technology for Viral Screening Panels Final Report CRADA No TC02132.0

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lenhoff, R.; Haushalter, R.

    This was a collaborative effort between Lawrence Livermore National Security, LLC, Lawrence Livermore National Laboratory (LLNL) and Parallel Synthesis Technologies, Inc. (PSTI), to develop Optical Encoding Technology for Viral Screening Panels. The goal for this effort was to prepare a portable bead reader system that would enable the development of viral and bacterial screening panels which could be used for the detection of any desired set of bacteria or viruses in any location. The main objective was to determine if the combination of a bead-based, PCR suspension array technology, formulated from Parallume encoded beads and PSTI’s multiplex assay reader systemmore » (MARS), could provide advantages in terms of the number of simultaneously measured samples, portability, ruggedness, ease of use, accuracy, precision or cost as compared to the Luminexbased system developed at LLNL. The project underwent several no cost extensions however the overall goal of demonstrating the utility of this new system was achieved. As a result of the project a significant change to the type of bead PSTI used for the suspension system was implemented allowing better performance than the commercial Luminex system.« less

  15. Mechanics model for actin-based motility

    NASA Astrophysics Data System (ADS)

    Lin, Yuan

    2009-02-01

    We present here a mechanics model for the force generation by actin polymerization. The possible adhesions between the actin filaments and the load surface, as well as the nucleation and capping of filament tips, are included in this model on top of the well-known elastic Brownian ratchet formulation. A closed form solution is provided from which the force-velocity relationship, summarizing the mechanics of polymerization, can be drawn. Model predictions on the velocity of moving beads driven by actin polymerization are consistent with experiment observations. This model also seems capable of explaining the enhanced actin-based motility of Listeria monocytogenes and beads by the presence of Vasodilator-stimulated phosphoprotein, as observed in recent experiments.

  16. Mechanics model for actin-based motility.

    PubMed

    Lin, Yuan

    2009-02-01

    We present here a mechanics model for the force generation by actin polymerization. The possible adhesions between the actin filaments and the load surface, as well as the nucleation and capping of filament tips, are included in this model on top of the well-known elastic Brownian ratchet formulation. A closed form solution is provided from which the force-velocity relationship, summarizing the mechanics of polymerization, can be drawn. Model predictions on the velocity of moving beads driven by actin polymerization are consistent with experiment observations. This model also seems capable of explaining the enhanced actin-based motility of Listeria monocytogenes and beads by the presence of Vasodilator-stimulated phosphoprotein, as observed in recent experiments.

  17. Enteric coating of granules containing the probiotic Lactobacillus acidophilus.

    PubMed

    Pyar, Hassan; Peh, Kok-Khiang

    2014-06-01

    In the present study, a capsule formulation composed of enteric coated granules of Lactobacillus acidophilus ATCC 4962 was developed using Eudragit L30D-55 as enteric polymer. Optimization of the capsule formulation was achieved with a maximum viable cell count after 2 h of incubation in acid medium and disintegration time of 1 h in buffer pH 6.8. The amount of Eudragit L30D-55 in the capsules correlated with gastric juice resistance. The best protective qualities against artificial gastric juice were observed when capsules were prepared from granules composed of L. acidophilus, corn starch, lactose monohydrate, polyvinylpyrrolidone and coated with 12.5 % (m/V) of Eudragit L30D-55. Capsule formulation of L. acidophilus in edible broth medium suspension serves as a cheap alternative to the expensive freeze-drying procedure for preparing L. acidophilus. In addition, the enteric coating using Eudragit L30D-55 could protect probiotics from the acidic gastric environment and enhance the bioactivity of probiotics along with replacement of pathogenic microbes in human intestine.

  18. Effect of particle size of parenteral suspensions on in vitro muscle damage.

    PubMed

    Brazeau, Gayle; Sauberan, Shauna L; Gatlin, Larry; Wisniecki, Peter; Shah, Jaymin

    2011-01-01

    Suspension particle size plays a key role in the release and stability of drugs for oral and parenteral formulations. However, the role of particle size in suspension formulations on tissue damage (myotoxicity) following intramuscular (IM) injection has not been systematically investigated. Myotoxicity was assessed by the release of cumulative creatine kinase (CCK) from the isolated extensor digitorium longus (EDL) and soleus (SOL) rat muscles for selected suspensions of phenytoin, bupivicane and diazepam. Particle size effects on myotoxicity, independent of any specific drug, were also investigated using characterized non-dissolving polystyrene beads. Myotoxicity was quantitated by the cumulative release of creatine kinase (CCK) from these isolated muscles over 90 or 120 min. The relationship between particle size and myotoxicity was dependent upon the drug in these suspensions. Diazepam and phenytoin suspensions were found to be less myotoxic than bupivicaine. Using unmodified and carboxy modified polystyrene beads, an optimal particle size for reduced myotoxicity following IM injection ranges from approx. 500 nm to 1 µM. The relationship between myotoxicity of IM suspensions and particle size is dependent upon the particular drug and suspension particle size.

  19. Cellular localization of the activated EGFR determines its effect on cell growth in MDA-MB-468 cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hyatt, Dustin C.; Ceresa, Brian P.

    2008-11-01

    The epidermal growth factor (EGF) receptor (EGFR) is a ubiquitously expressed receptor tyrosine kinase that regulates diverse cell functions that are dependent upon cell type, the presence of downstream effectors, and receptor density. In addition to activating biochemical pathways, ligand stimulation causes the EGFR to enter the cell via clathrin-coated pits. Endocytic trafficking influences receptor signaling by controlling the duration of EGFR phosphorylation and coordinating the receptor's association with downstream effectors. To better understand the individual contributions of cell surface and cytosolic EGFRs on cell physiology, we used EGF that was conjugated to 900 nm polystyrene beads (EGF-beads). EGF-beads canmore » stimulate the EGFR and retain the activated receptor at the plasma membrane. In MDA-MB-468 cells, a breast cancer cell line that over-expresses the EGFR, only internalized, activated EGFRs stimulate caspase-3 and induce cell death. Conversely, signaling cascades triggered from activated EGFR retained at the cell surface inhibit caspase-3 and promote cell proliferation. Thus, through endocytosis, the activated EGFR can differentially regulate cell growth in MDA-MB-468 cells.« less

  20. In vitro and in vivo evaluation of gastro-retentive carvedilol loaded chitosan beads using Gastroplus™.

    PubMed

    Praveen, Radhakrishnan; Prasad Verma, Priya Ranjan; Venkatesan, Jayachandran; Yoon, Dong-Han; Kim, Se-Kwon; Singh, Sandeep Kumar

    2017-09-01

    The objective of present investigation was to develop gastro-retentive controlled release system of carvedilol using biological macromolecule, chitosan. 3 2 full factorial design was adopted for optimization of tripolyphosphate (X 1 ) and curing time (X 2 ). Bead stability in 0.1N HCl, buoyancy duration, density, drug loading, dissolution efficiency and cumulative percentage release at 8th hour were evaluated as dependent variables. The levels of X 1 and X 2 of optimized formulation having maximum desirability was found to 2.0% w/v and 62.66min, respectively. The in silico predicted responses and observed response were found to be in good agreement (percent bias error: -13.295 to +13.269). SEM images showed numerous pores in the cross sectional image that renders buoyancy. AUC 0-∞ of optimized formulation was 1.47 times higher as compared to suspension corroborating enhanced extent of absorption. T max and mean residence time were significantly higher from optimized formulation vis a vis suspension. In silico study indicated maximum regional absorption from the duodenum (94.1%) followed by jejunum (5.6%). Wagner-Nelson and Loo-Reigelman method were the preferred deconvolution approach over numerical deconvolution to establish IVIVC. In conclusion, the study showed that gastro-retentive controlled release system prepared using chitosan could be a potential drug carrier of carvedilol with improved bioavailability. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Effect of food on the oral bioavailability of didanosine from encapsulated enteric-coated beads.

    PubMed

    Damle, Bharat D; Yan, Jing-He; Behr, Douglas; O'Mara, Edward; Nichola, Peter; Kaul, Sanjeev; Knupp, Catherine

    2002-04-01

    The objective of this study was to assess the effect of food and timing of meals on the bioavailability of didanosine from encapsulated enteric-coated beads. Four different independent, open-label, single-dose, randomized, crossover studies were conducted in healthy subjects (n = 20-30). Didanosine (400 mg) was given concomitantly with a high-fat meal, light meal, yogurt, and applesauce. In addition, didanosine was given 1, 1.5, 2, and 3 hours before and 2 hours after a light meal. Statistical comparison with fasting conditions was made using the equivalence approach for Cmax (70%-143%) and AUC (80%-125%). The high-fat meal, light meal, yogurt, and applesauce decreased the Cmax by 46%, 22%, 30%, and 24%, respectively, and lowered the AUC by 19%, 27%, 20%, and 18%, respectively; statistical analyses indicated an indeterminate food effect, except for the Cmax for the high-fat meal. For 1 hour before meal, Cmax and AUC were lower by 15% and 24% and, for 2 hours after meal, were lower by 15% and 10%, respectively. There was an indeterminate food effect for 1 hour before the meal treatment; in addition, 2 hours after the meal, treatment approached statistical equivalence, missing narrowly on the lower bounds. For 1.5, 2, and 3 hours before meal treatments, Cmax values were unchanged, but AUC was lower by 10%, 4%, and 0%, respectively; lack of food effect was observed for all three treatments. Across studies, median time to Cmix ranged from 1.67 to 2.67 hours but was delayed by 2.5 to 3 hours with high-fat and light meals compared to fasting conditions. The half-life of didanosine was 1.5 to 2 hours. It was concluded that the bioavailability of didanosine from encapsulated enteric-coated beads was reduced by approximately 20% to 25% with food, which can be circumvented by taking didanosine on an empty stomach. The clinical significance of such moderate reductions in didanosine exposure with food, especially as part of a highly active antiretroviral therapy, is not clear.

  2. Enteric protection of naproxen in a fixed-dose combination product produced by hot-melt co-extrusion.

    PubMed

    Vynckier, A-K; De Beer, M; Monteyne, T; Voorspoels, J; De Beer, T; Remon, J P; Vervaet, C

    2015-08-01

    In this study hot-melt co-extrusion is used as processing technique to manufacture a fixed-dose combination product providing enteric protection to naproxen incorporated in the core and immediate release to esomeprazole magnesium embedded in the coat. The plasticizing effect of naproxen and triethyl citrate (TEC) was tested on the enteric polymers investigated (Eudragit(®) L100-55, HPMC-AS-LF and HPMCP-HP-50). Core matrix formulations containing HPMC-AS-LF, TEC and a naproxen load of 15, 30 and 50% were processed and characterized. The in vitro naproxen release in 0.1N HCl was prevented for 2h for all formulations. The physicochemical state of the drug in the extrudates was determined and a stability study was performed. Intermolecular interactions between naproxen and polymer were identified using attenuated total reflection Fourier-transform infrared (ATR FT-IR) spectroscopy. When esomeprazole magnesium was formulated in a polyethylene oxide 100K:polyethylene glycol 4K (1:1) matrix, separated from the naproxen-containing layer, the formulation could be easily processed and complete in vitro drug release was observed after 45 min. When co-extruding the core/coat dosage form it was observed that a third layer of polymer, separating the naproxen loaded enteric formulation in the core from the coat, is required to prevent degradation of the acid-labile esomeprazole magnesium at the core/coat interface. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Formulation and characterization of polysaccharide beads for controlled release of plant growth regulators

    Treesearch

    Mei Li; Mandla A. Tshabalala; Gisela Buschle-Diller

    2016-01-01

    Owing to their chemical, physical, and functional characteristics, polysaccharides are considered to be the most versatile natural polymers. As a result, their properties have been exploited in various fields of research in the biomedical, pharmaceutical, cosmetic, food, and agricultural industries. A property of special interest is their ability to form systems or...

  4. Apparatus for the production of gel beads containing a biocatalyst

    DOEpatents

    Scott, C.D.; Scott, T.C.; Davison, B.H.

    1998-03-19

    An apparatus is described for the large-scale and continuous production of gel beads containing a biocatalyst. The apparatus is a columnar system based on the chemical cross-linking of hydrocolloidal gels that contain and immobilize a biocatalyst, the biocatalyst being a microorganism or an enzyme. Hydrocolloidal gels, such as alginate, carrageenan, and a mixture of bone gelatin and modified alginate, provide immobilization matrices that can be used to entrap and retain the biocatalyst while allowing effective contact with substrates and release of products. Such immobilized biocatalysts are generally formulated into small spheres or beads that have high concentrations of the biocatalyst within the gel matrix. The columnar system includes a gel dispersion nozzle submerged in a heated non-interacting liquid, typically an organic liquid, that is immiscible with water to allow efficient formation of spherical gel droplets, the non-interacting liquid having a specific gravity that is less than water so that the gel droplets will fall through the liquid by the force of gravity. The heated non-interacting liquid is in direct contact with a chilled upflowing non-interacting liquid that will provide sufficient residence time for the gel droplets as they fall through the liquid so that they will be cooled below the gelling temperature and form solid spheres. The upflowing non-interacting liquid is in direct contact with an upflowing temperature-controlled aqueous solution containing the necessary chemicals for cross-linking or fixing of the gel beads to add the necessary stability. The flow rates of the two liquid streams can be varied to control the proper residence time in each liquid section to accommodate the production of gel beads of differing settling velocities. A valve is provided for continuous removal of the stabilized gel beads from the bottom of the column. 1 fig.

  5. Apparatus and method for the production of gel beads containing a biocatalyst

    DOEpatents

    Scott, Charles D.; Scott, Timothy C.; Davison, Brian H.

    1998-01-01

    An apparatus and method for the large-scale and continuous production of gel beads containing a biocatalyst. The apparatus is a columnar system based on the chemical cross-linking of hydrocolloidal gels that contain and immobilize a biocatalyst, the biocatalyst being a microorganism or an enzyme. Hydrocolloidal gels, such as alginate, carrageenan, and a mixture of bone gelatin and modified alginate, provide immobilization matrices that can be used to entrap and retain the biocatalyst while allowing effective contact with substrates and release of products. Such immobilized biocatalysts are generally formulated into small spheres or beads that have high concentrations of the biocatalyst within the gel matrix. The columnar system includes a gel dispersion nozzle submerged in a heated non-interacting liquid, typically an organic liquid, that is immiscible with water to allow efficient formation of spherical gel droplets, the non-interacting liquid having a specific gravity that is less than water so that the gel droplets will fall through the liquid by the force of gravity. The heated non-interacting liquid is in direct contact with a chilled upflowing non-interacting liquid that will provide sufficient residence time for the gel droplets as they fall through the liquid so that they will be cooled below the gelling temperature and form solid spheres. The upflowing non-interacting liquid is in direct contact with an upflowing temperature-controlled aqueous solution containing the necessary chemicals for cross-linking or fixing of the gel beads to add the necessary stability. The flow rates of the two liquid streams can be varied to control the proper residence time in each liquid section to accommodate the production of gel beads of differing settling velocities. A valve is provided for continuous removal of the stabilized gel beads from the bottom of the column.

  6. Apparatus for the production of gel beads containing a biocatalyst

    DOEpatents

    Scott, Charles D.; Scott, Timothy C.; Davison, Brian H.

    1998-01-01

    An apparatus for the large-scale and continuous production of gel beads containing a biocatalyst. The apparatus is a columnar system based on the chemical cross-linking of hydrocolloidal gels that contain and immobilize a biocatalyst, the biocatalyst being a microorganism or an enzyme. Hydrocolloidal gels, such as alginate, carrageenan, and a mixture of bone gelatin and modified alginate, provide immobilization matrices that can be used to entrap and retain the biocatalyst while allowing effective contact with substrates and release of products. Such immobilized biocatalysts are generally formulated into small spheres or beads that have high concentrations of the biocatalyst within the gel matrix. The columnar system includes a gel dispersion nozzle submerged in a heated non-interacting liquid, typically an organic liquid, that is immiscible with water to allow efficient formation of spherical gel droplets, the non-interacting liquid having a specific gravity that is less than water so that the gel droplets will fall through the liquid by the force of gravity. The heated non-interacting liquid is in direct contact with a chilled upflowing non-interacting liquid that will provide sufficient residence time for the gel droplets as they fall through the liquid so that they will be cooled below the gelling temperature and form solid spheres. The upflowing non-interacting liquid is in direct contact with an upflowing temperature-controlled aqueous solution containing the necessary chemicals for cross-linking or fixing of the gel beads to add the necessary stability. The flow rates of the two liquid streams can be varied to control the proper residence time in each liquid section to accommodate the production of gel beads of differing settling velocities. A valve is provided for continuous removal of the stabilized gel beads from the bottom of the column.

  7. Controlled Release of 5-Fluorouracil from Alginate Beads Encapsulated in 3D Printed pH-Responsive Solid Dosage Forms.

    PubMed

    Gioumouxouzis, Christos I; Chatzitaki, Aikaterini-Theodora; Karavasili, Christina; Katsamenis, Orestis L; Tzetzis, Dimitrios; Mystiridou, Emmanouela; Bouropoulos, Nikolaos; Fatouros, Dimitrios G

    2018-06-14

    Three-dimensional printing is being steadily deployed as manufacturing technology for the development of personalized pharmaceutical dosage forms. In the present study, we developed a hollow pH-responsive 3D printed tablet encapsulating drug loaded non-coated and chitosan-coated alginate beads for the targeted colonic delivery of 5-fluorouracil (5-FU). A mixture of Eudragit® L100-55 and Eudragit® S100 was fabricated by means of hot-melt extrusion (HME) and the produced filaments were printed utilizing a fused deposition modeling (FDM) 3D printer to form the pH-responsive layer of the tablet with the rest comprising of a water-insoluble poly-lactic acid (PLA) layer. The filaments and alginate particles were characterized for their physicochemical properties (thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction), their surface topography was visualized by scanning electron microscopy and the filaments' mechanical properties were assessed by instrumented indentation testing and tensile testing. The optimized filament formulation was 3D printed and the structural integrity of the hollow tablet in increasing pH media (pH 1.2 to pH 7.4) was assessed by means of time-lapsed microfocus computed tomography (μCT). In vitro release studies demonstrated controlled release of 5-FU from the alginate beads encapsulated within the hollow pH-sensitive tablet matrix at pH values corresponding to the colonic environment (pH 7.4). The present study highlights the potential of additive manufacturing in fabricating controlled-release dosage forms rendering them pertinent formulations for further in vivo evaluation.

  8. Selective Optimization

    DTIC Science & Technology

    2015-07-06

    NUMBER 5b. GRANT NUMBER AFOSR FA9550-12-1-0154 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Shabbir Ahmed and Santanu S. Dey 5d. PROJECT NUMBER 5e. TASK...standard mixed-integer programming (MIP) formulations of selective optimization problems. While such formulations can be attacked by commercial...F33615-86-C-5169. 5b. GRANT NUMBER. Enter all grant numbers as they appear in the report, e.g. AFOSR-82-1234. 5c. PROGRAM ELEMENT NUMBER. Enter

  9. Assessment of different formulations of oral Mycobacterium bovis Bacille Calmette-Guérin (BCG) vaccine in rodent models for immunogenicity and protection against aerosol challenge with M. bovis.

    PubMed

    Clark, Simon; Cross, Martin L; Smith, Alan; Court, Pinar; Vipond, Julia; Nadian, Allan; Hewinson, R Glyn; Batchelor, Hannah K; Perrie, Yvonne; Williams, Ann; Aldwell, Frank E; Chambers, Mark A

    2008-10-29

    Bovine tuberculosis (bTB) caused by infection with Mycobacterium bovis is causing considerable economic loss to farmers and Government in the United Kingdom as its incidence is increasing. Efforts to control bTB in the UK are hampered by the infection in Eurasian badgers (Meles meles) that represent a wildlife reservoir and source of recurrent M. bovis exposure to cattle. Vaccination of badgers with the human TB vaccine, M. bovis Bacille Calmette-Guérin (BCG), in oral bait represents a possible disease control tool and holds the best prospect for reaching badger populations over a wide geographical area. Using mouse and guinea pig models, we evaluated the immunogenicity and protective efficacy, respectively, of candidate badger oral vaccines based on formulation of BCG in lipid matrix, alginate beads, or a novel microcapsular hybrid of both lipid and alginate. Two different oral doses of BCG were evaluated in each formulation for their protective efficacy in guinea pigs, while a single dose was evaluated in mice. In mice, significant immune responses (based on lymphocyte proliferation and expression of IFN-gamma) were only seen with the lipid matrix and the lipid in alginate microcapsular formulation, corresponding to the isolation of viable BCG from alimentary tract lymph nodes. In guinea pigs, only BCG formulated in lipid matrix conferred protection to the spleen and lungs following aerosol route challenge with M. bovis. Protection was seen with delivery doses in the range 10(6)-10(7) CFU, although this was more consistent in the spleen at the higher dose. No protection in terms of organ CFU was seen with BCG administered in alginate beads or in lipid in alginate microcapsules, although 10(7) in the latter formulation conferred protection in terms of increasing body weight after challenge and a smaller lung to body weight ratio at necropsy. These results highlight the potential for lipid, rather than alginate, -based vaccine formulations as suitable delivery vehicles for an oral BCG vaccine in badgers.

  10. Compounded Apixaban Suspensions for Enteral Feeding Tubes.

    PubMed

    Caraballo, Maria L; Donmez, Seda; Nathan, Kobi; Zhao, Fang

    2017-07-01

    Objective: There is limited information on compounded apixaban formulations for administration via enteral feeding tubes. This study was designed to identify a suitable apixaban suspension formulation that is easy to prepare in a pharmacy setting, is compatible with commonly used feeding tubes, and has a beyond-use date of 7 days. Methods: Apixaban suspensions were prepared from commercially available 5-mg Eliquis tablets. Several vehicles and compounding methods were screened for ease of preparation, dosage accuracy, and tube compatibility. Two tubing types, polyurethane and polyvinyl chloride, with varying lengths and diameters, were included in the study. They were mounted on a peg board during evaluation to mimic the patient body position. A 7-day stability study of the selected formulation was also conducted. Results: Vehicles containing 40% to 60% Ora-Plus in water all exhibited satisfactory flowability through the tubes. The mortar/pestle compounding method was found to produce more accurate and consistent apixaban suspensions than the pill crusher or crushing syringe method. The selected formulation, 0.25 mg/mL apixaban in 50:50 Ora-Plus:water, was compatible with both tubing types, retaining >98% drug in posttube samples. The stability study also confirmed that this formulation was stable physically and chemically over 7 days of storage at room temperature. Conclusions: A suitable apixaban suspension formulation was identified for administration via enteral feeding tubes. The formulation consisted of 0.25 mg/mL apixaban in 50:50 Ora-Plus:water. The stability study results supported a beyond-use date of 7 days at room temperature.

  11. Pharmacokinetic variability of long-acting stimulants in the treatment of children and adults with attention-deficit hyperactivity disorder.

    PubMed

    Ermer, James C; Adeyi, Ben A; Pucci, Michael L

    2010-12-01

    Methylphenidate- and amfetamine-based stimulants are first-line pharmacotherapies for attention-deficit hyperactivity disorder, a common neurobehavioural disorder in children and adults. A number of long-acting stimulant formulations have been developed with the aim of providing once-daily dosing, employing various means to extend duration of action, including a transdermal delivery system, an osmotic-release oral system, capsules with a mixture of immediate- and delayed-release beads, and prodrug technology. Coefficients of variance of pharmacokinetic measures can estimate the levels of pharmacokinetic variability based on the measurable variance between different individuals receiving the same dose of stimulant (interindividual variability) and within the same individual over multiple administrations (intraindividual variability). Differences in formulation clearly impact pharmacokinetic profiles. Many medications exhibit wide interindividual variability in clinical response. Stimulants with low levels of inter- and intraindividual variability may be better suited to provide consistent levels of medication to patients. The pharmacokinetic profile of stimulants using pH-dependent bead technology can vary depending on food consumption or concomitant administration of medications that alter gastric pH. While delivery of methylphenidate with the transdermal delivery system would be unaffected by gastrointestinal factors, intersubject variability is nonetheless substantial. Unlike the beaded formulations and, to some extent (when considering total exposure) the osmotic-release formulation, systemic exposure to amfetamine with the prodrug stimulant lisdexamfetamine dimesylate appears largely unaffected by such factors, likely owing to its dependence on systemic enzymatic cleavage of the precursor molecule, which occurs primarily in the blood involving red blood cells. The high capacity but as yet unidentified enzymatic system for conversion of lisdexamfetamine dimesylate may contribute to its consistent pharmacokinetic profile. The reasons underlying observed differential responses to stimulants are likely to be multifactorial, including pharmacodynamic factors. While the use of stimulants with low inter- and intrapatient pharmacokinetic variability does not obviate the need to titrate stimulant doses, stimulants with low intraindividual variation in pharmacokinetic parameters may reduce the likelihood of patients falling into subtherapeutic drug concentrations or reaching drug concentrations at which the risk of adverse events increases. As such, clinicians are urged both to adjust stimulant doses based on therapeutic response and the risk for adverse events and to monitor patients for potential causes of pharmacokinetic variability.

  12. Development of a new esomeprazole delayed release gastro-resistant pellet formulation with improved storage stability.

    PubMed

    Barmpalexis, Panagiotis; Grypioti, Agni

    2018-06-01

    This study describes the development of a new esomeprazole (ESO) delayed release gastro-resistant formulation with improved storage stability. A three-step (drug-, sub(seal)- and enteric-) coating process was employed with the aid of a fluid bed coater. Several formulation factors (namely, size and quantity of starting non-pareil sugar spheres, binder quantity during drug-layering, sub(seal)-coating polymer type, and quantity and enteric coating quantity) were evaluated and the whole process was modeled with the aid of feed-forward back-propagation artificial neural networks (ANNs). Results showed that the selection of small-sized starting spheres (45/60 mesh size) leads to pellet agglomeration, while as sub(seal)-coating weight gain increases a reduction in ESO dissolution rate is observed. The enteric-coating applied (Eudragit L30D-55) showed good gastro-resistant performance in both 0.1 N HCl and pH 4.5 media, while immediate release profiles with more than 85% of ESO being released in less than 30 min were obtained. The effect of cellulose-based sub(seal)-coating polymers, (namely, hydroxypropyl cellulose and hydroxypropylmethyl cellulose) on formulation's storage stability at 40 ± 2 °C/75 ± 5%RH indicated that only hydroxypropylmethyl cellulose was able to stabilize ESO delayed-release formulations in terms of assay, dissolution, impurities, and gastro-resistance performance. Finally, scanning electron microscopy (SEM) analysis revealed smooth and homogeneous external surface/coating layers in all three levels (drug-, sub(seal)-, and enteric- coating), while x-ray diffraction showed no polymorphic transformations.

  13. Field Trials of Attenuated Salmonella Typhi Live Oral Vaccine TY21A in Liquid and Enteric-Coated Capsule Formulations in Santiago, Chile

    DTIC Science & Technology

    1990-06-01

    inactive piacebo, children in the control group received viable Lactobacillus acidophilus because some experimental data suggest that L. acidophilus may...was the enteric-coating used to make the capsules acid-resistant. Such capsules, each containing 1-3 x 109 viable vaccine (or Lactobacillus ) organisms...formulation of vaccine (or of the Lactobacillus control preparation) consisted of two aluminum foil packets, one containing lyophilized vaccine (or

  14. Improving T Cell Expansion with a Soft Touch

    PubMed Central

    Lambert, Lester H.; Goebrecht, Geraldine K.E.; De Leo, Sarah E.; O’Connor, Roddy S.; Nunez-Cruz, Selene; Li, Tai-De; Yuan, Jinglun; Milone, Michael C.; Kam, Lance C.

    2017-01-01

    Protein-coated microbeads provide a consistent approach for activating and expanding populations of T cells for immunotherapy, but don’t fully capture the properties of antigen presenting cells. In this report, we enhance T cell expansion by replacing the conventional, rigid bead with a mechanically soft elastomer. Polydimethylsiloxane (PDMS) was prepared in a microbead format and modified with activating antibodies to CD3 and CD28. Three different formulations of PDMS provided an extended proliferative phase in both CD4+-only and mixed CD4+/CD8+ T cell preparations. CD8+ T cells retained cytotoxic function, as measured by a set of biomarkers (perforin production, LAMP2 mobilization, and IFN-γ secretion) and an in vivo assay of targeted cell killing. Notably, PDMS beads presented a nanoscale polymer structure and higher rigidity than associated with conventional bulk material. These data suggest T cells respond to this higher rigidity, indicating an unexpected effect of curing conditions. Together, these studies demonstrate that adopting mechanobiology ideas into the bead platform can provide new tools for T cell-based immunotherapy. PMID:28122453

  15. Dissipative structures, machines, and organisms: A perspective

    NASA Astrophysics Data System (ADS)

    Kondepudi, Dilip; Kay, Bruce; Dixon, James

    2017-10-01

    Self-organization in nonequilibrium systems resulting in the formation of dissipative structures has been studied in a variety of systems, most prominently in chemical systems. We present a study of a voltage-driven dissipative structure consisting of conducting beads immersed in a viscous medium of oil. In this simple system, we observed remarkably complex organism-like behavior. The dissipative structure consists of a tree structure that spontaneously forms and moves like a worm and exhibits many features characteristic of living organisms. The complex motion of the beads driven by the applied field, the dipole-dipole interaction between the beads, and the hydrodynamic flow of the viscous medium result in a time evolution of the tree structure towards states of lower resistance or higher dissipation and thus higher rates of entropy production. The resulting end-directed evolution manifests as the tree moving to locations seeking higher current, the current that sustains its structure and dynamics. The study of end-directed evolution in the dissipative structure gives us a means to distinguish the fundamental difference between machines and organisms and opens a path for the formulation of physics of organisms.

  16. A lysozyme and magnetic bead based method of separating intact bacteria.

    PubMed

    Diler, Ebru; Obst, Ursula; Schmitz, Katja; Schwartz, Thomas

    2011-07-01

    As a response to environmental stress, bacterial cells can enter a physiological state called viable but noncultivable (VBNC). In this state, bacteria fail to grow on routine bacteriological media. Consequently, standard methods of contamination detection based on bacteria cultivation fail. Although they are not growing, the cells are still alive and are able to reactivate their metabolism. The VBNC state and low bacterial densities are big challenges for cultivation-based pathogen detection in drinking water and the food industry, for example. In this context, a new molecular-biological separation method for bacteria using point-mutated lysozymes immobilised on magnetic beads for separating bacteria is described. The immobilised mutated lysozymes on magnetic beads serve as bait for the specific capture of bacteria from complex matrices or water due to their remaining affinity for bacterial cell wall components. Beads with bacteria can be separated using magnetic racks. To avoid bacterial cell lysis by the lysozymes, the protein was mutated at amino acid position 35, leading to the exchange of the catalytic glutamate for alanine (LysE35A) and glutamine (LysE35Q). As proved by turbidity assay with reference bacteria, the muramidase activity was knocked out. The mutated constructs were expressed by the yeast Pichia pastoris and secreted into expression medium. Protein enrichment and purification were carried out by SO(3)-functionalised nanoscale cationic exchanger particles. For a proof of principle, the proteins were biotinylated and immobilised on streptavidin-functionalised, fluorescence dye-labelled magnetic beads. These constructs were used for the successful capture of Syto9-marked Microccocus luteus cells from cell suspension, as visualised by fluorescence microscopy, which confirmed the success of the strategy.

  17. Impact of Enteral Nutrition with an Immunomodulating Diet Enriched with Hydrolyzed Whey Peptide on Infection After Liver Transplantation.

    PubMed

    Kamo, Naoko; Kaido, Toshimi; Hamaguchi, Yuhei; Uozumi, Ryuji; Okumura, Shinya; Kobayashi, Atsushi; Shirai, Hisaya; Yagi, Shintaro; Okajima, Hideaki; Uemoto, Shinji

    2018-05-21

    Infection is a leading cause of death after liver transplantation (LT). Therefore, prevention of infection is crucial for improving outcomes after LT. We examined the impact of early enteral nutrition with an immunomodulating diet (IMD) enriched with hydrolyzed whey peptide (HWP) formulation on infection after living donor LT (LDLT), focusing on sarcopenia. This study enrolled 279 consecutive patients who underwent primary LDLT at our institute between January 2008 and April 2015. Early enteral nutrition with the IMD enriched with HWP formulation and a conventional elemental diet were started within the first 24 h after surgery for 164 (IMD-HWP) and 115 (conventional) patients. Sequential changes in nutritional parameters, and the incidences of acute cellular rejection (ACR) and bacteremia were compared between the IMD-HWP and control groups. The comparison was made between those members of each group that did or did not exhibit sarcopenia. Risk factors for post-transplant bacteremia were also assessed. Postoperative nutritional parameters and the incidence of ACR were comparable between the groups, except for the prealbumin level. The incidence of bacteremia was significantly lower in the IMD-HWP group, and among patients without sarcopenia in the IMD-HWP group compared with the conventional group (24.4 vs. 41.7%; P = 0.002 and 20.8 vs. 39.0%; P = 0.040, respectively). Independent risk factor for bacteremia comprised bleeding ≥10,000 mL (P = 0.025). In contrast, enteral nutrition without HWP formulation was not significantly associated with bacteremia. However, enteral nutrition without HWP formulation (P = 0.080), MELD scores (P = 0.097), and ABO incompatibility (P = 0.088) showed a trend toward increased incidence of bacteremia, although they did not reach statistical significance in the multivariate analysis. Postoperative immunonutrition with an IMD enriched with HWP formulation was closely involved with post-transplant bacteremia.

  18. Formulation development and release studies of indomethacin suppositories.

    PubMed

    Sah, M L; Saini, T R

    2008-01-01

    Indomethacin suppositories were prepared by using water-soluble and oil soluble suppository bases, and evaluated for in vitro release by USP I and modified continuous flow through bead bed apparatus. Effect of the Tween 80 (1% and 5%) was further studied on in vitro release of the medicament. Release rate was good in water-soluble suppositories bases in comparison to oil soluble suppositories bases. Release was found to be greater in modified continuous flow through bead bed apparatus. When surfactant was used in low concentration then release rate was much greater, as compared to high concentration. When stability studies were performed on the prepared indomethacin suppositories it was found that suppositories made by water-soluble base had no significant changes while suppositories prepared by oil soluble bases, had some signs of instability.

  19. Enteral and Parenteral Nutrition in the Perioperative Period: State of the Art

    PubMed Central

    Abunnaja, Salim; Cuviello, Andrea; Sanchez, Juan A.

    2013-01-01

    Nutritional support of surgical and critically ill patients has undergone significant advances since 1936 when Studley demonstrated a direct relationship between pre-operative weight loss and operative mortality. The advent of total parenteral nutrition followed by the extraordinary progress in parenteral and enteral feedings, in addition to the increased knowledge of cellular biology and biochemistry, have allowed clinicians to treat malnutrition and improve surgical patient’s outcomes. We reviewed the literature for the current status of perioperative nutrition comparing parenteral nutrition with enteral nutrition. In a surgical patient with established malnutrition, nutritional support should begin at least 7–10 days prior to surgery. Those patients in whom eating is not anticipated beyond the first five days following surgery should receive the benefits of early enteral or parenteral feeding depending on whether the gut can be used. Compared to parenteral nutrition, enteral nutrition is associated with fewer complications, a decrease in the length of hospital stay, and a favorable cost-benefit analysis. In addition, many patients may benefit from newer enteral formulations such as Immunonutrition as well as disease-specific formulations. PMID:23429491

  20. Evaluation of an Extended-Release, Abuse-Deterrent, Microsphere-in-Capsule Analgesic for the Management of Patients with Chronic Pain With Dysphagia (CPD).

    PubMed

    Fleming, Alison B; Carlson, Douglas R; Varanasi, Ravi K; Grima, Michael; Mayock, Stephen P; Saim, Said; Kopecky, Ernest A

    2016-03-01

    Patients who have chronic pain with dysphagia (difficulty swallowing) (CPD) often have difficulty taking oral medication and, as such, alter their medications by crushing or chewing in an attempt to make it easier to swallow. Such manipulation of currently marketed, extended-release (ER) opioid analgesics can significantly alter the pharmacokinetic (PK) properties of the formulations, resulting in poor treatment outcome or serious adverse events. There is an unmet medical need for oral ER opioid formulations suitable for patients with CPD. The primary objectives of this study were to conduct in vitro studies to evaluate alternate means of administration of a new, extended-release (ER), abuse-deterrent, microsphere-in-capsule formulation of oxycodone for patients with CPD. Specifically, these studies investigated the in vitro equivalence of drug release rates from Oxycodone DETERx® ER intact capsules (control condition) and administration via alternate modes-opening the capsule and sprinkling the microspheres onto soft foods or administration through enteral tubes. Secondary objectives were to compare alternate modes of administration of Oxycodone DETERx® to a commercially available ER-morphine product. Soft food study: Oxycodone DETERx® microspheres were sprinkled onto and mixed with several soft foods (ie, applesauce, vanilla pudding, strawberry jam, yogurt, and vanilla ice cream); the effect of drug contact time (0, 30, and 60 minutes) on drug release was studied. Enteral tube study: Oxycodone DETERx® microspheres were administered through varying sizes of nasogastric (10 and 12 Fr.) tubes and a 16 Fr. gastrostomy tube using 5 different delivery vehicles (ie, water, liquid nutritional feeds [Jevity®, Ensure®], and milk [whole milk and 2% milk]). Drug release rate was characterized using a standard in vitro dissolution methodology; dissolution of intact Oxycodone DETERx® capsules served as the control for both the soft food and enteral tube studies. Oxycodone concentration was measured using a standardized high-performance liquid chromatography (HPLC) assay. Similarity factor (f2) analysis was used to compare similarity of the dissolution profiles of test and control conditions. The mean dissolution profile of Oxycodone DETERx® microspheres sprinkled onto and mixed with each of the soft foods were similar (f2 > 50) to that of the control. Study drug-food contact time did not impact dissolution profiles. The dissolution data obtained from Oxycodone DETERx® microspheres passed through enteral feeding tubes of varying sizes were similar (f2 > 50) to that of the control. Unlike a marketed morphine sulfate ER pellet formulation, Oxycodone DETERx® did not clog any of the studied enteral tubes. A new ER, abuse-deterrent, microsphere-in-capsule formulation of oxycodone can be administered by sprinkling onto soft food without affecting the drug release profile of the formulation. The formulation can also be administered directly via enteral tubes without affecting drug release and without clogging enteral tubes. Oxycodone DETERx® may offer physicians and patients with CPD an alternate treatment option, especially in those patients who have dysphagia or an aversion to swallowing monolithic tablet/capsule formulations and for whom analgesic patches or other opioid formulations are not a viable therapeutic option. © 2015 World Institute of Pain.

  1. Pharmacokinetic Studies of Gel System Containing Ibuprofen Solid Nanoparticles.

    PubMed

    Nagai, Noriaki; Tanino, Tadatoshi; Ito, Yoshimasa

    2016-12-01

    In the therapy of rheumatoid arthritis, ibuprofen (IBU) is widely used; however, it has been limited the clinical use by its systemic side effect, such as gastrointestinal lesions. Therefore, we prepared topical gel ointment used IBU solid nanoparticles (IBU nano -gel formulation). In addition, we demonstrated their anti-inflammatory effect by using arthritis model rat (adjuvant-induced arthritis rat, AA rat). The gel formulations were prepared using additives (Carbopol 934, 2-hydroxypropyl-β-cyclodextrin and methylcellulose) and bead mill-method. The IBU particle size in the IBU nano -gel formulation was 208 nm. The increase in inflammation of the hind feet of AA rats was attenuated by the treatment with the IBU nano -gel formulation, and preventive effect was higher than that of a gel formulation containing IBUmicroparticles (IBU micro -gel formulation, mean particle size 85.4 μm); the accumulation and permeability through the skin of IBU from the IBU nano -gel formulation were significantly larger in comparison with the IBU micro -gel formulation. Further, no gastrointestinal lesions were observed in AA rats following the repetitive administration of the 5% IBU nano -gel formulation (0.30 g) for 42 days (once a day). These results suggest that the dermal application of IBU-nanoparticles provide effective and efficient therapy that spares patients from unwanted side effects.

  2. Preparation and evaluation of enteric coated tablets of hot melt extruded lansoprazole

    PubMed Central

    Alsulays, Bader B.; Kulkarni, Vijay; Alshehri, Sultan M.; Almutairy, Bjad K.; Ashour, Eman A.; Morott, Joseph T.; Alshetaili, Abdullah S.; Park, Jun-Bom; Tiwari, Roshan V.; Repka, Michael A.

    2017-01-01

    The objective of this work was to use hot-melt extrusion (HME) technology to improve the physiochemical properties of lansoprazole (LNS) to prepare stable enteric coated LNS tablets. For the extrusion process, we chose Kollidon® 12 PF (K12) polymeric matrix. Lutrol® F 68 was selected as the plasticizer and magnesium oxide (MgO) as the alkalizer. With or without the alkalizer, LNS at 10% drug load was extruded with K12 and F68. LNS changed to the amorphous phase and showed better release compared to that of the pure crystalline drug. Inclusion of MgO improved LNS extrudability and release and resulted in over 80% drug release in the buffer stage. Hot-melt extruded LNS was physically and chemically stable after 12 months of storage. Both formulations were studied for compatibility with Eudragit® L 100-55. The optimized formulation was compressed into a tablet followed by coating process utilizing a pan coater using L 100-55 as an enteric coating polymer. In a two-step dissolution study, the release profile of the enteric coated LNS tablets in the acidic stage was less than 10% of the LNS, while that in the buffer stage was more than 80%. Drug content analysis revealed the LNS content to be 97%, indicating the chemical stability of the enteric coated tablet after storage for 6 months. HME, which has not been previously used for LNS, is a valuable technique to reduce processing time in the manufacture of enteric coated formulations of an acid-sensitive active pharmaceutical ingredient as compared to the existing methods. PMID:27486807

  3. Apparatus and method for the production of gel beads containing a biocatalyst

    DOEpatents

    Scott, C.D.; Scott, T.C.; Davison, B.H.

    1998-01-27

    An apparatus and method are disclosed for the large-scale and continuous production of gel beads containing a biocatalyst. The apparatus is a columnar system based on the chemical cross-linking of hydrocolloidal gels that contain and immobilize a biocatalyst, the biocatalyst being a microorganism or an enzyme. Hydrocolloidal gels, such as alginate, carrageenan, and a mixture of bone gelatin and modified alginate, provide immobilization matrices that can be used to entrap and retain the biocatalyst while allowing effective contact with substrates and release of products. Such immobilized biocatalysts are generally formulated into small spheres or beads that have high concentrations of the biocatalyst within the gel matrix. The columnar system includes a gel dispersion nozzle submerged in a heated non-interacting liquid, typically an organic liquid, that is immiscible with water to allow efficient formation of spherical gel droplets, the non-interacting liquid having a specific gravity that is less than water so that the gel droplets will fall through the liquid by the force of gravity. The heated non-interacting liquid is in direct contact with a chilled upflowing non-interacting liquid that will provide sufficient residence time for the gel droplets as they fall through the liquid so that they will be cooled below the gelling temperature and form solid spheres. The upflowing non-interacting liquid is in direct contact with an upflowing temperature-controlled aqueous solution containing the necessary chemicals for cross-linking or fixing of the gel beads to add the necessary stability. The flow rates of the two liquid streams can be varied to control the proper residence time in each liquid section to accommodate the production of gel beads of differing settling velocities. A valve is provided for continuous removal of the stabilized gel beads from the bottom of the column. 1 fig.

  4. Dirt-binding particles consisting of hydrogenated castor oil beads constitute a nonirritating alternative for abrasive cleaning of recalcitrant oily skin contamination in a three-step programme of occupational skin protection.

    PubMed

    Mahler, V; Erfurt-Berge, C; Schiemann, S; Michael, S; Egloffstein, A; Kuss, O

    2010-04-01

    In occupational fields with exposure to grease, oil, metal particles, coal, black lead or soot, cleansing formulations containing abrasive bodies (e.g. refined walnut shell, corn, wood, plastic or pumice) are used. These may constitute an irritant per se. As an alternative, hydrogenated castor oil (also known as castor wax) beads have been developed as dirt-binding particles. A polar surface contributes to their mechanical cleaning effects in removal of oily grime. Standardized examination of the in vivo effects upon the skin barrier of castor wax beads in comparison with abrasive bodies and pure detergent. Three cleansing preparations - (i) detergent, (ii) detergent containing castor wax beads, (iii) detergent containing walnut shell powder - were each repetitively applied in vivo (four times daily for 3 weeks), mimicking workplace conditions, in 30 healthy volunteers (15 with and 15 without an atopic skin diathesis) and compared vs. (iv) no treatment. The treatment effects upon the skin barrier were monitored by repeated measurements of functional parameters [transepidermal water loss (TEWL), redness] and surface topography. After a 3-week treatment, a significant global treatment effect (P < 0.0001) was found in the atopic group concerning TEWL as indicator for barrier function. A significantly higher TEWL and increasing erythema in the area treated with detergent containing walnut shell powder reflected its irritant effect compared with castor wax beads dispensed in the identical detergent. Cleaning properties of the two formulas were comparably superior to detergent alone. Castor wax beads constitute a novel nonirritating alternative for abrasive cleaning of recalcitrant oily skin contamination appropriate for individuals with an atopic skin diathesis in a three-step programme of occupational skin protection. As the skin barrier may additionally be influenced by the composition of dirt and use of skin protection and skin care measures under real workplace conditions, this component may now be used and examined further in different occupations.

  5. The Preparation of Capsaicin-Chitosan Microspheres (CCMS) Enteric Coated Tablets

    PubMed Central

    Chen, Jian; Huang, Gui-Dong; Tan, Si-Rong; Guo, Jiao; Su, Zheng-Quan

    2013-01-01

    This study aimed to research the preparation and content determination of capsaicin-chitosan microspheres (CCMS) enteric coated tablets. The core tablets were prepared with the method of wet granulation. Nine formulae were designed to determine the optimal formula of the core tablet. Eudragit L100 was used to prepare the CCMS enteric-coated tablets. The effect of enteric coated formulation variables such as content of talc (10%, 25% and 40%), plasticisers (TEC and DBS), dosage of plasticiser (10%, 20% and 30%) and coating weight (2%, 3% and 5%) were evaluated for drug release characteristics. The in vitro release was studied using 0.1 N HCl and pH 6.8 phosphate buffer. Enteric coated tablets without ruptures or swelling behaviour over 2 h in 0.1 N HCl indicated that these tablets showed acid resistance. The accumulated release rate in phosphate buffer (pH 6.8) revealed that the prepared tablets were able to sustain drug release into the intestine and a first-order release was obtained for capsaicin. This research is the first report of the preparation and content determination of CCMS enteric coated tablets. The sustained release behavior of enteric coated formulations in pH 6.8 phosphate buffer demonstrated that it would be a potential drug delivery platform for sustained delivery of gastric irritant drugs. PMID:24351818

  6. Design and evaluation of novel topical formulation with olive oil as natural functional active.

    PubMed

    Mota, Ana Henriques; Silva, Catarina Oliveira; Nicolai, Marisa; Baby, André; Palma, Lídia; Rijo, Patrícia; Ascensão, Lia; Reis, Catarina Pinto

    2017-07-03

    Currently, the innovative skin research is focused on the development of novel topical formulations loaded with natural functional actives. The health benefits of olive oil are unsurpassed and many others are revealed as research studies allow the understanding of its unlimited properties. Olive oil has a protective toning effect on skin, but it is not transported effectively into its layers. Aiming the development of a cosmetic formulation for skin photoprotection and hydration, we have prepared and characterized macro-sized particles, made of a hydrogel polymer, loaded with olive oil. Alginate beads were uniform in shape, with minimal oil leakage, offering interesting prospects for encapsulation of lipophilic and poorly stable molecules, like olive oil. In vitro photoprotection and in vivo tolerance tests were in favor of this application. Thus, this study suggests that the incorporation of the olive oil-loaded particles into a cream formulation provides strong moisturizing properties and a photoprotective potential, when applied to healthy subjects.

  7. Ca2+ Responses in Enteric Glia are Mediated by Connexin-43 Hemichannels and Modulate Colonic Transit in Mice

    PubMed Central

    Fried, David; Gomez-Suarez, Roberto A.; Leinninger, Gina M.; Sévigny, Jean; Parpura, Vladimir; Gulbransen, Brian D.

    2014-01-01

    Background & Aims In the enteric nervous system, neurotransmitters initiate changes in Ca2+ (Ca2+ responses) in glia, but it is not clear how this process affects intestinal function. We investigated whether Ca2+-mediated responses in enteric glial are required to maintain gastrointestinal function. Methods We used in situ Ca2+ imaging to monitor glial Ca2+ responses, which were manipulated with pharmacologic agents or via glia-specific disruption of the gene encoding connexin-43 (Cx43) (hGFAP::creERT2+/−/Cx43f/f mice). Gastrointestinal function was assessed based on pellet output, total gut transit, colonic bead expulsion, and muscle tension recordings. Proteins were localized and quantified by immunohistochemistry, immunoblot, and reverse transcription PCR analyses. Results Ca2+ responses in enteric glia of mice were mediated by Cx43 hemichannels. Cx43 immunoreactivity was confined to enteric glia within the myenteric plexus of the mouse colon; the Cx43 inhibitors carbenoxolone and 43Gap26 inhibited the ability of enteric glia to propagate Ca2+ responses. In vivo attenuation of Ca2+ responses in the enteric glial network slowed gut transit overall and delayed colonic transit—these changes are also observed during normal aging. Altered motility with increasing age was associated with reduced glial Ca2+-mediated responses and changes in glial expression of Cx43 mRNA and protein. Conclusions Ca2+-mediated responses in enteric glia regulate gastrointestinal function in mice. Altered intercellular signaling between enteric glia and neurons might contribute to motility disorders. PMID:24211490

  8. Horizontal Magnetic Tweezers for Micromanipulation of Single DNA-Protein Complexes

    NASA Astrophysics Data System (ADS)

    McAndrew, C.; Sarkar, A.; Mehl, P.

    2011-03-01

    We report on the development of a new magnetic force transducer or ``tweezer'' that can apply pico-Newton forces on single DNA molecules in the focus plane. Since the changes in DNA's end-to-end extension are coplanar with the pulling force, there is no need to continually refocus. The DNA constructs (λ -DNA end labeled with a 3 μ m polystyrene bead and a 2.8 μ m paramagnetic sphere) and appropriate buffer are introduced to a custom built 400 μ L to 650 μ L closed cell. This closed cell isolates our sample and produces low-noise force and extension measurements. This chamber rests on a stage fixed to a three axis micromanipulator. Entering the flat chamber are two micropipettes, a 2.5 μ m id pipette for aspirating the polystyrene bead and a 20 μ m id pipette for injecting proteins of interest. The suction and the injection pipettes are rigidly mounted to a hydraulic, three-axis micromanipulator. DNA-bead constructs, once introduced to the chamber, can be located by moving the stage over the objective. We have shown that we can easily and reputably find, capture, and manipulate single molecules of DNA within a force range of 0.1pN to 100pN.

  9. Development and characterization of enteric-coated immediate-release pellets of aceclofenac by extrusion/spheronization technique using kappa-carrageenan as a pelletizing agent.

    PubMed

    Kilor, Vaishali A; Sapkal, Nidhi P; Awari, Jasmine G; Shewale, Bharti D

    2010-03-01

    In the present study, an attempt was made to prepare immediate-release enteric-coated pellets of aceclofenac, a poorly soluble nonsteroidal anti-inflammatory drug that has a gastrointestinal intolerance as its serious side effect. Formulation of enteric-coated pellets with improved solubility of aceclofenac could address both of these problems. To achieve these goals, pellets were prepared by extrusion-spheronization method using pelletizing agents that can contribute to the faster disintegration and thereby improve the solubility of the drug. Different disintegrants like beta-cyclodextrin, kollidon CL, Ac-Di-Sol, and sodium starch glycolate were tried in order to further improve disintegration time. The pellets were characterized for drug content, particle size distribution, flow properties, infrared spectroscopy, surface morphology, disintegration rate, and dissolution profile. The formulations, which showed best disintegration and dissolution profiles, were coated with Eudragit L100-55, an enteric-coated polymer which does not dissolve at gastric pH but dissolves at intestinal pH, releasing the drug immediately in the dissolution medium. The optimized enteric-coated formulation containing 20% kappa-carrageenan, lactose, and sodium starch glycolate as a disintegrant did inhibit the release of the drug for 2 h in 0.1 N HCl, whereas 87% of the drug was released within 45 min. The improvement was substantial when it was compared with solubility of pure drug under the same conditions. Thus, dissolution profiles suggested that combination of kappa-carrageenan and sodium starch glycolate resulted into fast-disintegrating, immediate-release pellets, overcoming the bioavailability problem of the poorly soluble drug, aceclofenac, and enteric coating of these pellets avoids the exposure of aceclofenac to ulcer-prone areas of the gastrointestinal tract.

  10. Characterization and relevance of physicochemical interactions among components of a novel multiparticulate formulation for colonic delivery.

    PubMed

    Singh, Brahma N; Kim, Kwon H

    2007-08-16

    The primary objective of this study was to investigate potential interactions among a model drug (azathioprine; AZA), polymers and a divalent metal ion, which were utilized in the development of a novel multiparticulate formulation for colonic delivery. The approach involved preparation of beads by ionotropic gelation of deacylated gellan gum (DGG) in the presence of Ca(2+) ions, followed by coating with Eudragit S-100. Various possible physicochemical interactions among formulation components were characterized by DSC, FT-IR, XRPD, (1)H-NMR, and an isothermal stress test. Results of isothermal stress testing indicated that there was no significant interaction of AZA with DGG and Eudragit S-100. However, results of DSC and XRPD studies suggested that there could be interactions between AZA and DGG, and ionotropic gelation can affect the physical state of AZA, which may have implications for drug release characteristics and, physical and chemical stability. The results of FT-IR studies were suggestive of interactions of DGG with AZA and Eudragit S-100, and provided evidence for interactions of AZA and DGG with Ca(2+) ions. The electrostatic interaction of DGG with Ca(2+) was also supported by results of DSC studies while that between AZA and Ca(2+) was confirmed by (1)H-NMR studies. This study, to our knowledge, is first reported investigation in which the unique thermal property of gellan gum gels, and possible interactions between a drug and counter ions of an ionotropic agent have been demonstrated through bead characterization studies. The formation of AZA-Ca(2+) complex could have an impact on drug release kinetics, product stability and clinical efficacy for treatment of inflammatory bowel diseases or other diseases, which merit further investigation.

  11. A new esomeprazole packet (sachet) formulation for suspension: in vitro characteristics and comparative pharmacokinetics versus intact capsules/tablets in healthy volunteers.

    PubMed

    Bladh, Nina; Blychert, Eva; Johansson, Karin; Backlund, Anna; Lundin, Christina; Niazi, Mohammad; Pettersson, Gunilla; Fjellman, Mia

    2007-04-01

    A packet (sachet) formulation of esomeprazole for suspension has been developed for use in patients who have difficulty swallowing. This article reports the in vitro characteristics of the new esomeprazole formulation, including stability in suspension and suitability for administration orally or via enteral tubes. It also describes the pharmacokinetic profile of the esomeprazole 40-mg packet compared with that of existing solid dosage forms (capsules and tablets) in a clinical bioequivalence study. The stability in suspension of the packet formulation was assessed after reconstitution at various strengths (2.5, 10, and 40 mg) and a different pH (3.4-5.0) in strength-appropriate volumes of water held at temperatures ranging from 5 degrees C to 37 degrees C for up to 60 minutes. Suitability for oral administration was examined in terms of reconstitution time and the actual dose delivered after simulated oral administration, as well as in terms of the actual dose delivered by enteral tubes ranging in diameter from 6 to 20 Fr. Chemical stability and suspension characteristics were also analyzed using alternative reconstitution vehicles (applesauce, apple juice, and orange juice). The comparative pharmacokinetics of the packet, capsule, and tablet formulations of esomeprazole were evaluated in a randomized, open-label, 3-way crossover study in healthy volunteers, who received single 40-mg doses of each formulation. Bioequivalence was assumed if the 90% CIs for the ratios of the geometric mean AUC and CmaX were between 0.80 and 1.25. Reversephase liquid chromatography with ultraviolet detection was used to assess the esomeprazole content and/or degradation products of esomeprazole in the tests for in-suspension stability, dose delivery, and acid resistance. Normal-phase liquid chromatography was used to assess the esomeprazole content of the plasma samples in the bioequivalence study. At the pH and temperature ranges investigated, the packet formulation was stable for up to 60 minutes after reconstitution. Chemical degradation was low (<0.1%) for all reconstitution vehicles investigated. Reconstitution time was 2 minutes with water and 9 to 10 minutes with apple or orange juice. Dose delivery was >/=98% after simulated oral administration and was generally >/=96% after administration via enteral tubes. Ninety-six healthy volunteers (56 women, 40 men; mean age, 24.9 years; mean weight, 68.9 kg) participated in the randomized, crossover, comparative pharmacokinetic study of the packet and capsule/tablet formulations. The estimated ratios of the geometric mean AUC and C(max) for the packet:capsule and packet: tablet formulations were 0.98 (90% CI, 0.93-1.03) and 0.99 (90% CI, 0.94-1.04), respectively. In these analyses, the packet (sachet) formulation of esomeprazole was chemically stable in suspension and when administered orally and via enteral tubes. The formulation had a short reconstitution time, remaining fully dispersed in water for at least 30 minutes, and was dispersed in applesauce, apple juice, or orange juice without compromising its stability or dispersion characteristics. The packet formulation met the regulatory definition for bioequivalence to the tablet and capsule formulations.

  12. Compatibility of epirubicin-loaded DC bead™ with different non-ionic contrast media.

    PubMed

    Sarakbi, Iman; Krämer, Irene

    2016-12-01

    The aim of this study was to determine the compatibility of epirubicin-loaded DC bead™ with different non-ionic contrast media over a period of seven days when stored light protected under refrigerated conditions. DC bead™ (2 ml) (Biocompatibles UK Ltd) of the bead size 70-150 µm ( = DC bead M1) or bead size 100-300 µm were loaded with 75 mg epirubicin powder formulation (Farmorubicin® dissolved in 3 ml water for injection to a concentration of 25 mg/ml) or 76 mg epirubicin injection solution (Epimedac® 2 mg/ml) within 2 h or 6 h, respectively. After removal of the excess solution, the epirubicin-loaded beads were mixed in polypropylene syringes with an equal volume (∼1.5 ml) of contrast media, i.e. Accupaque™ 300 (Nycomed Inc.), Imeron® 300 (Bracco S.p.A), Ultravist® 300 (Bayer Pharma AG), Visipaque™ 320 (GE Healthcare) and agitated in a controlled manner to get a homogenous suspension. Syringes with loaded beads in contrast media were stored protected from light under refrigeration (2-8℃). Compatibility was determined by measuring epirubicin concentrations in the suspensions in triplicate on day 0, 1, and 7. A reversed phase high-performance liquid chromatography assay with ultraviolet detection was utilized to analyze the concentration and purity of epirubicin. Mixing of epirubicin-loaded beads with different non-ionic contrast media released 0.1-0.5% of epirubicin over a period of 24 h, irrespectively, of the DC bead™ size or type of contrast media. No further elution or degradation was observed after seven days when the admixtures were stored protected from light under refrigeration. Compatibility of epirubicin-loaded DC bead™ with an equal volume of different contrast media in polypropylene syringes is given over a period of seven days. Due to a maximum elution of 0.1-0.5% of epirubicin from loaded DC bead™, admixtures with contrast media can be prepared in advance in centralized cytotoxic preparation units. Microbiological aspects have to be considered when determining the expiration date of the product. © The Author(s) 2015.

  13. Emulsifier for intravenous cyclosporin inhibits neurite outgrowth, causes deficits in rapid axonal transport and leads to structural abnormalities in differentiating N1E.115 neuroblastoma.

    PubMed

    Brat, D J; Windebank, A J; Brimijoin, S

    1992-05-01

    The emulsifier for cyclosporin in clinical i.v. formulations, Cremophor EL, has recently come into question as a possible source of neurotoxic side effects in immunosuppressant therapy. To address this issue we tested Cremophor EL and cyclosporin on an in vitro neuronal model, the differentiating N1E.115 neuroblastoma cell. In terms of effects on elaboration of neurites by these cells, Cremophor accounted for nearly all the neurotoxicity of clinically formulated cyclosporin. At a concentration of 0.005% (v/v), Cremophor EL halved the number of cells that extended neurites after 48 hr in serum-free medium. Average neurite length was also reduced substantially. Inhibition of neurite outgrowth first became apparent 24 hr after exposure to Cremophor EL. Neurites that did grow in the presence of Cremophor were disfigured by a series of regularly spaced, gross dilatations (beads) filled with large (0.2-0.5 microns) lipid vesicles. Abnormalities of rapid axonal transport were documented in the beaded neurites by means of video-enhanced contrast, differential interference-contrast microscopy. Velocity of retrograde transport remained normal, but the velocity of anterograde transport and the total bidirectional flux of organelles were both reduced. It seems likely that the inhibition of neurite outgrowth, the swellings of the neurites and the abnormalities of transport are interrelated phenomena.

  14. Evaluating flow cytometer performance with weighted quadratic least squares analysis of LED and multi-level bead data

    PubMed Central

    Parks, David R.; Khettabi, Faysal El; Chase, Eric; Hoffman, Robert A.; Perfetto, Stephen P.; Spidlen, Josef; Wood, James C.S.; Moore, Wayne A.; Brinkman, Ryan R.

    2017-01-01

    We developed a fully automated procedure for analyzing data from LED pulses and multi-level bead sets to evaluate backgrounds and photoelectron scales of cytometer fluorescence channels. The method improves on previous formulations by fitting a full quadratic model with appropriate weighting and by providing standard errors and peak residuals as well as the fitted parameters themselves. Here we describe the details of the methods and procedures involved and present a set of illustrations and test cases that demonstrate the consistency and reliability of the results. The automated analysis and fitting procedure is generally quite successful in providing good estimates of the Spe (statistical photoelectron) scales and backgrounds for all of the fluorescence channels on instruments with good linearity. The precision of the results obtained from LED data is almost always better than for multi-level bead data, but the bead procedure is easy to carry out and provides results good enough for most purposes. Including standard errors on the fitted parameters is important for understanding the uncertainty in the values of interest. The weighted residuals give information about how well the data fits the model, and particularly high residuals indicate bad data points. Known photoelectron scales and measurement channel backgrounds make it possible to estimate the precision of measurements at different signal levels and the effects of compensated spectral overlap on measurement quality. Combining this information with measurements of standard samples carrying dyes of biological interest, we can make accurate comparisons of dye sensitivity among different instruments. Our method is freely available through the R/Bioconductor package flowQB. PMID:28160404

  15. Method To immobilize the aphid-pathogenic fungus erynia neoaphidis in an alginate matrix for biocontrol

    PubMed

    Shah; Aebi; Tuor

    1998-11-01

    Erynia neoaphidis is an important fungal pathogen of aphid pests worldwide. There have been few reported attempts to formulate this natural agent for use in biocontrol. In the current study, factors involved in the immobilization of E. neoaphidis hyphae in an alginate matrix were investigated. Hyphae of two isolates cultured in liquid medium were 220 to 620 &mgr;m in length and 7 to 19 &mgr;m in diameter with a 74 to 83% cytoplasmic content. The optimal concentration of low-viscosity sodium alginate for production of conidia from entrapped hyphae was 1.5% (wt/vol), and 0.1 and 0.25 M calcium chloride were equally suitable for use as the gelling solution. Alginate beads were rinsed with 10% sucrose after gelling. However, beads should not be left for longer than 40 min in 0.1 M calcium chloride or 10% sucrose to prevent a 10% loss in conidial production. A 40% (vol/vol) concentration of fungal biomass produced significantly more conidia than either 20% or the standard concentration of 10%. This effect persisted even after beads were dried overnight in a laminar flow hood and stored at 4 degreesC for 4 days. Conidia from freshly produced alginate beads caused 27 to 32% infection in Pea aphids as determined by standardized laboratory bioassays. This finding was not significantly different from infections in aphids inoculated with fresh mycelial mats or plugs from Petri dish cultures. In conclusion, algination appears to be a promising technique for utilizing E. neoaphidis in the biocontrol of aphid pests.

  16. Flavivirus internalization is regulated by a size-dependent endocytic pathway.

    PubMed

    Hackett, Brent A; Cherry, Sara

    2018-04-17

    Flaviviruses enter host cells through the process of clathrin-mediated endocytosis, and the spectrum of host factors required for this process are incompletely understood. Here we found that lymphocyte antigen 6 locus E (LY6E) promotes the internalization of multiple flaviviruses, including West Nile virus, Zika virus, and dengue virus. Perhaps surprisingly, LY6E is dispensable for the internalization of the endogenous cargo transferrin, which is also dependent on clathrin-mediated endocytosis for uptake. Since viruses are substantially larger than transferrin, we reasoned that LY6E may be required for uptake of larger cargoes and tested this using transferrin-coated beads of similar size as flaviviruses. LY6E was indeed required for the internalization of transferrin-coated beads, suggesting that LY6E is selectively required for large cargo. Cell biological studies found that LY6E forms tubules upon viral infection and bead internalization, and we found that tubule formation was dependent on RNASEK, which is also required for flavivirus internalization, but not transferrin uptake. Indeed, we found that RNASEK is also required for the internalization of transferrin-coated beads, suggesting it functions upstream of LY6E. These LY6E tubules resembled microtubules, and we found that microtubule assembly was required for their formation and flavivirus uptake. Since microtubule end-binding proteins link microtubules to downstream activities, we screened the three end-binding proteins and found that EB3 promotes virus uptake and LY6E tubularization. Taken together, these results highlight a specialized pathway required for the uptake of large clathrin-dependent endocytosis cargoes, including flaviviruses. Copyright © 2018 the Author(s). Published by PNAS.

  17. Fluorescence microscopy point spread function model accounting for aberrations due to refractive index variability within a specimen.

    PubMed

    Ghosh, Sreya; Preza, Chrysanthe

    2015-07-01

    A three-dimensional (3-D) point spread function (PSF) model for wide-field fluorescence microscopy, suitable for imaging samples with variable refractive index (RI) in multilayered media, is presented. This PSF model is a key component for accurate 3-D image restoration of thick biological samples, such as lung tissue. Microscope- and specimen-derived parameters are combined with a rigorous vectorial formulation to obtain a new PSF model that accounts for additional aberrations due to specimen RI variability. Experimental evaluation and verification of the PSF model was accomplished using images from 175-nm fluorescent beads in a controlled test sample. Fundamental experimental validation of the advantage of using improved PSFs in depth-variant restoration was accomplished by restoring experimental data from beads (6  μm in diameter) mounted in a sample with RI variation. In the investigated study, improvement in restoration accuracy in the range of 18 to 35% was observed when PSFs from the proposed model were used over restoration using PSFs from an existing model. The new PSF model was further validated by showing that its prediction compares to an experimental PSF (determined from 175-nm beads located below a thick rat lung slice) with a 42% improved accuracy over the current PSF model prediction.

  18. Wall effects in Stokes experiment with a liquid foam

    NASA Astrophysics Data System (ADS)

    Gao, Haijing; Subramani, Hariprasad; Harris, Michael; Basaran, Osman

    2011-11-01

    Liquid foams are widely used in numerous applications ranging from the oil and gas industry to beauty, healthcare, and household products industries. A fundamental understanding of the relationships between the properties of liquid foams and their flow responses is, however, still in its infancy compared to that involving the fluid dynamics of simple fluids. In this talk, the flow of a dry liquid foam around a spherical bead, i.e. the Stokes problem for liquid foams, is studied experimentally. In contrast to previous work (cf. Cantat 2006), the focus of the present research is to probe the effect of a solid wall that is located a few bubble radii from the bead. The new experimental results show that the elastic modulus of dry liquid foams is directly proportional to the surface tension of the foaming agents and inversely proportional to the average bubble size in the foams, in agreement with previous theoretical and experimental studies. The experiments further show that the close proximity of the solid wall causes profound structural changes to the gas bubbles as the foam flows past the bead. A good understanding of these structural changes and how they can affect the elastic modulus of foams can be indispensable in formulating improved models for accurately describing the dynamical response of foams within the realm of continuum mechanics.

  19. Effects of dietary selenium on host response to necrotic enteritis in young broilers

    USDA-ARS?s Scientific Manuscript database

    The effects of dietary supplementation of young broiler chickens with a new organic selenium (Se) formulation, B-Traxim Se, on the host response to experimental necrotic enteritis (NE) were studied. Broiler chickens treated with three Se doses (0.25, 0.50, 1.00 mg/kg) from hatch were orally challeng...

  20. Enhancement of in-vitro drug dissolution of ketoconazole for its optimal in-vivo absorption using Nanoparticles and Solid Dispersion forms of the drug

    NASA Astrophysics Data System (ADS)

    Syed, Mohammed Irfan

    Ketoconazole is one of the most widely prescribed oral antifungal drugs for the systemic treatment of various fungal infections. However, due its hydrophobic nature and poor solubility profiles in the gastro-intestinal fluids, variations in its bioavailability have been documented. Therefore, to enhance its dissolution in the biological fluids, this study was initiated to develop and evaluate Nanoparticles and Solid Dispersion forms of the drug. Nanoparticles of ketoconazole were developed by Wet Bead Milling technique using PVP-10k as the stabilizing material at a weight ratio of (2:1). Solid dispersion powder was prepared by Hot Melt method using PEG-8000 at a weight ratio of (1:2). A commercial product containing 200mg of ketoconazole tablet and pure drug powder were used as the control for comparison purposes. The dissolution studies were carried out in SGF, SIF, USP; and SIF with 0.2% sodium lauryl sulfate using the USP-II method for a 2 hours period. Physical characterizations were carried out using SEM, DSC, XRD and FTIR studies. Wet Bead Milling method yielded nanoparticles in the particles size range of (100-300nm.). First all samples were evaluated for their in-vitro dissolution in SGF at pH=1.2. After 15 minutes, the amounts of drug dissolved were observed to be 27% from both the pure powder and commercial tablet (control), 29% from solid dispersion and 100% from the Nanoparticles dosage form. This supports the fact that Nanoparticles had a strong influence on the dissolution rate of the drug and exhibited much faster dissolution of ketoconazole. When the same formulations were studied in the SIF, USP medium, the control formulation gave 3%, solid dispersion 8% and Nanoparticles 8% drug dissolution after 2 hours period. This could be because the weakly basic ketoconazole drug remained un-dissociated in the alkaline medium. Since this medium was unable to clearly distinguish the dissolution profiles from different formulation of the drug, the SIF solution was modified to include 0.02%, 0.05% and 0.1% sodium lauryl sulfate. Here, after 2 hours, the amount of drug dissolved was calculated to be 10% from controls, 21% from solid dispersion and 36% from nanoparticles in SIF with 0.02% SLS. Drug release was 20% from controls, 41% from solid dispersion and 52% from nanoparticle formulation in SIF with 0.05% SLS. Whereas amount of drug released in SIF with 0.1% SLS showed 21% from the control, 62% from solid dispersion and 85% from Nanoparticles respectively. This data supports that the ketoconazole Nanoparticles and its solid-dispersion exhibit many fold increase in dissolution of the drug, which could lead to a less variable and enhanced in-vivo drug absorption profiles. In addition, the data from the Physical Characterization (DSC, XRD and FTIR) supports that there were no interaction within the ingredients occurred in Nanoparticles and solid-dispersion formulations of the drug sample. Wet Bead Milling and Hot Melt methods proved useful in developing the Nanoparticles and solid dispersion form of ketoconazole. Results from particle size analysis were in correlation with data obtained from Scanning electron Microscopy and size of the nanoparticles was below 100nm. The dissolution studies with the modified simulated intestinal fluid (SIF) exhibited several fold increase in the dissolution of the drug compared to the pure drug powder and the commercial products used as the control. Also, the results from the physical characterization studies clearly support the stability of ketoconazole in both of these formulations.

  1. Centrifugal sedimentation immunoassays for multiplexed detection of enteric bacteria in ground water

    DOE PAGES

    Litvinov, Julia; Moen, Scott T.; Koh, Chung-Yan; ...

    2016-01-01

    Water-born pathogens pose significant threat to the global population and early detection plays an important role both in making drinking water safe, as well as in diagnostics and treatment of water-borne diseases. We present an innovative centrifugal microfluidic platform (SpinDx) for detection of bacterial pathogens using bead-based immunoassays. Our approach is based on binding of pathogens to antibody-functionalized capture particles followed by sedimentation of the particles through a density-media in a microfluidic disk and quantification by fluorescence microscopy. Our platform is fast (20 min), sensitive (10 3 CFU/mL), requires minimal sample preparation, and can detect multiple pathogens simultaneously with sensitivitymore » similar to that required by the EPA. We demonstrate detection of a panel of enteric bacteria (Escherichia coli, Salmonella typhimurium, Shigella, Listeria, and Campylobacter) at concentrations as low as 10 3 CFU/mL or 30 bacteria per reaction.« less

  2. Centrifugal sedimentation immunoassays for multiplexed detection of enteric bacteria in ground water

    PubMed Central

    Litvinov, Julia; Moen, Scott T.; Koh, Chung-Yan; Singh, Anup K.

    2016-01-01

    Waterborne pathogens pose significant threat to the global population and early detection plays an important role both in making drinking water safe, as well as in diagnostics and treatment of water-borne diseases. We present an innovative centrifugal sedimentation immunoassay platform for detection of bacterial pathogens in water. Our approach is based on binding of pathogens to antibody-functionalized capture particles followed by sedimentation of the particles through a density-media in a microfluidic disk. Beads at the distal end of the disk are imaged to quantify the fluorescence and determine the bacterial concentration. Our platform is fast (20 min), can detect as few as ∼10 bacteria with minimal sample preparation, and can detect multiple pathogens simultaneously. The platform was used to detect a panel of enteric bacteria (Escherichia coli, Salmonella typhimurium, Shigella, Listeria, and Campylobacter) spiked in tap and ground water samples. PMID:26858815

  3. Development of a nucleic Acid extraction procedure for simultaneous recovery of DNA and RNA from diverse microbes in water.

    PubMed

    Hill, Vincent R; Narayanan, Jothikumar; Gallen, Rachel R; Ferdinand, Karen L; Cromeans, Theresa; Vinjé, Jan

    2015-05-26

    Drinking and environmental water samples contain a diverse array of constituents that can interfere with molecular testing techniques, especially when large volumes of water are concentrated to the small volumes needed for effective molecular analysis. In this study, a suite of enteric viruses, bacteria, and protozoan parasites were seeded into concentrated source water and finished drinking water samples, in order to investigate the relative performance of nucleic acid extraction techniques for molecular testing. Real-time PCR and reverse transcription-PCR crossing threshold (CT) values were used as the metrics for evaluating relative performance. Experimental results were used to develop a guanidinium isothiocyanate-based lysis buffer (UNEX buffer) that enabled effective simultaneous extraction and recovery of DNA and RNA from the suite of study microbes. Procedures for bead beating, nucleic acid purification, and PCR facilitation were also developed and integrated in the protocol. The final lysis buffer and sample preparation procedure was found to be effective for a panel of drinking water and source water concentrates when compared to commercial nucleic acid extraction kits. The UNEX buffer-based extraction protocol enabled PCR detection of six study microbes, in 100 L finished water samples from four drinking water treatment facilities, within three CT values (i.e., within 90% difference) of the reagent-grade water control. The results from this study indicate that this newly formulated lysis buffer and sample preparation procedure can be useful for standardized molecular testing of drinking and environmental waters.

  4. Development of a Nucleic Acid Extraction Procedure for Simultaneous Recovery of DNA and RNA from Diverse Microbes in Water

    PubMed Central

    Hill, Vincent R.; Narayanan, Jothikumar; Gallen, Rachel R.; Ferdinand, Karen L.; Cromeans, Theresa; Vinjé, Jan

    2015-01-01

    Drinking and environmental water samples contain a diverse array of constituents that can interfere with molecular testing techniques, especially when large volumes of water are concentrated to the small volumes needed for effective molecular analysis. In this study, a suite of enteric viruses, bacteria, and protozoan parasites were seeded into concentrated source water and finished drinking water samples, in order to investigate the relative performance of nucleic acid extraction techniques for molecular testing. Real-time PCR and reverse transcription-PCR crossing threshold (CT) values were used as the metrics for evaluating relative performance. Experimental results were used to develop a guanidinium isothiocyanate-based lysis buffer (UNEX buffer) that enabled effective simultaneous extraction and recovery of DNA and RNA from the suite of study microbes. Procedures for bead beating, nucleic acid purification, and PCR facilitation were also developed and integrated in the protocol. The final lysis buffer and sample preparation procedure was found to be effective for a panel of drinking water and source water concentrates when compared to commercial nucleic acid extraction kits. The UNEX buffer-based extraction protocol enabled PCR detection of six study microbes, in 100 L finished water samples from four drinking water treatment facilities, within three CT values (i.e., within 90% difference) of the reagent-grade water control. The results from this study indicate that this newly formulated lysis buffer and sample preparation procedure can be useful for standardized molecular testing of drinking and environmental waters. PMID:26016775

  5. Investigation of a new pH-responsive nanoparticulate pore former for controlled release enteric coating with improved processability and stability.

    PubMed

    Chen, Kuan; Chang, Hao Han R; Shalviri, Alireza; Li, Jason; Lugtu-Pe, Jamie Anne; Kane, Anil; Wu, Xiao Yu

    2017-11-01

    Water-soluble polymers are often used as pore formers to tailor permeability of film-forming hydrophobic polymers on coated dosage forms. However, their addition to a coating formulation could significantly increase the viscosity thus making the coating process difficult. Moreover, the dissolution of pore formers after oral administration could compromise film integrity resulting in undesirable, inconsistent release profiles. Therefore, a non-leaching, pH-responsive nanoparticulate pore former is proposed herein to preserve film integrity and maintain pH-dependent permeability. Poly(methacrylic acid)-polysorbate 80-grafted-starch terpolymer nanoparticles (TPNs) were incorporated within an ethylcellulose (EC) film (TPN-EC) by casting or spray coating. TPNs at 10%wt (pore former level) only increased viscosity of EC coating suspension slightly while conventional pore formers increased the viscosity by 490-11,700%. Negligible leaching of TPNs led to superior mechanical properties of TPN-EC films compared to Eudragit® L-EC films. As pH increased from 1.2 to 6.8, TPN-EC films with 10% pore former level exhibited an 8-fold higher diltiazem permeability compared to Eudragit® L-EC films. The pH-dependent drug release kinetics of diltiazem HCl beads coated with TPN-EC films was tunable by adjusting the pore former level. These results suggest that the TPNs are promising pH-sensitive nanoparticulate pore formers in EC-coated dosage forms. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Pharmacy-based distribution system for enteral nutrition products.

    PubMed

    Craig, S A; Paulson, M F

    1985-12-01

    A hospital pharmacy department's implementation of enteral nutrition product distribution and its proposal for an enteral nutrition product admixture service are described. Responsibility for the distribution of enteral nutrition formulations was transferred from the central distribution department to the pharmacy after problems with inventory control, billing procedures, and inappropriate administration of enteral nutrition products were recognized by personnel from the central-distribution area and nutrition services. After additional problems were identified using a multi-disciplinary approach, the pharmacy department implemented an enteral nutrition product distribution system and developed an enteral nutrition product formulary. A proposal was developed for a pharmacy-based enteral nutrition admixture service, but implementation of this service was deferred because data from a cost-effectiveness evaluation and random bacteriologic monitoring did not justify adding the service. Pharmacy-based distribution and formulary control of enteral nutrition products alleviated problems with inaccurate patient charges and accumulation of stock on the nursing units. Pharmacists at this hospital hope to develop an enteral nutrition product admixture program that will result in cost savings for the institution.

  7. Evaluating flow cytometer performance with weighted quadratic least squares analysis of LED and multi-level bead data.

    PubMed

    Parks, David R; El Khettabi, Faysal; Chase, Eric; Hoffman, Robert A; Perfetto, Stephen P; Spidlen, Josef; Wood, James C S; Moore, Wayne A; Brinkman, Ryan R

    2017-03-01

    We developed a fully automated procedure for analyzing data from LED pulses and multilevel bead sets to evaluate backgrounds and photoelectron scales of cytometer fluorescence channels. The method improves on previous formulations by fitting a full quadratic model with appropriate weighting and by providing standard errors and peak residuals as well as the fitted parameters themselves. Here we describe the details of the methods and procedures involved and present a set of illustrations and test cases that demonstrate the consistency and reliability of the results. The automated analysis and fitting procedure is generally quite successful in providing good estimates of the Spe (statistical photoelectron) scales and backgrounds for all the fluorescence channels on instruments with good linearity. The precision of the results obtained from LED data is almost always better than that from multilevel bead data, but the bead procedure is easy to carry out and provides results good enough for most purposes. Including standard errors on the fitted parameters is important for understanding the uncertainty in the values of interest. The weighted residuals give information about how well the data fits the model, and particularly high residuals indicate bad data points. Known photoelectron scales and measurement channel backgrounds make it possible to estimate the precision of measurements at different signal levels and the effects of compensated spectral overlap on measurement quality. Combining this information with measurements of standard samples carrying dyes of biological interest, we can make accurate comparisons of dye sensitivity among different instruments. Our method is freely available through the R/Bioconductor package flowQB. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

  8. Immobilization of infant fecal microbiota and utilization in an in vitro colonic fermentation model.

    PubMed

    Cinquin, C; Le Blay, G; Fliss, I; Lacroix, C

    2004-07-01

    Bacteria isolated from infant feces were immobilized in polysaccharide gel beads (2.5% gellan gum, 0.25% xanthan gum) using a two-phase dispersion process. A 52-day continuous culture was carried out in a single-stage chemostat containing precolonized beads and fed with a medium formulated to approximate the composition of infant chyme. Different dilution rates and pH conditions were tested to simulate the proximal (PCS), transverse (TCS), and distal (DCS) colons. Immobilization preserved all nine bacterial groups tested with survival rates between 3 and 56%. After 1 week fermentation, beads were highly colonized with all populations tested (excepted Staphylococcus spp. present in low numbers), which remained stable throughout the 7.5 weeks of fermentation, with variations below 1 log unit. However, free-cell populations in the circulating liquid medium, produced by immobilized cell growth, cell-release activity from gel beads, and free-cell growth, were altered considerably by culture conditions. Compared to the stabilization period, PCS was characterized by a considerable and rapid increase in Bifidobacterium spp. concentrations (7.4 to 9.6 log CFU/mL), whereas Bifidobacterium spp., Lactobacillus spp., and Clostridium spp. concentrations decreased and Staphylococcus spp. and coliforms increased during TCS and DCS. Under pseudo-steady-state conditions, the community structure developed in the chemostat reflected the relative proportions of viable bacterial numbers and metabolites generally encountered in infant feces. This work showed that a complex microbiota such as infant fecal bacteria can be immobilized and used in a continuous in vitro intestinal fermentation model to reproduce the high bacterial concentration and bacterial diversity of the feces inoculum, at least at the genera level, with a high stability during long-term experiment.

  9. Encapsulated Essential Oils as an Alternative to Insecticides in Funnel Traps.

    PubMed

    Pascual-Villalobos, M J; López, M D; Castañé, C; Soler, A; Riudavets, J

    2015-08-01

    Pheromone-lured funnel traps are widely used for pest monitoring and mass trapping in agricultural fields and stores. DDVP vapona (dichlorvos), the insecticide of choice as a killing agent inside traps, has been banned, and research on new products is being pursued. Essential oils (EO) could be an alternative if properly formulated. To test their potential, beads of encapsulated coriander and basil EO were tested in funnel traps in stores of almonds and pet foods during 2 mo. The number of adult moth (Plodia interpunctella (Hübner) and Ephestia kuehniella Zeller) dead captures was similar with either coriander or basil EO beads and with vapona tablets while there were more insects alive in the control. These preliminary results indicate a good potential for the development of such natural products as an alternative to synthetic insecticides to include them inside funnel traps. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Assessing the influence of media composition and ionic strength on drug release from commercial immediate-release and enteric-coated aspirin tablets.

    PubMed

    Karkossa, Frank; Klein, Sandra

    2017-10-01

    The objective of this test series was to elucidate the importance of selecting the right media composition for a biopredictive in-vitro dissolution screening of enteric-coated dosage forms. Drug release from immediate-release (IR) and enteric-coated (EC) aspirin formulations was assessed in phosphate-based and bicarbonate-based media with different pH, electrolyte composition and ionic strength. Drug release from aspirin IR tablets was unaffected by media composition. In contrast, drug release from EC aspirin formulations was affected by buffer species and ionic strength. In all media, drug release increased with increasing ionic strength, but in bicarbonate-based buffers was delayed when compared with that in phosphate-based buffers. Interestingly, the cation species in the dissolution medium had also a clear impact on drug release. Drug release profiles obtained in Blank CarbSIF, a new medium simulating pH and average ionic composition of small intestinal fluid, were different from those obtained in all other buffer compositions studied. Results from this study in which the impact of various media parameters on drug release of EC aspirin formulations was systematically screened clearly show that when developing predictive dissolution tests, it is important to simulate the ionic composition of intraluminal fluids as closely as possible. © 2017 Royal Pharmaceutical Society.

  11. The surface protease ompT serves as Escherichia coli K1 adhesin in binding to human brain micro vascular endothelial cells.

    PubMed

    Wan, Lei; Guo, Yan; Hui, Chang-Ye; Liu, Xiao-Lu; Zhang, Wen-Bing; Cao, Hong; Cao, Hong

    2014-05-01

    Escherichia coli (E. coli) K1 is the most common bacteria that cause meningitis in the neonatal period. But it's not entirely clear about how E. coli crosses the blood-brain barrier. The features of the ompT deletion in meningitic E. coli infection were texted in vitro. In comparison with the parent strain, the isogenic ompT deletion mutant was significantly less adhesive to human brain microvascular endothelial cells (HBMEC). The adhesion-deficient phenotype of the mutant was restored to the level of the wild-type by complementing with low-level OmpT expression plasmid. Interestingly, the adhesion was enhanced by point mutation at the OmpT proposed catalytic residue D85. Compared with the poor adhesive activity of bovine serum albumin-coated fluorescent beads, recombinant OmpT or catalytically inactive variant of OmpT-coated beads bound to HBMEC monolayer effectively. Our study suggests that OmpT is important for bacterial adhesion while entering into central nervous system, and the adhesion does not involve in the proteolytic activity of OmpT.

  12. Salmonella biofilm formation on Aspergillus niger involves cellulose--chitin interactions.

    PubMed

    Brandl, Maria T; Carter, Michelle Q; Parker, Craig T; Chapman, Matthew R; Huynh, Steven; Zhou, Yaguang

    2011-01-01

    Salmonella cycles between host and nonhost environments, where it can become an active member of complex microbial communities. The role of fungi in the environmental adaptation of enteric pathogens remains relatively unexplored. We have discovered that S. enterica Typhimurium rapidly attaches to and forms biofilms on the hyphae of the common fungus, Aspergillus niger. Several Salmonella enterica serovars displayed a similar interaction, whereas other bacterial species were unable to bind to the fungus. Bacterial attachment to chitin, a major constituent of fungal cell walls, mirrored this specificity. Pre-incubation of S. Typhimurium with N-acetylglucosamine, the monomeric component of chitin, reduced binding to chitin beads by as much as 727-fold and inhibited attachment to A. niger hyphae considerably. A cellulose-deficient mutant of S. Typhimurium failed to attach to chitin beads and to the fungus. Complementation of this mutant with the cellulose operon restored binding to chitin beads to 79% of that of the parental strain and allowed for attachment and biofilm formation on A. niger, indicating that cellulose is involved in bacterial attachment to the fungus via the chitin component of its cell wall. In contrast to cellulose, S. Typhimurium curli fimbriae were not required for attachment and biofilm development on the hyphae but were critical for its stability. Our results suggest that cellulose-chitin interactions are required for the production of mixed Salmonella-A. niger biofilms, and support the hypothesis that encounters with chitinaceous alternate hosts may contribute to the ecological success of human pathogens.

  13. Salmonella Biofilm Formation on Aspergillus niger Involves Cellulose – Chitin Interactions

    PubMed Central

    Brandl, Maria T.; Carter, Michelle Q.; Parker, Craig T.; Chapman, Matthew R.; Huynh, Steven; Zhou, Yaguang

    2011-01-01

    Salmonella cycles between host and nonhost environments, where it can become an active member of complex microbial communities. The role of fungi in the environmental adaptation of enteric pathogens remains relatively unexplored. We have discovered that S. enterica Typhimurium rapidly attaches to and forms biofilms on the hyphae of the common fungus, Aspergillus niger. Several Salmonella enterica serovars displayed a similar interaction, whereas other bacterial species were unable to bind to the fungus. Bacterial attachment to chitin, a major constituent of fungal cell walls, mirrored this specificity. Pre-incubation of S. Typhimurium with N-acetylglucosamine, the monomeric component of chitin, reduced binding to chitin beads by as much as 727-fold and inhibited attachment to A. niger hyphae considerably. A cellulose-deficient mutant of S. Typhimurium failed to attach to chitin beads and to the fungus. Complementation of this mutant with the cellulose operon restored binding to chitin beads to 79% of that of the parental strain and allowed for attachment and biofilm formation on A. niger, indicating that cellulose is involved in bacterial attachment to the fungus via the chitin component of its cell wall. In contrast to cellulose, S. Typhimurium curli fimbriae were not required for attachment and biofilm development on the hyphae but were critical for its stability. Our results suggest that cellulose–chitin interactions are required for the production of mixed Salmonella-A. niger biofilms, and support the hypothesis that encounters with chitinaceous alternate hosts may contribute to the ecological success of human pathogens. PMID:22003399

  14. Enteral nutrition in the chronic obstructive pulmonary disease (COPD) patient.

    PubMed

    DeBellis, Heather F; Fetterman, James W

    2012-12-01

    Chronic obstructive pulmonary disease (COPD) is a progressive, chronic disease, in which malnutrition can have an undesirable effect. Therefore, the patient's nutritional status is critical for optimizing outcomes in COPD. The initial nutrition assessment is focused on identifying calorically compromised COPD patients in order to provide them with appropriate nutrition. Nutritional intervention consists of oral supplementation and enteral nutrition to prevent weight loss and muscle mass depletion. Evaluation of nutritional status should include past medical history (medications, lung function, and exercise tolerance) and dietary history (patient's dietary habits, food choices, meal patterns, food allergy information, and malabsorption issues), in addition to physiological stress, visceral proteins, weight, fat-free mass, and body mass index. The current medical literature conflicts regarding the appropriate type of formulation to select for nutritional intervention, especially regarding the amount of calories from fat to provide COPD patients. This review article focuses on the enteral product formulations currently available, and how they are most appropriately utilized in patients with COPD.

  15. Ephemeral profiles of prescription drug and formulation tampering: evolving pseudoscience on the Internet.

    PubMed

    Cone, Edward J

    2006-06-01

    The magnitude of non-therapeutic use, or misuse of prescription pharmaceuticals now rivals that of illicit drug abuse. Drug and formulation tampering enables misusers to administer higher doses by intended and non-intended routes. Perceived motives appear to be a combination of interests in achieving a faster onset and enhancing psychoactive effects. Narcotic analgesics, stimulants, and depressants are widely sought, examined, and tampered with for recreational use. This review examines tampering methods reported on the Internet for selected pharmaceutical products. The Internet provides broad and varied guidance on tampering methods that are specific to drug classes and unique formulations. Instructions are available on crushing, separating, purifying and chemically altering specific formulations to allow changes in dosage, route of administration, and time course of effects. Many pharmaceutical formulations contain features that serve as "barriers" to tampering. The nature and effectiveness of formulation barriers vary widely with many being overcome by adventurous misusers. Examples of successes and failures in tampering attempts are frequently described on Internet sites that support recreational drug use. Successful tampering methods that have widespread appeal evolve into recipes and become archived on multiple websites. Examples of tampering methods include: (1) how to separate narcotic drugs (codeine, hydrocodone, oxycodone) from excipients and non-desirable actives (aspirin, acetaminophen, ibuprofen); (2) overcoming time-release formulations (beads, layers, matrices); (3) removal of active drug from high-dose formulations (patches, pills); (4) alteration of dosage forms for alternate routes of administration. The development of successful formulations that inhibit or prevent drug/formulation tampering with drugs of abuse should take into consideration the scope and practice of tampering methods available to recreational drug users on the Internet.

  16. Prescribing and formulating neonatal intravenous feeding solutions by microcomputer.

    PubMed Central

    MacMahon, P

    1984-01-01

    This paper describes a computer programme for a low cost microcomputer designed to assist in the task of administering total parenteral nutrition to neonates: no knowledge of computers is necessary to operate the system. The programme displays recommended values for each of the total parenteral nutrition constituents that must be prescribed, based on detailed analysis of all the pertinent variables. The recommended values may be rejected but they do provide a useful prompt, especially for the more junior doctors. The programme includes a number of safeguards that protect against entering potentially dangerous values. As soon as the operator has completed the procedure of entering total parenteral nutrition requirements the calculations necessary to formulate a solution containing these are automatically performed. The print out contains this data plus instructions on the infusion rate and an analysis of the formulation's calorific content. This system makes it easier to vary the quantity of individual total parenteral nutrition constituents and time has been saved which was previously wasted performing laborious calculations. One of the most important contributions has been the virtual elimination of errors in the complex task of prescribing and formulating total parenteral nutrition for sick neonates. PMID:6430246

  17. Stability of dry coated solid dosage forms.

    PubMed

    Kablitz, Caroline Désirée; Urbanetz, Nora Anne

    2009-01-01

    The dry coating process was evaluated in terms of storage stability investigating drug release and agglomeration tendency of the different coated oral dosage forms; hydroxypropyl methylcellulose acetate succinate (HPMCAS) was used with triethylcitrate (TEC) as plasticizer and acetylated monoglyceride (Myvacet) as wetting agent. Talc or colloidal silicon dioxide (Aerosil) was used as anti-tacking agents. In contrast to coating formulations consisting of HPMCAS and Myvacet all formulations containing TEC showed enteric resistance and no agglomeration tendency after preparation. After storage at 10% RH +/- 5% enteric resistance is increased slightly. This increase is more pronounced at 60% RH +/- 5%. The formulations without anti-tacking agents showed higher drug releases after 12 and 24 months due to the damage of the film's integrity during sample preparation caused by the high tackiness of the film. Tackiness is not affected by storing if samples are stored at low relative humidity. At high relative humidity tackiness increases upon storage especially for formulations without anti-tacking agents. The sieving results of the agglomeration measurements after storage can be confirmed by ring shear measurements performed immediately after preparation and approved to be a tool, which is able to predict the agglomeration during storage.

  18. Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS): A rapid test for enteric coating thickness and integrity of controlled release pellet formulations.

    PubMed

    Alfarsi, Anas; Dillon, Amy; McSweeney, Seán; Krüse, Jacob; Griffin, Brendan; Devine, Ken; Sherry, Patricia; Henken, Stephan; Fitzpatrick, Stephen; Fitzpatrick, Dara

    2018-06-10

    There are no rapid dissolution based tests for determining coating thickness, integrity and drug concentration in controlled release pellets either during production or post-production. The manufacture of pellets requires several coating steps depending on the formulation. The sub-coating and enteric coating steps typically take up to six hours each followed by additional drying steps. Post production regulatory dissolution testing also takes up to six hours to determine if the batch can be released for commercial sale. The thickness of the enteric coating is a key factor that determines the release rate of the drug in the gastro-intestinal tract. Also, the amount of drug per unit mass decreases with increasing thickness of the enteric coating. In this study, the coating process is tracked from start to finish on an hourly basis by taking samples of pellets during production and testing those using BARDS (Broadband Acoustic Resonance Dissolution Spectroscopy). BARDS offers a rapid approach to characterising enteric coatings with measurements based on reproducible changes in the compressibility of a solvent due to the evolution of air during dissolution. This is monitored acoustically via associated changes in the frequency of induced acoustic resonances. A steady state acoustic lag time is associated with the disintegration of the enteric coatings in basic solution. This lag time is pH dependent and is indicative of the rate at which the coating layer dissolves. BARDS represents a possible future surrogate test for conventional USP dissolution testing as its data correlates directly with the thickness of the enteric coating, its integrity and also with the drug loading as validated by HPLC. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Effect of Calcium Ions on the Disintegration of Enteric-Coated Solid Dosage Forms.

    PubMed

    Al-Gousous, Jozef; Langguth, Peter

    2016-02-01

    To investigate the effect of calcium ions on the disintegration of enteric-coated dosage forms, disintegration testing was performed on enteric-coated aspirin tablets in the presence and absence of calcium in the test media. The results show that the presence of calcium ions retards the disintegration of enteric-coated dosage forms. This finding, which has not been reported in scientific literature, sheds light on the importance of conducting well-designed detailed investigations into the potential of calcium from dietary sources, calcium supplements, antacids, and/or phosphate binders affecting the absorption of drugs formulated into enteric-coated dosage forms. Moreover, it shows the necessity to investigate the potential of the occurrence of additional nutrient-excipient interactions. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  20. Transport of human adenoviruses in porous media

    NASA Astrophysics Data System (ADS)

    Kokkinos, Petros; Syngouna, Vasiliki I.; Tselepi, Maria A.; Bellou, Maria; Chrysikopoulos, Constantinos V.; Vantarakis, Apostolos

    2015-04-01

    Groundwater may be contaminated with infective human enteric viruses from various wastewater discharges, sanitary landfills, septic tanks, agricultural practices, and artificial groundwater recharge. Coliphages have been widely used as surrogates of enteric viruses, because they share many fundamental properties and features. Although a large number of studies focusing on various factors (i.e. pore water solution chemistry, fluid velocity, moisture content, temperature, and grain size) that affect biocolloid (bacteria, viruses) transport have been published over the past two decades, little attention has been given toward human adenoviruses (hAdVs). The main objective of this study was to evaluate the effect of pore water velocity on hAdV transport in water saturated laboratory-scale columns packed with glass beads. The effects of pore water velocity on virus transport and retention in porous media was examined at three pore water velocities (0.39, 0.75, and 1.22 cm/min). The results indicated that all estimated average mass recovery values for hAdV were lower than those of coliphages, which were previously reported in the literature by others for experiments conducted under similar experimental conditions. However, no obvious relationship between hAdV mass recovery and water velocity could be established from the experimental results. The collision efficiencies were quantified using the classical colloid filtration theory. Average collision efficiency, α, values decreased with decreasing flow rate, Q, and pore water velocity, U, but no significant effect of U on α was observed. Furthermore, the surface properties of viruses and glass beads were used to construct classical DLVO potential energy profiles. The results revealed that the experimental conditions of this study were unfavorable to deposition and that no aggregation between virus particles is expected to occur. A thorough understanding of the key processes governing virus transport is pivotal for public health protection.

  1. Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21(st) century.

    PubMed

    Trang, Tony; Chan, Johanna; Graham, David Y

    2014-09-07

    Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes, (e.g., giving unprotected enzymes at the start of the meal and acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy.

  2. Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21st century

    PubMed Central

    Trang, Tony; Chan, Johanna; Graham, David Y

    2014-01-01

    Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes, (e.g., giving unprotected enzymes at the start of the meal and acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy. PMID:25206255

  3. Gut microbial products regulate murine gastrointestinal motility via Toll-like Receptor 4 signaling

    PubMed Central

    Anitha, Mallappa; Vijay-Kumar, Matam; Sitaraman, Shanthi V.; Gewirtz, Andrew T.; Srinivasan, Shanthi

    2012-01-01

    Background & Aims Altered gastrointestinal motility is associated with significant morbidity and health care costs. Toll-like receptors regulate intestinal homeostasis. We examined the roles of Toll-like receptor (TLR)4 signaling in survival of enteric neurons and gastrointestinal motility. Methods We assessed changes in intestinal motility by assessing stool frequency, bead expulsion, and isometric muscle recordings of colonic longitudinal muscle strips from mice that do not express TLR4 (Tlr4Lps-d or TLR4−/−) or Myd88 (Myd88−/−), in wild-type germ-free mice or wild-type mice depleted of the microbiota, and in mice with neural crest-specific deletion of Myd88 (Wnt1Cre+/−/Myd88fl/fl). We studied the effects of the TLR4 agonist lipopolysaccharide (LPS) on survival of cultured, immortalized fetal enteric neurons (IM-FEN) and enteric neuronal cells isolated from wild-type and Tlr4Lps-d mice at embryonic day 13.5. Results There was a significant delay in gastrointestinal motility and reduced numbers of nitrergic neurons in TLR4Lps-d, TLR4−/−, and Myd88−/− mice, compared with wild-type mice. A similar phenotype was observed in germ-free mice, mice depleted of intestinal microbiota, and Wnt1Cre+/−/Myd88fl/fl mice. Incubation of enteric neuronal cells with LPS led to activation of the transcription factor NF-κB and increased cell survival. Conclusions Interactions between enteric neurons and microbes increases neuron survival and gastrointestinal motility in mice. LPS activation of TLR4 and NF-κB appears to promote survival of enteric neurons. Factors that regulate TLR4 signaling by neurons might be developed to alter gastrointestinal motility. PMID:22732731

  4. Enteric-coated epichlorohydrin crosslinked dextran microspheres for site-specific delivery to colon.

    PubMed

    Rai, Gopal; Yadav, Awesh K; Jain, Narendra K; Agrawal, Govind P

    2015-01-01

    Enteric-coated epichlorohydrin crosslinked dextran microspheres containing 5-Fluorouracil (5-FU) for colon drug delivery was prepared by emulsification-crosslinking method. The formulation variables studied includes different molecular weights of dextran, volume of crosslinking agent, stirring speed, time and temperature. Dextran microspheres showed mean entrapment efficiencies ranging between 77 and 87% and mean particle size ranging between 10 and 25 µm. About 90% of drug was released from uncoated dextran microspheres within 8 h, suggesting the fast release and indicated the drug loaded in uncoated microspheres, released before they reached colon. Enteric coating (Eudragit-S-100 and Eudragit-L-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method. The release study of 5-FU from coated dextran microspheres was complete retardation in simulated gastric fluid (pH 1.2) and once the coating layer of enteric polymer was dissolved at higher pH (7.4 and 6.8), a controlled release of the drug from the microspheres was observed. Further, the release of drug was found to be higher in the presence of dextranase and rat caecal contents, indicating the susceptibility of dextran microspheres to colonic enzymes. Organ distribution and pharmacokinetic study in albino rats was performed to establish the targeting potential of optimized formulation in the colon.

  5. Formulation Strategies to Improve the Bioavailability of Poorly Absorbed Drugs with Special Emphasis on Self-Emulsifying Systems

    PubMed Central

    Gupta, Shweta; Kesarla, Rajesh

    2013-01-01

    Poorly water-soluble drug candidates are becoming more prevalent. It has been estimated that approximately 60–70% of the drug molecules are insufficiently soluble in aqueous media and/or have very low permeability to allow for their adequate and reproducible absorption from the gastrointestinal tract (GIT) following oral administration. Formulation scientists have to adopt various strategies to enhance their absorption. Lipidic formulations are found to be a promising approach to combat the challenges. In this review article, potential advantages and drawbacks of various conventional techniques and the newer approaches specifically the self-emulsifying systems are discussed. Various components of the self-emulsifying systems and their selection criteria are critically reviewed. The attempts of various scientists to transform the liquid self-emulsifying drug delivery systems (SEDDS) to solid-SEDDS by adsorption, spray drying, lyophilization, melt granulation, extrusion, and so forth to formulate various dosage forms like self emulsifying capsules, tablets, controlled release pellets, beads, microspheres, nanoparticles, suppositories, implants, and so forth have also been included. Formulation of SEDDS is a potential strategy to deliver new drug molecules with enhanced bioavailability mostly exhibiting poor aqueous solubility. The self-emulsifying system offers various advantages over other drug delivery systems having potential to solve various problems associated with drugs of all the classes of biopharmaceutical classification system (BCS). PMID:24459591

  6. Design of Novel Ophthalmic Formulation Containing Drug Nanoparticles and Its Usefulness as Anti-glaucoma Drugs.

    PubMed

    Nagai, Noriaki

    2016-01-01

    The ophthalmic application of drugs is the primary route of administration for the therapy of glaucoma; however, in traditional formulations, only small amounts of the administered drug penetrate the cornea to reach the desired intraocular tissue due to corneal barriers. Recently, nanoparticulate drug delivery is expected as a technology to overcome the difficulties in delivering drugs across biological barriers (improvement of bioavailability). In this study, we attempted to establish a new method for preparing solid drug nanoparticles by using a bead mill and various additives, and succeeded in preparing a high quality dispersion containing drug nanoparticles. For a more concrete example, a mean particle size of disulfiram (DSF) treated with bead mill is 183 nm. The corneal penetration and corneal residence time of DSF from the ophthalmic dispersion containing DSF nanoparticles were significantly higher than those from a 2-hydroxypropyl-β-cyclodextrin solution containing DSF (DSF solution). It is known that the administration of DSF has intraocular pressure (IOP)-reducing effects. The IOP-reducing effects of the ophthalmic dispersion containing DSF nanoparticles were significantly greater than those of the DSF solution in rabbits (the IOP was enhanced by placing the rabbits in a dark room for 5 h). In addition, the ophthalmic dispersion containing DSF nanoparticles is better tolerated by corneal epithelial cells than DSF solution. It is possible that dispersions containing DSF nanoparticles provide new possibilities for effectively treating glaucoma, and that ocular drug delivery systems using drug nanoparticles may expand their usage for therapy in the ophthalmologic field.

  7. Biosensing and bioremediation of Cr(VI) by cell free extract of Enterobacter aerogenes T2.

    PubMed

    Panda, Jigisha; Sarkar, Priyabrata

    2014-01-01

    Hexavalent chromium or Cr(VI) enters the environment through several anthropogenic activities and it is highly toxic and carcinogenic. Hence it is required to be detected and remediated from the environment. In this study, low-cost and environment-friendly methods of biosensing and bioremediation of Cr(VI) have been proposed. Crude cell free extract (CFE) of previously isolated Enterobacter aerogenes T2 (GU265554; NII 1111) was prepared and exploited to develop a stable biosensor for direct estimation of Cr(VI) in waste water, by using three electrodes via cyclic voltammetry. For bioremediation studies, a homogeneous solution of commercially available sodium alginate and CFE was added dropwise in a continuously stirred calcium chloride solution. Biologically modified calcium alginate beads were produced and these were further utilized for bioremediation studies. The proposed sensor showed linear response in the range of 10-40 μg L(-1) Cr(VI) and the limit of detection was found to be 6.6 μg L(-1) Cr(VI). No interference was observed in presence of metal ions, e.g., lead, cadmium, arsenic, tin etc., except for insignificant interference with molybdenum and manganese. In bioremediation studies, modified calcium alginate beads showed encouraging removal rate 900 mg Cr(VI)/m(3) water per day with a removal efficiency of 90%, much above than reported in literature. The proposed sensing system could be a viable alternative to costly measurement procedures. Calcium alginate beads, modified with CFE of E. aerogenes, could be used in bioremediation of Cr(VI) since it could work in real conditions with extraordinarily high capacity.

  8. Identification of internal properties of fibres and micro-swimmers

    NASA Astrophysics Data System (ADS)

    Plouraboué, Franck; Thiam, E. Ibrahima; Delmotte, Blaise; Climent, Eric

    2017-01-01

    In this paper, we address the identifiability of constitutive parameters of passive or active micro-swimmers. We first present a general framework for describing fibres or micro-swimmers using a bead-model description. Using a kinematic constraint formulation to describe fibres, flagellum or cilia, we find explicit linear relationship between elastic constitutive parameters and generalized velocities from computing contact forces. This linear formulation then permits one to address explicitly identifiability conditions and solve for parameter identification. We show that both active forcing and passive parameters are both identifiable independently but not simultaneously. We also provide unbiased estimators for generalized elastic parameters in the presence of Langevin-like forcing with Gaussian noise using a Bayesian approach. These theoretical results are illustrated in various configurations showing the efficiency of the proposed approach for direct parameter identification. The convergence of the proposed estimators is successfully tested numerically.

  9. Unusual presentation of calcaneal osteomyelitis. Twenty-five years after inoculation.

    PubMed

    Rogoff, R S; Tinkle, J D; Bartis, D G

    1997-03-01

    An unusual presentation of calcaneal osteomyelitis is described, where-by the infection remained undiagnosed for 25 years. The 36-year-old patient recently sought medical treatment for a reported ankle sprain, but the pain was recalcitrant to conservative care. Further investigation yielded a history significant for stepping on a chicken bone as a child, which entered the inferior lateral heel. Magnetic resonance imaging revealed what plain radiographs did not: a well demarcated lytic lesion in the body of the calcaneus. Intraoperative findings were consistent with an abscess of chronic osteomyelitis. The treatment included incision and drainage, antibiotic beads, and a tricortical bone graft.

  10. Use of a novel docosahexaenoic acid formulation vs control in a neonatal porcine model of short bowel syndrome leads to greater intestinal absorption and higher systemic levels of DHA

    USDA-ARS?s Scientific Manuscript database

    Infants with short bowel syndrome (SBS) are at high risk for malabsorption, malnutrition, and failure to thrive. The objective of this study was to evaluate in a porcine model of SBS, the systemic absorption of a novel enteral Docosahexaenoic acid (DHA) formulation that forms micelles independent of...

  11. Bilayer tablets of Paliperidone for Extended release osmotic drug delivery

    NASA Astrophysics Data System (ADS)

    Chowdary, K. Sunil; Napoleon, A. A.

    2017-11-01

    The purpose of this study is to develop and optimize the formulation of paliperidone bilayer tablet core and coating which should meet in vitro performance of trilayered Innovator sample Invega. Optimization of core formulations prepared by different ratio of polyox grades and optimization of coating of (i) sub-coating build-up with hydroxy ethyl cellulose (HEC) and (ii).enteric coating build-up with cellulose acetate (CA). Some important influence factors such as different core tablet compositions and different coating solution ingredients involved in the formulation procedure were investigated. The optimization of formulation and process was conducted by comparing different in vitro release behaviours of Paliperidone. In vitro dissolution studies of Innovator sample (Invega) with formulations of different release rate which ever close release pattern during the whole 24 h test is finalized.

  12. Photon polarizability and its effect on the dispersion of plasma waves

    NASA Astrophysics Data System (ADS)

    Dodin, I. Y.; Ruiz, D. E.

    2017-04-01

    High-frequency photons travelling in plasma exhibit a linear polarizability that can influence the dispersion of linear plasma waves. We present a detailed calculation of this effect for Langmuir waves as a characteristic example. Two alternative formulations are given. In the first formulation, we calculate the modified dispersion of Langmuir waves by solving the governing equations for the electron fluid, where the photon contribution enters as a ponderomotive force. In the second formulation, we provide a derivation based on the photon polarizability. Then, the calculation of ponderomotive forces is not needed, and the result is more general.

  13. Photon polarizability and its effect on the dispersion of plasma waves

    DOE PAGES

    Dodin, I. Y.; Ruiz, D. E.

    2017-03-06

    High-frequency photons travelling in plasma exhibit a linear polarizability that can influence the dispersion of linear plasma waves. We present a detailed calculation of this effect for Langmuir waves as a characteristic example. Here, two alternative formulations are given. In the first formulation, we calculate the modified dispersion of Langmuir waves by solving the governing equations for the electron fluid, where the photon contribution enters as a ponderomotive force. In the second formulation, we provide a derivation based on the photon polarizability. Then, the calculation of ponderomotive forces is not needed, and the result is more general.

  14. A Novel Inherently Radiopaque Bead for Transarterial Embolization to Treat Liver Cancer - A Pre-clinical Study.

    PubMed

    Duran, Rafael; Sharma, Karun; Dreher, Matthew R; Ashrafi, Koorosh; Mirpour, Sahar; Lin, MingDe; Schernthaner, Ruediger E; Schlachter, Todd R; Tacher, Vania; Lewis, Andrew L; Willis, Sean; den Hartog, Mark; Radaelli, Alessandro; Negussie, Ayele H; Wood, Bradford J; Geschwind, Jean-François H

    2016-01-01

    Embolotherapy using microshperes is currently performed with soluble contrast to aid in visualization. However, administered payload visibility dimishes soon after delivery due to soluble contrast washout, leaving the radiolucent bead's location unknown. The objective of our study was to characterize inherently radiopaque beads (RO Beads) in terms of physicomechanical properties, deliverability and imaging visibility in a rabbit VX2 liver tumor model. RO Beads, which are based on LC Bead® platform, were compared to LC Bead. Bead size (light microscopy), equilibrium water content (EWC), density, X-ray attenuation and iodine distribution (micro-CT), suspension (settling times), deliverability and in vitro penetration were investigated. Fifteen rabbits were embolized with either LC Bead or RO Beads + soluble contrast (iodixanol-320), or RO Beads+dextrose. Appearance was evaluated with fluoroscopy, X-ray single shot, cone-beam CT (CBCT). Both bead types had a similar size distribution. RO Beads had lower EWC (60-72%) and higher density (1.21-1.36 g/cc) with a homogeneous iodine distribution within the bead's interior. RO Beads suspension time was shorter than LC Bead, with durable suspension (>5 min) in 100% iodixanol. RO Beads ≤300 µm were deliverable through a 2.3-Fr microcatheter. Both bead types showed similar penetration. Soluble contrast could identify target and non-target embolization on fluoroscopy during administration. However, the imaging appearance vanished quickly for LC Bead as contrast washed-out. RO Beads+contrast significantly increased visibility on X-ray single shot compared to LC Bead+contrast in target and non-target arteries (P=0.0043). Similarly, RO beads demonstrated better visibility on CBCT in target arteries (P=0.0238) with a trend in non-target arteries (P=0.0519). RO Beads+dextrose were not sufficiently visible to monitor embolization using fluoroscopy. RO Beads provide better conspicuity to determine target and non-target embolization compared to LC Bead which may improve intra-procedural monitoring and post-procedural evaluation of transarterial embolization.

  15. Analysis of Non-Pivotal Bioequivalence Studies Submitted in Abbreviated New Drug Submissions for Delayed-Release Drug Products.

    PubMed

    Kaur, Paramjeet; Jiang, Xiaojian; Stier, Ethan

    2017-01-01

    The US FDA's rule on "Requirements for Submission of Bioequivalence Data" requiring submission of all bioequivalence (BE) studies conducted on the same formulation of the drug product submitted for approval was published in Federal Register in January 2009. With the publication of this rule, we evaluated the impact of data from non-pivotal BE studies in assessing BE and identified the reasons for failed in vivo BE studies for generic oral delayed-release (DR) drug products only. We searched the Agency databases from January 2009 toDecember 2016 to identify Abbreviated New Drug Applications (ANDAs) submitted for DR drug products containing non-pivotal BE studies. Out of 202 ANDAs, 43 ANDAs contained 102 non-pivotal BE studies. Forty-nine non-pivotal BE studies were conducted on the to-be-marketed (TBM) formulation and 53 were conducted on formulations different from the TBM formulation. These experimental formulations primarily differed in the ratio of components of the enteric coating layer and/or amount (i.e., %w/w) of enteric coating layer. Of the 49 non-pivotal BE studies conducted on the TBM formulation, 41 failed to meet the BE acceptance criteria. The majority of failed non-pivotal BE studies on the TBM DR generic products had insufficient power, which was expected as these studies are exploratory in nature and not designed to have adequate power to pass the BE statistical criteria. In addition, among the failed non-pivotal BE studies on the TBM DR generic products, the most commonly failing pharmacokinetic parameter was Cmax. The data from these non-pivotal BE studies indicate that inadequate BE study design can lead to failure of the BE on the same formulation. Also, the non-pivotal BE studies on formulations different from the TBM formulation help us link the formulation design to the product performance in vivo. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  16. Dermal miconazole nitrate nanocrystals - formulation development, increased antifungal efficacy & skin penetration.

    PubMed

    Pyo, Sung Min; Hespeler, David; Keck, Cornelia M; Müller, Rainer H

    2017-10-05

    Miconazole nitrate nanosuspension was developed to increase its antifungal activity and dermal penetration. In addition, the nanosuspension was combined with the synergistic additive chlorhexidine digluconate. The production was performed by wet bead milling and both production and formulation parameters were optimized. A stabilizer screening revealed poloxamer 407 and Tween 80 both at 0.15% as the most effective stabilizers for miconazole nanosuspensions at 1.0%. The nanocrystals were incorporated into a hydroxypropyl cellulose gel base. Short-term stability (3months) of the nanocrystal bulk population could be shown at room temperature and fridge. Besides the stable bulk nanocrystals, some longitudinal crystal growth to needle like crystals occurred. The addition of ionic compounds as the chlorhexidine digluconate often destabilizes suspensions. Surprisingly here, the addition minimized the crystal growth. An underlying mechanism is proposed. An inhibition zone assay was performed using Candida albicans (ATCC ® 10231™). When comparing the nanocrystals in suspension and in gel to μm-sized miconazole nitrate formulations and two market products, the increase in inhibition zone diameter for the nanosuspension formulations was most pronounced in the chlorhexidine digluconate free formulations. These nanocrystal formulations were closely or similarly effective as the microsuspensions and the market products containing the synergistic chlorhexidine digluconate, showing the potential of the nanosuspension formulation. Nanosuspension performance was even further increased when chlorhexidine digluconate was added. Ex-vivo skin penetration studies on porcine ears revealed distinctly less remaining miconazole nitrate on the skin surface for nanocrystals (e.g., 76-86%) compared to market products (e.g. 94%). Also, penetration was increased e.g. in skin depth of 5-10μm from <1.0/1.7% to e.g. 3.3-6.2% for nanocrystals. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Confocal nanoscanning, bead picking (CONA): PickoScreen microscopes for automated and quantitative screening of one-bead one-compound libraries.

    PubMed

    Hintersteiner, Martin; Buehler, Christof; Uhl, Volker; Schmied, Mario; Müller, Jürgen; Kottig, Karsten; Auer, Manfred

    2009-01-01

    Solid phase combinatorial chemistry provides fast and cost-effective access to large bead based libraries with compound numbers easily exceeding tens of thousands of compounds. Incubating one-bead one-compound library beads with fluorescently labeled target proteins and identifying and isolating the beads which contain a bound target protein, potentially represents one of the most powerful generic primary high throughput screening formats. On-bead screening (OBS) based on this detection principle can be carried out with limited automation. Often hit bead detection, i.e. recognizing beads with a fluorescently labeled protein bound to the compound on the bead, relies on eye-inspection under a wide-field microscope. Using low resolution detection techniques, the identification of hit beads and their ranking is limited by a low fluorescence signal intensity and varying levels of the library beads' autofluorescence. To exploit the full potential of an OBS process, reliable methods for both automated quantitative detection of hit beads and their subsequent isolation are needed. In a joint collaborative effort with Evotec Technologies (now Perkin-Elmer Cellular Technologies Germany GmbH), we have built two confocal bead scanner and picker platforms PS02 and a high-speed variant PS04 dedicated to automated high resolution OBS. The PS0X instruments combine fully automated confocal large area scanning of a bead monolayer at the bottom of standard MTP plates with semiautomated isolation of individual hit beads via hydraulic-driven picker capillaries. The quantification of fluorescence intensities with high spatial resolution in the equatorial plane of each bead allows for a reliable discrimination between entirely bright autofluorescent beads and real hit beads which exhibit an increased fluorescence signal at the outer few micrometers of the bead. The achieved screening speed of up to 200,000 bead assayed in less than 7 h and the picking time of approximately 1 bead/min allow exploitation of one-bead one-compound libraries with high sensitivity, accuracy, and speed.

  18. Computational Modeling of Hydroxypropyl-Methylcellulose Acetate Succinate (HPMCAS) and Phenytoin Interactions: A Systematic Coarse-Graining Approach.

    PubMed

    Huang, Wenjun; Mandal, Taraknath; Larson, Ronald G

    2017-03-06

    We present coarse-grained (CG) force fields for hydroxypropyl-methylcellulose acetate succinate (HPMCAS) polymers and the drug molecule phenytoin using a bead/stiff spring model, with each bead representing a HPMCAS monomer or monomer side group (hydroxypropyl acetyl, acetyl, or succinyl) or a single phenytoin ring. We obtain the bonded and nonbonded interaction parameters in our CG model using the RDFs from atomistic simulations of short HPMCAS model oligomers (20-mer) and atomistic simulations of phenytoin molecules. The nonbonded interactions are modeled using a LJ 12-6 potential, with separate parameters for each monomer substitution type, which allows heterogeneous polymer chains to be modeled. The cross interaction terms between the polymer and phenytoin CG beads are obtained explicitly from atomistic level polymer-phenytoin simulations, rather than from mixing rules. We study the solvation behavior of 50-mer and 100-mer polymer chains and find chain-length-dependent aggregation. We also compare the phenytoin CG force field developed in this work with that in Mandal et al. (Soft Matter, 2016, 12, 8246-8255) and conclude both are suitable for studying the interaction between polymer and drug in solvated solid dispersion formulation, in the absence of drug crystallization. Finally, we present simulations of heterogeneous HPMCAS model polymer chains and phenytoin molecules. Polymer and drug form a complex in a short period of simulation time due to strong intermolecular interactions. Moreover, the protonated polymer chains are more effective than deprotonated ones in inhibiting the drug aggregation in the polymer-drug complex.

  19. Thermal Inactivation of Enteric Viruses and Bioaccumulation of Enteric Foodborne Viruses in Live Oysters (Crassostrea virginica)

    PubMed Central

    Araud, Elbashir; DiCaprio, Erin; Ma, Yuanmei; Lou, Fangfei; Gao, Yu; Kingsley, David; Hughes, John H.

    2016-01-01

    Human enteric viruses are among the main causative agents of shellfish-associated outbreaks. In this study, the kinetics of viral bioaccumulation in live oysters and the heat stabilities of the predominant enteric viruses were determined both in tissue culture and in oyster tissues. A human norovirus (HuNoV) GII.4 strain, HuNoV surrogates (murine norovirus [MNV-1], Tulane virus [TV]), hepatitis A virus (HAV), and human rotavirus (RV) bioaccumulated to high titers within oyster tissues, with different patterns of bioaccumulation for the different viruses. We tested the thermal stability of each virus at 62, 72, and 80°C in culture medium. The viruses can be ranked from the most heat resistant to the least stable as follows: HAV, RV, TV, MNV-1. In addition, we found that oyster tissues provided protection to the viruses during heat treatment. To decipher the mechanism underlying viral inactivation by heat, purified TV was treated at 80°C for increasing time intervals. It was found that the integrity of the viral capsid was disrupted, whereas viral genomic RNA remained intact. Interestingly, heat treatment leading to complete loss of TV infectivity was not sufficient to completely disrupt the receptor binding activity of TV, as determined by the porcine gastric mucin–magnetic bead binding assay. Similarly, HuNoV virus-like particles (VLPs) and a HuNoV GII.4 strain retained some receptor binding ability following heat treatment. Although foodborne viruses have variable heat stability, 80°C for >6 min was sufficient to completely inactivate enteric viruses in oysters, with the exception of HAV. PMID:26826225

  20. Association between aspirin and upper gastrointestinal complications: Systematic review of epidemiologic studies

    PubMed Central

    Rodríguez, Luis A García; Hernández-Díaz, Sonia; de Abajo, Francisco J

    2001-01-01

    Aims Because of the widespread use of aspirin for prevention of cardiovascular diseases, side-effects associated with thromboprophylactic doses are of interest. This study summarizes the relative risk (RR) for serious upper gastrointestinal complications (UGIC) associated with aspirin exposure in general and with specific aspirin doses and formulations in particular. Methods After a systematic review, 17 original epidemiologic studies published between 1990 and 2001 were selected according to predefined criteria. Heterogeneity of effects was explored. Pooled estimates were calculated according to different study characteristics and patterns of aspirin use. Results The overall relative risk of UGIC associated with aspirin use was 2.2 (95% confidence interval (CI): 2.1, 2.4) for cohort studies and nested case-control studies and 3.1 (95% CI: 2.8, 3.3) for non-nested case-control studies. Original studies found a dose–response relationship between UGIC and aspirin, although the risk was still elevated for doses lower or up to 300 mg day−1. The summary RR was 2.6 (95% CI: 2.3, 2.9) for plain, 5.3 (95% CI: 3.0, 9.2) for buffered, and 2.4 (95% CI: 1.9, 2.9) for enteric-coated aspirin formulations. Conclusions Aspirin was associated with UGIC even when used at low doses or in buffered or enteric-coated formulations. The latter findings may be partially explained by channeling of susceptible patients to these formulations. PMID:11736865

  1. 76 FR 14058 - Notice of Inventory Completion: Fremont County Coroner, Riverton, WY

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-15

    ... associated funerary objects are 2 fragments of freshwater clam shells, 32 dentalia shell beads, 2 bird bone beads, 8 chokecherry seed beads, 162 bone heishi-style beads, 158 lignite heishi-style beads, 5 fragmentary bone heishi-style beads, 1 shell bead, and 3 chert microflakes. The Sinks Canyon site is located...

  2. Solvated dissipative electro-elastic network model of hydrated proteins

    NASA Astrophysics Data System (ADS)

    Martin, Daniel

    2013-03-01

    Elastic network models coarse grain proteins into a network of residue beads connected by springs. We add dissipative dynamics to this mechanical system by applying overdamped Langevin equations of motion to normal-mode vibrations of the network. In addition, the network is made heterogeneous and softened at the protein surface by accounting for hydration of the ionized residues. Solvation changes the network Hessian in two ways. Diagonal solvation terms soften the spring constants and off-diagonal dipole-dipole terms correlate displacements of the ionized residues. The model is used to formulate the response functions of the electrostatic potential and electric field appearing in theories of redox reactions and spectroscopy. We also formulate the dielectric response of the protein and find that solvation of the surface ionized residues leads to a slow relaxation peak in the dielectric loss spectrum, about two orders of magnitude slower than the main peak of protein relaxation. Finally, the solvated network is used to formulate the allosteric response of the protein to ion binding. The global thermodynamics of ion binding is not strongly affected by the network solvation, but it dramatically enhances conformational changes in response to placing a charge at the a the active site.

  3. Solvated dissipative electro-elastic network model of hydrated proteins

    NASA Astrophysics Data System (ADS)

    Martin, Daniel R.; Matyushov, Dmitry V.

    2012-10-01

    Elastic network models coarse grain proteins into a network of residue beads connected by springs. We add dissipative dynamics to this mechanical system by applying overdamped Langevin equations of motion to normal-mode vibrations of the network. In addition, the network is made heterogeneous and softened at the protein surface by accounting for hydration of the ionized residues. Solvation changes the network Hessian in two ways. Diagonal solvation terms soften the spring constants and off-diagonal dipole-dipole terms correlate displacements of the ionized residues. The model is used to formulate the response functions of the electrostatic potential and electric field appearing in theories of redox reactions and spectroscopy. We also formulate the dielectric response of the protein and find that solvation of the surface ionized residues leads to a slow relaxation peak in the dielectric loss spectrum, about two orders of magnitude slower than the main peak of protein relaxation. Finally, the solvated network is used to formulate the allosteric response of the protein to ion binding. The global thermodynamics of ion binding is not strongly affected by the network solvation, but it dramatically enhances conformational changes in response to placing a charge at the active site of the protein.

  4. Osmolality, pH, and compatibility of selected oral liquid medications with an enteral nutrition product.

    PubMed

    Klang, Mark; McLymont, Veronica; Ng, Nicole

    2013-09-01

    When selecting medication for feeding tube administration, the liquid formulation is selected, so as to avoid obstructions that may occur from incompletely crushing a solid dosage form. Liquid medications can present issues of intolerance and compatibility when administered via a feeding tube. A predictor of intolerance is the liquid's osmolarity, and a predicator of compatibility is the liquid's pH value. This study examines 62 liquid formulations for their osmolality, pH, and physical compatibility with enteral nutrition (EN) formulas. These medications were selected as being the most commonly dispensed liquid medications from our outpatient pharmacy department. This study measures osmolality using freezing point depression. Depending on the dose, the osmotic load of a liquid medication may cause cramping and diarrhea. The pH value is predictive of potential interactions with the EN formula. Many drugs are weak bases and require acidic vehicles for optimal stability. The acidic liquids are especially reactive with enteral formulas that contain intact proteins. The result of this interaction can result in an occlusion of the feeding tube as the proteins form a gel-like clog. This study combined the liquid medication directly with the EN formula to determine the potential for feeding tube occlusion. Some drugs formed a solid mass in the test tube immediately, whereas others only presented granules, which may later contribute to obstructing the feeding tube. The prescriber should be aware of the potential impact of their choice in formulation, both in terms of the gastrointestinal tolerance and potential for interaction with coadministered nutrition.

  5. Deterministic bead-in-droplet ejection utilizing an integrated plug-in bead dispenser for single bead-based applications

    NASA Astrophysics Data System (ADS)

    Kim, Hojin; Choi, In Ho; Lee, Sanghyun; Won, Dong-Joon; Oh, Yong Suk; Kwon, Donghoon; Sung, Hyung Jin; Jeon, Sangmin; Kim, Joonwon

    2017-04-01

    This paper presents a deterministic bead-in-droplet ejection (BIDE) technique that regulates the precise distribution of microbeads in an ejected droplet. The deterministic BIDE was realized through the effective integration of a microfluidic single-particle handling technique with a liquid dispensing system. The integrated bead dispenser facilitates the transfer of the desired number of beads into a dispensing volume and the on-demand ejection of bead-encapsulated droplets. Single bead-encapsulated droplets were ejected every 3 s without any failure. Multiple-bead dispensing with deterministic control of the number of beads was demonstrated to emphasize the originality and quality of the proposed dispensing technique. The dispenser was mounted using a plug-socket type connection, and the dispensing process was completely automated using a programmed sequence without any microscopic observation. To demonstrate a potential application of the technique, bead-based streptavidin-biotin binding assay in an evaporating droplet was conducted using ultralow numbers of beads. The results evidenced the number of beads in the droplet crucially influences the reliability of the assay. Therefore, the proposed deterministic bead-in-droplet technology can be utilized to deliver desired beads onto a reaction site, particularly to reliably and efficiently enrich and detect target biomolecules.

  6. Deterministic bead-in-droplet ejection utilizing an integrated plug-in bead dispenser for single bead-based applications.

    PubMed

    Kim, Hojin; Choi, In Ho; Lee, Sanghyun; Won, Dong-Joon; Oh, Yong Suk; Kwon, Donghoon; Sung, Hyung Jin; Jeon, Sangmin; Kim, Joonwon

    2017-04-10

    This paper presents a deterministic bead-in-droplet ejection (BIDE) technique that regulates the precise distribution of microbeads in an ejected droplet. The deterministic BIDE was realized through the effective integration of a microfluidic single-particle handling technique with a liquid dispensing system. The integrated bead dispenser facilitates the transfer of the desired number of beads into a dispensing volume and the on-demand ejection of bead-encapsulated droplets. Single bead-encapsulated droplets were ejected every 3 s without any failure. Multiple-bead dispensing with deterministic control of the number of beads was demonstrated to emphasize the originality and quality of the proposed dispensing technique. The dispenser was mounted using a plug-socket type connection, and the dispensing process was completely automated using a programmed sequence without any microscopic observation. To demonstrate a potential application of the technique, bead-based streptavidin-biotin binding assay in an evaporating droplet was conducted using ultralow numbers of beads. The results evidenced the number of beads in the droplet crucially influences the reliability of the assay. Therefore, the proposed deterministic bead-in-droplet technology can be utilized to deliver desired beads onto a reaction site, particularly to reliably and efficiently enrich and detect target biomolecules.

  7. Heterogeneous immunoassays using magnetic beads on a digital microfluidic platform.

    PubMed

    Sista, Ramakrishna S; Eckhardt, Allen E; Srinivasan, Vijay; Pollack, Michael G; Palanki, Srinivas; Pamula, Vamsee K

    2008-12-01

    A digital microfluidic platform for performing heterogeneous sandwich immunoassays based on efficient handling of magnetic beads is presented in this paper. This approach is based on manipulation of discrete droplets of samples and reagents using electrowetting without the need for channels where the droplets are free to move laterally. Droplet-based manipulation of magnetic beads therefore does not suffer from clogging of channels. Immunoassays on a digital microfluidic platform require the following basic operations: bead attraction, bead washing, bead retention, and bead resuspension. Several parameters such as magnetic field strength, pull force, position, and buffer composition were studied for effective bead operations. Dilution-based washing of magnetic beads was demonstrated by immobilizing the magnetic beads using a permanent magnet and splitting the excess supernatant using electrowetting. Almost 100% bead retention was achieved after 7776-fold dilution-based washing of the supernatant. Efficient resuspension of magnetic beads was achieved by transporting a droplet with magnetic beads across five electrodes on the platform and exploiting the flow patterns within the droplet to resuspend the beads. All the magnetic-bead droplet operations were integrated together to generate standard curves for sandwich heterogeneous immunoassays on human insulin and interleukin-6 (IL-6) with a total time to result of 7 min for each assay.

  8. Heterogeneous Immunoassays Using Magnetic beads On a Digital Microfluidic Platform

    PubMed Central

    Sista, Ramakrishna S.; Eckhardt, Allen E.; Srinivasan, Vijay; Pollack, Michael G.; Palanki, Srinivas; Pamula, Vamsee K.

    2009-01-01

    A digital microfluidic platform for performing heterogeneous sandwich immunoassays based on efficient handling of magnetic beads is presented in this paper. This approach is based on manipulation of discrete droplets of samples and reagents using electrowetting without the need for channels where the droplets are free to move laterally. Droplet-based manipulation of magnetic beads therefore does not suffer from clogging of channels. Immunoassays on a digital microfluidic platform require the following basic operations: bead attraction, bead washing, bead retention, and bead resuspension. Several parameters such as magnetic field strength, pull force, position, and buffer composition were studied for effective bead operations. Dilution-based washing of magnetic beads was demonstrated by immobilizing the magnetic beads using a permanent magnet and splitting the excess supernatant using electrowetting. Almost 100% bead retention was achieved after 7776 fold dilution-based washing of the supernatant. Efficient resuspension of magnetic beads was achieved by transporting a droplet with magnetic beads across five electrodes on the platform and exploiting the flow patterns within the droplet to resuspend the beads. All the magnetic-bead droplet operations were integrated together to generate standard curves for sandwich heterogeneous immunoassays on Human Insulin and Interleukin-6 (IL-6) with a total time to result of seven minutes for each assay. PMID:19023486

  9. Novel method for screening of enteric film coatings properties with magnetic resonance imaging.

    PubMed

    Dorożyński, Przemysław; Jamróz, Witold; Niwiński, Krzysztof; Kurek, Mateusz; Węglarz, Władysław P; Jachowicz, Renata; Kulinowski, Piotr

    2013-11-18

    The aim of the study is to present the concept of novel method for fast screening of enteric coating compositions properties without the need of preparation of tablets batches for fluid bed coating. Proposed method involves evaluation of enteric coated model tablets in specially designed testing cell with application of MRI technique. The results obtained in the testing cell were compared with results of dissolution studies of mini-tablets coated in fluid bed apparatus. The method could be useful in early stage of formulation development for screening of film coating properties that will shorten and simplify the development works. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. NIST/ISAC standardization study: variability in assignment of intensity values to fluorescence standard beads and in cross calibration of standard beads to hard dyed beads.

    PubMed

    Hoffman, Robert A; Wang, Lili; Bigos, Martin; Nolan, John P

    2012-09-01

    Results from a standardization study cosponsored by the International Society for Advancement of Cytometry (ISAC) and the US National Institute of Standards and Technology (NIST) are reported. The study evaluated the variability of assigning intensity values to fluorophore standard beads by bead manufacturers and the variability of cross calibrating the standard beads to stained polymer beads (hard-dyed beads) using different flow cytometers. Hard dyed beads are generally not spectrally matched to the fluorophores used to stain cells, and spectral response varies among flow cytometers. Thus if hard dyed beads are used as fluorescence calibrators, one expects calibration for specific fluorophores (e.g., FITC or PE) to vary among different instruments. Using standard beads surface-stained with specific fluorophores (FITC, PE, APC, and Pacific Blue™), the study compared the measured intensity of fluorophore standard beads to that of hard dyed beads through cross calibration on 133 different flow cytometers. Using robust CV as a measure of variability, the variation of cross calibrated values was typically 20% or more for a particular hard dyed bead in a specific detection channel. The variation across different instrument models was often greater than the variation within a particular instrument model. As a separate part of the study, NIST and four bead manufacturers used a NIST supplied protocol and calibrated fluorophore solution standards to assign intensity values to the fluorophore beads. Values assigned to the reference beads by different groups varied by orders of magnitude in most cases, reflecting differences in instrumentation used to perform the calibration. The study concluded that the use of any spectrally unmatched hard dyed bead as a general fluorescence calibrator must be verified and characterized for every particular instrument model. Close interaction between bead manufacturers and NIST is recommended to have reliable and uniformly assigned fluorescence standard beads. Copyright © 2012 International Society for Advancement of Cytometry.

  11. Innovative formulation of nystatin particulate systems in toothpaste for candidiasis treatment.

    PubMed

    Pinto Reis, Catarina; Vasques Roque, Luís; Baptista, Marina; Rijo, Patrícia

    2016-01-01

    Oral candidiasis is a mycosis on the mucous membranes of the mouth but not limited to the mouth. Nystatin is one of the most frequently employed antifungal agents to treat infections and may be safely given orally as well as applied topically but its absorption through mucocutaneous membranes such as the gut and the skin is minimal. The purpose of this study is to enhance the effectiveness of nystatin using particulate system such as beads, micro- and nanoparticles of alginate incorporated into toothpaste. Those particulate systems of nystatin were prepared by extrusion/external gelation for beads and emulsification/internal gelation for micro- and nanoparticles and characterized. Small, anionic charged and monodispersed particles were successfully produced. The type of particulate system influenced all previous parameters, being microparticles the most suitable particulate system of nystatin showing the slowest release, the highest inhibitory effect of Candida albicans over a period of one year. Those results allowed the conclusion that alginate exhibits properties that enable the in vitro functionality of encapsulated nystatin and thus may provide the basis for new successful approaches for the treatment of oral antifungal infections such as oral candidiasis.

  12. Reconfiguration of a flexible flat plate under snow loading

    NASA Astrophysics Data System (ADS)

    Gosselin, Frédérick; de Langre, Emmanuel

    2015-11-01

    Snow and wind constitute two of the main sources of mechanical loading on terrestrial plants. Plants bend and twist with large amplitude to bear these loads. For the past ten years, various authors have sought to decompose the problem of plant reconfiguration under fluid flow into its fundamental mechanical ingredients by studying the reconfiguration of simple flexible structures such as beams, plates, rods and strips. Here, we adopt a similar approach to these studies and consider the snow interception of a flexible flat plate. We performed two sets of experiments on thin flexible rectangular plates supported at their center: in the first one, a plate was subjected to real snowing events; in the second one, a plate was loaded with glass beads acting as a granular media similar to snow. Moreover, a theoretical model coupling the Elastica formulation to a loading with a set angle of repose is developed. The model is found to be in good agreement with the experiments on glass beads. Asymptotic scaling laws can be found similarly to the Vogel exponents of reconfiguring structures. For the real snow loading, it is found that the cohesive force in snow which is highly dependent on the snow temperature complicate things greatly.

  13. Quantum identities for the action

    NASA Astrophysics Data System (ADS)

    Gozzi, E.

    2018-04-01

    In this paper we derive various identities involving the action functional which enters the path-integral formulation of quantum mechanics. They provide some kind of generalisations of the Ehrenfest theorem giving correlations between powers of the action and its functional derivatives.

  14. Influence of Immobilized Biomolecules on Magnetic Bead Plug Formation and Retention in Capillary Electrophoresis

    PubMed Central

    Henken, Rachel L.; Chantiwas, Rattikan; Gilman, S. Douglass

    2012-01-01

    Significant changes in the formation and retention of magnetic bead plugs in a capillary during electrophoresis were studied, and it was demonstrated that these effects were due to the type of biological molecule immobilized on the surface of these beads. Three biological molecules, an antibody, an oligonucleotide and alkaline phosphatase, were attached to otherwise identical streptavidin-coated magnetic beads through biotin-avidin binding in order to isolate differences in bead immobilization in a magnetic field resulting from the type of biological molecule immobilized on the bead surface. Alkaline phosphatase also was attached to the magnetic beads using epoxy groups on the bead surfaces (instead of avidin-biotin binding) to study the impact of immobilization chemistry. The formation and retention of magnetic bead plugs were studied quantitatively using light scattering detection of magnetic particles eluting from the bead plugs and qualitatively using microscopy. Both the type of biomolecule immobilized on the magnetic bead surface and the chemistry used to link the biomolecule to the magnetic bead impacted the formation and retention of the bead plugs. PMID:22437880

  15. Diclofenac and metabolite pharmacokinetics in children.

    PubMed

    van der Marel, Caroline D; Anderson, Brian J; Rømsing, Janne; Jacqz-Aigrain, Evelyne; Tibboel, Dick

    2004-06-01

    Data concerning metabolism of diclofenac in children are limited to intravenous and enteric coated oral formulations. There are no data examining diclofenac or its hydroxyl metabolite pharmacokinetics after rectal administration in children. Infants (n = 26) undergoing tonsillectomy were given diclofenac 2 mg.kg(-1) followed by 1 mg.kg(-1) 8 h as suppository formulation for postoperative analgesia. Serum was assayed for diclofenac, 4'-hydroxydiclofenac and 5'-hydroxydiclofenac concentrations during the procedure and 1, 2 and 4 h postoperatively. The formation clearances of diclofenac to hydroxyl metabolites were estimated using nonlinear mixed effects models. A single compartment, first order absorption and first order elimination model was used to describe diclofenac pharmacokinetics. Published data from 11 children given enteric-coated diclofenac tablets were used to assess relative bioavailability. Mean (sd) age and weight of the patients were 4.5 (1.5) years and 20.5 (4.1) kg. The formation clearance to 4'-hydroxydiclofenac (% CV) and to 5'-hydroxydiclofenac were 8.41 (8.1) and 3.41 (113) l.h(-1) respectively, standardized to a 70 kg person using allometric '1/4 power' models. Clearance by other routes contributed 33.0 (64) l.h(-1) 70 kg(-1). Elimination clearance of hydroxyl metabolites was fixed at 27.5 l.h(-1) 70 kg(-1). The volumes of distribution of parent diclofenac and its hydroxyl metabolite were 22.8 (19.0) and 45.3 (l.70) kg(-1). The suppository formulation had an absorption half-life of 0.613 (33.2) h with a lag time of 0.188 (24.9) h. Interoccasion variability of formation clearance to 4'-hydroxydiclofenac, diclofenac volume of distribution, absorption half-time and lag time for the suppository was 36%, 55%, 14% and 119%, respectively. The relative bioavailability of the suppository compared with an enteric-coated tablet was 1.26. The formation clearance of the active metabolite 4'-hydroxydiclofenac contributed 19% of total clearance (44.82 l.h(-1) 70 kg(-1)). The rectum is a suitable route for administration of diclofenac in children 2-8 year of age and was associated with a higher relative bioavailabilty than enteric-coated tablets and an earlier maximum concentration (50 vs. 108 min). This pharmacokinetic profile renders diclofenac suppository a suitable formulation for short duration surgery.

  16. Superfield quantization

    NASA Astrophysics Data System (ADS)

    Batalin, I. A.; Bering, K.; Damgaard, P. H.

    1998-03-01

    We present a superfield formulation of the quantization program for theories with first-class constraints. An exact operator formulation is given, and we show how to set up a phase-space path integral entirely in terms of superfields. BRST transformations and canonical transformations enter on equal footing, and they allow us to establish a superspace analog of the BFV theorem. We also present a formal derivation of the Lagrangian superfield analogue of the field-antifield formalism by an integration over half of the phase-space variables.

  17. Development of formulations to improve the controlled-release of linalool to be applied as an insecticide.

    PubMed

    Lopez, M D; Maudhuit, A; Pascual-Villalobos, M J; Poncelet, D

    2012-02-08

    In recent studies, insecticide activity of a monoterpene, linalool, has been demonstrated, finding, however, limitations in application because of its rapid volatilization. Potential effectiveness of microcapsules and effects of various types of matrices on its stability as controlled-release systems for the slow volatilization of linalool to be applied as insecticide were evaluated. To study controlled-release, linalool was entrapped into microcapsules, inclusion complexes, and beads, obtained by different methods, inverse gelation (IG1, IG2, IG3, IG4, and IG5), oil-emulsion-entrapment (OEE), interfacial coacervation (INCO), and chemical precipitation (Cyc5 and Cyc10). The encapsulation yield turned out to be different for each formulation, reaching the maximum retention for IG1 and OEE. In controlled-release, OEE followed by INCO presented a long time necessary for releasing as a result of the presence of glycerol or chitosan. These results pointed out remarkable differences in the release behavior of linalool depending on matrix composition and the method of encapsulation.

  18. Identification of internal properties of fibers and micro-swimmers

    NASA Astrophysics Data System (ADS)

    Plouraboue, Franck; Thiam, Ibrahima; Delmotte, Blaise; Climent, Eric; PSC Collaboration

    2016-11-01

    In this presentation we discuss the identifiability of constitutive parameters of passive or active micro-swimmers. We first present a general framework for describing fibers or micro-swimmers using a bead-model description. Using a kinematic constraint formulation to describe fibers, flagellum or cilia, we find explicit linear relationship between elastic constitutive parameters and generalised velocities from computing contact forces. This linear formulation then permits to address explicitly identifiability conditions and solve for parameter identification. We show that both active forcing and passive parameters are both identifiable independently but not simultaneously. We also provide unbiased estimators for elastic parameters as well as active ones in the presence of Langevin-like forcing with Gaussian noise using normal linear regression models and maximum likelihood method. These theoretical results are illustrated in various configurations of relaxed or actuated passives fibers, and active filament of known passive properties, showing the efficiency of the proposed approach for direct parameter identification. The convergence of the proposed estimators is successfully tested numerically.

  19. Development and optimization of enteric coated mucoadhesive microspheres of duloxetine hydrochloride using 3(2) full factorial design.

    PubMed

    Setia, Anupama; Kansal, Sahil; Goyal, Naveen

    2013-07-01

    Microspheres constitute an important part of oral drug delivery system by virtue of their small size and efficient carrier capacity. However, the success of these microspheres is limited due to their short residence time at the site of absorption. The objective of the present study was to formulate and systematically evaluate in vitro performance of enteric coated mucoadhesive microspheres of duloxetine hydrochloride (DLX), an acid labile drug. DLX microspheres were prepared by simple emulsification phase separation technique using chitosan as carrier and glutaraldehyde as a cross-linking agent. Microspheres prepared were coated with eudragit L-100 using an oil-in-oil solvent evaporation method. Eudragit L-100was used as enteric coating polymer with the aim to release the drug in small intestine The microspheres prepared were characterized by particle size, entrapment efficiency, swelling index (SI), mucoadhesion time, in vitro drug release and surface morphology. A 3(2) full factorial design was employed to study the effect of independent variables polymer-to-drug ratio (X1) and stirring speed (X2) on dependent variables, particle size, entrapment efficiency, SI, in vitro mucoadhesion and drug release up to 24 h (t24). Microspheres formed were discrete, spherical and free flowing. The microspheres exhibited good mucoadhesive property and also showed high percentage entrapment efficiency. The microspheres were able to sustain the drug release up to 24 h. Thus, the prepared enteric coated mucoadhesive microspheres may prove to be a potential controlled release formulation of DLX for oral administration.

  20. Detection of mitochondrial DNA with the compact bead array sensor system (cBASS)

    NASA Astrophysics Data System (ADS)

    Mulvaney, Shawn P.; Ibe, Carol N.; Caldwell, Jane M.; Levine, Jay F.; Whitman, Lloyd J.; Tamanaha, Cy R.

    2009-02-01

    Enteric pathogens are a significant contaminant in surface waters used for recreation, fish and shellfish harvesting, crop irrigation, and human consumption. The need for water monitoring becomes more pronounced when industrial, agricultural, and residential lands are found in close proximity. Fecal contamination is particularly problematic and identification of the pollution source essential to remediation efforts. Standard monitoring for fecal contamination relies on indicator organisms, but the technique is too broad to identify the source of contamination. Instead, real-time PCR of mitochondrial DNA (mtDNA) is an emerging method for identification of the contamination source. Presented herein, we evaluate an alternative technology, the compact Bead Array Sensor System (cBASS®) and its assay approach Fluidic Force Discrimination (FFD), for the detection of mtDNA. Previously, we achieved multiplexed, attomolar detection of toxins and femtomolar detection of nucleic acids in minutes with FFD assays. More importantly, FFD assays are compatible with a variety of complex matrices and therefore potentially applicable for samples where the matrix would interfere with PCR amplification. We have designed a triplex assay for the NADH gene found in human, swine, and bovine mtDNA and demonstrated the specific detection of human mtDNA spiked into a waste water sample.

  1. Activation, orientation and landing of female Culex quinquefasciatus in response to carbon dioxide and odour from human feet: 3-D flight analysis in a wind tunnel.

    PubMed

    Lacey, E S; Cardé, R T

    2011-03-01

    This study investigated the interaction between carbon dioxide (CO(2) ) and human foot odour on activation, upwind orientation and landing of host-seeking female Culex quinquefasciatus (Say) (Diptera: Culicidae) in a wind tunnel. More mosquitoes landed on warmed glass beads coated with foot odour than on clean beads; adding a plume of 4% CO(2) did not influence the proportion of mosquitoes landing. A second experiment used 3-dimensional video tracking to assess flight performance. Activation was more rapid with CO(2) and with CO(2) + foot odour than with clean air or with foot odour alone. Upwind flights were fastest with CO(2) and with clean air, and slowest with foot odour; the CO(2) + foot odour treatment overlapped the previous three treatments in significance. Flight headings tended more towards due upwind with CO(2) and with clean air than with CO(2) + foot odour or with foot odour alone. In both experiments, many mosquitoes flew upwind in clean air. There was little evidence of females changing course upon entering or exiting the CO(2) plume or reacting to foot odour during flight. © 2010 The Authors. Medical and Veterinary Entomology © 2010 The Royal Entomological Society.

  2. A highly efficient bead extraction technique with low bead number for digital microfluidic immunoassay

    PubMed Central

    Tsai, Po-Yen; Lee, I-Chin; Hsu, Hsin-Yun; Huang, Hong-Yuan; Fan, Shih-Kang; Liu, Cheng-Hsien

    2016-01-01

    Here, we describe a technique to manipulate a low number of beads to achieve high washing efficiency with zero bead loss in the washing process of a digital microfluidic (DMF) immunoassay. Previously, two magnetic bead extraction methods were reported in the DMF platform: (1) single-side electrowetting method and (2) double-side electrowetting method. The first approach could provide high washing efficiency, but it required a large number of beads. The second approach could reduce the required number of beads, but it was inefficient where multiple washes were required. More importantly, bead loss during the washing process was unavoidable in both methods. Here, an improved double-side electrowetting method is proposed for bead extraction by utilizing a series of unequal electrodes. It is shown that, with proper electrode size ratio, only one wash step is required to achieve 98% washing rate without any bead loss at bead number less than 100 in a droplet. It allows using only about 25 magnetic beads in DMF immunoassay to increase the number of captured analytes on each bead effectively. In our human soluble tumor necrosis factor receptor I (sTNF-RI) model immunoassay, the experimental results show that, comparing to our previous results without using the proposed bead extraction technique, the immunoassay with low bead number significantly enhances the fluorescence signal to provide a better limit of detection (3.14 pg/ml) with smaller reagent volumes (200 nl) and shorter analysis time (<1 h). This improved bead extraction technique not only can be used in the DMF immunoassay but also has great potential to be used in any other bead-based DMF systems for different applications. PMID:26858807

  3. Seeds used for Bodhi beads in China

    PubMed Central

    2014-01-01

    Background Bodhi beads are a Buddhist prayer item made from seeds. Bodhi beads have a large and emerging market in China, and demand for the beads has particularly increased in Buddhism regions, especially Tibet. Many people have started to focus on and collect Bodhi beads and to develop a Bodhi bead culture. But no research has examined the source plants of Bodhi beads. Therefore, ethnobotanical surveys were conducted in six provinces of China to investigate and document Bodhi bead plants. Reasons for the development of Bodhi bead culture were also discussed. Methods Six provinces of China were selected for market surveys. Information was collected using semi-structured interviews, key informant interviews, and participatory observation with traders, tourists, and local residents. Barkhor Street in Lhasa was focused on during market surveys because it is one of the most popular streets in China. Results Forty-seven species (including 2 varieties) in 19 families and 39 genera represented 52 types of Bodhi beads that were collected. The most popular Bodhi bead plants have a long history and religious significance. Most Bodhi bead plants can be used as medicine or food, and their seeds or fruits are the main elements in these uses. ‘Bodhi seeds’ have been historically used in other countries for making ornaments, especially seeds of the legume family. Many factors helped form Bodhi bead culture in China, but its foundation was in Indian Buddhist culture. Conclusions As one of the earliest adornment materials, seeds played an important role for human production and life. Complex sources of Bodhi beads have different cultural and historical significance. People bought and collected Bodhi beads to reflect their love and admiration for the plants. Thus, the documentation of Bodhi bead plants can serve as a basis for future investigation of Bodhi bead culture and modern Buddhist culture. PMID:24479788

  4. Seeds used for Bodhi beads in China.

    PubMed

    Li, Feifei; Li, Jianqin; Liu, Bo; Zhuo, Jingxian; Long, Chunlin

    2014-01-30

    Bodhi beads are a Buddhist prayer item made from seeds. Bodhi beads have a large and emerging market in China, and demand for the beads has particularly increased in Buddhism regions, especially Tibet. Many people have started to focus on and collect Bodhi beads and to develop a Bodhi bead culture. But no research has examined the source plants of Bodhi beads. Therefore, ethnobotanical surveys were conducted in six provinces of China to investigate and document Bodhi bead plants. Reasons for the development of Bodhi bead culture were also discussed. Six provinces of China were selected for market surveys. Information was collected using semi-structured interviews, key informant interviews, and participatory observation with traders, tourists, and local residents. Barkhor Street in Lhasa was focused on during market surveys because it is one of the most popular streets in China. Forty-seven species (including 2 varieties) in 19 families and 39 genera represented 52 types of Bodhi beads that were collected. The most popular Bodhi bead plants have a long history and religious significance. Most Bodhi bead plants can be used as medicine or food, and their seeds or fruits are the main elements in these uses. 'Bodhi seeds' have been historically used in other countries for making ornaments, especially seeds of the legume family. Many factors helped form Bodhi bead culture in China, but its foundation was in Indian Buddhist culture. As one of the earliest adornment materials, seeds played an important role for human production and life. Complex sources of Bodhi beads have different cultural and historical significance. People bought and collected Bodhi beads to reflect their love and admiration for the plants. Thus, the documentation of Bodhi bead plants can serve as a basis for future investigation of Bodhi bead culture and modern Buddhist culture.

  5. Metal-Containing Polystyrene Beads as Standards for Mass Cytometry

    PubMed Central

    Abdelrahman, Ahmed I.; Ornatsky, Olga; Bandura, Dmitry; Kinach, Robert; Dai, Sheng; Thickett, Stuart C.; Tanner, Scott

    2010-01-01

    We examine the suitability of metal-containing polystyrene beads for the calibration of a mass cytometer instrument, a single particle analyser based on an inductively coupled plasma ion source and a time of flight mass spectrometer. These metal-containing beads are also verified for their use as internal standards for this instrument. These beads were synthesized by multiple-stage dispersion polymerization with acrylic acid as a comonomer. Acrylic acid acts as a ligand to anchor the metal ions within the interior of the beads. Mass cytometry enabled the bead-by-bead measurement of the metal-content and determination of the metal-content distribution. Beads synthesized by dispersion polymerization that involved three stages were shown to have narrower bead-to-bead variation in their lanthanide content than beads synthesized by 2-stage dispersion polymerization. The beads exhibited insignificant release of their lanthanide content to aqueous solutions of different pHs over a period of six months. When mixed with KG1a or U937 cell lines, metal-containing polymer beads were shown not to affect the mass cytometry response to the metal content of element-tagged antibodies specifically attached to these cells. PMID:20390041

  6. Metal-Containing Polystyrene Beads as Standards for Mass Cytometry.

    PubMed

    Abdelrahman, Ahmed I; Ornatsky, Olga; Bandura, Dmitry; Baranov, Vladimir; Kinach, Robert; Dai, Sheng; Thickett, Stuart C; Tanner, Scott; Winnik, Mitchell A

    2010-01-01

    We examine the suitability of metal-containing polystyrene beads for the calibration of a mass cytometer instrument, a single particle analyser based on an inductively coupled plasma ion source and a time of flight mass spectrometer. These metal-containing beads are also verified for their use as internal standards for this instrument. These beads were synthesized by multiple-stage dispersion polymerization with acrylic acid as a comonomer. Acrylic acid acts as a ligand to anchor the metal ions within the interior of the beads. Mass cytometry enabled the bead-by-bead measurement of the metal-content and determination of the metal-content distribution. Beads synthesized by dispersion polymerization that involved three stages were shown to have narrower bead-to-bead variation in their lanthanide content than beads synthesized by 2-stage dispersion polymerization. The beads exhibited insignificant release of their lanthanide content to aqueous solutions of different pHs over a period of six months. When mixed with KG1a or U937 cell lines, metal-containing polymer beads were shown not to affect the mass cytometry response to the metal content of element-tagged antibodies specifically attached to these cells.

  7. Brownian dynamics simulations with stiff finitely extensible nonlinear elastic-Fraenkel springs as approximations to rods in bead-rod models.

    PubMed

    Hsieh, Chih-Chen; Jain, Semant; Larson, Ronald G

    2006-01-28

    A very stiff finitely extensible nonlinear elastic (FENE)-Fraenkel spring is proposed to replace the rigid rod in the bead-rod model. This allows the adoption of a fast predictor-corrector method so that large time steps can be taken in Brownian dynamics (BD) simulations without over- or understretching the stiff springs. In contrast to the simple bead-rod model, BD simulations with beads and FENE-Fraenkel (FF) springs yield a random-walk configuration at equilibrium. We compare the simulation results of the free-draining bead-FF-spring model with those for the bead-rod model in relaxation, start-up of uniaxial extensional, and simple shear flows, and find that both methods generate nearly identical results. The computational cost per time step for a free-draining BD simulation with the proposed bead-FF-spring model is about twice as high as the traditional bead-rod model with the midpoint algorithm of Liu [J. Chem. Phys. 90, 5826 (1989)]. Nevertheless, computations with the bead-FF-spring model are as efficient as those with the bead-rod model in extensional flow because the former allows larger time steps. Moreover, the Brownian contribution to the stress for the bead-FF-spring model is isotropic and therefore simplifies the calculation of the polymer stresses. In addition, hydrodynamic interaction can more easily be incorporated into the bead-FF-spring model than into the bead-rod model since the metric force arising from the non-Cartesian coordinates used in bead-rod simulations is absent from bead-spring simulations. Finally, with our newly developed bead-FF-spring model, existing computer codes for the bead-spring models can trivially be converted to ones for effective bead-rod simulations merely by replacing the usual FENE or Cohen spring law with a FENE-Fraenkel law, and this convertibility provides a very convenient way to perform multiscale BD simulations.

  8. Brownian dynamics simulations with stiff finitely extensible nonlinear elastic-Fraenkel springs as approximations to rods in bead-rod models

    NASA Astrophysics Data System (ADS)

    Hsieh, Chih-Chen; Jain, Semant; Larson, Ronald G.

    2006-01-01

    A very stiff finitely extensible nonlinear elastic (FENE)-Fraenkel spring is proposed to replace the rigid rod in the bead-rod model. This allows the adoption of a fast predictor-corrector method so that large time steps can be taken in Brownian dynamics (BD) simulations without over- or understretching the stiff springs. In contrast to the simple bead-rod model, BD simulations with beads and FENE-Fraenkel (FF) springs yield a random-walk configuration at equilibrium. We compare the simulation results of the free-draining bead-FF-spring model with those for the bead-rod model in relaxation, start-up of uniaxial extensional, and simple shear flows, and find that both methods generate nearly identical results. The computational cost per time step for a free-draining BD simulation with the proposed bead-FF-spring model is about twice as high as the traditional bead-rod model with the midpoint algorithm of Liu [J. Chem. Phys. 90, 5826 (1989)]. Nevertheless, computations with the bead-FF-spring model are as efficient as those with the bead-rod model in extensional flow because the former allows larger time steps. Moreover, the Brownian contribution to the stress for the bead-FF-spring model is isotropic and therefore simplifies the calculation of the polymer stresses. In addition, hydrodynamic interaction can more easily be incorporated into the bead-FF-spring model than into the bead-rod model since the metric force arising from the non-Cartesian coordinates used in bead-rod simulations is absent from bead-spring simulations. Finally, with our newly developed bead-FF-spring model, existing computer codes for the bead-spring models can trivially be converted to ones for effective bead-rod simulations merely by replacing the usual FENE or Cohen spring law with a FENE-Fraenkel law, and this convertibility provides a very convenient way to perform multiscale BD simulations.

  9. Modeling of weld bead geometry for rapid manufacturing by robotic GMAW

    NASA Astrophysics Data System (ADS)

    Yang, Tao; Xiong, Jun; Chen, Hui; Chen, Yong

    2015-03-01

    Weld-based rapid prototyping (RP) has shown great promises for fabricating 3D complex parts. During the layered deposition of forming metallic parts with robotic gas metal arc welding, the geometry of a single weld bead has an important influence on surface finish quality, layer thickness and dimensional accuracy of the deposited layer. In order to obtain accurate, predictable and controllable bead geometry, it is essential to understand the relationships between the process variables with the bead geometry (bead width, bead height and ratio of bead width to bead height). This paper highlights an experimental study carried out to develop mathematical models to predict deposited bead geometry through the quadratic general rotary unitized design. The adequacy and significance of the models were verified via the analysis of variance. Complicated cause-effect relationships between the process parameters and the bead geometry were revealed. Results show that the developed models can be applied to predict the desired bead geometry with great accuracy in layered deposition with accordance to the slicing process of RP.

  10. Deterministic bead-in-droplet ejection utilizing an integrated plug-in bead dispenser for single bead–based applications

    PubMed Central

    Kim, Hojin; Choi, In Ho; Lee, Sanghyun; Won, Dong-Joon; Oh, Yong Suk; Kwon, Donghoon; Sung, Hyung Jin; Jeon, Sangmin; Kim, Joonwon

    2017-01-01

    This paper presents a deterministic bead-in-droplet ejection (BIDE) technique that regulates the precise distribution of microbeads in an ejected droplet. The deterministic BIDE was realized through the effective integration of a microfluidic single-particle handling technique with a liquid dispensing system. The integrated bead dispenser facilitates the transfer of the desired number of beads into a dispensing volume and the on-demand ejection of bead-encapsulated droplets. Single bead–encapsulated droplets were ejected every 3 s without any failure. Multiple-bead dispensing with deterministic control of the number of beads was demonstrated to emphasize the originality and quality of the proposed dispensing technique. The dispenser was mounted using a plug-socket type connection, and the dispensing process was completely automated using a programmed sequence without any microscopic observation. To demonstrate a potential application of the technique, bead-based streptavidin–biotin binding assay in an evaporating droplet was conducted using ultralow numbers of beads. The results evidenced the number of beads in the droplet crucially influences the reliability of the assay. Therefore, the proposed deterministic bead-in-droplet technology can be utilized to deliver desired beads onto a reaction site, particularly to reliably and efficiently enrich and detect target biomolecules. PMID:28393911

  11. Microscopic Examination of Chitosan Polyphosphate Beads with Entrapped Spores of the Biocontrol Agent, Streptomyces melanosporofaciens EF-76

    NASA Astrophysics Data System (ADS)

    Jobin, Guy; Grondin, Gilles; Couture, Geneviève; Beaulieu, Carole

    2005-04-01

    Spores of the biocontrol agent, Streptomyces melanosporofaciens EF-76, were entrapped by complex coacervation in beads composed of a macromolecular complex (MC) of chitosan and polyphosphate. A proportion of spores entrapped in beads survived the entrapment procedure as shown by treating spores from chitosan beads with a dye allowing the differentiation of live and dead cells. The spore-loaded chitosan beads could be digested by a chitosanase, suggesting that, once introduced in soil, the beads would be degraded to release the biocontrol agent. Spore-loaded beads were examined by optical and scanning electron microscopy because the release of the biological agent depends on the spore distribution in the chitosan beads. The microscopic examination revealed that the beads had a porous surface and contained a network of inner microfibrils. Spores were entrapped in both the chitosan microfibrils and the bead lacuna.

  12. Clinical Efficacy and Residue Depletion of 10% Enrofloxacin Enteric-Coated Granules in Pigs.

    PubMed

    Lei, Zhixin; Liu, Qianying; Yang, Bing; Xiong, Jincheng; Li, Kun; Ahmed, Saeed; Hong, Liping; Chen, Pin; He, Qigai; Cao, Jiyue

    2017-01-01

    A new, more palatable formulation of 10% enrofloxacin enteric-coated granules was investigated to evaluate the pharmacokinetic effect in plasma, the residue elimination in tissues and the clinical efficacy against Actinobacillus pleuropneumonia (APP) and Mycoplasam suis (MS) in pigs. In this study, the enrofloxacin concentrations in plasma and tissues were detected using high-performance liquid chromatography with phosphate buffer (pH = 3) and acetonitrile. The pharmacokinetics and elimination of enrofloxacin enteric-coated granules were performed after oral administration at a single dose of 10 mg/kg body weight (bw) and 5 mg/kg twice per day for 5 consecutive days, respectively. The in vivo antibacterial efficacy and clinical effectiveness of enrofloxacin enteric-coated granules against APP and MS were assayed at 2.5, 5, 10 mg/kg, compared with tiamulin (8 mg/kg) based on establishment of APP and MS infection models. 56 APP strains were selected and tested for in vitro antibacterial activity of enrofloxacin enteric-coated granules. The main parameters of elimination half-life (t 1/2β ), T max , and area under the curve (AUC) were 14.99 ± 4.19, 3.99 ± 0.10, and 38.93 ± 1.52 μg h/ml, respectively, revealing that the enrofloxacin concentration remained high and with a sustainable distribution in plasma. Moreover, the analysis on the evaluation of enrofloxacin and ciprofloxacin in muscle, fat, liver and kidney showed that the recovery were more than 84% recovery in accordance with the veterinary drug residue guidelines of United States pharmacopeia, and the withdrawal periods were 4.28, 3.81, 4.84, and 3.51 days, respectively, suggesting that the withdrawal period was 5 d after oral administration of 5 mg/kg twice per day. The optimal dosage of enrofloxacin enteric-coated granules against APP and MS was 5 mg/kg, with over 90% efficacy, which was significantly different ( p < 0.05) to the 2.5 mg/kg group, but not to the 10 mg/kg group or the positive control group (tiamulin). In conclusion, 10% enrofloxacin enteric-coated granules had significant potential for treating APP and MS , and it provided an alternative enrofloxacin palatability formulation.

  13. Contact angle and surface free energy of experimental resin-based dental restorative materials after chewing simulation.

    PubMed

    Rüttermann, Stefan; Beikler, Thomas; Janda, Ralf

    2014-06-01

    To investigate contact angle and surface free energy of experimental dental resin composites containing novel delivery systems of polymeric hollow beads and low-surface tension agents after chewing simulation test. A delivery system of novel polymeric hollow beads differently loaded with two low-surface tension agents was used in different amounts to modify commonly formulated experimental dental resin composites. The non-modified resin was used as standard. Surface roughness Ra, contact angle Θ, total surface free energy γS, its apolar γS(LW), polar γS(AB), Lewis acid γS(+) and base γS(-) terms were determined and the results prior to and after chewing simulation test were compared. Significance was p<0.05. After chewing simulation Ra increased, Θ decreased, Ra increased for two test materials and γS decreased or remained constant for the standard or the test materials after chewing simulation. Ra of one test material was higher than of the standard, Θ and γS of the test materials remained lower than of the standard and, indicating their highly hydrophobic character (Θ≈60-75°, γS≈30mJm(-2)). γS(LW), and γS(-) of the test materials were lower than of the standard. Some of the test materials had lower γS(AB) and γS(+) than of the standard. Delivery systems based on novel polymeric hollow beads highly loaded with low-surface tension agents were found to significantly increase contact angle and thus to reduce surface free energy of experimental dental resin composites prior to and after chewing simulation test. Copyright © 2014 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  14. Formulation and evaluation of Bacillus coagulans-loaded hypromellose mucoadhesive microspheres.

    PubMed

    Alli, Sk Md Athar

    2011-01-01

    Development of a novel delivery system has been attempted to deliver viable probiotic cells into the gut for a prolonged period of time while maintaining high numbers of viable cells within the formulation throughout the shelf-life of the product and during the gastrointestinal transit. Core mucoadhesive microspheres of Bacillus coagulans were developed employing several grades of hypromellose, a mucoadhesive polymer, following coacervation and phase separation technique and were subsequently enteric-coated with hypromellose phthalate. Microspheres were evaluated for percent yield; entrapment efficiency; in vitro swelling; surface morphology; particle size, size distribution, and zeta potential; flow property, mucoadhesion property by the ex vivo mucoadhesive strength test and the in vitro wash off test; in vitro release profile and release kinetic; in vivo probiotic activity; and stability. The values for the kinetic constant and regression coefficient of model-dependent approaches and the difference factor (f(1)), the similarity factor (f(2)), and the Rescigno index (ξ(1) and ξ(2)) of model independent approaches were determined for comparing in vitro dissolution profiles. Freeze dried B. coagulans cells were successfully formulated as enteric-coated mucoadhesive microspheres with satisfactory physical structure and yield. The viability of B. coagulans was maintained in the simulated gastric conditions and during processing; in simulated intestinal conditions exhibiting mucoadhesion, and controlling and extending the viable cell release following zero-order; and was satisfactorily stable at room temperature. Test results depict statistically significant effects of the hypromellose grade and their concentration on the performance and release profile of formulations.

  15. Formulation and evaluation of Bacillus coagulans-loaded hypromellose mucoadhesive microspheres

    PubMed Central

    Alli, Sk Md Athar

    2011-01-01

    Development of a novel delivery system has been attempted to deliver viable probiotic cells into the gut for a prolonged period of time while maintaining high numbers of viable cells within the formulation throughout the shelf-life of the product and during the gastrointestinal transit. Core mucoadhesive microspheres of Bacillus coagulans were developed employing several grades of hypromellose, a mucoadhesive polymer, following coacervation and phase separation technique and were subsequently enteric-coated with hypromellose phthalate. Microspheres were evaluated for percent yield; entrapment efficiency; in vitro swelling; surface morphology; particle size, size distribution, and zeta potential; flow property, mucoadhesion property by the ex vivo mucoadhesive strength test and the in vitro wash off test; in vitro release profile and release kinetic; in vivo probiotic activity; and stability. The values for the kinetic constant and regression coefficient of model-dependent approaches and the difference factor (f1), the similarity factor (f2), and the Rescigno index (ξ1 and ξ2) of model independent approaches were determined for comparing in vitro dissolution profiles. Freeze dried B. coagulans cells were successfully formulated as enteric-coated mucoadhesive microspheres with satisfactory physical structure and yield. The viability of B. coagulans was maintained in the simulated gastric conditions and during processing; in simulated intestinal conditions exhibiting mucoadhesion, and controlling and extending the viable cell release following zero-order; and was satisfactorily stable at room temperature. Test results depict statistically significant effects of the hypromellose grade and their concentration on the performance and release profile of formulations. PMID:21674019

  16. Micronutrient content in enteral nutrition formulas: comparison with the dietary reference values for healthy populations.

    PubMed

    Iacone, Roberto; Scanzano, Clelia; Santarpia, Lidia; D'Isanto, Anna; Contaldo, Franco; Pasanisi, Fabrizio

    2016-03-31

    The micronutrient content in standard enteral mixtures should be closer to the dietary reference values for a healthy population since standard enteral diets are formulated for subjects with no special nutritional needs. This study compares the micronutrient content of the most common enteral nutrition (EN) formulas with European dietary reference values (DRVs) for healthy population. Sixty-two nutritionally complete enteral formulas were considered. The micronutrient content was calculated by multiplying the value reported on the nutritional information panel of each formula by the daily dose usually prescribed. The comparison between the micronutrient content of all enteral formulas evaluated and the DRVs indicates that daily fluoride and vitamin K requirements were not covered, while an oversupply of many other micronutrients was provided. Moreover, in some enteral formulas, at a dose of 2000 Kcal/day, zinc and vitamin A content exceeded the tolerable upper limits and, for one diabetes-specific enteral formula, the chromium content exceeded the relevant European standards in both 1500 and 2000 Kcal/day diets. Most enteral formulas evaluated are generally suitable for patients on long-term total EN and formulas with higher content of a specific micronutrient may be a useful tool for patients affected by specific clinical conditions, at least for a period of time, then switching to standard enteral mixtures. The availability of nutritional enteral formulas, well balanced also for micronutrient intake, will further improve individualized treatments, particularly for patients on long-term total EN.

  17. Novel Glucagon-Like Peptide-1 Analog Delivered Orally Reduces Postprandial Glucose Excursions in Porcine and Canine Models

    PubMed Central

    Eldor, Roy; Kidron, Miriam; Greenberg-Shushlav, Yael; Arbit, Ehud

    2010-01-01

    Background Glucagon-like peptide-1 (GLP-1) and its analogs are associated with a gamut of physiological processes, including induction of insulin release, support of normoglycemia, β-cell function preservation, improved lipid profiles, and increased insulin sensitivity. Thus, GLP-1 harbors significant therapeutic potential for regulating type 2 diabetes mellitus, where its physiological impact is markedly impaired. To date, GLP-1 analogs are only available as injectable dosage forms, and its oral delivery is expected to provide physiological portal/peripheral concentration ratios while fostering patient compliance and adherence. Methods Healthy, fasting, enterically cannulated pigs and beagle canines were administered a single dose of the exenatide-based ORMD-0901 formulation 30 min before oral glucose challenges. Blood samples were collected every 15 min for evaluation of ORMD-0901 safety and efficacy in regulating postchallenge glucose excursions. Results Enterically delivered ORMD-0901 was well tolerated by all animals. ORMD-0901 formulations RG3 and AG2 led to reduced glucose excursions in pigs when delivered prior to a 5 g/kg glucose challenge, where area under the curve (AUC)0–120 values were up to 43% lower than in control sessions. All canines challenged with a glucose load with no prior exposure to exenatide, demonstrated higher AUC0–150 values than in their exenatide-treated sessions. Subcutaneous exenatide delivery amounted to a 51% reduction in mean glucose AUC0–150, while formulations AG4 and AG3 prompted 43% and 29% reductions, respectively. Conclusions When delivered enterically, GLP-1 (ORMD-0901) is absorbed from the canine and porcine gastrointestinal tracts and retains its biological activity. Further development of this drug class in an oral dosage form is expected to enhance diabetes control and patient compliance. PMID:21129350

  18. Formulation Development, Process Optimization, and In Vitro Characterization of Spray-Dried Lansoprazole Enteric Microparticles

    PubMed Central

    Vora, Chintan; Patadia, Riddhish; Mittal, Karan; Mashru, Rajashree

    2016-01-01

    This research focuses on the development of enteric microparticles of lansoprazole in a single step by employing the spray drying technique and studies the effects of variegated formulation/process variables on entrapment efficiency and in vitro gastric resistance. Preliminary trials were undertaken to optimize the type of Eudragit and its various levels. Further trials included the incorporation of plasticizer triethyl citrate and combinations of other polymers with Eudragit S 100. Finally, various process parameters were varied to investigate their effects on microparticle properties. The results revealed Eudragit S 100 as the paramount polymer giving the highest gastric resistance in comparison to Eudragit L 100-55 and L 100 due to its higher pH threshold and its polymeric backbone. Incorporation of plasticizer not only influenced entrapment efficiency, but diminished gastric resistance severely. On the contrary, polymeric combinations reduced entrapment efficiency for both sodium alginate and glyceryl behenate, but significantly influenced gastric resistance for only sodium alginate and not for glyceryl behenate. The optimized process parameters were comprised of an inlet temperature of 150°C, atomizing air pressure of 2 kg/cm2, feed solution concentration of 6% w/w, feed solution spray rate of 3 ml/min, and aspirator volume of 90%. The SEM analysis revealed smooth and spherical shape morphologies. The DSC and PXRD study divulged the amorphous nature of the drug. Regarding stability, the product was found to be stable under 3 months of accelerated and long-term stability conditions as per ICH Q1A(R2) guidelines. Thus, the technique offers a simple means to generate polymeric enteric microparticles that are ready to formulate and can be directly filled into hard gelatin capsules. PMID:27222612

  19. Use of a novel docosahexaenoic acid formulation vs control in a neonatal porcine model of short bowel syndrome leads to greater intestinal absorption and higher systemic levels of DHA.

    PubMed

    Martin, Camilia R; Stoll, Barbara; Cluette-Brown, Joanne; Akinkuotu, Adesola C; Olutoye, Oluyinka O; Gura, Kathleen M; Singh, Pratibha; Zaman, Munir M; Perillo, Michael C; Puder, Mark; Freedman, Steven D; Burrin, Doug

    2017-03-01

    Infants with short bowel syndrome (SBS) are at high risk for malabsorption, malnutrition, and failure to thrive. The objective of this study was to evaluate in a porcine model of SBS, the systemic absorption of a novel enteral Docosahexaenoic acid (DHA) formulation that forms micelles independent of bile salts (DHA-ALT®). We hypothesized that enteral delivery of DHA-ALT® would result in higher blood levels of DHA compared to a control DHA preparation due to improved intestinal absorption. SBS was induced in term piglets through a 75% mid-jejunoileal resection and the piglets randomized to either DHA-ALT® or control DHA formulation (N=5 per group) for 4 postoperative days. The median±IQR difference in final vs starting weight was 696±425 g in the DHA-ALT® group compared to 132±278 g in the controls (P=.08). Within 12 hours, median±IQR DHA and eicosapentaenoic acid plasma levels (mol%) were significantly higher in the DHA-ALT® vs control group (4.1±0.3 vs 2.5±0.5, P=.009; 0.7±0.3 vs 0.2±0.005, P=.009, respectively). There were lower fecal losses of DHA and greater ileal tissue incorporation with DHA-ALT® vs the control. Morphometric analyses demonstrated an increase in proximal jejunum and distal ileum villus height in the DHA-ALT® group compared to controls (P=.01). In a neonatal porcine model of SBS, enteral administration of a novel DHA preparation that forms micelles independent of bile salts resulted in increased fatty acid absorption, increased ileal tissue incorporation, and increased systemic levels of DHA. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Use of a novel docosahexaenoic acid (DHA) formulation versus control in a neonatal porcine model of short bowel syndrome leads to greater intestinal absorption and higher systemic levels of DHA

    PubMed Central

    Martin, Camilia R.; Stoll, Barbara; Cluette-Brown, Joanne; Akinkuotu, Adesola C.; Olutoye, Oluyinka O.; Gura, Kathleen M.; Singh, Pratibha; Zaman, Munir M.; Perillo, Michael C.; Puder, Mark; Freedman, Steven D.; Burrin, Doug

    2017-01-01

    Infants with short bowel syndrome (SBS) are at high risk for malabsorption, malnutrition, and failure to thrive. The objective of this study was to evaluate in a porcine model of SBS, the systemic absorption of a novel enteral Docosahexaenoic acid (DHA) formulation that forms micelles independent of bile salts (DHA-ALT®). We hypothesized that enteral delivery of DHA-ALT® would result in higher blood levels of DHA compared to a control DHA preparation due to improved intestinal absorption. SBS was induced in term piglets through a 75% mid-jejunoileal resection and the piglets randomized to either DHA-ALT® or control DHA formulation (N=5 per group) for 4 postoperative days. The median ± IQR difference in final versus starting weight was 696 ± 425g in the DHA-ALT® group compared to 132 ± 278g in the controls (p=.08). Within 12 hours, median ± IQR DHA and eicosapentaenoic acid plasma levels (mol%) were significantly higher in the DHA-ALT® vs. control group (4.1 ± 0.3 vs 2.5 ± 0.5, p=0.009; 0.7 ± 0.3 vs 0.2 ± 0.005, p=0.009, respectively). There were lower fecal losses of DHA and greater ileal tissue incorporation with DHA-ALT® versus the control. Morphometric analyses demonstrated an increase in proximal jejunum and distal ileum villus height in the DHA-ALT® group compared to controls (p=0.01). In a neonatal porcine model of SBS, enteral administration of a novel DHA preparation that forms micelles independent of bile salts resulted in increased fatty acid absorption, increased ileal tissue incorporation, and increased systemic levels of DHA. PMID:28385289

  1. Dual stimuli-responsive smart beads that allow "on-off" manipulation of cancer cells.

    PubMed

    Kim, Young-Jin; Kim, Soo Hyeon; Fujii, Teruo; Matsunaga, Yukiko T

    2016-06-24

    Temperature- and electric field-responsive polymer-conjugated polystyrene beads, termed smart beads, are designed to isolate cancer cells. In smart beads, the reversible "on-off" antigen-antibody reaction and dielectrophoresis force on an electrode are accomplished to realize "on-off" remote manipulation of smart beads and cancer cells. Both the zeta-potential and the hydrodynamic diameter of the smart beads are sensitive to temperature, allowing "on-off" reversible capture and release of cancer cells. Cancer cell-captured smart beads are then localized on electrodes by applying an electrical signal.

  2. An Attempt to Shorten Loading Time of Epirubicin into DC Beads® Using Vibration and a Sieve.

    PubMed

    Sonoda, Akinaga; Nitta, Norihisa; Yamamoto, Takefumi; Tomozawa, Yuki; Ohta, Shinichi; Watanabe, Shobu; Murata, Kiyoshi

    2017-04-01

    We investigated the possibility of shortening the time required for loading epirubicin into calibrated polyvinyl alcohol-based hydrogel beads (DC Beads ® ) to be used for transarterial chemoembolization. After separating the beads suspended in phosphate-buffered saline (PBS) solution by the use of a sieve (clearance 75 µm), epirubicin hydrochloride (EH) was loaded for 20, 30, or 60 s under vibration into DC beads. The EH loading rate into conventionally prepared (control) beads, i.e., beads loaded for 30 min without vibration, and vibration-loaded beads were calculated from the residual EH concentration in the bead-depleted EH solution. The amount of EH eluted from conventionally and vibration-loaded samples into a PBS solution (pH 7.0) was measured at 15 and 30 min and 1, 2, 6, 12, and 24 h. We also recorded the inhibitory effect of the PBS solution on the loading time. Using frozen sections, the EH load in the beads was evaluated visually under a fluorescence microscope. Spectrophotometry (495 nm) showed that the loading rate was 98.98 ± 0.34, 99.02 ± 0.32, and 99.50 ± 0.11 % with 20-, 30-, and 60-s vibration, respectively. The eluted rate was statistically similar between vibration- and statically loaded (control) beads. The PBS solution hampered EH loading into the beads. Visually, the distribution of EH in conventionally and vibration-loaded DC beads was similar. The use of vibration and the removal of PBS solution when epirubicin hydrochloride was loaded into DC beads dramatically shortened the loading time of epirubicin hydrochloride into DC beads.

  3. Rare Earth Adsorption and Desorption with PEGDA Beads

    DOE Data Explorer

    Jiao, Yongqin; Brewer, Aaron; Park, Dan

    2017-03-01

    We synthesized PEGDA polymer hydrogel beads for cell embedding and compared REE biosorption with these beads via a gravity-driven flow through setup. One way to set up a flow through system is by cell encapsulation into polymer beads with a column setup similar to that used in the chromatography industry. To achieve this, we tested PEGDA for cell encapsulation, and tested REE biosorption under both batch mode and a follow through setup based on gravity . For making the cell embedded polymer beads, we used a fluidic device by which homogenous spherical particles of 0.5 to1 mm in diameter were synthesized. The beads are made relatively quickly, and the size of the beads can be controlled. PEGDA beads were polymerized by UV. Tb adsorption experiment was performed with beads with or without cells embedded.

  4. Scaling, clustering and avalanches for steel beads in an external magnetic field

    NASA Astrophysics Data System (ADS)

    Marquinez, Alyse; Thvedt, Ingrid; Lehman, S. Y.; Jacobs, D. T.

    2011-03-01

    We investigated avalanches using uniform 3mm steel spheres (``beads'') dropped onto a conical bead pile within a uniform magnetic field. The bead pile is built by pouring beads onto a circular base where the bottom layer of beads had been glued randomly. Beads are then individually dropped from a fixed height after which the pile is massed. This process is repeated for thousands of bead drops. By measuring the number of avalanches of a given size that occurred during the experiment, the resulting avalanche size distribution was compared to a power law description as predicted by self-organized criticality. As the magnetic field intensity increased, the beads clustered to give a larger angle of repose and we measured the change in the avalanche size distribution. The moments of the distribution give a sensitive test of mean-field theory as the universality class for these bead piles. We acknowledge support from Research Corporation and NSF-REU grant DMR 0649112.

  5. Preparation of ionic-crosslinked chitosan-based gel beads and effect of reaction conditions on drug release behaviors.

    PubMed

    Chen, Shilan; Liu, Mingzhu; Jin, Shuping; Wang, Bin

    2008-02-12

    Drug-loaded chitosan (CS) beads were prepared under simple and mild condition using trisodium citrate as ionic crosslinker. The beads were further coated with poly(methacrylic acid) (PMAA) by dipping the beads in PMAA aqueous solution. The surface and cross-section morphology of these beads were observed by scanning electron microscopy and the observation showed that the coating beads had core-shell structure. In vitro release of model drug from these beads obtained under different reaction conditions was investigated in buffer medium (pH 1.8). The results showed that the rapid drug release was restrained by PMAA coating and the optimum conditions for preparing CS-based drug-loaded beads were decided through the effect of reaction conditions on the drug release behaviors. In addition, the drug release mechanism of CS-based drug-loaded beads was analyzed by Peppa's potential equation. According to this study, the ionic-crosslinked CS beads coated by PMAA could serve as suitable candidate for drug site-specific carrier in stomach.

  6. Influence of polymeric subcoats on the drug release properties of tablets powder-coated with pre-plasticized Eudragit L 100-55.

    PubMed

    Sauer, Dorothea; Watts, Alan B; Coots, Lonique B; Zheng, Weijia C; McGinity, James W

    2009-02-09

    The aim of the study was to investigate the properties of sodium valproate tablets that were dry powder-coated with pre-plasticized Eudragit L 100-55. Polyethylene glycol 3350 (PEG 3350) was used as primer to facilitate initial coating powder adhesion. Solubility parameters were employed to determine the wetting properties of the PEG 3350 primer. Additional PEG 3350 within the powder coating formulation was required to enable powder adhesion to the tablet cores. The application of a subcoat of either Eudragit E PO or Eudragit RL PO facilitated adhesion of the enteric polymer to the tablet cores and reduced the amount PEG 3350 required in the coating formulation. Since reduction of the PEG 3350 content produced less water-vapor permeable films, the enteric coating level necessary to control the drug release was decreased. PEG 3350 and Methocel K4M were incorporated in both Eudragit E PO and Eudragit RL PO subcoating formulations as pore forming agents. The influence of the pore forming excipients on physicochemical properties of free powder-cast films was investigated. The miscibility of the PEG 3350 and Methocel K4M in the film coating was correlated with their ability to function as pore forming agent.

  7. Charging of multiple interacting particles by contact electrification.

    PubMed

    Soh, Siowling; Liu, Helena; Cademartiri, Rebecca; Yoon, Hyo Jae; Whitesides, George M

    2014-09-24

    Many processes involve the movement of a disordered collection of small particles (e.g., powders, grain, dust, and granular foods). These particles move chaotically, interact randomly among themselves, and gain electrical charge by contact electrification. Understanding the mechanisms of contact electrification of multiple interacting particles has been challenging, in part due to the complex movement and interactions of the particles. To examine the processes contributing to contact electrification at the level of single particles, a system was constructed in which an array of millimeter-sized polymeric beads of different materials were agitated on a dish. The dish was filled almost completely with beads, such that beads did not exchange positions. At the same time, during agitation, there was sufficient space for collisions with neighboring beads. The charge of the beads was measured individually after agitation. Results of systematic variations in the organization and composition of the interacting beads showed that three mechanisms determined the steady-state charge of the beads: (i) contact electrification (charging of beads of different materials), (ii) contact de-electrification (discharging of beads of the same charge polarity to the atmosphere), and (iii) a long-range influence across beads not in contact with one another (occurring, plausibly, by diffusion of charge from a bead with a higher charge to a bead with a lower charge of the same polarity).

  8. Integration of Magnetic Bead-Based Cell Selection into Complex Isolations

    PubMed Central

    2018-01-01

    Magnetic bead-based analyte capture has emerged as a ubiquitous method in cell isolation, enabling the highly specific capture of target populations through simple magnetic manipulation. To date, no “one-size fits all” magnetic bead has been widely adopted leading to an overwhelming number of commercial beads. Ultimately, the ideal bead is one that not only facilitates cell isolation but also proves compatible with the widest range of downstream applications and analytic endpoints. Despite the diverse offering of sizes, coatings, and conjugation chemistries, few studies exist to benchmark the performance characteristics of different commercially available beads; importantly, these bead characteristics ultimately determine the ability of a bead to integrate into the user’s assay. In this report, we evaluate bead-based cell isolation considerations, approaches, and results across a subset of commercially available magnetic beads (Dynabeads FlowComps, Dynabeads CELLection, GE Healthcare Sera-Mag SpeedBeads streptavidin-blocked magnetic particles, Dynabeads M-270s, Dynabeads M-280s) to compare and contrast both capture-specific traits (i.e., purity, capture efficacy, and contaminant isolations) and endpoint compatibility (i.e., protein localization, fluorescence imaging, and nucleic acid extraction). We identify specific advantages and contexts of use in which distinct bead products may facilitate experimental goals and integrate into downstream applications. PMID:29732449

  9. Nanoscale interactions between engineered nanomaterials and black carbon (Biochar) in soil

    USDA-ARS?s Scientific Manuscript database

    Engineered nanomaterials (NMs) enter agricultural soils directly as additives in agrichemical formulations1 and indirectly as contaminants in municipal sewage sludge.2 NIFA has a vested interest in developing predictive models for the fate and nanotoxicity of NMs in agroecosystems. An understanding ...

  10. Controlling the size of alginate gel beads by use of a high electrostatic potential.

    PubMed

    Klokk, T I; Melvik, J E

    2002-01-01

    The effect of several parameters on the size of alginate beads produced by use of an electrostatic potential bead generator was examined. Parameters studied included needle diameter, electrostatic potential, alginate solution flow rate, gelling ion concentration and alginate concentration and viscosity, as well as alginate composition. Bead size was found to decrease with increasing electrostatic potential, but only down to a certain level. Minimum bead size was reached at between 2-4 kV/cm for the needles tested. The smallest alginate beads produced (using a needle with inner diameter 0.18 mm) had a mean diameter of approximately 300 microm. Bead size was also found to be dependent upon the flow rate of the fed alginate solution. Increasing the gelling ion concentration resulted in a moderate decrease in bead size. The concentration and viscosity of the alginate solution also had an effect on bead size as demonstrated by an increased bead diameter when the concentration or viscosity was increased. This effect was primarily an effect of the viscosity properties of the solution, which led to changes in the rate of droplet formation in the bead generator. Lowering the flow rate of the alginate solution could partly compensate for the increase in bead size with increased viscosity. For a constant droplet size, alginates with a low G block content (F(GG) approximately 0.20) resulted in approximately 30% smaller beads than alginates with a high G block content (F(GG) approximately 0.60). This is explained as a result of differences in the shrinking properties of the beads.

  11. Elution of Clindamycin and Enrofloxacin From Calcium Sulfate Hemihydrate Beads In Vitro.

    PubMed

    Phillips, Heidi; Boothe, Dawn M; Bennett, R Avery

    2015-11-01

    To compare the in vitro elution characteristics of clindamycin and enrofloxacin from calcium sulfate hemihydrate beads containing a single antibiotic, both antibiotics, and each antibiotic incubated in the same eluent well. Experimental in vitro study. Calcium sulfate hemihydrate beads were formed by mixing with clindamycin and/or enrofloxacin to create 4 study groups: (1) 160 mg clindamycin/10 beads; (2) 160 mg enrofloxacin/10 beads; (3) 160 mg clindamycin + 160 mg enrofloxacin/10 beads; and (4) 160 mg clindamycin/5 beads and 160 mg enrofloxacin/5 beads. Chains of beads were formed in triplicate and placed in 5 mL phosphate buffered saline (PBS; pH 7.4 and room temperature) with constant agitation. Antibiotic-conditioned PBS was sampled at 14 time points from 1 hour to 30 days. Clindamycin and enrofloxacin concentrations in PBS were determined using high-performance liquid chromatography. Eluent concentrations from clindamycin-impregnated beads failed to remain sufficiently above minimum inhibitory concentration (MIC) for common infecting bacteria over the study period. Enrofloxacin eluent concentrations remained sufficiently above MIC for common wound pathogens of dogs and cats and demonstrated an atypical biphasic release pattern. No significant differences in elution occurred as a result of copolymerization of the antibiotics into a single bead or from individual beads co-eluting in the same eluent well. Clindamycin-impregnated beads cannot be recommended for treatment of infection at the studied doses; however, use of enrofloxacin-impregnated beads may be justified when susceptible bacteria are cultured. © Copyright 2015 by The American College of Veterinary Surgeons.

  12. Digital microfluidics-enabled single-molecule detection by printing and sealing single magnetic beads in femtoliter droplets.

    PubMed

    Witters, Daan; Knez, Karel; Ceyssens, Frederik; Puers, Robert; Lammertyn, Jeroen

    2013-06-07

    Digital microfluidics is introduced as a novel platform with unique advantages for performing single-molecule detection. We demonstrate how superparamagnetic beads, used for capturing single protein molecules, can be printed with unprecedentedly high loading efficiency and single bead resolution on an electrowetting-on-dielectric-based digital microfluidic chip by micropatterning the Teflon-AF surface of the device. By transporting droplets containing suspended superparamagnetic beads over a hydrophilic-in-hydrophobic micropatterned Teflon-AF surface, single beads are trapped inside the hydrophilic microwells due to their selective wettability and tailored dimensions. Digital microfluidics presents the following advantages for printing and sealing magnetic beads for single-molecule detection: (i) droplets containing suspended beads can be transported back and forth over the array of hydrophilic microwells to obtain high loading efficiencies of microwells with single beads, (ii) the use of hydrophilic-in-hydrophobic patterns permits the use of a magnet to speed up the bead transfer process to the wells, while the receding droplet meniscus removes excess beads off the chip surface and thereby shortens the bead patterning time, and (iii) reagents can be transported over the printed beads multiple times, while capillary forces and a magnet hold the printed beads in place. High loading efficiencies (98% with a CV of 0.9%) of single beads in microwells were obtained by transporting droplets of suspended beads over the array 10 times in less than 1 min, which is much higher than previously reported methods (40-60%), while the total surface area needed for performing single-molecule detection can be decreased. The performance of the device was demonstrated by fluorescent detection of the presence of the biotinylated enzyme β-galactosidase on streptavidin-coated beads with a linear dynamic range of 4 orders of magnitude ranging from 10 aM to 90 fM.

  13. Development and optimization of enteric coated mucoadhesive microspheres of duloxetine hydrochloride using 32 full factorial design

    PubMed Central

    Setia, Anupama; Kansal, Sahil; Goyal, Naveen

    2013-01-01

    Background: Microspheres constitute an important part of oral drug delivery system by virtue of their small size and efficient carrier capacity. However, the success of these microspheres is limited due to their short residence time at the site of absorption. Objective: The objective of the present study was to formulate and systematically evaluate in vitro performance of enteric coated mucoadhesive microspheres of duloxetine hydrochloride (DLX), an acid labile drug. Materials and Methods: DLX microspheres were prepared by simple emulsification phase separation technique using chitosan as carrier and glutaraldehyde as a cross-linking agent. Microspheres prepared were coated with eudragit L-100 using an oil-in-oil solvent evaporation method. Eudragit L-100was used as enteric coating polymer with the aim to release the drug in small intestine The microspheres prepared were characterized by particle size, entrapment efficiency, swelling index (SI), mucoadhesion time, in vitro drug release and surface morphology. A 32 full factorial design was employed to study the effect of independent variables polymer-to-drug ratio (X1) and stirring speed (X2) on dependent variables, particle size, entrapment efficiency, SI, in vitro mucoadhesion and drug release up to 24 h (t24). Results: Microspheres formed were discrete, spherical and free flowing. The microspheres exhibited good mucoadhesive property and also showed high percentage entrapment efficiency. The microspheres were able to sustain the drug release up to 24 h. Conclusion: Thus, the prepared enteric coated mucoadhesive microspheres may prove to be a potential controlled release formulation of DLX for oral administration. PMID:24167786

  14. Enteral Feeding Tube Clogging: What Are the Causes and What Are the Answers? A Bench Top Analysis.

    PubMed

    Garrison, Christopher M

    2018-02-01

    Clogged enteral feeding tubes remain a significant barrier to the delivery of nutrition, hydration, and medications to patients who cannot tolerate oral intake. There is limited research that compares the relative efficacy of different methods used to clear a clogged feeding tube. The objectives of this study were to better understand the factors that contribute to enteral feeding tube clogging and to test the efficacy of 3 methods for clearing clogged feeding tubes. Three formulations of clogs were artificially created and tested in vitro and composed of various quantities of crushed medication (ie, aspirin) and 0.15 g coagulated protein (ie, tofu). The following 3 clog clearing strategies were tested on all clog types (n = 5 clogs/formulation/treatment): warm water flushes, an enzyme treatment, and an actuated mechanical occlusion clearing device. The variable among the clog types that appears most responsible for decreased clearing success is the state of the coagulated protein. Dried-out protein appears to makes a greater difference than increasing the medication quantity. The actuated mechanical occlusion clearing device was significantly more successful (93%) when compared with warm water flushes (20%) and the commercially available enzyme treatment (33%; P < .005) at clearing the clogs. The actuated device required significantly less total procedure time (P < .005) and total nursing time (P < .005) when compared with the other 2 clearing methods. When clogs occur, they can be quickly and effectively resolved by the actuated device, but other methodologies such as water and enzyme treatments may be of assistance. © 2018 American Society for Parenteral and Enteral Nutrition.

  15. Method of synthesizing bulk transition metal carbide, nitride and phosphide catalysts

    DOEpatents

    Choi, Jae Soon; Armstrong, Beth L; Schwartz, Viviane

    2015-04-21

    A method for synthesizing catalyst beads of bulk transmission metal carbides, nitrides and phosphides is provided. The method includes providing an aqueous suspension of transition metal oxide particles in a gel forming base, dropping the suspension into an aqueous solution to form a gel bead matrix, heating the bead to remove the binder, and carburizing, nitriding or phosphiding the bead to form a transition metal carbide, nitride, or phosphide catalyst bead. The method can be tuned for control of porosity, mechanical strength, and dopant content of the beads. The produced catalyst beads are catalytically active, mechanically robust, and suitable for packed-bed reactor applications. The produced catalyst beads are suitable for biomass conversion, petrochemistry, petroleum refining, electrocatalysis, and other applications.

  16. Optimization and Prediction of Angular Distortion and Weldment Characteristics of TIG Square Butt Joints

    NASA Astrophysics Data System (ADS)

    Narang, H. K.; Mahapatra, M. M.; Jha, P. K.; Biswas, P.

    2014-05-01

    Autogenous arc welds with minimum upper weld bead depression and lower weld bead bulging are desired as such welds do not require a second welding pass for filling up the upper bead depressions (UBDs) and characterized with minimum angular distortion. The present paper describes optimization and prediction of angular distortion and weldment characteristics such as upper weld bead depression and lower weld bead bulging of TIG-welded structural steel square butt joints. Full factorial design of experiment was utilized for selecting the combinations of welding process parameter to produce the square butts. A mathematical model was developed to establish the relationship between TIG welding process parameters and responses such as upper bead width, lower bead width, UBD, lower bead height (bulging), weld cross-sectional area, and angular distortions. The optimal welding condition to minimize UBD and lower bead bulging of the TIG butt joints was identified.

  17. A Wide-Field Fluorescence Microscope Extension for Ultrafast Screening of One-Bead One-Compound Libraries Using a Spectral Image Subtraction Approach.

    PubMed

    Heusermann, Wolf; Ludin, Beat; Pham, Nhan T; Auer, Manfred; Weidemann, Thomas; Hintersteiner, Martin

    2016-05-09

    The increasing involvement of academic institutions and biotech companies in drug discovery calls for cost-effective methods to identify new bioactive molecules. Affinity-based on-bead screening of combinatorial one-bead one-compound libraries combines a split-mix synthesis design with a simple protein binding assay operating directly at the bead matrix. However, one bottleneck for academic scale on-bead screening is the unavailability of a cheap, automated, and robust screening platform that still provides a quantitative signal related to the amount of target protein binding to individual beads for hit bead ranking. Wide-field fluorescence microscopy has long been considered unsuitable due to significant broad spectrum autofluorescence of the library beads in conjunction with low detection sensitivity. Herein, we demonstrate how such a standard microscope equipped with LED-based excitation and a modern CMOS camera can be successfully used for selecting hit beads. We show that the autofluorescence issue can be overcome by an optical image subtraction approach that yields excellent signal-to-noise ratios for the detection of bead-associated target proteins. A polymer capillary attached to a semiautomated bead-picking device allows the operator to efficiently isolate individual hit beads in less than 20 s. The system can be used for ultrafast screening of >200,000 bead-bound compounds in 1.5 h, thereby making high-throughput screening accessible to a wider group within the scientific community.

  18. Dermal quercetin smartCrystals®: Formulation development, antioxidant activity and cellular safety.

    PubMed

    Hatahet, T; Morille, M; Hommoss, A; Dorandeu, C; Müller, R H; Bégu, S

    2016-05-01

    Flavonoids are natural plant pigments, which possess high antioxidative and antiradical activities. However, their poor water solubility led to a limited bioavailability. To overcome this major hurdle, quercetin nanocrystals were produced implementing smartCrystals® technology. This process combines bead milling and subsequent high-pressure homogenization at relatively low pressure (300bar). To test the possibility to develop a dermal formulation from quercetin smartCrystals®, quercetin nanosuspensions were admixed to Lutrol® F127 and hydroxythylcellulose nonionic gels. The physicochemical properties (morphology, size and charge), saturation solubility, dissolution velocity and the antioxidant properties (DPPH assay) as well as the cellular interaction of the produced quercetin smartCrystals® were studied and compared to crude quercetin powder. Quercetin smartCrystals® showed a strong increase in the saturation solubility and the dissolution velocity (7.6 fold). SmartCrystals® loaded or not into gels proved to be physically stable over a period of three months at 25°C. Interestingly, in vitro DPPH assay confirmed the preservation of quercetin antioxidative properties after nanonization. In parallel, the nanocrystalline form did not display cellular toxicity, even at high concentration (50μg/ml), as assayed on an epithelial cell line (VERO cells). In addition, the nanocrystalline form confirmed a protective activity for VERO cells against hydrogen peroxide induced toxicity in vitro. This new formulation presents a promising approach to deliver quercetin efficiently to skin in well-tolerated formulations. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Entropy gives rise to topologically associating domains

    PubMed Central

    Vasquez, Paula A.; Hult, Caitlin; Adalsteinsson, David; Lawrimore, Josh; Forest, Mark G.; Bloom, Kerry

    2016-01-01

    We investigate chromosome organization within the nucleus using polymer models whose formulation is closely guided by experiments in live yeast cells. We employ bead-spring chromosome models together with loop formation within the chains and the presence of nuclear bodies to quantify the extent to which these mechanisms shape the topological landscape in the interphase nucleus. By investigating the genome as a dynamical system, we show that domains of high chromosomal interactions can arise solely from the polymeric nature of the chromosome arms due to entropic interactions and nuclear confinement. In this view, the role of bio-chemical related processes is to modulate and extend the duration of the interacting domains. PMID:27257057

  20. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sonoda, Akinaga, E-mail: akinagasonoda@yahoo.co.jp; Nitta, Norihisa; Yamamoto, Takefumi

    PurposeWe investigated the possibility of shortening the time required for loading epirubicin into calibrated polyvinyl alcohol-based hydrogel beads (DC Beads{sup ®}) to be used for transarterial chemoembolization.MethodAfter separating the beads suspended in phosphate-buffered saline (PBS) solution by the use of a sieve (clearance 75 µm), epirubicin hydrochloride (EH) was loaded for 20, 30, or 60 s under vibration into DC beads. The EH loading rate into conventionally prepared (control) beads, i.e., beads loaded for 30 min without vibration, and vibration-loaded beads were calculated from the residual EH concentration in the bead-depleted EH solution. The amount of EH eluted from conventionally and vibration-loadedmore » samples into a PBS solution (pH 7.0) was measured at 15 and 30 min and 1, 2, 6, 12, and 24 h. We also recorded the inhibitory effect of the PBS solution on the loading time. Using frozen sections, the EH load in the beads was evaluated visually under a fluorescence microscope.ResultsSpectrophotometry (495 nm) showed that the loading rate was 98.98 ± 0.34, 99.02 ± 0.32, and 99.50 ± 0.11 % with 20-, 30-, and 60-s vibration, respectively. The eluted rate was statistically similar between vibration- and statically loaded (control) beads. The PBS solution hampered EH loading into the beads. Visually, the distribution of EH in conventionally and vibration-loaded DC beads was similar.DiscussionThe use of vibration and the removal of PBS solution when epirubicin hydrochloride was loaded into DC beads dramatically shortened the loading time of epirubicin hydrochloride into DC beads.« less

  1. Stimulation of wound healing by positively charged dextran beads depends upon clustering of beads and cells in close proximity to the wound.

    PubMed

    Tawil, N J; Connors, D; Gies, D; Bennett, S; Gruskin, E; Mustoe, T

    1999-01-01

    We have previously shown that positively charged dextran (DEAE A25) increases wound breaking strength in linear incisions in rats and nonhuman primates at days 10-14 postwounding. In this article, we examined the cellular responses to different types of charged dextran beads (DEAE A50 and Cytodex-1) in culture studies and in rat incisional wounds. We show that Cytodex 1 and DEAE A50 beads also increased wound breaking strength in a rat linear incisional model. However, the increase was approximately 30-40% less than that observed in wounds treated with DEAE A25 beads. The main distinction between the three types of beads was the presence of bead clusters observed in tissue sections. Wounds treated with DEAE A25 beads formed distinct clusters while both Cytodex 1 and DEAE A50 beads clustered to a lesser extent or failed to cluster at all. We propose that the different types of charged dextran beads improve healing by promoting cell adhesion and encouraging proliferation in close proximity to the wound. We also hypothesize that the 30-40% improvement in wound breaking strength seen with DEAE A25 beads compared to other types of charged dextran beads (DEAE A50 and Cytodex-1) originates from the unique characteristic of DEAE A25 beads in forming cell-bead aggregates adjacent to the wounded area. This clustering, in turn, affects the distribution of cells infiltrating the wounded area (such as macrophages) during the healing process and, as a consequence, alters the distribution of matrix molecules and growth factors secreted by these cells.

  2. Surface adsorption and hopping cause probe-size-dependent microrheology of actin networks

    NASA Astrophysics Data System (ADS)

    He, Jun; Tang, Jay X.

    2011-04-01

    A network of filaments formed primarily by the abundant cytoskeletal protein actin gives animal cells their shape and elasticity. The rheological properties of reconstituted actin networks have been studied by tracking micron-sized probe beads embedded within the networks. We investigate how microrheology depends on surface properties of probe particles by varying the stickiness of their surface. For this purpose, we chose carboxylate polystyrene (PS) beads, silica beads, bovine serum albumin (BSA) -coated PS beads, and polyethylene glycol (PEG) -grafted PS beads, which show descending stickiness to actin filaments, characterized by confocal imaging and microrheology. Probe size dependence of microrheology is observed for all four types of beads. For the slippery PEG beads, particle-tracking microrheology detects weaker networks using smaller beads, which tend to diffuse through the network by hopping from one confinement “cage” to another. This trend is reversed for the other three types of beads, for which microrheology measures stiffer networks for smaller beads due to physisorption of nearby filaments to the bead surface. We explain the probe size dependence with two simple models. We also evaluate depletion effect near nonadsorption bead surface using quantitative image analysis and discuss the possible impact of depletion on microrheology. Analysis of these effects is necessary in order to accurately define the actin network rheology both in vitro and in vivo.

  3. An Integrated Microfluidic Processor for DNA-Encoded Combinatorial Library Functional Screening

    PubMed Central

    2017-01-01

    DNA-encoded synthesis is rekindling interest in combinatorial compound libraries for drug discovery and in technology for automated and quantitative library screening. Here, we disclose a microfluidic circuit that enables functional screens of DNA-encoded compound beads. The device carries out library bead distribution into picoliter-scale assay reagent droplets, photochemical cleavage of compound from the bead, assay incubation, laser-induced fluorescence-based assay detection, and fluorescence-activated droplet sorting to isolate hits. DNA-encoded compound beads (10-μm diameter) displaying a photocleavable positive control inhibitor pepstatin A were mixed (1920 beads, 729 encoding sequences) with negative control beads (58 000 beads, 1728 encoding sequences) and screened for cathepsin D inhibition using a biochemical enzyme activity assay. The circuit sorted 1518 hit droplets for collection following 18 min incubation over a 240 min analysis. Visual inspection of a subset of droplets (1188 droplets) yielded a 24% false discovery rate (1166 pepstatin A beads; 366 negative control beads). Using template barcoding strategies, it was possible to count hit collection beads (1863) using next-generation sequencing data. Bead-specific barcodes enabled replicate counting, and the false discovery rate was reduced to 2.6% by only considering hit-encoding sequences that were observed on >2 beads. This work represents a complete distributable small molecule discovery platform, from microfluidic miniaturized automation to ultrahigh-throughput hit deconvolution by sequencing. PMID:28199790

  4. An Integrated Microfluidic Processor for DNA-Encoded Combinatorial Library Functional Screening.

    PubMed

    MacConnell, Andrew B; Price, Alexander K; Paegel, Brian M

    2017-03-13

    DNA-encoded synthesis is rekindling interest in combinatorial compound libraries for drug discovery and in technology for automated and quantitative library screening. Here, we disclose a microfluidic circuit that enables functional screens of DNA-encoded compound beads. The device carries out library bead distribution into picoliter-scale assay reagent droplets, photochemical cleavage of compound from the bead, assay incubation, laser-induced fluorescence-based assay detection, and fluorescence-activated droplet sorting to isolate hits. DNA-encoded compound beads (10-μm diameter) displaying a photocleavable positive control inhibitor pepstatin A were mixed (1920 beads, 729 encoding sequences) with negative control beads (58 000 beads, 1728 encoding sequences) and screened for cathepsin D inhibition using a biochemical enzyme activity assay. The circuit sorted 1518 hit droplets for collection following 18 min incubation over a 240 min analysis. Visual inspection of a subset of droplets (1188 droplets) yielded a 24% false discovery rate (1166 pepstatin A beads; 366 negative control beads). Using template barcoding strategies, it was possible to count hit collection beads (1863) using next-generation sequencing data. Bead-specific barcodes enabled replicate counting, and the false discovery rate was reduced to 2.6% by only considering hit-encoding sequences that were observed on >2 beads. This work represents a complete distributable small molecule discovery platform, from microfluidic miniaturized automation to ultrahigh-throughput hit deconvolution by sequencing.

  5. Curriculum Connection. Take Technology Outdoors.

    ERIC Educational Resources Information Center

    Dean, Bruce Robert

    1992-01-01

    Technology can support hands-on science as elementary students use computers to formulate field guides to nature surrounding their school. Students examine other field guides; open databases for recording information; collect, draw, and identify plants, insects, and animals; enter data into the database; then generate a computerized field guide.…

  6. 5 CFR 2635.802 - Conflicting outside employment and activities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... expected again to be instrumental in formulating new OSHA safety standards applicable to manufacturers that... in restructuring its manufacturing operations to comply with the OSHA standards. The employee should not enter into the consulting arrangement even though he is not currently working on OSHA standards...

  7. A novel magnet focusing plate for matrix-assisted laser desorption/ionization analysis of magnetic bead-bound analytes.

    PubMed

    Gode, David; Volmer, Dietrich A

    2013-05-15

    Magnetic beads are often used for serum profiling of peptide and protein biomarkers. In these assays, the bead-bound analytes are eluted from the beads prior to mass spectrometric analysis. This study describes a novel matrix-assisted laser desorption/ionization (MALDI) technique for direct application and focusing of magnetic beads to MALDI plates by means of dedicated micro-magnets as sample spots. Custom-made MALDI plates with magnetic focusing spots were made using small nickel-coated neodymium micro-magnets integrated into a stainless steel plate in a 16 × 24 (384) pattern. For demonstrating the proof-of-concept, commercial C-18 magnetic beads were used for the extraction of a test compound (reserpine) from aqueous solution. Experiments were conducted to study focusing abilities, the required laser energies, the influence of a matrix compound, dispensing techniques, solvent choice and the amount of magnetic beads. Dispensing the magnetic beads onto the micro-magnet sample spots resulted in immediate and strong binding to the magnetic surface. Light microscope images illustrated the homogeneous distribution of beads across the surfaces of the magnets, when the entire sample volume containing the beads was pipetted onto the surface. Subsequent MALDI analysis of the bead-bound analyte demonstrated excellent and reproducible ionization yields. The surface-assisted laser desorption/ionization (SALDI) properties of the strongly light-absorbing γ-Fe2O3-based beads resulted in similar ionization efficiencies to those obtained from experiments with an additional MALDI matrix compound. This feasibility study successfully demonstrated the magnetic focusing abilities for magnetic bead-bound analytes on a novel MALDI plate containing small micro-magnets as sample spots. One of the key advantages of this integrated approach is that no elution steps from magnetic beads were required during analyses compared with conventional bead experiments. Copyright © 2013 John Wiley & Sons, Ltd.

  8. Development of extended release dosage forms using non-uniform drug distribution techniques.

    PubMed

    Huang, Kuo-Kuang; Wang, Da-Peng; Meng, Chung-Ling

    2002-05-01

    Development of an extended release oral dosage form for nifedipine using the non-uniform drug distribution matrix method was conducted. The process conducted in a fluid bed processing unit was optimized by controlling the concentration gradient of nifedipine in the coating solution and the spray rate applied to the non-pareil beads. The concentration of nifedipine in the coating was controlled by instantaneous dilutions of coating solution with polymer dispersion transported from another reservoir into the coating solution at a controlled rate. The USP dissolution method equipped with paddles at 100 rpm in 0.1 N hydrochloric acid solution maintained at 37 degrees C was used for the evaluation of release rate characteristics. Results indicated that (1) an increase in the ethyl cellulose content in the coated beads decreased the nifedipine release rate, (2) incorporation of water-soluble sucrose into the formulation increased the release rate of nifedipine, and (3) adjustment of the spray coating solution and the transport rate of polymer dispersion could achieve a dosage form with a zero-order release rate. Since zero-order release rate and constant plasma concentration were achieved in this study using the non-uniform drug distribution technique, further studies to determine in vivo/in vitro correlation with various non-uniform drug distribution dosage forms will be conducted.

  9. Molecular diagnostics using magnetic nanobeads

    NASA Astrophysics Data System (ADS)

    Zardán Gómez de la Torre, Teresa; Strömberg, Mattias; Göransson, Jenny; Gunnarsson, Klas; Nilsson, Mats; Svedlindh, Peter; Strømme, Maria

    2010-01-01

    In this paper, we investigate the volume-amplified magnetic nanobead detection assay with respect to bead size, bead concentration and bead oligonucleotide surface coverage in order to improve the understanding of the underlying microscopic mechanisms. It has been shown that: (i) the immobilization efficiency of the beads depends on the surface coverage of oligonucleotides, (ii) by using lower amounts of probe-tagged beads, detection sensitivity can be improved and (iii) using small enough beads enables both turn-off and turn-on detection. Finally, biplex detection was demonstrated.

  10. A microhydrodynamic rationale for selection of bead size in preparation of drug nanosuspensions via wet stirred media milling.

    PubMed

    Li, Meng; Alvarez, Paulina; Bilgili, Ecevit

    2017-05-30

    Although wet stirred media milling has proven to be a robust process for producing nanoparticle suspensions of poorly water-soluble drugs and thereby enhancing their bioavailability, selection of bead size has been largely empirical, lacking fundamental rationale. This study aims to establish such rationale by investigating the impact of bead size at various stirrer speeds on the drug breakage kinetics via a microhydrodynamic model. To this end, stable suspensions of griseofulvin, a model BCS Class II drug, were prepared using hydroxypropyl cellulose and sodium dodecyl sulfate. The suspensions were milled at four different stirrer speeds (1000-4000rpm) using various sizes (50-1500μm) of zirconia beads. Laser diffraction, SEM, and XRPD were used for characterization. Our results suggest that there is an optimal bead size that achieves fastest breakage at each stirrer speed and that it shifts to a smaller size at higher speed. Calculated microhydrodynamic parameters reveal two counteracting effects of bead size: more bead-bead collisions with less energy/force upon a decrease in bead size. The optimal bead size exhibits a negative power-law correlation with either specific energy consumption or the microhydrodynamic parameters. Overall, this study rationalizes the use of smaller beads for more energetic wet media milling. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Characterisation of physico-mechanical properties and degradation potential of calcium alginate beads for use in embolisation.

    PubMed

    Forster, Richard E J; Thürmer, Frank; Wallrapp, Christine; Lloyd, Andrew W; Macfarlane, Wendy; Phillips, Gary J; Boutrand, Jean-Pierre; Lewis, Andrew L

    2010-07-01

    High molecular weight alginate beads with 59% mannuronic acid content or 68% guluronic acid were prepared using a droplet generator and crosslinked in calcium chloride. The alginate beads were compared to current embolisation microspheres for compressibility and monitored over 12 weeks for size and weight change at 37 degrees C in low volumes of ringers solutions. A sheep uterine model was used to analyse bead degradation and inflammatory response over 12 weeks. Both the in vitro and in vivo data show good delivery, with a compressibility similar to current embolic beads. In vitro, swelling was noted almost immediately and after 12 weeks the first signs of degradation were noted. No difference was noted in vivo. This study has shown that high molecular weight alginate gel beads were well tolerated by the body, but beads associated with induced thrombi were susceptible to inflammatory cell infiltration. The beads were shown to be easy to handle and were still observable after 3 months in vivo. The beads were robust enough to be delivered through a 2.7 Fr microcatheter. This study has demonstrated that high molecular weight, high purity alginate bead can be considered as semi-permanent embolisation beads, with the potential to bioresorb over time.

  12. Highly sensitive bacteria quantification using immunomagnetic separation and electrochemical detection of guanine-labeled secondary beads.

    PubMed

    Jayamohan, Harikrishnan; Gale, Bruce K; Minson, Bj; Lambert, Christopher J; Gordon, Neil; Sant, Himanshu J

    2015-05-22

    In this paper, we report the ultra-sensitive indirect electrochemical detection of E. coli O157:H7 using antibody functionalized primary (magnetic) beads for capture and polyguanine (polyG) oligonucleotide functionalized secondary (polystyrene) beads as an electrochemical tag. Vacuum filtration in combination with E. coli O157:H7 specific antibody modified magnetic beads were used for extraction of E. coli O157:H7 from 100 mL samples. The magnetic bead conjugated E. coli O157:H7 cells were then attached to polyG functionalized secondary beads to form a sandwich complex (magnetic bead/E. coli secondary bead). While the use of magnetic beads for immuno-based capture is well characterized, the use of oligonucleotide functionalized secondary beads helps combine amplification and potential multiplexing into the system. The antibody functionalized secondary beads can be easily modified with a different antibody to detect other pathogens from the same sample and enable potential multiplexing. The polyGs on the secondary beads enable signal amplification up to 10⁸ guanine tags per secondary bead (7.5 x 10⁶ biotin-FITC per secondary bead, 20 guanines per oligonucleotide) bound to the target (E. coli). A single-stranded DNA probe functionalized reduced graphene oxide modified glassy carbon electrode was used to bind the polyGs on the secondary beads. Fluorescent imaging was performed to confirm the hybridization of the complex to the electrode surface. Differential pulse voltammetry (DPV) was used to quantify the amount of polyG involved in the hybridization event with tris(2,2'-bipyridine)ruthenium(II) (Ru(bpy)3(2+)) as the mediator. The amount of polyG signal can be correlated to the amount of E. coli O157:H7 in the sample. The method was able to detect concentrations of E. coli O157:H7 down to 3 CFU/100 mL, which is 67 times lower than the most sensitive technique reported in literature. The signal to noise ratio for this work was 3. We also demonstrate the use of the protocol for detection of E. coli O157:H7 seeded in waste water effluent samples.

  13. Formulation of multiparticulate systems as lyophilised orally disintegrating tablets.

    PubMed

    Alhusban, Farhan; Perrie, Yvonne; Mohammed, Afzal R

    2011-11-01

    The current study aimed to exploit the electrostatic associative interaction between carrageenan and gelatin to optimise a formulation of lyophilised orally disintegrating tablets (ODTs) suitable for multiparticulate delivery. A central composite face centred (CCF) design was applied to study the influence of formulation variables (gelatin, carrageenan and alanine concentrations) on the crucial responses of the formulation (disintegration time, hardness, viscosity and pH). The disintegration time and viscosity were controlled by the associative interaction between gelatin and carrageenan upon hydration which forms a strong complex that increases the viscosity of the stock solution and forms tablet with higher resistant to disintegration in aqueous medium. Therefore, the levels of carrageenan, gelatin and their interaction in the formulation were the significant factors. In terms of hardness, increasing gelatin and alanine concentration was the most effective way to improve tablet hardness. Accordingly, optimum concentrations of these excipients were needed to find the best balance that fulfilled all formulation requirements. The revised model showed high degree of predictability and optimisation reliability and therefore was successful in developing an ODT formulation with optimised properties that were able deliver enteric coated multiparticulates of omeprazole without compromising their functionality. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. An abuse-deterrent, microsphere-in-capsule formulation of extended-release oxycodone: alternative modes of administration to facilitate pain management in patients with dysphagia.

    PubMed

    McCarberg, Bill H; Kopecky, Ernest A; O'Connor, Melinda; Marseilles, Ann; Varanasi, Ravi K; Thompson, Christy; Fleming, Alison B

    2016-12-01

    Patients with chronic pain may experience difficulty swallowing, in part due to worsening disease, comorbid conditions, iatrogenic etiology, or age. Patients or caregivers may manipulate extended-release (ER) opioid formulations to facilitate oral dosing due to a lack of therapeutic options that allow for sprinkle or enteral feeding tube administration. If crushed or broken, current oral ER opioids can be associated with adverse sequelae, including risk of potentially fatal overdose. To review the safety, in vitro dissolution data, and in vivo pharmacokinetic data that support alternative modes of administration of oxycodone DETERx (Xtampza ER) via sprinkling onto soft foods for oral ingestion or via enteral feeding tubes. A review of oxycodone DETERx data from in vitro and in vivo studies was conducted to demonstrate support for alternative routes and modes of administration. There was no difference in the dissolution profile when administered with various soft foods or when mixed with various liquid vehicles and administered via nasogastric (NG) or gastrostomy (G) tubes, based on in vitro studies. When sprinkled onto applesauce and administered orally, the microspheres were bioequivalent to the intact oxycodone capsules. When crushed or chewed, the formulation maintained its pharmacokinetic profile; no bolus dose of opioid was released. The sprinkle-dose study was limited by the single-dose study design, as well as the small sample size. Oxycodone DETERx is the first ER oxycodone formulation that can be administered either intact, sprinkled onto soft foods, or via NG/G tubes, thereby providing options for treating pain in patients who have difficulty swallowing.

  15. Bolstering Components of the Immune Response Compromised by Prior Exposure to Adenovirus: Guided Formulation Development for a Nasal Ebola Vaccine

    PubMed Central

    2014-01-01

    The severity and longevity of the current Ebola outbreak highlight the need for a fast-acting yet long-lasting vaccine for at-risk populations (medical personnel and rural villagers) where repeated prime-boost regimens are not feasible. While recombinant adenovirus (rAd)-based vaccines have conferred full protection against multiple strains of Ebola after a single immunization, their efficacy is impaired by pre-existing immunity (PEI) to adenovirus. To address this important issue, a panel of formulations was evaluated by an in vitro assay for their ability to protect rAd from neutralization. An amphiphilic polymer (F16, FW ∼39,000) significantly improved transgene expression in the presence of anti-Ad neutralizing antibodies (NAB) at concentrations of 5 times the 50% neutralizing dose (ND50). In vivo performance of rAd in F16 was compared with unformulated virus, virus modified with poly(ethylene) glycol (PEG), and virus incorporated into poly(lactic-co-glycolic) acid (PLGA) polymeric beads. Histochemical analysis of lung tissue revealed that F16 promoted strong levels of transgene expression in naive mice and those that were exposed to adenovirus in the nasal cavity 28 days prior to immunization. Multiparameter flow cytometry revealed that F16 induced significantly more polyfunctional antigen-specific CD8+ T cells simultaneously producing IFN-γ, IL-2, and TNF-α than other test formulations. These effects were not compromised by PEI. Data from formulations that provided partial protection from challenge consistently identified specific immunological requirements necessary for protection. This approach may be useful for development of formulations for other vaccine platforms that also employ ubiquitous pathogens as carriers like the influenza virus. PMID:25549696

  16. Spatial Distribution of Triclosan in a Semi-enclosed Estuarine Embayment, Greenwich Bay, Rhode Island

    EPA Science Inventory

    Triclosan is an anti-microbial agent commonly used in the formulation of many personal care and consumer products. Much of the triclosan used by consumers enters the aqueous waste stream following use and is partially removed in waste water treatment plants (WWTP). However, the...

  17. An anthology of advances in enteral tube feeding formulations.

    PubMed

    Campbell, Sheila M

    2006-08-01

    This article summarizes several major advances in tube feeding formulas marketed in the United States. It traces the progress in tube feeding formulas, starting with blenderized formulas to commercially available intact-nutrient formulas and culminating in the introduction of the concept of immunonutrition. The impact of packaging is also described.

  18. CD-ROMSs and Laserdiscs for Science.

    ERIC Educational Resources Information Center

    Harris, Julia, Ed.

    1997-01-01

    This issue of ENC Focus highlights laserdiscs and CD-ROMs that encourage students to raise searching questions, enter debates, formulate opinions, and engage in problem solving and critical thinking. The laserdiscs and CD-ROMs were chosen based on the criteria of instructional design, content, and interest. Items featured include: The Chemistry…

  19. Effects of selected surfactants on nutrient uptake in corn (Zea mays L.)

    USDA-ARS?s Scientific Manuscript database

    Surfactants with solvent and wetting abilities are used in the formulation of herbicides to enhance spraying capabilities. These chemicals eventually enter into the soil and may disrupt different chemical, physical and biological processes. The aim of this study was to examine the effects on nutrien...

  20. Dissemination of Persistent Intestinal Bacteria via the Mesenteric Lymph Nodes Causes Typhoid Relapse▿

    PubMed Central

    Griffin, Amanda J.; Li, Lin-Xi; Voedisch, Sabrina; Pabst, Oliver; McSorley, Stephen J.

    2011-01-01

    Enteric pathogens can cause relapsing infections in a proportion of treated patients, but greater understanding of this phenomenon is hindered by the lack of appropriate animal models. We report here a robust animal model of relapsing primary typhoid that initiates after apparently successful antibiotic treatment of susceptible mice. Four days of enrofloxacin treatment were sufficient to reduce bacterial loads below detectable levels in all major organs, and mice appeared otherwise healthy. However, any interruption of further antibiotic therapy allowed renewed fecal shedding and renewed bacterial growth in systemic tissues to occur, and mice eventually succumbed to relapsing infection. In vivo imaging of luminescent Salmonella identified the mesenteric lymph nodes (MLNs) as a major reservoir of relapsing infection. A magnetic-bead enrichment strategy isolated MLN-resident CD11b+ Gr-1− monocytes associated with low numbers of persistent Salmonella. However, the removal of MLNs increased the severity of typhoid relapse, demonstrating that this organ serves as a protective filter to restrain the dissemination of bacteria during antibiotic therapy. Together, these data describe a robust animal model of typhoid relapse and identify an important intestinal phagocyte subset involved in protection against the systemic spread of enteric infection. PMID:21263018

  1. Floating dosage forms to prolong gastro-retention--the characterisation of calcium alginate beads.

    PubMed

    Stops, Frances; Fell, John T; Collett, John H; Martini, Luigi G

    2008-02-28

    Floating calcium alginate beads, designed to improve drug bioavailability from oral preparations compared with that from many commercially available and modified release products, have been investigated as a possible gastro-retentive dosage form. A model drug, riboflavin, was also incorporated into the formula. The aims of the current work were (a) to obtain information regarding the structure, floating ability and changes that occurred when the dosage form was placed in aqueous media, (b) to investigate riboflavin release from the calcium alginate beads in physiologically relevant media prior to in vivo investigations. Physical properties of the calcium alginate beads were investigated. Using SEM and ESEM, externally the calcium alginate beads were spherical in shape, and internally, air filled cavities were present thereby enabling floatation of the beads. The calcium alginate beads remained buoyant for times in excess of 13h, and the density of the calcium alginate beads was <1.000gcm(-3). Riboflavin release from the calcium alginate beads showed that riboflavin release was slow in acidic media, whilst in more alkali media, riboflavin release was more rapid. The characterisation studies showed that the calcium alginate beads could be considered as a potential gastro-retentive dosage form.

  2. Controlled drug release properties of ionically cross-linked chitosan beads: the influence of anion structure.

    PubMed

    Shu, X Z; Zhu, K J

    2002-02-21

    By adopting a novel chitosan cross-linked method, i.e. chitosan/gelatin droplet coagulated at low temperature and then cross-linked by anions (sulfate, citrate and tripolyphosphate (TPP)), the chitosan beads were prepared. Scanning electron microscopy (SEM) observation showed that sulfate/chitosan and citrate/chitosan beads usually had a spherical shape, smooth surface morphology and integral inside structure. Cross-sectional analysis indicated that the cross-linking process of sulfate and citrate to chitosan was much faster than that of TPP due to their smaller molecular size. But, once completely cross-linked, TPP/chitosan beads possessed much better mechanical strength and the force to break the beads was approximately ten times higher than that of sulfate/chitosan or citrate/chitosan beads. Release media pH and ionic strength seriously influenced the controlled drug release properties of the beads, which related to the strength of electrostatic interaction between anions and chitosan. Sulfate and citrate cross-linked chitosan beads swelled and even dissociated in simulated gastric fluid (SGF) and hence, model drug (riboflavin) released completely in 5 h; while in simulated intestinal fluid (SIF), beads remained in a shrinkage state and drug released slowly (release % usually <70% in 24 h). However, swelling and drug release of TPP/chitosan bead was usually insensitive to media pH. Chitosan beads, cross-linked by a combination of TPP and citrate (or sulfate) together, not only had a good shape, but also improved pH-responsive drug release properties. Salt weakened the interaction of citrate, especially sulfate with chitosan and accelerated beads swelling and hence drug release rate, but it was insensitive to that of TPP/chitosan. These results indicate that ionically cross-linked chitosan beads may be useful in stomach specific drug delivery.

  3. Elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate beads in vitro.

    PubMed

    Tulipan, Rachel J; Phillips, Heidi; Garrett, Laura D; Dirikolu, Levent; Mitchell, Mark A

    2016-11-01

    OBJECTIVE To characterize the elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate (CSH) beads in vitro. SAMPLE 60 carboplatin-impregnated CSH beads and 9 CSH beads without added carboplatin (controls). PROCEDURES Carboplatin-impregnated CSH beads (each containing 4.6 mg of carboplatin [2.4 mg of platinum]) were placed into separate 10-mL plastic tubes containing 5 mL of PBSS in groups of 1, 3, 6, or 10; 3 control beads were placed into a single tube of PBSS at the same volume. Experiments were conducted in triplicate at 37°C and a pH of 7.4 with constant agitation. Eluent samples were collected at 1, 2, 3, 6, 12, 24, and 72 hours. Samples were analyzed for platinum content by inductively coupled plasma-mass spectrometry. RESULTS The mean concentration of platinum released per carboplatin-impregnated bead over 72 hours was 445.3 mg/L. Cumulative concentrations of platinum eluted increased as the number of beads per tube increased. There was a significant difference in platinum concentrations over time, with values increasing over the first 12 hours and then declining for all tubes. There was also a significant difference in percentage of total incorporated platinum released into tubes with different numbers of beads: the percentage of eluted platinum was higher in tubes containing 1 or 3 beads than in those containing 6 or 10 beads. CONCLUSIONS AND CLINICAL RELEVANCE Carboplatin-impregnated CSH beads eluted platinum over 72 hours. Further studies are needed to determine whether implantation of carboplatin-impregnated CSH beads results in detectable levels of platinum systemically and whether the platinum concentrations eluted locally are toxic to tumor cells.

  4. Analysis of platinum content in biodegradable carboplatin-impregnated beads and retrospective assessment of tolerability for intralesional use of the beads in dogs following excision of subcutaneous sarcomas: 29 cases (2011-2014).

    PubMed

    Hess, Theresa A; Drinkhouse, Macy E; Prey, Joshua D; Miller, Jonathan M; Fettig, Arthur A; Carberry, Carol A; Brenn, Stephen H; Bailey, Dennis B

    2018-02-15

    OBJECTIVE To evaluate platinum content in biodegradable carboplatin-impregnated beads and retrospectively assess tolerability and outcome data for dogs treated by intralesional placement of such beads following surgical excision of subcutaneous sarcomas. DESIGN Evaluation study and retrospective case series. SAMPLE 9 carboplatin-impregnated beads and 29 client-owned dogs. PROCEDURES Platinum content in 9 carboplatin-impregnated beads from 3 lots was measured by spectrophotometry, and calculated carboplatin content was compared with the labeled content. Medical records were searched to identify dogs with subcutaneous sarcomas for which treatment included placement of carboplatin-impregnated beads between 2011 and 2014. Signalment, tumor characteristics, surgical and histologic data, adverse events, and local recurrences were recorded. Associations between variables of interest and adverse events or local disease-free interval were analyzed. RESULTS In vitro analysis identified a mean ± SD platinum content of 5.38 ± 0.97 mg/bead. Calculated carboplatin content (10.24 ± 1.84 mg/bead) was significantly greater than the labeled amount (4.6 mg/bead). Bead weight and total platinum content differed significantly among lots, but platinum content per bead weight did not. Mild-to-moderate local adverse events were reported for 11 of 29 tumors; all resolved without additional surgery. No dogs had signs of systemic toxicosis. Overall local disease-free rates 1, 2, and 3 years after surgery were 70%, 70%, and 58%, respectively, as determined by Kaplan-Meier analysis. CONCLUSIONS AND CLINICAL RELEVANCE Carboplatin-impregnated beads were well tolerated; however, results of in vitro tests indicated that caution is needed because of manufacturing inconsistencies.

  5. Literature Review: An Overview of Epoxy Resin Syntactic Foams with Glass Microballoons

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Keller, Jennie

    2014-03-12

    Syntactic foams are an important category of composite materials that have abundant applications in a wide variety of fields. The bulk phase of syntactic foams is a three-part epoxy resin formulation that consists of a base resin, a curative (curing agent) and a modifier (diluent and/or accelerator) [12]. These thermoset materials [12] are used frequently for their thermal stability [9], low moisture absorption and high compressive strength [10]. The characteristic feature of a syntactic foam is a network of beads that forms pores within the epoxy matrix [3]. In this review, hollow glass beads (known as glass microballoons) are considered,more » however, solid beads or microballoons made from materials such as ceramic, polymer or metal can also be used [3M, Peter]. The network of hollow beads forms a closed-cell foam; the term closed-cell comes from the fact that the microspheres used in the resin matrix are completely closed and filled with gas (termed hollow). In contrast, the microspheres used in open-cell foams are either not completely closed or broken so that matrix material can fill the spheres [11]. Although closed foams have been found to possess higher densities than open cell foams, their rigid structures give them superior mechanical properties [12]. Past research has extensively studied the effects that changing the volume fraction of microballoons to epoxy will have on the resulting syntactic foam [3,4,9]. In addition, published literature also explores how the microballoon wall thickness affects the final product [4,9,10]. Findings detail that indeed both the mechanical and some thermal properties of syntactic foams can be tailored to a specific application by varying either the volume fraction or the wall thickness of the microballoons used [10]. The major trends in syntactic foam research show that microballoon volume fraction has an inversely proportionate relationship to dynamic properties, while microballoon wall thickness is proportional to those same properties [3,4,9,10]. The glass transition temperature has a proportional relationship to the volume fraction of microballoons used, however, there is limited research that supports correlations between other thermal variables and microballoons specifications. In fact, very little experimental data exists to relate thermal conductivity and volume fraction or wall thickness of microballoons [5]. This review proposes that thermal conductivity should be a topic of interest for future researchers because of how frequently syntactic foams are used in insulating applications. This paper will explore three aspects pertaining to epoxy resin syntactic foams with glass microballoons: the immense range of applications that syntactic foams are used for, the materials and fabrication techniques most commonly used, and lastly the results from characterization of syntactic foams with varying microballoon volume fractions and wall thicknesses. In addition to varying microballoon parameters, it is also possible to change the base, accelerator and curing agent used in the epoxy formulation. For simplicity, this paper will focus on a very common combination of materials produced by the Dow Chemical Company®.« less

  6. Fibrin matrices: The versatile therapeutic delivery systems.

    PubMed

    Ahmad, Ejaj; Fatima, Munazza Tamkeen; Hoque, Mehboob; Owais, Mohammad; Saleemuddin, Mohammed

    2015-11-01

    Fibrin sealants, that have been employed for over a century by surgeons to stop post surgery bleeding, are finding novel applications in the controlled delivery of antibiotics and several other therapeutics. Fibrinogen can be easily purified from blood plasma and converted by thrombolysis to fibrin that undergoes spontaneous aggregation to form insoluble clot. During the gelling, fibrin can be formulated into films, clots, threads, microbeads, nanoconstructs and nanoparticles. Whole plasma clots in the form of beads and microparticles can also be prepared by activating endogenous thrombin, for possible drug delivery. Fibrin formulations offer remarkable scope for controlling the porosity as well as in vivo degradability and hence the release of the associated therapeutics. Binding/covalent-linking of therapeutics to the fibrin matrix, crosslinking of the matrix with bifunctional reagents and coentrapment of protease inhibitors have been successful in regulating both in vitro and in vivo release of the therapeutics. The release rates can also be remarkably lowered by preentrapment of therapeutics in insoluble particles like liposomes or by anchoring them to the matrix via molecules that bind them as well as fibrin. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. From the one-bead-one-compound concept to one-bead-one-reactor.

    PubMed

    Marani, Mariela M; Paradís-Bas, Marta; Tulla-Puche, Judit; Côté, Simón; Camperi, Silvia A; Cascone, Osvaldo; Albericio, Fernando

    2007-01-01

    The one-bead-one-compound method gives access to millions of compounds that can be screened directly on the bead. Although characterization techniques are increasingly potent and reliable, problems can still be encountered in deciphering the sequence of the active compound because of sensitiveness or manipulation of the bead. ChemMatrix, a totally PEG-based resin, has resolved the synthesis of peptides of outstanding difficulty. Like other PEG-based resins, it permits on-bead screening because of its compatibility in aqueous media and has the further advantage of having a high loading, comparable to polystyrene resins. ChemMatrix beads previously swelled in water can be nicely divided into four parts that can be characterized using different analytical techniques or just stored for safety or for further testing. The four bead parts show high homogeneity and can thus be considered to be replicas.

  8. Synthesis and characterization of nanoporous silica aerogel beads using cheap industrial grade sodium silacte precursor

    NASA Astrophysics Data System (ADS)

    Khan, Tasneem M. A.; Khan, Asiya; Sarawade, Pradip B.

    2018-05-01

    We report a method to synthesize low-density transparent mesoporous silica aerogel beads by ambient pressure drying (APD). The beads were prepared by acid-base sol-gel polymerization of sodium silicate in via the ball dropping method (BDM). To minimize shrinkage during drying, wet silica beads were initially prepared; their surfaces were then modified using trimethylchlorosilane (TMCS) via simultaneous solvent exchange and surface modification. The specific surface area and cumulative pore volume of the silica aerogel beads increased with an increase in the %V of TMCS. Silica aerogel beads with low packing bed density, high surface area, and large cumulative pore volume was obtained when TMCS was used. Properties of the final product were examined by BET, and TG-DT analyses. The hydrophobic silica aerogel beads were thermally stable up to 350°C. We discuss our results and compare our findings for modified versus unmodified silica beads.

  9. Bead mediated separation of microparticles in droplets.

    PubMed

    Wang, Sida; Sung, Ki-Joo; Lin, Xiaoxia Nina; Burns, Mark A

    2017-01-01

    Exchange of components such as particles and cells in droplets is important and highly desired in droplet microfluidic assays, and many current technologies use electrical or magnetic fields to accomplish this process. Bead-based microfluidic techniques offer an alternative approach that uses the bead's solid surface to immobilize targets like particles or biological material. In this paper, we demonstrate a bead-based technique for exchanging droplet content by separating fluorescent microparticles in a microfluidic device. The device uses posts to filter surface-functionalized beads from a droplet and re-capture the filtered beads in a new droplet. With post spacing of 7 μm, beads above 10 μm had 100% capture efficiency. We demonstrate the efficacy of this system using targeted particles that bind onto the functionalized beads and are, therefore, transferred from one solution to another in the device. Binding capacity tests performed in the bulk phase showed an average binding capacity of 5 particles to each bead. The microfluidic device successfully separated the targeted particles from the non-targeted particles with up to 98% purity and 100% yield.

  10. Method for preparing spherical ferrite beads and use thereof

    DOEpatents

    Lauf, Robert J.; Anderson, Kimberly K.; Montgomery, Frederick C.; Collins, Jack L.

    2002-01-01

    The invention allows the fabrication of small, dense, highly polished spherical beads of hexagonal ferrites with selected compositions for use in nonreciprocal microwave and mm-wave devices as well as in microwave absorbent or reflective coatings, composites, and the like. A porous, generally spherical bead of hydrous iron oxide is made by a sol-gel process to form a substantially rigid bead having a generally fine crystallite size and correspondingly finely distributed internal porosity. The resulting gel bead is washed and hydrothermally reacted with a soluble alkaline earth salt (typically Ba or Sr) under conditions of elevated temperature and pressure to convert the bead into a mixed hydrous iron-alkaline earth oxide while retaining the generally spherical shape. This mixed oxide bead is then washed, dried, and calcined to produce the desired (BaFe.sub.12 O.sub.19 or SrFe.sub.12 O.sub.19) crystal structure. The calcined bead is then sintered to form a dense bead of the BaFe.sub.12 O.sub.19 and SrFe.sub.12 O.sub.19 phase suitable for polishing and incorporation into various microwave devices and components.

  11. Congo red adsorption from aqueous solutions by using chitosan hydrogel beads impregnated with nonionic or anionic surfactant.

    PubMed

    Chatterjee, Sudipta; Lee, Dae S; Lee, Min W; Woo, Seung H

    2009-09-01

    The adsorption performance of CS beads impregnated with triton X-100 (TX-100) as a nonionic surfactant and sodium dodecyl sulfate (SDS) as an anionic surfactant was investigated for the removal of anionic dye (congo red) from aqueous solution. While the adsorption capacity of CS/TX-100 beads was enhanced at all concentrations of TX-100 (0.005-0.1%), the increase in the concentration of SDS above 0.01% in the CS/SDS beads gradually reduced the adsorption capacity of the beads. Equilibrium adsorption isotherm data indicated a good fit to the Sips isotherm model and a heterogeneous adsorption process. The Sips maximum adsorption capacity in dry weight of the CS/TX-100 beads was 378.79 mg/g and 318.47 mg/g for the CS/SDS beads, higher than the 223.25mg/g of the CS beads. Modification of CS beads by impregnation with nonionic surfactant, or even anionic surfactant, at low concentrations is a possible way to enhance adsorption of anionic dye.

  12. Optical Manipulation of Single Magnetic Beads in a Microwell Array on a Digital Microfluidic Chip.

    PubMed

    Decrop, Deborah; Brans, Toon; Gijsenbergh, Pieter; Lu, Jiadi; Spasic, Dragana; Kokalj, Tadej; Beunis, Filip; Goos, Peter; Puers, Robert; Lammertyn, Jeroen

    2016-09-06

    The detection of single molecules in magnetic microbead microwell array formats revolutionized the development of digital bioassays. However, retrieval of individual magnetic beads from these arrays has not been realized until now despite having great potential for studying captured targets at the individual level. In this paper, optical tweezers were implemented on a digital microfluidic platform for accurate manipulation of single magnetic beads seeded in a microwell array. Successful optical trapping of magnetic beads was found to be dependent on Brownian motion of the beads, suggesting a 99% chance of trapping a vibrating bead. A tailor-made experimental design was used to screen the effect of bead type, ionic buffer strength, surfactant type, and concentration on the Brownian activity of beads in microwells. With the optimal conditions, the manipulation of magnetic beads was demonstrated by their trapping, retrieving, transporting, and repositioning to a desired microwell on the array. The presented platform combines the strengths of digital microfluidics, digital bioassays, and optical tweezers, resulting in a powerful dynamic microwell array system for single molecule and single cell studies.

  13. [Determination of oxaprozin in human plasma with high performance liquid chromatography (HPLC) and its application].

    PubMed

    Mao, Mian; Wang, Ling; Jiang, Xuehua; Yang, Lin

    2013-06-01

    The present research was aimed to develop a high performance liquid chromatography (HPLC) method to determine oxaprozin in plasma and to evaluate the bioavailability of two oxaprozin enteric coated tablets. A C18 column was used to separate the plasma after protein precipitation and the mobile phase was methanol-12. 5mmol/L ammonium acetate buffer solution (pH=3.0)(71:29). The calibration curve was linear in the concentration range of 0. 50-70. 56 microg . mL-1, and the intra and inter-day RSDs were less than 12. 33% and 10. 42% respectively. A single dose of 0. 4 g reference preparation or test preparation of oxaprozin enteric coated tablets was administered to 20 healthy volunteers according to a randomized crossover study. AUC0-->264h were (4 917. 44 +/- 629. 57) microg . h . mL-1 and (4 604. 30+/-737. 83) microg . h . mL-1, respectively; Cmax were (52. 34+/-7. 68) microg . mL-1 and (48. 66+/-4. 87) microg . mL-1, respectively; Tmax were (18. 70+/-2.27) h and (19. 30+/-1. 63) h, respectively; The relative bioavailability of test preparation was 94.0% +/- 13. 7%. The method is simple, rapid and selective for oxaprozin determination. There is no significant difference in the main pharmacokinetic parameters between the test formulation and reference formulation and the two formulations are in bioequivalence.

  14. 77 FR 32986 - Notice of Inventory Completion: The University of Alabama Museums, Tuscaloosa, AL

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-04

    ... than 2,032 glass beads, 1 lot of more than 17 shell beads, 1 unidentified bead, 1 gun lock, 1 gun butt plate, 1 gun stock, 2 gun barrels, 1 brass ramrod support, 8 musket balls, 2 iron buckles, 1 iron handle... fragments, 1 unidentified bead, 2 glass beads, 1 gun flint, 1 iron knife blade, 1 iron nail, 1 musket ball...

  15. Magnetic bead detection using nano-transformers.

    PubMed

    Kim, Hyung Kwon; Hwang, Jong Seung; Hwang, Sung Woo; Ahn, Doyeol

    2010-11-19

    A novel scheme to detect magnetic beads using a nano-scale transformer with a femtoweber resolution is reported. We have performed a Faraday's induction experiment with the nano-transformer at room temperature. The transformer shows the linear output voltage responses to the sinusoidal input current. When magnetic beads are placed on the transformer, the output responses are increased by an amount corresponding to the added magnetic flux from the beads when compared with the case of no beads on the transformer. In this way, we could determine whether magnetic beads are on top of the transformer in a single particle level.

  16. Phosphate uptake studies of cross-linked chitosan bead materials.

    PubMed

    Mahaninia, Mohammad H; Wilson, Lee D

    2017-01-01

    A systematic experimental study is reported that provides a molecular based understanding of cross-linked chitosan beads and their adsorption properties in aqueous solution containing phosphate dianion (HPO 4 2- ) species. Synthetically modified chitosan using epichlorohydrin and glutaraldehyde cross-linkers result in surface modified beads with variable hydrophile-lipophile character and tunable HPO 4 2- uptake properties. The kinetic and thermodynamic adsorption properties of cross-linked chitosan beads with HPO 4 2- species were studied in aqueous solution. Complementary structure and physicochemical characterization of chitosan beads via potentiometry, Raman spectroscopy, DSC, and dye adsorption measurements was carried out to establish structure-property relationships. The maximum uptake (Q m ) of bead systems with HPO 4 2- at equilibrium was 52.1mgg -1 ; whereas, kinetic uptake results for chitosan bead/phosphate systems are relatively rapid (0.111-0.113min -1 ) with an intraparticle diffusion rate-limiting step. The adsorption process follows a multi-step pathway involving inner- and outer-sphere complexes with significant changes in hydration. Phosphate uptake strongly depends on the composition and type of cross-linker used for preparation of chitosan beads. The adsorption isotherms and structural characterization of bead systems illustrate the role of surface charge, hydrophile-lipophile balance, adsorption site accessibility, and hydration properties of the chitosan bead surface. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Determining the unique refractive index properties of solid polystyrene aerosol using broadband Mie scattering from optically trapped beads.

    PubMed

    Jones, Stephanie H; King, Martin D; Ward, Andrew D

    2013-12-21

    A method is described to measure the refractive index dispersion with wavelength of optically trapped solid particles in air. Knowledge of the refraction properties of solid particles is critical for the study of aerosol; both in the laboratory and in the atmosphere for climate studies. Single micron-sized polystyrene beads were optically trapped in air using a vertically aligned counter-propagating configuration of focussed laser beams. Each bead was illuminated using white light from a broadband light emitting diode (LED) and elastic scattering within the bead was collected onto a spectrograph. The resulting Mie spectra were analysed to accurately determine polystyrene bead radii to ±0.4 nm and values of the refractive index to ±0.0005 over a wavelength range of 480-700 nm. We demonstrate that optical trapping combined with elastic scattering can be used to both accurately size polystyrene beads suspended in air and determine their wavelength dependent refractive index. The refractive index dispersions are in close agreement with reported values for polystyrene beads in aqueous dispersion. Our results also demonstrate a variation in the refractive index of polystyrene, from bead to bead, in a commercial sample. The measured variation highlights that care must be taken when using polystyrene beads as a calibration aerosol.

  18. Carryover effects associated with the single-trial passive avoidance learning task in the young chick.

    PubMed

    Crowe, Simon F; Hale, Matthew W

    2002-09-01

    The single-trial passive avoidance task is a useful procedure for examining learning and memory in the young chick. However, it has recently been suggested that discrepant results reported by different laboratories are due to differences in training procedure. The present study investigated a number of parameters surrounding the passive avoidance task, using day-old White Leghorn, Black Australorp cockerels. The results suggested that presentation of a water-dipped bead immediately after the aversive bead significantly altered retention levels. In addition, when the water-dipped bead was presented after the aversive bead, chicks failed to discriminate between beads for a period of 10 min following exposure to the aversant experience. A novel variant of the passive avoidance procedure, involving pretraining with a water-dipped red bead, training with an aversant-coated red bead, and testing with a dry red bead, was evaluated. A measure of avoidance was calculated using all three trials. It is suggested that the use of a single bead, measured both before and after the training experience and using both aversant- and water-trained controls, results in the most concise characterization of memory-related phenomena in the chick which is not contaminated by a carryover effect from the aversive training experience to the nonaversive bead.

  19. Echicetin Coated Polystyrene Beads: A Novel Tool to Investigate GPIb-Specific Platelet Activation and Aggregation

    PubMed Central

    Petunin, Alexey; Clemetson, Kenneth J.; Gambaryan, Stepan; Walter, Ulrich

    2014-01-01

    von Willebrand factor/ristocetin (vWF/R) induces GPIb-dependent platelet agglutination and activation of αIIbβ3 integrin, which also binds vWF. These conditions make it difficult to investigate GPIb-specific signaling pathways in washed platelets. Here, we investigated the specific mechanisms of GPIb signaling using echicetin-coated polystyrene beads, which specifically activate GPIb. We compared platelet activation induced by echicetin beads to vWF/R. Human platelets were stimulated with polystyrene beads coated with increasing amounts of echicetin and platelet activation by echicetin beads was then investigated to reveal GPIb specific signaling. Echicetin beads induced αIIbβ3-dependent aggregation of washed platelets, while under the same conditions vWF/R treatment led only to αIIbβ3-independent platelet agglutination. The average distance between the echicetin molecules on the polystyrene beads must be less than 7 nm for full platelet activation, while the total amount of echicetin used for activation is not critical. Echicetin beads induced strong phosphorylation of several proteins including p38, ERK and PKB. Synergistic signaling via P2Y12 and thromboxane receptor through secreted ADP and TxA2, respectively, were important for echicetin bead triggered platelet activation. Activation of PKG by the NO/sGC/cGMP pathway inhibited echicetin bead-induced platelet aggregation. Echicetin-coated beads are powerful and reliable tools to study signaling in human platelets activated solely via GPIb and GPIb-triggered pathways. PMID:24705415

  20. Basket design as a factor in retention and release of calculi in vitro.

    PubMed

    Zeltser, Ilia S; Bagley, Demetrius H

    2007-03-01

    To compare stone retrieval and release from seven basket designs in vitro. We tested two tipped and one tipless NCompass models, three other tipless Nitinol designs (NCircle, Sur-Catch, and Dimension), and the Segura Hemisphere for their ability to retrieve and release single beads 8, 6, 5.6, and 5 mm diameter and multiple beads 3.6 mm diameter in both a ureteral and a caliceal model in three separate attempts. In the ureteral model, all baskets were successful in retrieving all sizes of single beads. With multiple 3.6-mm beads, only the NCompass and Dimension designs were able to retrieve at least two of three beads in all attempts. With the exception of the Segura Hemisphere, all designs were successful in releasing all bead sizes. In the caliceal model, only the NCircle, Dimension, and tipless NCompass models were able to retrieve all bead sizes in 100% of the trials. The tipped NCompass and Hemisphere designs were unable to retrieve any beads in this model. The Sur-Catch basket was successful in the retrieval of large beads only. The Dimension articulating design was the only basket able to release all bead sizes in all attempts. The tipless NCompass basket did not release any of the beads once engaged. Nitinol basket designs show excellent retrieval and release capabilities in the in-vitro ureteral model. The articulating Nitinol basket has the best stone-releasing capability of all baskets tested.

  1. Rhenium-coated glass beads for intracolonic administration attenuate TNBS-induced colitis in mice: Proof-of-Concept Study.

    PubMed

    Siczek, Krzysztof; Zatorski, Hubert; Pawlak, Wojciech; Fichna, Jakub

    2015-01-01

    In search for novel effective treatments in inflammatory bowel diseases, a new strategy employing glass beads coated with rhenium nanolayer has been developed and validated in the mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Briefly, mice were randomly divided into 5 experimental groups: control (vehicle alone, Group 1); control treated with rhenium-coated glass beads (Group 2); TNBS (Group 3); TNBS treated with rhenium-coated glass beads (Group 4); and TNBS treated with uncoated glass beads (Group 5). Mice from Group 2, 4 and 5 were treated with respective beads (once daily, 5 beads / animal, i.c.) between D3-D6 post-TNBS/vehicle and evaluation of colonic damage was performed on D7, based on macroscopic scoring and clinical parameters. Severe colonic inflammation developed in post-TNBS mice (Group 3) [P <0.001 vs. control (Group 1) for macroscopic score], which was significantly attenuated by treatment with rhenium-coated glass beads (Group 4) [P <0.01 vs. TNBS (Group 3), for macroscopic score]. Neither rhenium-coated glass beads had any effect in control animals (Group 2), nor uncoated glass beads influenced TNBS-induced colitis (Group 5). In conclusion, a novel and attractive strategy for the treatment of colonic inflammation has been proposed; therapy with rhenium-coated glass beads already proved effective in the mouse model of TNBS-induced colitis, now requires further characterization in clinical conditions.

  2. Structurally stable gel bead containing entrapped enzyme and method for manufacture thereof

    DOEpatents

    Woodward, J.

    1998-12-08

    This research provides a structurally stable gel bead containing an entrapped enzyme and a method for its manufacture. The enzyme is covalently cross-linked to gelatin in the presence of glutaraldehyde prior to the formation of the gel bead, to prevent leakage of the enzyme. Propylene glycol alginate is then added to the mixture. Once the gel beads are formed, they are then soaked in glutaraldehyde, which imparts structural stability to the gel beads. This method can be used with many types of enzymes, such as proteases, carbohydrases, proteases, ligases, isomerases, oxidoreductases, and specialty enzymes. These and other enzymes can be immobilized in the gel beads and utilized in a number of enzymatic processes. Exogenously added ions are not required to maintain the structural stability of these gel beads. 7 figs.

  3. Structurally stable gel bead containing entrapped enzyme and method for manufacture thereof

    DOEpatents

    Woodward, Jonathan

    1998-01-01

    A structurally stable gel bead containing an entrapped enzyme and a method for its manufacture. The enzyme is covalently cross-linked to gelatin in the presence of glutaraldehyde prior to the formation of the gel bead, to prevent leakage of the enzyme. Propylene glycol alginate is then added to the mixture. Once the gel beads are formed, they are then soaked in glutaraldehyde, which imparts structural stability to the gel beads. This method can be used with many types of enzymes, such as proteases, carbohydrases, proteases, ligases, isomerases, oxidoreductases, and specialty enzymes. These and other enzymes can be immobilized in the gel beads and utilized in a number of enzymatic processes. Exogenously added ions are not required to maintain the structural stability of these gel beads.

  4. Development of electrospun beaded fibers from Thai silk fibroin and gelatin for controlled release application.

    PubMed

    Somvipart, Siraporn; Kanokpanont, Sorada; Rangkupan, Rattapol; Ratanavaraporn, Juthamas; Damrongsakkul, Siriporn

    2013-04-01

    Thai silk fibroin and gelatin are attractive biomaterials for tissue engineering and controlled release applications due to their biocompatibility, biodegradability, and bioactive properties. The development of electrospun fiber mats from silk fibroin and gelatin were reported previously. However, burst drug release from such fiber mats remained the problem. In this study, the formation of beads on the fibers aiming to be used for the sustained release of drug was of our interest. The beaded fiber mats were fabricated using electrospinning technique by controlling the solution concentration, weight blending ratio of Thai silk fibroin/gelatin blend, and applied voltage. It was found that the optimal conditions including the solution concentration and the weight blending ratio of Thai silk fibroin/gelatin at 8-10% (w/v) and 70/30, respectively, with the applied voltage at 18 kV provided the fibers with homogeneous formation of beads. Then, the beaded fiber mats obtained were crosslinked by the reaction of carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS). Methylene blue as a model active compound was loaded on the fiber mats. The release test of methylene blue from the beaded fiber mats was carried out in comparison to that of the smooth fiber mats without beads. It was found that the beaded fiber mats could prolong the release of methylene blue, comparing to the smooth fiber mats without beads. This was possibly due to the beaded fiber mats that would absorb and retain higher amount of methylene blue than the fiber mats without beads. Thai silk fibroin/gelatin beaded fiber mats were established as an effective carrier for the controlled release applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Guar gum succinate-sodium alginate beads as a pH-sensitive carrier for colon-specific drug delivery.

    PubMed

    Seeli, D Sathya; Dhivya, S; Selvamurugan, N; Prabaharan, M

    2016-10-01

    Guar gum succinate - sodium alginate (GGS-SA) beads cross-linked with barium ions were prepared and characterized as a pH sensitive carrier for colon-specific drug delivery. The structure of GGS-SA beads was confirmed by FT-IR spectroscopy. Scanning Electron Microscope (SEM) studies revealed that the drug loaded GGS-SA beads prepared using 2:2 (w/v) weight percent of GGS and SA had a diameter about 1.4mm and roughly spherical in shape. X-ray diffraction (XRD) studies showed that the peaks corresponding to GGS and SA at 13.5°, 17.5°, 20.2° and 13.5°, 22°, 24.1°, respectively were destroyed in GGS-SA beads which show that these beads are more amorphous in nature. Swelling studies demonstrated the pH-dependent swelling behavior of GGS-SA beads. The beads showed higher swelling degrees in pH 7.4 than that in pH 1.2 due to the existence of anionic groups in the polymer chains. The drug release study showed that the amount of model drug, ibuprofen, released from the GGS-SA beads was higher in pH 7.4 than that in pH 1.2 due to the pH-dependent swelling behavior of the beads. MTT assay revealed that GGS-SA beads at a concentration range of 0-30μg/ml had no cytotoxic effect on the cultured mouse mesenchymal stem cells (C3H10T1/2). These results suggest that GGS-SA beads can be used as effective colon-specific drug delivery system with pH-dependent drug release ability. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Steady-state force-velocity relation in the ATP-dependent sliding movement of myosin-coated beads on actin cables in vitro studied with a centrifuge microscope.

    PubMed Central

    Oiwa, K; Chaen, S; Kamitsubo, E; Shimmen, T; Sugi, H

    1990-01-01

    To eliminate the gap between the biochemistry of actomyosin in solution and the physiology of contracting muscle, we developed an in vitro force-movement assay system in which the steady-state force-velocity relation in the actin-myosin interaction can be studied. The assay system consists of the internodal cells of an alga, Nitellopsis obtusa, containing well-organized actin filament arrays (actin cables); tosyl-activated polystyrene beads (diameter, 2.8 microns; specific gravity, 1.3) coated with skeletal muscle myosin; and a centrifuge microscope equipped with a stroboscopic light source and a video system. The internodal cell preparation was mounted on the rotor of the centrifuge microscope, so that centrifugal forces were applied to the myosin-coated beads moving along the actin cables in the presence of ATP. Under constant centrifugal forces directed opposite to the bead movement ("positive" loads), the beads continued to move with constant velocities, which decreased with increasing centrifugal forces. The steady-state force-velocity curve thus obtained was analogous to the double-hyperbolic force-velocity curve of single muscle fibers. The unloaded velocity of bead movement was 1.6-3.6 microns/s (20-23 degrees C), while the maximum "isometric" force generated by the myosin molecules on the bead was 1.9-39 pN. If, on the other hand, the beads were subjected to constant centrifugal forces in the direction of bead movement ("negative" loads), the bead also moved with constant velocities. Unexpectedly, the velocity of bead movement did not increase with increasing negative loads but first decreased by 20-60% and then increased towards the initial unloaded velocity until the beads were eventually detached from the actin cables. Images PMID:2236007

  7. Steady-state force-velocity relation in the ATP-dependent sliding movement of myosin-coated beads on actin cables in vitro studied with a centrifuge microscope.

    PubMed

    Oiwa, K; Chaen, S; Kamitsubo, E; Shimmen, T; Sugi, H

    1990-10-01

    To eliminate the gap between the biochemistry of actomyosin in solution and the physiology of contracting muscle, we developed an in vitro force-movement assay system in which the steady-state force-velocity relation in the actin-myosin interaction can be studied. The assay system consists of the internodal cells of an alga, Nitellopsis obtusa, containing well-organized actin filament arrays (actin cables); tosyl-activated polystyrene beads (diameter, 2.8 microns; specific gravity, 1.3) coated with skeletal muscle myosin; and a centrifuge microscope equipped with a stroboscopic light source and a video system. The internodal cell preparation was mounted on the rotor of the centrifuge microscope, so that centrifugal forces were applied to the myosin-coated beads moving along the actin cables in the presence of ATP. Under constant centrifugal forces directed opposite to the bead movement ("positive" loads), the beads continued to move with constant velocities, which decreased with increasing centrifugal forces. The steady-state force-velocity curve thus obtained was analogous to the double-hyperbolic force-velocity curve of single muscle fibers. The unloaded velocity of bead movement was 1.6-3.6 microns/s (20-23 degrees C), while the maximum "isometric" force generated by the myosin molecules on the bead was 1.9-39 pN. If, on the other hand, the beads were subjected to constant centrifugal forces in the direction of bead movement ("negative" loads), the bead also moved with constant velocities. Unexpectedly, the velocity of bead movement did not increase with increasing negative loads but first decreased by 20-60% and then increased towards the initial unloaded velocity until the beads were eventually detached from the actin cables.

  8. Force measurements of a magnetic micro actuator proposed for a microvalve array

    NASA Astrophysics Data System (ADS)

    Chang, Pauline J.; Chang, Frank W.; Yuen, Michelle C.; Otillar, Robert; Horsley, David A.

    2014-03-01

    Low-cost, easily-fabricated and power-efficient microvalves are necessary for many microfluidic lab-on-a-chip applications. In this study, we present a simple, low-power, scalable, CMOS-compatible magnetic actuator for microvalve applications composed of a paramagnetic bead as the ball valve over a picoliter reaction well etched into a silicon substrate. The paramagnetic bead, composed of either pure FeSi or magnetite in a SiO2 matrix, is actuated by the local magnetic field gradient generated by a microcoil in an aqueous environment, and the reaction well is situated at the microcoil center. A permanent magnet beneath the microvalve device provides an external magnetic biasing field that magnetizes the bead, enabling bidirectional actuation and reducing the current required to actuate the bead to a level below 10 mA. The vertical and radial magnetic forces exerted on the bead by the microcoil were measured for both pure FeSi and composite beads and agree well with the predictions of 2D axisymmetric finite element method models. Vertical forces were within a range of 13-80 nN, and radial forces were 11-60 nN depending on the bead type. The threshold current required to initiate bead actuation was measured as a function of bead diameter and is found to scale inversely with volume for small beads, as expected based on the magnetic force model. To provide an estimate of the stiction force acting between the bead and the passivation layer on the substrate, repeated actuation trials were used to study the bead throw distance for substrates coated with silicon dioxide, Parylene-C, and photoresist. The stiction observed was lowest for a photoresist-coated substrate, while silicon dioxide and Parylene-C coated substrates exhibited similar levels of stiction.

  9. Micro-Encapsulated Porphyrins and Phthalocyanines - New Formulations in Photodynamic Therapy

    NASA Astrophysics Data System (ADS)

    Ion, R. M.

    2017-06-01

    Photodynamic therapy (PDT), as an innovative method for cancer tretament is based on a concerted action of some drugs, called sensitizers, which generate reactive oxygen species via a photochemical mechanism, leading to cellular necrosis or apoptosis. The present work aims at loading some sensitizers, as porphyrins (P) and phthalocyanines (Pc) into alginate particles. Particles were prepared by dropping alginate into an aqueous solution containing P or Pc and CaCl2, which allows the formation of particles through ionic crosslinking. It was obtained P or Pc loaded alginate beads with an average diameter of about 100 μm. For these systems, this paper analyses the spectroscopic properties, encapsulation into microcapsules, controlled releasing action and their photosensitizer capacity (singlet oxygen generation).

  10. Method for preparing dielectric composite materials

    DOEpatents

    Lauf, Robert J.; Anderson, Kimberly K.; Montgomery, Frederick C.; Collins, Jack L.; Felten, John J.

    2004-11-23

    The invention allows the fabrication of small, dense beads of dielectric materials with selected compositions, which are incorporated into a polymeric matrix for use in capacitors, filters, and the like. A porous, generally spherical bead of hydrous metal oxide containing titanium or zirconium is made by a sol-gel process to form a substantially rigid bead having a generally fine crystallite size and correspondingly finely distributed internal porosity. The resulting gel bead may be washed and hydrothermally reacted with a soluble alkaline earth salt (typically Ba or Sr) at elevated temperature and pressure to convert the bead into a mixed hydrous titanium- or zirconium-alkaline earth oxide while retaining the generally spherical shape. Alternatively, the gel bead may be made by coprecipitation. This mixed oxide bead is then washed, dried and calcined to produce the desired (BaTiO.sub.3, PbTiO.sub.3, SrZrO.sub.3) structure. The sintered beads are incorporated into a selected polymer matrix. The resulting dielectric composite material may be electrically "poled" if desired.

  11. Dielectric composite materials and method for preparing

    DOEpatents

    Lauf, Robert J.; Anderson, Kimberly K.; Montgomery, Frederick C.; Collins, Jack L.; Felten, John J.

    2003-07-29

    The invention allows the fabrication of small, dense beads of dielectric materials with selected compositions, which are incorporated into a polymeric matrix for use in capacitors, filters, and the like. A porous, generally spherical bead of hydrous metal oxide containing titanium or zirconium is made by a sol-gel process to form a substantially rigid bead having a generally fine crystallite size and correspondingly finely distributed internal porosity. The resulting gel bead may be washed and hydrothermally reacted with a soluble alkaline earth salt (typically Ba or Sr) at elevated temperature and pressure to convert the bead into a mixed hydrous titanium- or zirconium-alkaline earth oxide while retaining the generally spherical shape. Alternatively, the gel bead may be made by coprecipitation. This mixed oxide bead is then washed, dried and calcined to produce the desired (BaTiO.sub.3, PbTiO.sub.3, SrZrO.sub.3) structure. The sintered beads are incorporated into a selected polymer matrix. The resulting dielectric composite material may be electrically "poled" if desired.

  12. Superparamagnetic poly(methyl methacrylate) beads for nattokinase purification from fermentation broth.

    PubMed

    Yang, Chengli; Xing, Jianmin; Guan, Yueping; Liu, Huizhou

    2006-09-01

    An effective method for purification of nattokinase from fermentation broth using magnetic poly(methyl methacrylate) (PMMA) beads immobilized with p-aminobenzamidine was proposed in this study. Firstly, magnetic PMMA beads with a narrow size distribution were prepared by spraying suspension polymerization. Then, they were highly functionalized via transesterification reaction with polyethylene glycol. The surface hydroxyl-modified magnetic beads obtained were further modified with chloroethylamine to transfer the surface amino-modified magnetic functional beads. The morphology and surface functionality of the magnetic beads were examined by scanning electron microscopy and Fourier transform infrared. An affinity ligand, p-aminobenzamidine was covalently immobilized to the amino-modified magnetic beads by the glutaraldehyde method for nattokinase purification directly from the fermentation broth. The purification factor and the recovery of the enzyme activity were found to be 8.7 and 85%, respectively. The purification of nattokinase from fermentation broth by magnetic beads only took 40 min, which shows a very fast purification of nattokinase compared to traditional purification methods.

  13. Clinical review: optimizing enteral nutrition for critically ill patients - a simple data-driven formula

    PubMed Central

    2011-01-01

    In modern critical care, the paradigm of 'therapeutic nutrition' is replacing traditional 'supportive nutrition'. Standard enteral formulas meet basic macro- and micronutrient needs; therapeutic enteral formulas meet these basic needs and also contain specific pharmaconutrients that may attenuate hyperinflammatory responses, enhance the immune responses to infection, or improve gastrointestinal tolerance. Choosing the right enteral feeding formula may positively affect a patient's outcome; targeted use of therapeutic formulas can reduce the incidence of infectious complications, shorten lengths of stay in the ICU and in the hospital, and lower risk for mortality. In this paper, we review principles of how to feed (enteral, parenteral, or both) and when to feed (early versus delayed start) patients who are critically ill. We discuss what to feed these patients in the context of specific pharmaconutrients in specialized feeding formulations, that is, arginine, glutamine, antioxidants, certain ω-3 and ω-6 fatty acids, hydrolyzed proteins, and medium-chain triglycerides. We summarize current expert guidelines for nutrition in patients with critical illness, and we present specific clinical evidence on the use of enteral formulas supplemented with anti-inflammatory or immune-modulating nutrients, and gastrointestinal tolerance-promoting nutritional formulas. Finally, we introduce an algorithm to help bedside clinicians make data-driven feeding decisions for patients with critical illness. PMID:22136305

  14. Lifelong Learning NCES Task Force: Final Report, Volume II. Working Paper Series.

    ERIC Educational Resources Information Center

    National Center for Education Statistics (ED), Washington, DC.

    This document contains the eight appendixes from the National Center for Education Statistics's (NCES's) final report on lifelong learning in the United States. Appendix A discusses the considerations that entered into the formulation of the definition of lifelong learning adopted for the NCES study. Appendix B, "Literature Review on Lifelong…

  15. Stability optimization of microbial surface-enhanced Raman spectroscopy detection with immunomagnetic separation beads

    NASA Astrophysics Data System (ADS)

    Uusitalo, Sanna; Kögler, Martin; Välimaa, Anna-Liisa; Petäjä, Jarno; Kontturi, Ville; Siitonen, Samuli; Laitinen, Riitta; Kinnunen, Matti; Viitala, Tapani; Hiltunen, Jussi

    2017-03-01

    Immunomagnetic separation (IMS) beads with antibody coating are an interesting option for biosensing applications for the identification of biomolecules and biological cells, such as bacteria. The paramagnetic properties of the beads can be utilized with optical sensing by migrating and accumulating the beads and the bound analytes toward the focus depth of the detection system by an external magnetic field. The stability of microbial detection with IMS beads was studied by combining a flexible, inexpensive, and mass producible surface-enhanced Raman spectroscopy (SERS) platform with gold nanoparticle detection and antibody recognition by the IMS beads. Listeria innocua ATCC 33090 was used as a model sample and the effect of the IMS beads on the detected Raman signal was studied. The IMS beads were deposited into a hydrophobic sample well and accumulated toward the detection plane by a neodymium magnet. For the first time, it was shown that the spatial stability of the detection could be improved up to 35% by using IMS bead capture and sample well placing. The effect of a neodymium magnet under the SERS chip improved the temporal detection and significantly reduced the necessary time for sample stabilization for advanced laboratory testing.

  16. Facile fabrication and characterization of a novel oral pH-sensitive drug delivery system based on CMC hydrogel and HNT-AT nanohybrid.

    PubMed

    Hossieni-Aghdam, Seyed Jamal; Foroughi-Nia, Behrouz; Zare-Akbari, Zhila; Mojarad-Jabali, Solmaz; Motasadizadeh, Hamidreza; Farhadnejad, Hassan

    2018-02-01

    The main aim of the present study was to design pH-sensitive bionanocomposite hydrogel beads based on CMC and HNT-AT nanohybrid and evaluate whether prepared bionanocomposite beads have the potential to be used in drug delivery applications. Atenolol (AT), as a model drug, was incorporated into the lumen of HA nanotubes via the co-precipitation technique. HNT/AT nanohybrid and CMC/HNT-AT beads were characterized via XRD, SEM, TGA, and FT-IR techniques. Drug loading and encapsulation efficiency was found to be high for CMC/HNT3 beads. Moreover, the swelling and drug release properties of the prepared CMC/HA-AT beads were investigated, and showed a pH sensitive swelling behavior with maximum its content at pH 6.8. Also, it was found that the swelling ratio of CMC/HNT beads was lower than that of pristine CMC beads. Drug release behavior of CMC/HNT-AT bionanocomposite hydrogel beads were investigated. A more sustained and controlled drug releases were observed for CMC/HNT-AT beads. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. The elution of colistimethate sodium from polymethylmethacrylate and calcium phosphate cement beads.

    PubMed

    Waterman, Paige; Barber, Melissa; Weintrob, Amy C; VanBrakle, Regina; Howard, Robin; Kozar, Michael P; Andersen, Romney; Wortmann, Glenn

    2012-06-01

    Gram-negative bacilli resistance to all antibiotics, except for colistimethate sodium (CMS), is an emerging healthcare concern. Incorporating CMS into orthopedic cement to treat bone and soft-tissue infections due to these bacteria is attractive, but the data regarding the elution of CMS from cement are conflicting. The in vitro analysis of the elution of CMS from polymethylmethacrylate (PMMA) and calcium phosphate (CP) cement beads is reported. PMMA and CP beads containing CMS were incubated in phosphate-buffered saline and the eluate sampled at sequential time points. The inhibition of the growth of a strain of Acinetobacter baumannii complex by the eluate was measured by disk diffusion and microbroth dilution assays, and the presence of CMS in the eluate was measured by mass spectroscopy. Bacterial growth was inhibited by the eluate from both PMMA and CP beads. Mass spectroscopy demonstrated greater elution of CMS from CP beads than PMMA beads. The dose of CMS in PMMA beads was limited by failure of bead integrity. CMS elutes from both CP and PMMA beads in amounts sufficient to inhibit bacterial growth in vitro. The clinical implications of these findings require further study.

  18. Alginate Beads as Synthetic Inoculant Carriers for Slow Release of Bacteria That Affect Plant Growth †‡

    PubMed Central

    Bashan, Yoav

    1986-01-01

    Uniform synthetic beads were developed as carriers for the bacterial inoculation of plants. The beads are made of sodium alginate and skim milk and contain a large reservoir of bacterial culture which releases the bacteria at a slow and constant rate. The beads are biodegradable and produce no environmental pollution. The strength of the beads, the rate of bacterial release, and the time of their survival in the soil can be controlled by several hardening treatments. The final product, lyophilized beads, is simple to use and is applied to the seeds concomitantly with sowing. The released bacteria are available for root colonization immediately at seed germination. Dry beads containing bacteria can be stored at ambient temperature over a long period without loss of bacterial content; storage requires a limited space, and the quality control of a number of bacteria in the bead is simple. The level of plant inoculation with beads was similar to that with previously used peat inoculants, but the former method yielded more consistent results, as the frequency of inoculated plants was much higher. The former method provides a different approach for inoculation of plants with beneficial rhizosphere bacteria. Images PMID:16347055

  19. A new efficient method of generating photoaffinity beads for drug target identification.

    PubMed

    Nishiya, Yoichi; Hamada, Tomoko; Abe, Masayuki; Takashima, Michio; Tsutsumi, Kyoko; Okawa, Katsuya

    2017-02-15

    Affinity purification is one of the most prevalent methods for the target identification of small molecules. Preparation of an appropriate chemical for immobilization, however, is a tedious and time-consuming process. A decade ago, a photoreaction method for generating affinity beads was reported, where compounds are mixed with agarose beads carrying a photoreactive group (aryldiazirine) and then irradiated with ultraviolet light under dry conditions to form covalent attachment. Although the method has proven useful for identifying drug targets, the beads suffer from inefficient ligand incorporation and tend to shrink and aggregate, which can cause nonspecific binding and low reproducibility. We therefore decided to craft affinity beads free from these shortcomings without compromising the ease of preparation. We herein report a modified method; first, a compound of interest is mixed with a crosslinker having an activated ester and a photoreactive moiety on each end. This mixture is then dried in a glass tube and irradiated with ultraviolet light. Finally, the conjugates are dissolved and reacted with agarose beads with a primary amine. This protocol enabled us to immobilize compounds more efficiently (approximately 500-fold per bead compared to the original method) and generated beads without physical deterioration. We herein demonstrated that the new FK506-immobilized beads specifically isolated more FKBP12 than the original beads, thereby proving our method to be applicable to target identification experiments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. The profile of adsorbed plasma and serum proteins on methacrylic acid copolymer beads: Effect on complement activation.

    PubMed

    Wells, Laura A; Guo, Hongbo; Emili, Andrew; Sefton, Michael V

    2017-02-01

    Polymer beads made of 45% methacrylic acid co methyl methacrylate (MAA beads) promote vascular regenerative responses in contrast to control materials without methacrylic acid (here polymethyl methacrylate beads, PMMA). In vitro and in vivo studies suggest that MAA copolymers induce differences in macrophage phenotype and polarization and inflammatory responses, presumably due to protein adsorption differences between the beads. To explore differences in protein adsorption in an unbiased manner, we used high resolution shotgun mass spectrometry to identify and compare proteins that adsorb from human plasma or serum onto MAA and PMMA beads. From plasma, MAA beads adsorbed many complement proteins, such as C1q, C4-related proteins and the complement inhibitor factor H, while PMMA adsorbed proteins, such as albumin, C3 and apolipoproteins. Because of the differences in complement protein adsorption, follow-up studies focused on using ELISA to assess complement activation. When incubated in serum, MAA beads generated significantly lower levels of soluble C5b9 and C3a/C3a desarg in comparison to PMMA beads, indicating a decrease in complement activation with MAA beads. The differences in adsorbed protein on the two materials likely alter subsequent cell-material interactions that ultimately result in different host responses and local vascularization. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Preparation of porous 2,3-dialdehyde cellulose beads crosslinked with chitosan and their application in adsorption of Congo red dye.

    PubMed

    Ruan, Chang-Qing; Strømme, Maria; Lindh, Jonas

    2018-02-01

    Micrometer sized 2,3-dialdehyde cellulose (DAC) beads were produced via a recently developed method relying on periodate oxidation of Cladophora nanocellulose. The produced dialdehyde groups and pristine hydroxyl groups provided the DAC beads with a vast potential for further functionalization. The sensitivity of the DAC beads to alkaline conditions, however, limits their possible functionalization and applications. Hence, alkaline-stable and porous cellulose beads were prepared via a reductive amination crosslinking reaction between 2,3-dialdehyde cellulose beads and chitosan. The produced materials were thoroughly characterized with different methods. The reaction conditions, including the amount of chitosan used, conditions for reductive amination, reaction temperature and time, were investigated and the maintained morphology of the beads after exposure to 1M NaOH (aq.) was verified with SEM. Different washing and drying procedures were used and the results were studied by SEM and BET analysis. Furthermore, FTIR, TGA, EDX, XPS, DLS and elemental analysis were performed to characterize the properties of the prepared beads. Finally, the alkaline-stable porous chitosan cross-linked 2,3-dialdehyde cellulose beads were applied as adsorbent for the dye Congo red. The crosslinked beads displayed fast and high adsorption capacity at pH 2 and good desorption properties at pH 12, providing a promising sorption material. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Dispersion of fine phosphor particles by newly developed beads mill

    NASA Astrophysics Data System (ADS)

    Joni, I. Made; Panatarani, C.; Maulana, Dwindra W.

    2016-02-01

    Fine phosphor Y2O3:Eu3+ particles has advanced properties compare to conventional particles applied for compact fluorescent lamp (CFL) as three band phosphor. However, suspension of fine particles easily agglomerated during preparation of spray coating of the CFL tube. Therefore, it is introduced newly developed beads mill system to disperse fine phosphor. The beads mill consist of glass beads, dispersing chamber (impellers), separator chamber, slurry pump and motors. The first important performance of beads mill is the performance of the designed on separating the beads with the suspended fine particles. We report the development of beads mill and its separation performance vary in flow rate and separator rotation speeds. The 27 kg of glass beads with 30 µm in size was poured into dispersing chamber and then water was pumped continuously through the slurry pump. The samples for the separation test was obtained every 1 hours vary in rotation speed and slurry flow rate. The results shows that the separation performance was 99.99 % obtained for the rotation speed of >1000 rpm and flow rate of 8 L/minute. The performances of the system was verified by dispersing fine phosphor Y2O3:Eu3+ particles with concentration 1 wt.%. From the observed size distribution of particles after beads mill, it is concluded that the current design of bead mill effectively dispersed fine phosphor Y2O3:Eu3+.

  3. Characterization of product capture resin during microbial cultivations.

    PubMed

    Frykman, Scott; Tsuruta, Hiroko; Galazzo, Jorge; Licari, Peter

    2006-06-01

    Various bioactive small molecules produced by microbial cultivation are degraded in the culture broth or may repress the formation of additional product. The inclusion of hydrophobic adsorber resin beads to capture these products in situ and remove them from the culture broth can reduce or prevent this degradation and repression. These product capture beads are often subjected to a dynamic and stressful microenvironment for a long cultivation time, affecting their physical structure and performance. Impact and collision forces can result in the fracturing of these beads into smaller pieces, which are difficult to recover at the end of a cultivation run. Various contaminating compounds may also bind in a non-specific manner to these beads, reducing the binding capacity of the resin for the product of interest (fouling). This study characterizes resin bead binding capacity (to monitor bead fouling), and resin bead volume distributions (to monitor bead fracture) for an XAD-16 adsorber resin used to capture epothilone produced during myxobacterial cultivations. Resin fouling was found to reduce the product binding capacity of the adsorber resin by 25-50%. Additionally, the degree of resin bead fracture was found to be dependent on the cultivation length and the impeller rotation rate. Microbial cultivations and harvesting processes should be designed in such a way to minimize bead fragmentation and fouling during cultivation to maximize the amount of resin and associated product harvested at the end of a run.

  4. Inertial-ordering-assisted droplet microfluidics for high-throughput single-cell RNA-sequencing.

    PubMed

    Moon, Hui-Sung; Je, Kwanghwi; Min, Jae-Woong; Park, Donghyun; Han, Kyung-Yeon; Shin, Seung-Ho; Park, Woong-Yang; Yoo, Chang Eun; Kim, Shin-Hyun

    2018-02-27

    Single-cell RNA-seq reveals the cellular heterogeneity inherent in the population of cells, which is very important in many clinical and research applications. Recent advances in droplet microfluidics have achieved the automatic isolation, lysis, and labeling of single cells in droplet compartments without complex instrumentation. However, barcoding errors occurring in the cell encapsulation process because of the multiple-beads-in-droplet and insufficient throughput because of the low concentration of beads for avoiding multiple-beads-in-a-droplet remain important challenges for precise and efficient expression profiling of single cells. In this study, we developed a new droplet-based microfluidic platform that significantly improved the throughput while reducing barcoding errors through deterministic encapsulation of inertially ordered beads. Highly concentrated beads containing oligonucleotide barcodes were spontaneously ordered in a spiral channel by an inertial effect, which were in turn encapsulated in droplets one-by-one, while cells were simultaneously encapsulated in the droplets. The deterministic encapsulation of beads resulted in a high fraction of single-bead-in-a-droplet and rare multiple-beads-in-a-droplet although the bead concentration increased to 1000 μl -1 , which diminished barcoding errors and enabled accurate high-throughput barcoding. We successfully validated our device with single-cell RNA-seq. In addition, we found that multiple-beads-in-a-droplet, generated using a normal Drop-Seq device with a high concentration of beads, underestimated transcript numbers and overestimated cell numbers. This accurate high-throughput platform can expand the capability and practicality of Drop-Seq in single-cell analysis.

  5. Development of hydrogel TentaGel shell-core beads for ultrahigh throughput solution-phase screening of encoded OBOC combinatorial small molecule libraries.

    PubMed

    Baek, Hyoung Gee; Liu, Ruiwu; Lam, Kit S

    2009-01-01

    The one-bead one-compound (OBOC) combinatorial library method enables the rapid generation and screening of millions of discrete chemical compounds on beads. Most of the OBOC screening methods require the library compounds to remain tethered to the bead during screening process. Methods have also been developed to release library compounds from immobilized beads for in situ solution phase or "lawn" assays. However, this latter approach, while extremely powerful, is severely limited by the lack of suitable solid supports for such assays. Here, we report on the development of a novel hydrogel TentaGel shell-core (HTSC) bead in which hydrogel is grafted onto the polystyrene-based TentaGel (TG) bead as an outer shell (5-80 mum thick) via free radical surface-initiated polymerization. This novel shell-core bilayer resin enables the preparation of encoded OBOC combinatorial small molecule libraries, such that the library compounds reside on the highly hydrophilic outer layer and the coding tags reside in the polystyrene-based TG core. Using fluorescein as a model small molecule compound, we have demonstrated that fluorescein molecules that have been linked covalently to the hydrogel shell via a disulfide bond could readily diffuse out of the hydrogel layer into the bead surrounding after reduction with dithiothreitol. In contrast, under identical condition, the released fluorescein molecules remained bound to unmodified TG bead. We have prepared an encoded OBOC small molecule library on the novel shell-core beads and demonstrated that the beads can be readily decoded.

  6. Immobilized OBOC combinatorial bead array to facilitate multiplicative screening.

    PubMed

    Xiao, Wenwu; Bononi, Fernanda C; Townsend, Jared; Li, Yuanpei; Liu, Ruiwu; Lam, Kit S

    2013-07-01

    One-bead-one-compound (OBOC) combinatorial library screening has been broadly utilized for the last two decades to identify small molecules, peptides or peptidomimetics targeting variable screening probes such as cell surface receptors, bacteria, protein kinases, phosphatases, proteases etc. In previous screening methods, library beads were suspended in solution and screened against one single probe. Only the positive beads were tracked and isolated for additional screens and finally selected for chemical decoding. During this process, the remaining negative beads were not tracked and discarded. Here we report a novel bead immobilization method such that a bead library array can be conveniently prepared and screened in its entirety, sequentially many times with a series of distinct probes. This method not only allows us to increase the screening efficiency but also permits us to determine the binding profile of each and every library bead against a large number of target receptors. As proof of concept, we serially screened a random OBOC disulfide containing cyclic heptapeptide library with three water soluble dyes as model probes: malachite green, bromocresol purple and indigo carmine. This multiplicative screening approach resulted in a rapid determination of the binding profile of each and every bead respective to each of the three dyes. Beads that interacted with malachite green only, bromocresol purple only, or both indigo carmine and bromocresol purple were isolated, and their peptide sequences were determined with microsequencer. Ultimately, the novel OBOC multiplicative screening approach could play a key role in the enhancement of existing on-bead assays such as whole cell binding, bacteria binding, protein binding, posttranslational modifications etc. with increased efficiency, capacity, and specificity.

  7. Fused Bead Analysis of Diogenite Meteorites

    NASA Technical Reports Server (NTRS)

    Mittlefehldt, D.W.; Beck, B.W.; McSween, H.Y.; Lee, C.T. A.

    2009-01-01

    Bulk rock chemistry is an essential dataset in meteoritics and planetary science [1]. A common method used to obtain the bulk chemistry of meteorites is ICP-MS. While the accuracy, precision and low detection limits of this process are advantageous [2], the sample size used for analysis (approx.70 mg) can be a problem in a field where small and finite samples are the norm. Fused bead analysis is another bulk rock analytical technique that has been used in meteoritics [3]. This technique involves forming a glass bead from 10 mg of sample and measuring its chemistry using a defocused beam on a microprobe. Though the ICP-MS has lower detection limits than the microprobe, the fused bead method destroys a much smaller sample of the meteorite. Fused bead analysis was initially designed for samples with near-eutectic compositions and low viscosities. Melts generated of this type homogenize at relatively low temperatures and produce primary melts near the sample s bulk composition [3]. The application of fused bead analysis to samples with noneutectic melt compositions has not been validated. The purpose of this study is to test if fused bead analysis can accurately determine the bulk rock chemistry of non-eutectic melt composition meteorites. To determine this, we conduct two examinations of the fused bead. First, we compare ICP-MS and fused bead results of the same samples using statistical analysis. Secondly, we inspect the beads for the presence of crystals and chemical heterogeneity. The presence of either of these would indicate incomplete melting and quenching of the bead.

  8. An oral multi-particulate, modified release, hydrocortisone replacement therapy that provides physiological cortisol exposure

    PubMed Central

    Huatan, Hiep; Merke, Deborah; Arlt, Wiebke; Ross, Richard J.

    2013-01-01

    Objective It is not possible with current hydrocortisone replacement to mimic the diurnal cortisol profile in patients with adrenal insufficiency. Previous attempts with modified release technology were unsuccessful. Our objective was to develop hydrocortisone formulations that recreate the diurnal cortisol profile using multi-particulate technology. Design and Measurements Screening by in-vitro dissolution profiles, pharmacokinetic testing in dexamethasone suppressed dogs and humans, and comparison to a reference population. Setting Field laboratories and clinical research facility. Results Formulations were generated using an enteric (delayed-release) design configuration with an extended (sustained-release) dissolution profile. In-vitro dissolution confirmed delayed and sustained hydrocortisone release. However, in dogs and humans, sustained release resulted in reduced bioavailability. A formulation, DIURF-006, was developed that maintained delayed release but omitted the sustained release functionality. Pharmacokinetic characterisation of DIURF-006 showed that, despite absence of a sustained release component, absorption was sufficiently sustained to deliver extended hydrocortisone absorption. In dexamethasone-suppressed volunteers (n=16) receiving a twice daily ‘toothbrush’ regimen (20mg at 23:00h and 10mg at 07:00h), DIURF-006 gave a similar cortisol profile to physiological cortisol levels: DIURF-006 vs physiological, Geomean AUC 5610 vs 4706 hr*nmol/l, Geomean Cmax 665 vs 594 nmol/l and Median Tmax 8.5h vs clock time 08:12 hours for peak cortisol. The relative bioavailability of DIURF-006 vs hydrocortisone was 89% and cortisol levels increased linearly with doses between 5 and 30mg. Conclusion A multi-particulate oral hydrocortisone formulation with only an enteric coat provides delayed and sustained absorption and when given in a ‘toothbrush’ regimen provides physiological cortisol exposure. PMID:23980724

  9. An oral multiparticulate, modified-release, hydrocortisone replacement therapy that provides physiological cortisol exposure.

    PubMed

    Whitaker, Martin; Debono, Miguel; Huatan, Hiep; Merke, Deborah; Arlt, Wiebke; Ross, Richard J

    2014-04-01

    It is not possible with current hydrocortisone replacement to mimic the diurnal cortisol profile in patients with adrenal insufficiency. Previous attempts with modified-release technology were unsuccessful. Our objective was to develop hydrocortisone formulations that recreate the diurnal cortisol profile using multiparticulate technology. Screening by in vitro dissolution profiles, pharmacokinetic (PK) testing in dexamethasone-suppressed dogs and humans, and comparison with a reference population. Field laboratories and clinical research facility. Formulations were generated using an enteric (delayed release) design configuration with an extended (sustained release) dissolution profile. In vitro dissolution confirmed delayed and sustained hydrocortisone release. However, in dogs and humans, sustained release resulted in reduced bioavailability. A formulation, DIURF-006, was developed that maintained delayed release but omitted the sustained-release functionality. PK characterization of DIURF-006 showed that, despite absence of a sustained-release component, absorption was sufficiently sustained to deliver extended hydrocortisone absorption. In dexamethasone-suppressed volunteers (n = 16) receiving a twice-daily 'toothbrush' regimen (20 mg at 23:00 h and 10 mg at 07:00 h), DIURF-006 gave a similar cortisol profile to physiological cortisol levels: DIURF-006 vs physiological, Geomean AUC 5610 vs 4706 h * nmol/l, Geomean Cmax 665 vs 594 nmol/l and Median Tmax 8·5 h vs clock time 08:12 h for peak cortisol. The relative bioavailability of DIURF-006 vs hydrocortisone was 89%, and cortisol levels increased linearly with doses between 5 and 30 mg. A multiparticulate oral hydrocortisone formulation with only an enteric coat provides delayed and sustained absorption and when given in a 'toothbrush' regimen provides physiological cortisol exposure. © 2013 John Wiley & Sons Ltd.

  10. Colon targeted delivery systems of metronidazole based on osmotic technology: development and evaluation.

    PubMed

    Kumar, Pramod; Singh, Sanjay; Mishra, Brahmeshwar

    2008-09-01

    Colon targeted delivery systems of metronidazole (MTZ) based on osmotic technology were developed. The developed systems consisted of osmotic core (drug, osmotic agent and wicking agent), coated with semipermeable membrane (SPM) containing guar gum as pore former, coated core were then further coated with enteric coating to protect the system from acidic environment of stomach. The effect of various formulation variables namely the level of wicking agent (sodium lauryl sulphate), osmotic agent in the osmotic core, the level of pore former (guar gum) in SPM, and the thickness of SPM, were studied on physical parameters and drug release characteristics of developed formulations. MTZ release was inversely proportional to SPM thickness, but directly related to the level of pore former, wicking agent and osmotic agent. On the other hand burst strength of the exhausted shells was decreased with the increase in level of pore former in the membrane but increased with the increase in the thickness of SPM. The drug release from the developed formulations was independent of pH, and agitation intensity, but dependent on the osmotic pressure of the release media. The thickness of enteric coating could prevent formation of delivery pores before contact with simulated colonic fluid, but had no effect on drug release. Result of SEM studies showed the formation of in-situ delivery pores in the membrane from where the drug release occurred, and the number of pores formed were directly related to the initial level of pore former (guar gum) in SPM. The manufacturing procedure was found to be reproducible and formulations were found to be stable during 3 months of accelerated stability studies.

  11. Feasibility studies of concomitant administration of optimized formulation of probiotic-loaded Vancomycin hydrochloride pellets for colon delivery.

    PubMed

    Avachat, Amelia M; Shinde, Amol S

    2016-01-01

    Objective of this study was to develop Vancomycin HCl pellets loaded with Saccharomyces boulardii (S.b.) for pH-dependent system and CODES™ for augmenting the efficacy of Vancomycin HCl in the treatment of colitis. Pellets were prepared by extrusion-spheronization. In the pH-dependent system, the pellets were coated with Eudragit FS 30D. These pellets exhibited spherical form and a uniform surface coating. The CODES™ system consisted of three components: core containing mannitol, drug and probiotic, an inner acid-soluble coating layer, and an outer layer of enteric coating material. Statistical factorial design was used to optimize both formulations. Scanning electron micrographs of coated pellets revealed uniform coating. In vitro drug release of these coated pellets was studied sequentially in various buffers with (2%) and without rat cecal content for a period of 12 h. From the optimized pH-dependent formulation, F6 (20% w/w coating level and 15% w/v concentration of polymer), higher amount of probiotic was released in earlier time phase (first 5 h) as compared to the CODES™ and so R5 [containing acid-soluble inner coating layer (15% w/w coating level and 12% w/v concentration of Eudragit E100), and an outer layer of enteric coating material (12% w/w coating level and 10% w/v concentration of Eudragit L100)] was considered as the best formulation after confirming in vivo X-ray studies conducted on rabbits, suggesting that Vancomycin HCl and S.b. may be co-administered as pellets [CODES™] to enhance the effectiveness of Vancomycin HCl in the treatment of colitis without its associated side effects, which can only be confirmed after clinical trials.

  12. Wetting behavior on hexagonally close-packed polystyrene bead arrays with different topographies.

    PubMed

    Park, Yi-Seul; Yoon, Seo Young; Lee, Jin Seok

    2016-01-21

    Herein, we investigated the wetting behavior of hexagonally close-packed polystyrene bead arrays with different bead diameters and surface flatness. The contact angle was found to be influenced by the surface roughness as well as the contact area of the polystyrene bead array with a water droplet.

  13. 49 CFR 173.221 - Polymeric beads, expandable and Plastic molding compound.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false Polymeric beads, expandable and Plastic molding... Than Class 1 and Class 7 § 173.221 Polymeric beads, expandable and Plastic molding compound. (a) Non-bulk shipments of Polymeric beads (or granules), expandable, evolving flammable vapor and Plastic...

  14. 49 CFR 173.221 - Polymeric beads, expandable and Plastic molding compound.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Polymeric beads, expandable and Plastic molding... Than Class 1 and Class 7 § 173.221 Polymeric beads, expandable and Plastic molding compound. (a) Non-bulk shipments of Polymeric beads (or granules), expandable, evolving flammable vapor and Plastic...

  15. 49 CFR 173.221 - Polymeric beads, expandable and Plastic molding compound.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 2 2012-10-01 2012-10-01 false Polymeric beads, expandable and Plastic molding... Than Class 1 and Class 7 § 173.221 Polymeric beads, expandable and Plastic molding compound. (a) Non-bulk shipments of Polymeric beads (or granules), expandable, evolving flammable vapor and Plastic...

  16. 49 CFR 173.221 - Polymeric beads, expandable and Plastic molding compound.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false Polymeric beads, expandable and Plastic molding... Than Class 1 and Class 7 § 173.221 Polymeric beads, expandable and Plastic molding compound. (a) Non-bulk shipments of Polymeric beads (or granules), expandable evolving flammable vapor and Plastic...

  17. 49 CFR 173.221 - Polymeric beads, expandable and Plastic molding compound.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Polymeric beads, expandable and Plastic molding... Than Class 1 and Class 7 § 173.221 Polymeric beads, expandable and Plastic molding compound. (a) Non-bulk shipments of Polymeric beads (or granules), expandable evolving flammable vapor and Plastic...

  18. Induced movement of the magnetic beads and DNA-based dumbbell in a micro fluidic channel

    NASA Astrophysics Data System (ADS)

    Babić, B.; Ghai, R.; Dimitrov, K.

    2007-12-01

    We have explored controlled movement of magnetic beads and a dumbbell structure composed of DNA, a magnetic and a non-magnetic bead in a micro fluidic channel. Movement of the beads and dumbbells is simulated assuming that a net force is described as a superposition between the magnetic and hydrodynamic drag forces. Trajectories of beads and dumbbells are observed with optical light microscopy. The experimentally measured data show a good agreement with the simulations. This dynamical approach offers the prospect to stretch the DNA within the dumbbell and investigate its conformational changes. Further on, we demonstrate that short sonication can reduce multiple attachments of DNA to the beads.

  19. Analogs, formulations and derivatives of imatinib: a patent review.

    PubMed

    Musumeci, Francesca; Schenone, Silvia; Grossi, Giancarlo; Brullo, Chiara; Sanna, Monica

    2015-01-01

    The Bcr-Abl inhibitor imatinib was approved in 2001 for chronic myeloid leukemia therapy, and dramatically changed the lives of patients affected by this disease. Since it also inhibits platelet derived growth factor receptor (PDGFR) and c-Kit, imatinib is used for various other tumors caused by abnormalities of one or both these two enzymes. This review presents an overview on imatinib formulations and derivatives, synthetic methodologies and therapeutic uses that have appeared in the patent literature since 2008. Innovative imatinib formulations, such as nanoparticles containing the drug, will improve its bioavailability. Moreover, oral solutions or high imatinib content tablets or capsules will improve patient compliance. Some solid formulations and innovative syntheses that have appeared in the last few years will reduce the cost of the drug, offering big advantages for poor countries. Some recently patented efficacious imatinib derivatives are in preclinical studies and could enter clinical trials in the next few years. Overall, Bcr-Abl inhibitors constitute a very appealing research field that can be expected to expand further.

  20. Thick resist for MEMS processing

    NASA Astrophysics Data System (ADS)

    Brown, Joe; Hamel, Clifford

    2001-11-01

    The need for technical innovation is always present in today's economy. Microfabrication methods have evolved in support of the demand for smaller and faster integrated circuits with price performance improvements always in the scope of the manufacturing design engineer. The dispersion of processing technology spans well beyond IC fabrication today with batch fabrication and wafer scale processing lending advantages to MEMES applications from biotechnology to consumer electronics from oil exploration to aerospace. Today the demand for innovative processing techniques that enable technology is apparent where only a few years ago appeared too costly or not reliable. In high volume applications where yield and cost improvements are measured in fractions of a percent it is imperative to have process technologies that produce consistent results. Only a few years ago thick resist coatings were limited to thickness less than 20 microns. Factors such as uniformity, edge bead and multiple coatings made high volume production impossible. New developments in photoresist formulation combined with advanced coating equipment techniques that closely controls process parameters have enable thick photoresist coatings of 70 microns with acceptable uniformity and edge bead in one pass. Packaging of microelectronic and micromechanical devices is often a significant cost factor and a reliability issue for high volume low cost production. Technologies such as flip- chip assembly provide a solution for cost and reliability improvements over wire bond techniques. The processing for such technology demands dimensional control and presents a significant cost savings if it were compatible with mainstream technologies. Thick photoresist layers, with good sidewall control would allow wafer-bumping technologies to penetrate the barriers to yield and production where costs for technology are the overriding issue. Single pass processing is paramount to the manufacturability of packaging technology. Uniformity and edge bead control defined the success of process implementation. Today advanced packaging solutions are created with thick photoresist coatings. The techniques and results will be presented.

  1. Markov Random Field Based Automatic Image Alignment for ElectronTomography

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moussavi, Farshid; Amat, Fernando; Comolli, Luis R.

    2007-11-30

    Cryo electron tomography (cryo-ET) is the primary method for obtaining 3D reconstructions of intact bacteria, viruses, and complex molecular machines ([7],[2]). It first flash freezes a specimen in a thin layer of ice, and then rotates the ice sheet in a transmission electron microscope (TEM) recording images of different projections through the sample. The resulting images are aligned and then back projected to form the desired 3-D model. The typical resolution of biological electron microscope is on the order of 1 nm per pixel which means that small imprecision in the microscope's stage or lenses can cause large alignment errors.more » To enable a high precision alignment, biologists add a small number of spherical gold beads to the sample before it is frozen. These beads generate high contrast dots in the image that can be tracked across projections. Each gold bead can be seen as a marker with a fixed location in 3D, which provides the reference points to bring all the images to a common frame as in the classical structure from motion problem. A high accuracy alignment is critical to obtain a high resolution tomogram (usually on the order of 5-15nm resolution). While some methods try to automate the task of tracking markers and aligning the images ([8],[4]), they require user intervention if the SNR of the image becomes too low. Unfortunately, cryogenic electron tomography (or cryo-ET) often has poor SNR, since the samples are relatively thick (for TEM) and the restricted electron dose usually results in projections with SNR under 0 dB. This paper shows that formulating this problem as a most-likely estimation task yields an approach that is able to automatically align with high precision cryo-ET datasets using inference in graphical models. This approach has been packaged into a publicly available software called RAPTOR-Robust Alignment and Projection estimation for Tomographic Reconstruction.« less

  2. Introduction of a deformable x-ray CT polymer gel dosimetry system

    NASA Astrophysics Data System (ADS)

    Maynard, E.; Heath, E.; Hilts, M.; Jirasek, A.

    2018-04-01

    This study introduces the first 3D deformable dosimetry system based on x-ray computed tomography (CT) polymer gel dosimetry and establishes the setup reproducibility, deformation characteristics and dose response of the system. A N-isopropylacrylamide (NIPAM)-based gel formulation optimized for x-ray CT gel dosimetry was used, with a latex balloon serving as the deformable container and low-density polyethylene and polyvinyl alcohol providing additional oxygen barrier. Deformable gels were irradiated with a 6 MV calibration pattern to determine dosimetric response and a dosimetrically uniform plan to determine the spatial uniformity of the response. Wax beads were added to each gel as fiducial markers to track the deformation and setup of the gel dosimeters. From positions of the beads on CT images the setup reproducibility and the limits and reproducibility of gel deformation were determined. Comparison of gel measurements with Monte Carlo dose calculations found excellent dosimetric accuracy, comparable to that of an established non-deformable dosimetry system, with a mean dose discrepancy of 1.5% in the low-dose gradient region and a gamma pass rate of 97.9% using a 3%/3 mm criterion. The deformable dosimeter also showed good overall spatial dose uniformity throughout the dosimeter with some discrepancies within 20 mm of the edge of the container. Tracking of the beads within the dosimeter found that sub-millimetre setup accuracy is achievable with this system. The dosimeter was able to deform and relax when externally compressed by up to 30 mm without sustaining any permanent damage. Internal deformations in 3D produced average marker movements of up to 12 mm along the direction of compression. These deformations were also shown to be reproducible over 100 consecutive deformations. This work has established several important characteristics of a new deformable dosimetry system which shows promise for future clinical applications, including the validation of deformable dose accumulation algorithms.

  3. A Controlled Drug-Delivery Experiment Using Alginate Beads

    ERIC Educational Resources Information Center

    Farrell, Stephanie; Vernengo, Jennifer

    2012-01-01

    This paper describes a simple, cost-effective experiment which introduces students to drug delivery and modeling using alginate beads. Students produce calcium alginate beads loaded with drug and measure the rate of release from the beads for systems having different stir rates, geometries, extents of cross-linking, and drug molecular weight.…

  4. Degradation of synthetic pollutants in real wastewater using laccase encapsulated in core-shell magnetic copper alginate beads.

    PubMed

    Le, Thao Thanh; Murugesan, Kumarasamy; Lee, Chung-Seop; Vu, Chi Huong; Chang, Yoon-Seok; Jeon, Jong-Rok

    2016-09-01

    Immobilization of laccase has been highlighted to enhance their stability and reusability in bioremediation. In this study, we provide a novel immobilization technique that is very suitable to real wastewater treatment. A perfect core-shell system composing copper alginate for the immobilization of laccase (Lac-beads) was produced. Additionally, nFe2O3 was incorporated for the bead recycling through magnetic force. The beads were proven to immobilize 85.5% of total laccase treated and also to be structurally stable in water, acetate buffer, and real wastewater. To test the Lac-beads reactivity, triclosan (TCS) and Remazol Brilliant Blue R (RBBR) were employed. The Lac-beads showed a high percentage of TCS removal (89.6%) after 8h and RBBR decolonization at a range from 54.2% to 75.8% after 4h. Remarkably, the pollutants removal efficacy of the Lac-beads was significantly maintained in real wastewater with the bead recyclability, whereas that of the corresponding free laccase was severely deteriorated. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Microfluidic Bead Suspension Hopper

    PubMed Central

    2014-01-01

    Many high-throughput analytical platforms, from next-generation DNA sequencing to drug discovery, rely on beads as carriers of molecular diversity. Microfluidic systems are ideally suited to handle and analyze such bead libraries with high precision and at minute volume scales; however, the challenge of introducing bead suspensions into devices before they sediment usually confounds microfluidic handling and analysis. We developed a bead suspension hopper that exploits sedimentation to load beads into a microfluidic droplet generator. A suspension hopper continuously delivered synthesis resin beads (17 μm diameter, 112,000 over 2.67 h) functionalized with a photolabile linker and pepstatin A into picoliter-scale droplets of an HIV-1 protease activity assay to model ultraminiaturized compound screening. Likewise, trypsinogen template DNA-coated magnetic beads (2.8 μm diameter, 176,000 over 5.5 h) were loaded into droplets of an in vitro transcription/translation system to model a protein evolution experiment. The suspension hopper should effectively remove any barriers to using suspensions as sample inputs, paving the way for microfluidic automation to replace robotic library distribution. PMID:24761972

  6. Bead mediated separation of microparticles in droplets

    PubMed Central

    Sung, Ki-Joo; Lin, Xiaoxia Nina; Burns, Mark A.

    2017-01-01

    Exchange of components such as particles and cells in droplets is important and highly desired in droplet microfluidic assays, and many current technologies use electrical or magnetic fields to accomplish this process. Bead-based microfluidic techniques offer an alternative approach that uses the bead’s solid surface to immobilize targets like particles or biological material. In this paper, we demonstrate a bead-based technique for exchanging droplet content by separating fluorescent microparticles in a microfluidic device. The device uses posts to filter surface-functionalized beads from a droplet and re-capture the filtered beads in a new droplet. With post spacing of 7 μm, beads above 10 μm had 100% capture efficiency. We demonstrate the efficacy of this system using targeted particles that bind onto the functionalized beads and are, therefore, transferred from one solution to another in the device. Binding capacity tests performed in the bulk phase showed an average binding capacity of 5 particles to each bead. The microfluidic device successfully separated the targeted particles from the non-targeted particles with up to 98% purity and 100% yield. PMID:28282412

  7. Growth and morphology of thermophilic dairy starters in alginate beads.

    PubMed

    Lamboley, Laurence; St-Gelais, Daniel; Champagne, Claude P; Lamoureux, Maryse

    2003-06-01

    The aim of this research was to produce concentrated biomasses of thermophilic lactic starters using immobilized cell technology (ICT). Fermentations were carried out in milk using pH control with cells microentrapped in alginate beads. In the ICT fermentations, beads represented 17% of the weight. Some assays were carried out with free cells without pH control, in order to compare the ICT populations with those of classical starters. With Streptococcus thermophilus, overall populations in the fermentor were similar, but maximum bead population for (8.2 x 10(9) cfu/g beads) was 13 times higher than that obtained in a traditional starter (4.9 x 10(8) cfu/ml). For both Lactobacillus helveticus strains studied, immobilized-cell populations were about 3 x 10(9) cfu/g beads. Production of immobilized Lb. bulgaricus 210R strain was not possible, since no increases in viable counts occurred in beads. Therefore, production of concentrated cell suspension in alginate beads was more effective for S. thermophilus. Photomicrographs of cells in alginate beads demonstrated that, while the morphology of S. thermophilus remained unchanged during the ICT fermentation, immobilized cells of Lb. helveticus appeared wider. In addition, cells of Lb. bulgaricus were curved and elongated. These morphological changes would also impair the growth of immobilized lactobacilli.

  8. Development of bioactive porous α-TCP/HAp beads for bone tissue engineering.

    PubMed

    Asaoka, Teruo; Ohtake, Shoji; Furukawa, Katsuko S; Tamura, Akito; Ushida, Takashi

    2013-11-01

    Porous beads of bioactive ceramics such as hydroxyapatite (HAp) and tribasic calcium phosphate (TCP) are considered a promising scaffold for cultivating bone cells. To realize this, α-TCP/HAp functionally graded porous beads are fabricated with two main purposes: to maintain the function of the scaffold with sufficient strength up to the growth of new bone, and is absorbed completely after the growth. HAp is a bioactive material that has both high strength and strong tissue-adhesive properties, but is not readily absorbed by the human body. On the contrary, α-TCP is highly bioabsorbable, resulting in a scaffold that is absorbed before it is completely replaced by bone. In this study, we produced porous, bead-shaped carriers as scaffolds for osteoblast culture. To control the solubility in vivo, the fabricated beads contained α-TCP at the center and HAp at the surface. Cell adaptability of these beads for bone tissue engineering was confirmed in vitro. It was found that α-TCP/HAp bead carriers exhibit low toxicity in the initial stages of cell seeding and cell adhesion. The presence of HAp in the composite bead form effectively increased ALP activity. In conclusion, it is suggested that these newly developed α-TCP/HAp beads are a promising tool for bone tissue engineering. Copyright © 2013 Wiley Periodicals, Inc.

  9. Lipase in biphasic alginate beads as a biocatalyst for esterification of butyric acid and butanol in aqueous media.

    PubMed

    Ng, Choong Hey; Yang, Kun-Lin

    2016-01-01

    Esterification of organic acids and alcohols in aqueous media is very inefficient due to thermodynamic constraints. However, fermentation processes used to produce organic acids and alcohols are often conducted in aqueous media. To produce esters in aqueous media, biphasic alginate beads with immobilized lipase are developed for in situ esterification of butanol and butyric acid. The biphasic beads contain a solid matrix of calcium alginate and hexadecane together with 5 mg/mL of lipase as the biocatalyst. Hexadecane in the biphasic beads serves as an organic phase to facilitate the esterification reaction. Under optimized conditions, the beads are able to catalyze the production of 0.16 mmol of butyl butyrate from 0.5 mmol of butyric acid and 1.5 mmol of butanol. In contrast, when monophasic beads (without hexadecane) are used, only trace amount of butyl butyrate is produced. One main application of biphasic beads is in simultaneous fermentation and esterification (SFE) because the organic phase inside the beads is very stable and does not leach out into the culture medium. SFE is successfully conducted with an esterification yield of 6.32% using biphasic beads containing iso-octane even though the solvent is proven toxic to the butanol-producing Clostridium spp. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Microfabricated Renewable Beads-Trapping/Releasing Flow Cell for Rapid Antigen-Antibody Reaction in Chemiluminescent Immunoassay

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fu, Zhifeng; Shao, Guocheng; Wang, Jun

    2011-04-01

    A filter pillar-array microstructure was coupled with a pneumatic micro-valve to fabricate a reusable miniaturized beads-trapping/releasing flow cell, in which trapping and releasing beads can be conveniently realized by switching the micro-valve. This miniaturized device was suitable to construct automatic fluidic system for “renewable surface analysis”. The renewable surface strategy based on pneumatic micro-valve enabled capture of beads in beads chamber prior to each assay, and release of the used beads after the assay. Chemiluminescent competitive immunoassay of 3,5,6-trichloropyridinol (TCP) was performed as a model to demonstrate the application potential of this reusable miniaturized flow cell. The whole fluidic assaymore » process including beads trapping, immuno-binding, beads washing, beads releasing and signal collection could be completed in 10 min. Immunoassay of TCP using this miniaturized device showed a linear range of 0.20-70 ng/mL with a limit of detection of 0.080 ng/mL. The device had been successfully used for detection of TCP spiked in rat serum with average recovery of 97%. This investigation provides a rapid, sensitive, reusable, low-cost and automatic miniaturized device for solid-phase biochemical analysis for various purposes.« less

  11. Orbeez: the magic water absorbing bead--risk of pediatric bowel obstruction?

    PubMed

    Darracq, Michael A; Cullen, Jennifer; Rentmeester, Landen; Cantrell, F Lee; Ly, Binh T

    2015-06-01

    In December 2012, the U.S. Consumer Product Safety Commission recalled the water-absorbing toy WaterBalz after reports of small intestine obstruction after ingestion by children. Orbeez, another water-absorbing bead, remains available and is marketed as a children's toy. We sought to determine the extent to which Orbeez enlarge in various liquid media and the potential risk for bowel obstruction. Three Orbeez beads were added to 210 mL of the following liquid media: room temperature tap water, whole milk, simulated gastric fluid, GoLytely (polyethelyelene glycol, 3350 and electrolytes), and vodka (40% ethanol by volume). Diameters before exposure to media were measured using a caliper to the nearest 0.1 mm and again at 1, 2, 4, 6, 12, and 24 hours. Ten beads were then added to the beads already immersed in simulated gastric fluid and water and observed for an additional 72 hours (96 hours total) for clumping or increase in diameter. Clumping was defined as two or more beads remaining persistently adherent to one another despite gentle circular movement (swirling) of the liquid. Growth in each of the media was observed. Growth in simulated gastric fluid was minimal, whereas the beads were observed to be the largest after 24 hours in vodka. Clumping of the beads was not observed to occur. Orbeez beads enlarge to a different extent in different liquid media. It is unlikely that Orbeez beads would expand to sizes or demonstrate clumping that would be concerning for intestinal obstruction.

  12. Capturing and concentrating adenovirus using magnetic anionic nanobeads

    PubMed Central

    Sakudo, Akikazu; Baba, Koichi; Ikuta, Kazuyoshi

    2016-01-01

    We recently demonstrated how various enveloped viruses can be efficiently concentrated using magnetic beads coated with an anionic polymer, poly(methyl vinyl ether-maleic anhydrate). However, the exact mechanism of interaction between the virus particles and anionic beads remains unclear. To further investigate whether these magnetic anionic beads specifically bind to the viral envelope, we examined their potential interaction with a nonenveloped virus (adenovirus). The beads were incubated with either adenovirus-infected cell culture medium or nasal aspirates from adenovirus-infected individuals and then separated from the supernatant by applying a magnetic field. After thoroughly washing the beads, adsorption of adenovirus was confirmed by a variety of techniques, including immunochromatography, polymerase chain reaction, Western blotting, and cell culture infection assays. These detection methods positively identified the hexon and penton capsid proteins of adenovirus along with the viral genome on the magnetic beads. Furthermore, various types of adenovirus including Types 5, 6, 11, 19, and 41 were captured using the magnetic bead procedure. Our bead capture method was also found to increase the sensitivity of viral detection. Adenovirus below the detectable limit for immunochromatography was efficiently concentrated using the magnetic bead procedure, allowing the virus to be successfully detected using this methodology. Moreover, these findings clearly demonstrate that a viral envelope is not required for binding to the anionic magnetic beads. Taken together, our results show that this capture procedure increases the sensitivity of detection of adenovirus and would, therefore, be a valuable tool for analyzing both clinical and experimental samples. PMID:27274228

  13. Pooling of Immunomagnetic Separation Beads Does Not Affect Detection Sensitivity of Six Major Serogroups of Shiga Toxin-Producing Escherichia coli in Cattle Feces.

    PubMed

    Noll, Lance W; Baumgartner, William C; Shridhar, Pragathi B; Cull, Charley A; Dewsbury, Diana M; Shi, Xiaorong; Cernicchiaro, Natalia; Renter, David G; Nagaraja, T G

    2016-01-01

    Shiga toxin-producing Escherichia coli (STEC) of the serogroups O26, O45, O103, O111, O121, and O145, often called non-O157 STEC, are foodborne pathogens. Cattle are asymptomatic reservoirs for STEC; the organisms reside in the hindgut and are shed in the feces, which serve as the source of food product contaminations. Culture-based detection of non-O157 STEC involves an immunomagnetic separation (IMS) step to capture the specific serogroups in complex matrices, such as feces. The IMS procedure is time consuming and labor intensive because of the need to subject each fecal sample to six individual beads. Therefore, our objective was to evaluate whether pooling of IMS beads affects sensitivity of non-O157 STEC detection compared with using individual IMS beads. The evaluation was done by comparing detection of serogroups in feces spiked with pure cultures (experiments 1 and 2) and from feces (n = 384) of naturally shedding cattle (experiment 3). In spiked fecal samples, detection with pools of three, four, six, or seven beads was similar to, or at times higher than, detection with individual IMS beads. In experiment 3, the proportions of fecal samples that tested positive for the six serogroups as detected by individual or pooled beads were similar. Based on noninferiority tests, detection with pooled beads was not substantially inferior to detection with individual beads (P > 0.05). In conclusion, the pooling of IMS beads is a better option for detection of STEC serogroups in fecal samples compared with individual beads because the procedure saves time and labor and has the prospect of a higher throughput.

  14. Effect of Heat Input on Geometry of Austenitic Stainless Steel Weld Bead on Low Carbon Steel

    NASA Astrophysics Data System (ADS)

    Saha, Manas Kumar; Hazra, Ritesh; Mondal, Ajit; Das, Santanu

    2018-05-01

    Among different weld cladding processes, gas metal arc welding (GMAW) cladding becomes a cost effective, user friendly, versatile method for protecting the surface of relatively lower grade structural steels from corrosion and/or erosion wear by depositing high grade stainless steels onto them. The quality of cladding largely depends upon the bead geometry of the weldment deposited. Weld bead geometry parameters, like bead width, reinforcement height, depth of penetration, and ratios like reinforcement form factor (RFF) and penetration shape factor (PSF) determine the quality of the weld bead geometry. Various process parameters of gas metal arc welding like heat input, current, voltage, arc travel speed, mode of metal transfer, etc. influence formation of bead geometry. In the current experimental investigation, austenite stainless steel (316) weld beads are formed on low alloy structural steel (E350) by GMAW using 100% CO2 as the shielding gas. Different combinations of current, voltage and arc travel speed are chosen so that heat input increases from 0.35 to 0.75 kJ/mm. Nine number of weld beads are deposited and replicated twice. The observations show that weld bead width increases linearly with increase in heat input, whereas reinforcement height and depth of penetration do not increase with increase in heat input. Regression analysis is done to establish the relationship between heat input and different geometrical parameters of weld bead. The regression models developed agrees well with the experimental data. Within the domain of the present experiment, it is observed that at higher heat input, the weld bead gets wider having little change in penetration and reinforcement; therefore, higher heat input may be recommended for austenitic stainless steel cladding on low alloy steel.

  15. A biotin-drug extraction and acid dissociation (BEAD) procedure to eliminate matrix and drug interference in a protein complex anti-drug antibody (ADA) isotype specific assay.

    PubMed

    Niu, Hongmei; Klem, Thomas; Yang, Jinsong; Qiu, Yongchang; Pan, Luying

    2017-07-01

    Monitoring anti-drug antibody (ADA) responses in patients receiving protein therapeutics treatment is an important safety assessment for regulatory agencies, drug manufacturers, clinicians and patients. Recombinant human IGF-1/IGFBP-3 (rhIGF-1/rhIGFBP-3) is a 1:1 formulation of naturally occurring protein complex. The individual IGF-1 and IGFBP-3 proteins have multiple binding partners in serum matrix with high binding affinity to each other, which presents challenges in ADA assay development. We have developed a biotin-drug extraction with acid dissociation (BEAD) procedure followed by an electrochemiluminescence (ECL) direct assay to overcome matrix and drug interference. The method utilizes two step acid dissociation and excess biotin-drug to extract total ADA, which are further captured by soluble biotin-drug and detected in an ECL semi-homogeneous direct assay format. The pre-treatment method effectively eliminates interference by serum matrix and free drug, and enhances assay sensitivity. The assays passed acceptance criteria for all validation parameters, and have been used for clinical sample Ab testing. This method principle exemplifies a new approach for anti-isotype ADA assays, and could be an effective strategy for neutralizing antibody (NAb), pharmacokinetic (PK) and biomarker analysis in need of overcoming interference factors. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Small Versus Large-Sized Drug-Eluting Beads (DEBIRI) for the Treatment of Hepatic Colorectal Metastases: A Propensity Score Matching Analysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Akinwande, Olaguoke K., E-mail: gokeakin@gmail.com; Philips, Prejesh, E-mail: prejesh.philips@louisville.edu; Duras, Petr, E-mail: durasp@seznam.cz

    2015-04-15

    PurposeTo compare the feasibility, safety, and efficacy with small and large irinotecan drug-eluting beads (DEBIRI) for treating hepatic colorectal metastases.MethodsUsing our prospectively maintained, multi-center, intra-arterial therapy registry, we identified 196 patients treated with a combination of large beads (100–300 to 500–700 μm) and patients treated with a combination of small beads (70–150 to 100–300 μm). To minimize selection bias, a propensity score analysis was performed to compare both groups.ResultsUnadjusted analysis consisted of 196 and 30 patients treated with large and small beads, respectively. The adjusted analysis consisted of 19 patients each. Unadjusted analysis showed decreased all-grade (p = <0.001) and high-grade adverse effects (p = 0.02)more » in the small bead group, with a persisting trend toward decreased overall side effects in the adjusted analysis favoring small beads (p = 0.09) The adjusted analysis showed the percentage dose delivered (delivered dose/intended dose) was significantly greater in the small bead group compared to the large bead group (96 vs 79 %; p = 0.005). There were also a lower percentage of treatments terminating in complete stasis in the adjusted analysis (0.0035). Adjusted analysis also showed increased objective response rate (ORR) at 12 months (p = 0.04), with a corresponding trend also seen in the unadjusted analysis (0.09).ConclusionSmaller beads result in increased dose delivery probably due to less propensity to reach complete stasis. It may also lead to more durable long-term efficacy. Smaller beads also demonstrate similarly low toxicity compared to large-sized beads with a trend toward less toxicity.« less

  17. Jeffamine derivatized TentaGel beads and poly(dimethylsiloxane) microbead cassettes for ultrahigh-throughput in situ releasable solution-phase cell-based screening of one-bead-one-compound combinatorial small molecule libraries.

    PubMed

    Townsend, Jared B; Shaheen, Farzana; Liu, Ruiwu; Lam, Kit S

    2010-09-13

    A method to efficiently immobilize and partition large quantities of microbeads in an array format in microfabricated poly(dimethylsiloxane) (PDMS) cassette for ultrahigh-throughput in situ releasable solution-phase cell-based screening of one-bead-one-compound (OBOC) combinatorial libraries is described. Commercially available Jeffamine triamine T-403 (∼440 Da) was derivatized such that two of its amino groups were protected by Fmoc and the remaining amino group capped with succinic anhydride to generate a carboxyl group. This resulting trifunctional hydrophilic polymer was then sequentially coupled two times to the outer layer of topologically segregated bilayer TentaGel (TG) beads with solid phase peptide synthesis chemistry resulting in beads with increased loading capacity, hydrophilicity, and porosity at the outer layer. We have found that such bead configuration can facilitate ultrahigh-throughput in situ releasable solution-phase screening of OBOC libraries. An encoded releasable OBOC small molecule library was constructed on Jeffamine derivatized TG beads with library compounds tethered to the outer layer via a disulfide linker and coding tags in the interior of the beads. Compound-beads could be efficiently loaded (5-10 min) into a 5 cm diameter Petri dish containing a 10,000-well PDMS microbead cassette, such that over 90% of the microwells were each filled with only one compound-bead. Jurkat T-lymphoid cancer cells suspended in Matrigel were then layered over the microbead cassette to immobilize the compound-beads. After 24 h of incubation at 37 °C, dithiothreitol was added to trigger the release of library compounds. Forty-eight hours later, MTT reporter assay was used to identify regions of reduced cell viability surrounding each positive bead. From a total of about 20,000 beads screened, 3 positive beads were detected and physically isolated for decoding. A strong consensus motif was identified for these three positive compounds. These compounds were resynthesized and found to be cytotoxic (IC(50) 50-150 μM) against two T-lymphoma cell lines and less so against the MDA-MB 231 breast cancer cell line. This novel ultrahigh-throughput OBOC releasable method can potentially be adapted to many existing 96- or 384-well solution-phase cell-based or biochemical assays.

  18. Bead-based microfluidic immunoassay for diagnosis of Johne's disease

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wadhwa, Ashutosh; Foote, Robert; Shaw, Robert W

    2012-01-01

    Microfluidics technology offers a platform for development of point-of-care diagnostic devices for various infectious diseases. In this study, we examined whether serodiagnosis of Johne s disease (JD) can be conducted in a bead-based microfluidic assay system. Magnetic micro-beads were coated with antigens of the causative agent of JD, Mycobacterium avium subsp. paratuberculosis. The antigen-coated beads were incubated with serum samples of JD-positive or negative serum samples and then with a fluorescently-labeled secondary antibody (SAB). To confirm binding of serum antibodies to the antigen, the beads were subjected to flow cytometric analysis. Different conditions (dilutions of serum and SAB, types ofmore » SAB, and types of magnetic beads) were optimized for a great degree of differentiation between the JD-negative and JD-positive samples. Using the optimized conditions, we tested a well-classified set of 155 serum samples from JD negative and JD-positive cattle by using the bead-based flow cytometric assay. Of 105 JD-positive samples, 63 samples (60%) showed higher antibody binding levels than a cut-off value determined by using antibody binding levels of JD-negative samples. In contrast, only 43-49 JD-positive samples showed higher antibody binding levels than the cut-off value when the samples were tested by commercially-available immunoassays. Microfluidic assays were performed by magnetically immobilizing a number of beads within a microchannel of a glass microchip and detecting antibody on the collected beads by laser-induced fluorescence. Antigen-coated magnetic beads treated with bovine serum sample and fluorescently-labeled SAB were loaded into a microchannel to measure the fluorescence (reflecting level of antibody binding) on the beads in the microfluidic system. When the results of five bovine serum samples obtained with the system were compared to those obtained with the flow cytometer, a high level of correlation (linear regression, r2 = 0.994) was observed. In a further experiment, we magnetically immobilized antigen-coated beads in a microchannel, reacted the beads with serum and SAB in the channel, and detected antibody binding to the beads in the microfluidic system. A strong antibody binding in JD-positive serum was detected, whereas there was only negligible binding in negative control experiments. Our data suggest that the bead-based microfluidic system may form a basis for development of an on-site serodiagnosis of JD. Key Words: Mycobacterium avium ssp. paratuberculosis, Johne s disease, microfluidics, lab-on-a-chip.« less

  19. The Science Identity and Entering a Science Occupation*

    PubMed Central

    Stets, Jan E.; Brenner, Philip S.; Burke, Peter J.; Serpe, Richard T.

    2016-01-01

    The initiative to increase the number of students in STEM disciplines and train them for a science-related job is a current national focus. Using longitudinal panel data from a national study that followed underrepresented college students in STEM fields, we investigate the neglected role that social psychological processes play in influencing science activity among the young. We study the impact of identity processes related to being a science student on entering a science occupation. More broadly, we examine whether an identity formulated in one institutional setting (education) has effects that persist to another institutional setting (the economy). We find that the science identity positively impacts the likelihood of entering a science occupation. It also serves as a mediator for other factors that are related to educational success. This provides insight into how an identity can guide behavior to move persons into structural positions across institutional domains. PMID:28364837

  20. Factors Influencing the Accessibility of Education for Children with Disabilities in India

    ERIC Educational Resources Information Center

    Limaye, Sandhya

    2016-01-01

    The Central and State governments in India have formulated programs and policies over the years for children with disabilities in order to help them to enter mainstream society. However, despite these policies, children with disabilities are amongst the most disadvantaged in terms of access to schooling and completion of elementary education, as…

  1. Assessment of Integrated Learning: Suggested Application of Concept Mapping to Prior Learning Assessment Practices

    ERIC Educational Resources Information Center

    Popova-Gonci, Viktoria; Lamb, Monica C.

    2012-01-01

    Prior learning assessment (PLA) students enter academia with different types of concepts--some of them have been formally accepted and labeled by academia and others are informally formulated by students via independent and/or experiential learning. The critical goal of PLA practices is to assess an intricate combination of prior learning…

  2. To Enter the Text as into a Dream: Tracing the Unconscious Effects of Reading Experience

    ERIC Educational Resources Information Center

    Lewkowich, David

    2016-01-01

    In this article, I suggest that, when readers speak about reading, the language they use is closely related to the modes and movements of speech employed by the dreamer recounting their dream. With reference to the psychoanalytic formulations of unconscious desire and transferential attachment, this article--with its focus on…

  3. 75 FR 68377 - Notice of Inventory Completion: Anthropological Studies Center, Archaeological Collections...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-05

    ... basalt tool, 317 non-human bone fragments, 1 abalone shell fragment, 2 ash/soil samples, 1 groundstone, 1 quartz chunk, 3 abalone pendants and 4 olivella beads. One of the burials identified was associated with... groundstones, 2 steatite beads, 1 abalone pendant, 2 clamshell disk beads, 23 olivella beads and 2 steatite...

  4. COMPARATIVE EVALUATION OF R3f GARNET BEAD FILTRATION AND MULTIMEDIA FILTRATION SYSTEMS; FINAL REPORT

    EPA Science Inventory

    This report summarizes the results of tests conducted to date at the EPA T&E Facility on the R3f filtration system utilizing fine beads (such as garnet beads or glass beads) and a conventional multimedia filtration system. Both systems have been designed and built by Enprotec, a...

  5. Computer-aided diagnostic detection system of venous beading in retinal images

    NASA Astrophysics Data System (ADS)

    Yang, Ching-Wen; Ma, DyeJyun; Chao, ShuennChing; Wang, ChuinMu; Wen, Chia-Hsien; Lo, ChienShun; Chung, Pau-Choo; Chang, Chein-I.

    2000-05-01

    The detection of venous beading in retinal images provides an early sign of diabetic retinopathy and plays an important role as a preprocessing step in diagnosing ocular diseases. We present a computer-aided diagnostic system to automatically detect venous beading of blood vessels. It comprises of two modules, referred to as the blood vessel extraction module and the venus beading detection module. The former uses a bell-shaped Gaussian kernel with 12 azimuths to extract blood vessels while the latter applies a neural network-based shape cognitron to detect venous beading among the extracted blood vessels for diagnosis. Both modules are fully computer-automated. To evaluate the proposed system, 61 retinal images (32 beaded and 29 normal images) are used for performance evaluation.

  6. Integrated air stream micromixer for performing bioanalytical assays on a plastic chip.

    PubMed

    Geissler, Matthias; Li, Kebin; Zhang, Xuefeng; Clime, Liviu; Robideau, Gregg P; Bilodeau, Guillaume J; Veres, Teodor

    2014-10-07

    This paper describes the design, functioning and use of an integrated mixer that relies on air flux to agitate microliter entities of fluid in an embedded microfluidic cavity. The system was fabricated from multiple layers of a thermoplastic elastomer and features circuits for both liquid and air supply along with pneumatic valves for process control. Internally-dyed polymer particles have been used to visualize flow within the fluid phase during agitation. Numerical modelling of the micromixer revealed an overall efficacy of 10(-1) to 10(-2) for momentum transfer at the air-water interface. Simulation of air vortex dynamics showed dependency of the flow pattern on the velocity of the flux entering the cavity. Three bioanalytical assays have been performed as proof-of-concept demonstrations. In a first assay, cells of Listeria monocytogenes were combined with magnetic nanoparticles (NPs), resulting in high-density coverage of the bacteria's surface with NPs after 1 min of agitation. This finding is contrasted by a control experiment without agitation for which interaction between bacteria and NPs remains low. In a second one, capture and release of genomic DNA from fungi through adsorption onto magnetic beads was tested and shown to be improved by agitation compared to non-agitated controls. A third assay finally involved fluorescently-labelled target oligonucleotide strands and polystyrene particles modified with DNA capture probes to perform detection of nucleic acids on beads. Excellent selectivity was obtained in a competitive hybridization process using a multiplexed micromixer chip design.

  7. [Case Study - A Successful Outpatient Design of Cross-Professional Pharmaceutical Cooperation in Home Health Care - Reduction of Financial and Care-Related Burden by Shifting to R-Compound Enteral Semisolid Formulation].

    PubMed

    Takeda, Namihiro; Hamana, Tomoko; Oka, Toyoka; Matsuyama, Narihisa; Hirohara, Masayoshi; Kushida, Kazuki

    2015-12-01

    Among patients who receive enteral nutrition through a gastric fistula, some are concomitantly administered viscosity modifiers to avoid aspiration pneumonitis caused by gastroesophageal reflux. These patients(and families)often bear the high economic and care burdens associated with enteral nutritional management. We developed an outpatient-based pharmacy service through multidisciplinary cooperation, facilitating a shift from enteral nutrition to semi-solid formula. This shift is expected to reduce the economic burden by approximately 120 thousand yen, and the hours of care by about 550 hours annually. Owing to family circumstances or economic conditions, some patients(and families)do not receive at-home guidance of pharmaceutical management by pharmacists. The family members of such patients visit the pharmacy to obtain the prescribed medications. Such patients and families could be supported within the outpatient-based pharmacy services, through proactively participating in home health care daily(collaborative relationship with the local community)and re-counting experiences of providing home guidance of pharmaceutical management.

  8. Formulation of Granules for Site-Specific Delivery of an Antimicrobial Essential Oil to the Animal Intestinal Tract.

    PubMed

    Ma, Yin-Hing; Wang, Qi; Gong, Joshua; Wu, Xiao Yu

    2016-03-01

    Owing to proliferation of antibiotic-resistant bacteria, the use of antibiotics for livestock growth promotion is banned in many countries and alternatives to in-feed antibiotics are needed. Cinnamon essential oil exhibits strong in vitro antibacterial activity; however, direct addition of essential oils to animal feed has limited practicality due to their high volatility, odor, fast decomposition, and poor availability in the lower intestines. To solve these problems, we formulated trans-cinnamaldehyde (CIN) with an adsorbent powder and fatty acid via a melt-solidification technique. Core granules of an optimized composition contained up to 48% wt/wt CIN. The granules were then coated with an enteric polymer to impart site-specific release of CIN. CIN was mostly retained in simulated gastric fluid and released rapidly (>80% under 2 h) in simulated intestinal fluids. Rapid CIN autoxidation into cinnamic acid was inhibited by adding 1% vol/vol eugenol, which maintained CIN stability for at least 1 y. The granule formulation increased the antimicrobial activity of CIN against Escherichia coli K88 slightly with a minimum bactericidal concentration of 450 μg/mL for CIN in lauric acid-based granules compared with 550-600 μg/mL for palmitic acid-based granules and free CIN, respectively. These results encourage the potential use of encapsulated CIN for control of animal enteric pathogens by oral in-feed administration. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  9. An Intensified Vibratory Milling Process for Enhancing the Breakage Kinetics during the Preparation of Drug Nanosuspensions.

    PubMed

    Li, Meng; Zhang, Lu; Davé, Rajesh N; Bilgili, Ecevit

    2016-04-01

    As a drug-sparing approach in early development, vibratory milling has been used for the preparation of nanosuspensions of poorly water-soluble drugs. The aim of this study was to intensify this process through a systematic increase in vibration intensity and bead loading with the optimal bead size for faster production. Griseofulvin, a poorly water-soluble drug, was wet-milled using yttrium-stabilized zirconia beads with sizes ranging from 50 to 1500 μm at low power density (0.87 W/g). Then, this process was intensified with the optimal bead size by sequentially increasing vibration intensity and bead loading. Additional experiments with several bead sizes were performed at high power density (16 W/g), and the results were compared to those from wet stirred media milling. Laser diffraction, scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and dissolution tests were used for characterization. Results for the low power density indicated 800 μm as the optimal bead size which led to a median size of 545 nm with more than 10% of the drug particles greater than 1.8 μm albeit the fastest breakage. An increase in either vibration intensity or bead loading resulted in faster breakage. The most intensified process led to 90% of the particles being smaller than 300 nm. At the high power intensity, 400 μm beads were optimal, which enhanced griseofulvin dissolution significantly and signified the importance of bead size in view of the power density. Only the optimally intensified vibratory milling led to a comparable nanosuspension to that prepared by the stirred media milling.

  10. Use of Antibiotic Impregnated Resorbable Beads Reduces Pressure Ulcer Recurrence: A Retrospective Analysis.

    PubMed

    Khansa, Ibrahim; Barker, Jenny C; Ghatak, Piya Das; Sen, Chandan K; Gordillo, Gayle M

    2018-05-17

    Recurrence of pressure ulcers remains common. We have employed resorbable antibiotic beads as a therapeutic strategy to deliver high local antibiotic concentrations to the debridement site. Our objective was to determine whether the use of resorbable antibiotic- beads would reduce pressure ulcer recurrence. We reviewed all stage IV pressure ulcers treated with excision, partial ostectomy and flap coverage over 16 years. Baseline patient factors (location of ulcer, presence of osteomyelitis, preoperative prealbumin), surgical factors (type of flap, use of antibiotic beads, bone culture results) and postoperative outcomes (ulcer recurrence at 1 year, dehiscence, seroma, cellulitis) were collected. Outcomes of patients who received antibiotic-impregnated beads were compared to those who did not. 86 patients with 120 stage IV pressure ulcers underwent excision and flap coverage. This included 16 ulcers where antibiotic beads were used, and 104 where they were not. The overall ulcer recurrence rate at 12 months was 35.8%. The recurrence rate in the group treated with antibiotic beads was significantly lower than the group without beads (12.5% vs. 39.4%, p=0.03). Overall, complication rates between the two groups were similar (43.8% vs. 51.9%, p=0.54). No systemic or local toxicity from antibiotic beads occurred. Scanning electron microscopy images of sacral bone from one case showed bacterial biofilm even after debridement. Pressure ulcer recurrence at 1 year after excision and flap coverage decreased significantly with the use of resorbable antibiotic beads. This article is protected by copyright. All rights reserved. © 2018 by the Wound Healing Society.

  11. Development of a novel colorimetric sensor based on alginate beads for monitoring rainbow trout spoilage.

    PubMed

    Majdinasab, Marjan; Hosseini, Seyed Mohammad Hashem; Sepidname, Marziyeh; Negahdarifar, Manizheh; Li, Peiwu

    2018-05-01

    Alginate is a non-toxic, renewable, and linear copolymer obtained from the brown algae Laminaria digitata that can be easily shaped into beads. Its good gel forming properties have made it useful for entrapping food and pharmaceutical ingredients. In this study, alginate beads were used in a novel application as a colorimetric sensor in food intelligent packaging. Colorimetric sensor was developed through entrapping red cabbage extract as a pH indicator in alginate beads. The pH indicator beads were used in rainbow trout packaging for monitoring fillets spoilage. Color change of beads during fish storage was measured using the CIELab method. The alginate bead colorimetric sensor is validated by measuring total volatile basic nitrogen (TVB-N) levels and microbial populations in fish samples. Moreover, peroxide value (PV) and thiobarbituric acid reactive substances (TBARS) were evaluated during storage. Results indicated that increasing the bacterial population during storage and production of proteolytic enzymes resulted in protein degradation, accumulation of volatile amine compounds, increase in the pH and finally color change of alginate beads. The values of TVB-N, pH, PV and TBARS increased with time of storage. The results of TVB-N and microbial growth were in accordance with color change of beads and CIELab data. Therefore, the proposed system enjoys a high sensitivity to pH variations and is capable of monitoring the spoilage of fish or other protein-rich products through its wide range of color changes. The alginate beads containing the red cabbage extract can, thus, be used as a low-cost colorimetric sensor for intelligent packaging applications.

  12. Medication administration through enteral feeding tubes.

    PubMed

    Williams, Nancy Toedter

    2008-12-15

    An overview of enteral feeding tubes, drug administration techniques, considerations for dosage form selection, common drug interactions with enteral formulas, and methods to minimize tube occlusion is given. Enteral nutrition through a feeding tube is the preferred method of nutrition support in patients who have a functioning gastrointestinal tract but who are unable to be fed orally. This method of delivering nutrition is also commonly used for administering medications when patients cannot swallow safely. However, several issues must be considered with concurrent administration of oral medications and enteral formulas. Incorrect administration methods may result in clogged feeding tubes, decreased drug efficacy, increased adverse effects, or drug-formula incompatibilities. Various enteral feeding tubes are available and are typically classified by site of insertion and location of the distal tip of the feeding tube. Liquid medications, particularly elixirs and suspensions, are preferred for enteral administration; however, these formulations may be hypertonic or contain large amounts of sorbitol, and these properties increase the potential for adverse effects. Before solid dosage forms are administered through the feeding tube, it should be determined if the medications are suitable for manipulation, such as crushing a tablet or opening a capsule. Medications should not be added directly to the enteral formula, and feeding tubes should be properly flushed with water before and after each medication is administered. To minimize drug-nutrient interactions, special considerations should be taken when administering phenytoin, carbamazepine, warfarin, fluoroquinolones, and proton pump inhibitors via feeding tubes. Precautions should be implemented to prevent tube occlusions, and immediate intervention is required when blockages occur. Successful drug delivery through enteral feeding tubes requires consideration of the tube size and placement as well as careful selection and appropriate administration of drug dosage forms.

  13. Nanofibrous polymeric beads from aramid fibers for efficient bilirubin removal.

    PubMed

    Peng, Zihang; Yang, Ye; Luo, Jiyue; Nie, Chuanxiong; Ma, Lang; Cheng, Chong; Zhao, Changsheng

    2016-08-16

    Polymer based hemoperfusion has been developed as an effective therapy to remove the extra bilirubin from patients. However, the currently applied materials suffer from either low removal efficiency or poor blood compatibility. In this study, we report the development of a new class of nanofibrous absorbent that exhibited high bilirubin removal efficiency and good blood compatibility. The Kevlar nanofiber was prepared by dissolving micron-sized Kevlar fiber in proper solvent, and the beads were prepared by dropping Kevlar nanofiber solutions into ethanol. Owing to the nanofiborous structure of the Kevlar nanofiber, the beads displayed porous structures and large specific areas, which would facilitate the adsorption of toxins. In the adsorption test, it was noticed that the beads possessed an adsorption capacity higher than 40 mg g(-1) towards bilirubin. In plasma mimetic solutions, the beads still showed high bilirubin removal efficiency. Furthermore, after incorporating with carbon nanotubes, the beads were found to have increased adsorption capacity for human degradation waste. Moreover, the beads showed excellent blood compatibility in terms of a low hemolysis ratio, prolonged clotting times, suppressed coagulant activation, limited platelet activation, and inhibited blood related inflammatory activation. Additionally, the beads showed good compatibility with endothelial cells. In general, the Kevlar nanofiber beads, which integrated with high adsorption capacity, good blood compatibility and low cytotoxicity, may have great potential for hemoperfusion and some other applications in biomedical fields.

  14. Simultaneous detection of Escherichia coli O157:H7 and Salmonella Typhimurium: The use of magnetic beads conjugated with multiple capture antibodies

    USDA-ARS?s Scientific Manuscript database

    Streptavidin-coated magnetic beads were conjugated with biotinylated capture antibodies to both Escherichia coli O157:H7 and Samonella Typhimurium to form multi-pathogen capture immunomagnetic beads (IMB-M). The efficacy of these beads was investigated and compared to the use of a mixture of IMB ag...

  15. The Beads of Translation: Using Beads to Translate mRNA into a Polypeptide Bracelet

    ERIC Educational Resources Information Center

    Dunlap, Dacey; Patrick, Patricia

    2012-01-01

    During this activity, by making beaded bracelets that represent the steps of translation, students simulate the creation of an amino acid chain. They are given an mRNA sequence that they translate into a corresponding polypeptide chain (beads). This activity focuses on the events and sites of translation. The activity provides students with a…

  16. Mesoporous zirconium titanium oxides. Part 2: Synthesis, porosity, and adsorption properties of beads.

    PubMed

    Sizgek, G Devlet; Sizgek, Erden; Griffith, Christopher S; Luca, Vittorio

    2008-11-04

    Mesoporous zirconium titanium mixed-oxide beads having disordered wormhole textures and mole fractions of Zr (x) ranging from x=0.25 to 0.67 have been prepared. The bead preparation method combined the forced hydrolysis of mixtures of zirconium-titanium alkoxides in the presence of long-chain carboxylates with external gelation. Uniformly sized beads could be produced in the size range 0.5-1.1 mm by varying the droplet size and viscosity of the mixed-oxide sol, thus making them suitable for large-scale column chromatographic applications. The beads exhibited narrow pore size distributions with similar mean pore diameters of around 3.7 nm. The specific surface areas of the beads were linked to the Zr mole fraction in the precursor solution and were generally greater than 350 m2/g for x=0.5. A combination of scanning transmission electron microscopy and X-ray absorption fine structure analysis indicated that the pore walls of the beads were composed of atomically dispersed Zr and Ti to form a continuous network of Zr-O-Ti bonds. Mass transport in the beads was evaluated by monitoring the kinetics of vanadate and vanadyl adsorption at pH 10.5 and 0.87, respectively.

  17. Analysis of surface properties of fixed and live cells using derivatized agarose beads.

    PubMed

    Navarro, Vanessa M; Walker, Sherri L; Badali, Oliver; Abundis, Maria I; Ngo, Lylla L; Weerasinghe, Gayani; Barajas, Marcela; Zem, Gregory; Oppenheimer, Steven B

    2002-01-01

    A novel assay has been developed for the histochemical characterization of surface properties of cells based on their adhesion to agarose beads derivatized with more than 100 types of molecules, including sugars, lectins and other proteins, and amino acids. The assay simply involves mixing small quantities of washed cells and beads in droplets on glass microscope slides and determining to which beads various cell types adhere. Distilled water was found to be the best medium for this assay because added ions or molecules in other media inhibit adhesion in some cases. Many cells, however, cannot tolerate distilled water. Here we show that cells fixed with either of two fixatives (1% formaldehyde or Prefer fixative) displayed similar bead-binding properties as did live cells. Specificity of cell-bead binding was tested by including specific free molecules in the test suspensions in hapten-type inhibition experiments. If a hapten compound inhibited live-cell adhesion to a specific bead, it also inhibited fixed-cell adhesion to a specific bead. The results of these experiments suggest that fixed cells display authentic surface properties, opening the door for the use of this assay with many cell types that cannot tolerate distilled water.

  18. Effect of matrix composition and process conditions on casein-gelatin beads floating properties.

    PubMed

    Bulgarelli, E; Forni, F; Bernabei, M T

    2000-04-05

    Casein-gelatin beads have been prepared by emulsification extraction method and cross-linked with D,L-glyceraldehyde in an acetone-water mixture 3:1 (v/v). Casein emulsifying properties cause air bubble incorporation and the formation of large holes in the beads. The high porosity of the matrix influences the bead properties such as drug loading, drug release and floatation. These effects have been stressed by comparison with low porous beads, artificially prepared without cavities. The percentage of casein in the matrix increases the drug loading of both low and high porous matrices, although the loading of high porous matrices is lower than that of low porous matrices. As a matter of fact, the drug should be more easily removed during washing and recovery because of the higher superficial pore area of the beads. This can explain the drug release rate increase, observed in high porous matrix, in comparison with beads without cavities. This is due to the rapid diffusion of the drug through water filled pores. The study shows that cavities act as an air reservoir and enable beads to float. Therefore, casein seems to be a material suitable to the inexpensive formation of an air reservoir for floating systems.

  19. Sorption kinetics of zinc and nickel on modified chitosan.

    PubMed

    Tripathi, Nimisha; Choppala, Girish; Singh, Raj S; Srivastava, Prashant; Seshadri, Balaji

    2016-09-01

    This study was conducted to evaluate the effect of equilibration time on adsorption of zinc [Zn(II)] and nickel [Ni(II)] on pure and modified chitosan beads. The initial adsorption of Zn(II) was high on molybdenum (Mo)-impregnated chitosan beads (MoCB) during the initial 60 min. However, after 240 min, Zn(II) adsorption occurred more on single super phosphate chitosan beads (SSPCB), followed by monocalcium phosphate chitosan beads (MCPCB), untreated pure chitosan beads (UCB), and MoCB. Similarly, Ni(II) adsorption was greatest on MoCB during the initial 60 min. At the conclusion of the experiment (at 240 min), the greatest adsorption was occurred on MCPCB, followed by MoCB, UCB, and SSPCB. Chemical sorption and intra-particle diffusion were probably the dominant processes responsible for Zn(II) and Ni(II) sorption onto chitosan beads. The results demonstrated that modified chitosan beads were effective in adsorbing Zn and Ni and hence, could be used for the removal of these toxic metals from soil.

  20. Ionic liquid as a potential solvent for preparation of collagen-alginate-hydroxyapatite beads as bone filler.

    PubMed

    Iqbal, Bushra; Sarfaraz, Zenab; Muhammad, Nawshad; Ahmad, Pervaiz; Iqbal, Jibran; Khan, Zia Ul Haq; Gonfa, Girma; Iqbal, Farasat; Jamal, Arshad; Rahim, Abdur

    2018-07-01

    In this study, collagen/alginate/hydroxyapatite beads having different proportions were prepared as bone fillers for the restoration of osteological defects. Ionic liquid was used to dissolve the collagen and subsequently the solution was mixed with sodium alginate solution. Hydroxyapatite was added in different proportions, with the rationale to enhance mechanical as well as biological properties. The prepared solutions were given characteristic bead shapes by dropwise addition into calcium chloride solution. The prepared beads were characterized using FTIR, XRD, TGA and SEM analysis. Microhardness testing was used to evaluate the mechanical properties. The prepared beads were investigated for water adsorption behavior to ascertain its ability for body fluid uptake and adjusted accordingly to the bone cavity. Drug loading and subsequently the antibacterial activity was investigated for the prepared beads. The biocompatibility was assessed using the hemolysis testing and cell proliferation assay. The prepared collagen-alginate-HA beads, having biocompatibility and good mechanical properties, have showed an option of promising biologically active bone fillers for bone regeneration.

  1. Energy efficient bead milling of microalgae: Effect of bead size on disintegration and release of proteins and carbohydrates.

    PubMed

    Postma, P R; Suarez-Garcia, E; Safi, C; Yonathan, K; Olivieri, G; Barbosa, M J; Wijffels, R H; Eppink, M H M

    2017-01-01

    The disintegration of three industry relevant algae (Chlorella vulgaris, Neochloris oleoabundans and Tetraselmis suecica) was studied in a lab scale bead mill at different bead sizes (0.3-1mm). Cell disintegration, proteins and carbohydrates released into the water phase followed a first order kinetics. The process is selective towards proteins over carbohydrates during early stages of milling. In general, smaller beads led to higher kinetic rates, with a minimum specific energy consumption of ⩽0.47kWhkg DW -1 for 0.3mm beads. After analysis of the stress parameters (stress number and stress intensity), it appears that optimal disintegration and energy usage for all strains occurs in the 0.3-0.4mm range. During the course of bead milling, the native structure of the marker protein Rubisco was retained, confirming the mildness of the disruption process. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Using a laser source to measure the refractive index of glass beads and Debye theory analysis.

    PubMed

    Li, Shui-Yan; Qin, Shuang; Li, Da-Hai; Wang, Qiong-Hua

    2015-11-20

    Using a monochromatic laser beam to illuminate a homogeneous glass bead, some rainbows will appear around it. This paper concentrates on the study of the scattering intensity distribution and the method of measuring the refractive index for glass beads based on the Debye theory. It is found that the first rainbow due to the scattering superposition of backward light of the low-refractive-index glass beads can be explained approximately with the diffraction, the external reflection plus the one internal reflection, while the second rainbow of high-refractive-index glass beads is due to the contribution from the diffraction, the external reflection, the direct transmission, and the two internal reflections. The scattering intensity distribution is affected by the refractive index, the radius of the glass bead, and the incident beam width. The effects of the refractive index and the glass bead size on the first and second minimum deviation angle position are analyzed in this paper. The results of the measurements agree very well with the specifications.

  3. Pulsed laser manipulation of an optically trapped bead: averaging thermal noise and measuring the pulsed force amplitude.

    PubMed

    Lindballe, Thue B; Kristensen, Martin V G; Berg-Sørensen, Kirstine; Keiding, Søren R; Stapelfeldt, Henrik

    2013-01-28

    An experimental strategy for post-eliminating thermal noise on position measurements of optically trapped particles is presented. Using a nanosecond pulsed laser, synchronized to the detection system, to exert a periodic driving force on an optically trapped 10 μm polystyrene bead, the laser pulse-bead interaction is repeated hundreds of times. Traces with the bead position following the prompt displacement from equilibrium, induced by each laser pulse, are averaged and reveal the underlying deterministic motion of the bead, which is not visible in a single trace due to thermal noise. The motion of the bead is analyzed from the direct time-dependent position measurements and from the power spectrum. The results show that the bead is on average displaced 208 nm from the trap center and exposed to a force amplitude of 71 nanoNewton, more than five orders of magnitude larger than the trapping forces. Our experimental method may have implications for microrheology.

  4. Accuracy of semen counting chambers as determined by the use of latex beads.

    PubMed

    Seaman, E K; Goluboff, E; BarChama, N; Fisch, H

    1996-10-01

    To assess the accuracy of the Hemacytometer (Hausser Scientific, Horsham, PA), Makler (Sefi-Medical Instrument, Haifa, Israel), Cell-VU (Millennium Sciences Inc., New York, NY), and Micro-Cell chambers (Conception Technologies, San Diego, CA) counting chambers. A solution containing a known concentration of latex beads was used as the standard to perform counts on the four different counting chambers. Bead counts for the four different chambers were compared with the bead counts of the standard solution. Variability within chambers also was determined. Mean bead concentrations for both the Cell-VU and Micro-Cell chambers were consistently similar to the bead concentration of the standard solution. Both the hemacytometer and the Makler chambers overestimated the actual bead concentration of the standard solution by as much as 50% and revealed significant interchamber variability. Our data revealed marked differences in the accuracy and reliability of the different counting chambers tested and emphasized the need for standardization and quality control of laboratory procedures.

  5. Equalizer technology--Equal rights for disparate beads.

    PubMed

    Keidel, Eva-Maria; Ribitsch, Doris; Lottspeich, Friedrich

    2010-06-01

    One major limitation in proteomics is the detection and analysis of low-abundant proteins, i.e. in plasma. Several years ago, a technique to selectively enrich the relative concentration of low-abundant proteins was introduced by Boschetti and co-workers. It is based on a specific and saturable interaction of proteins to a high diversity of binding sites, realized by a hexapeptide library coupled to beads. This technology was commercialized as Equalizer beads or ProteoMiner. However, during application of ProteoMiner beads to plasma samples unexpected results questioned the proposed mode of action. Therefore, ProteoMiner beads were compared with chromatographic beads exhibiting completely different surface chemistry. Sepabeads FP-OD400 octadecyl, FP-DA400 diethylamine, FP-BU400 butyl, FP-HG400 hydroxyl and EXE056 epoxy were used. The results show that ProteoMiner or the different Sepabeads behave surprisingly similarly in the separation of complex protein mixtures. ProteoMiner beads interact with protein mixtures according to a general hydrophobic binding mechanism, where diversity in surface ligands plays only a negligible role.

  6. Blends of jackfruit seed starch-pectin in the development of mucoadhesive beads containing metformin HCl.

    PubMed

    Nayak, Amit Kumar; Pal, Dilipkumar

    2013-11-01

    In this work, calcium pectinate-jackfruit (Artocarpus heterophyllus Lam.) seed starch (JFSS) mucoadhesive beads containing metformin HCl were developed through ionotropic-gelation. Effects of pectin and JFSS amounts on drug encapsulation efficiency (DEE), and cumulative drug release after 10 h (R10 h) were optimized using 3(2) factorial design. The optimized calcium pectinate-JFSS beads containing metformin HCl showed DEE of 94.11 ± 3.92%, R10 h of 48.88 ± 2.02%, and mean diameter of 2.06 ± 0.20 mm. The in vitro drug release from these beads was followed controlled-release (zero-order) pattern with super case-II transport mechanism. The beads were also characterized by SEM and FTIR. The pH of test mediums was found critical for swelling and mucoadhesion of these beads. The optimized calcium pectinate-JFSS beads also exhibited good mucoadhesivity and significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Silver nanoparticle-alginate composite beads for point-of-use drinking water disinfection.

    PubMed

    Lin, Shihong; Huang, Rixiang; Cheng, Yingwen; Liu, Jie; Lau, Boris L T; Wiesner, Mark R

    2013-08-01

    Silver nanoparticles (AgNPs)-alginate composite beads were synthesized using three different approaches as filler materials of packed columns for simultaneous filtration-disinfection as an alternative portable water treatment process. The prepared composite beads were packed into a column through which Escherichia coli containing water was filtered to evaluate the disinfection efficacy. Excellent disinfection performance (no detectable viable colony) was achieved with a hydraulic retention time (HRT) as short as 1 min (the shortest tested) with the SGR (Simultaneous-Gelation-Reduction) and AR (Adsorption-Reduction) beads that were prepared using in situ reduction of Ag(+). Comparatively, the SGR beads released significantly less Ag(+)/AgNPs than the AR beads did within the same HRT. From the results of this study it was identified that SGR may be the best choice among all three different synthesis approaches in that the SGR beads can achieve satisfactory bactericidal performance with a relatively low material consumption rate. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Polymerase chain reaction system using magnetic beads for analyzing a sample that includes nucleic acid

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nasarabadi, Shanavaz

    2011-01-11

    A polymerase chain reaction system for analyzing a sample containing nucleic acid includes providing magnetic beads; providing a flow channel having a polymerase chain reaction chamber, a pre polymerase chain reaction magnet position adjacent the polymerase chain reaction chamber, and a post pre polymerase magnet position adjacent the polymerase chain reaction chamber. The nucleic acid is bound to the magnetic beads. The magnetic beads with the nucleic acid flow to the pre polymerase chain reaction magnet position in the flow channel. The magnetic beads and the nucleic acid are washed with ethanol. The nucleic acid in the polymerase chain reactionmore » chamber is amplified. The magnetic beads and the nucleic acid are separated into a waste stream containing the magnetic beads and a post polymerase chain reaction mix containing the nucleic acid. The reaction mix containing the nucleic acid flows to an analysis unit in the channel for analysis.« less

  9. Effect of decrease in both postprandial blood glucose (PBG) and fasting blood glucose (FBG) levels in normal beagle dogs with nateglinide enteric coated granules and immediate release tablets.

    PubMed

    Makino, Chisato; Ninomiya, Nobutaka; Sakai, Hidetoshi; Orita, Haruo; Okano, Akira; Yabuki, Akira

    2006-04-01

    Nateglinide is a new quick action/short duration (QRSD) type of oral blood glucose regulator, and nateglinide immediate release tablets are used for patients with mild diabetes under the trade name of Fastic((R)) tablets. In this study, we attempted to determine if it was possible to control both post-prandial blood glucose level (PBG) and fasting blood glucose level (FBG) for moderate or severe diabetes through controlled release of nateglinide. Enteric coated granules were selected for the administration form for controlled release of nateglinide, and three types of enteric coated granules were prepared having dissolution pH values of 5.5, 6.5 and 7.2. The three types of enteric coated granules were each administered separately or the enteric coated granules having an dissolution pH of 6.5 were administered simultaneous to administration of nateglinide immediate release tablets to normal beagle dogs just before feeding followed by measurement of plasma nateglinide concentration, plasma insulin concentration and blood glucose level. In the case of administering enteric coated granules alone (nateglinide: 9 mg/kg), the absorption of nateglinide was confirmed to tend to be delayed as the dissolution pH increased. In the case of an dissolution pH of 5.5, decreases in both PBG and FBG were observed. In the case of dissolution pH values of 6.5 and 7.2, only decrease in FBG was observed. In case of nateglinide immediate release tablets (nateglinide: 9 mg/kg), only decrease in PBG was observed. Decreases in both PBG and FBG were observed in the case of simultaneous administration of dissolution pH 6.5 enteric coated granules and nateglinide immediate release tablets just before feeding (nateglinide: 90 mg/head+60 mg/head). A correlation was observed between plasma nateglinide concentrations and blood glucose levels. On the other hand, there were no correlations observed between changes in plasma insulin concentrations and blood glucose levels. In case of nateglinide immediate release tablets (nateglinide: 150 mg/head), Decreases in both PBG and FBG were observed. However, the nateglinide controlled release formulation is more useful than the nateglinide immediate release tablets from the view point of avoidance of side effect, or of easy control of both PBG and FBG. On the basis of these results, the design of a controlled release formulation that contains nateglinide was suggested to enable control of both PBG and FBG for moderate and severe diabetes patients.

  10. Size of the Dynamic Bead in Polymers

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Agapov, Alexander L; Sokolov, Alexei P

    2010-01-01

    Presented analysis of neutron, mechanical, and MD simulation data available in the literature demonstrates that the dynamic bead size (the smallest subchain that still exhibits the Rouse-like dynamics) in most of the polymers is significantly larger than the traditionally defined Kuhn segment. Moreover, our analysis emphasizes that even the static bead size (e.g., chain statistics) disagrees with the Kuhn segment length. We demonstrate that the deficiency of the Kuhn segment definition is based on the assumption of a chain being completely extended inside a single bead. The analysis suggests that representation of a real polymer chain by the bead-and-spring modelmore » with a single parameter C cannot be correct. One needs more parameters to reflect correctly details of the chain structure in the bead-and-spring model.« less

  11. Self-organizing magnetic beads for biomedical applications

    NASA Astrophysics Data System (ADS)

    Gusenbauer, Markus; Kovacs, Alexander; Reichel, Franz; Exl, Lukas; Bance, Simon; Özelt, Harald; Schrefl, Thomas

    2012-03-01

    In the field of biomedicine magnetic beads are used for drug delivery and to treat hyperthermia. Here we propose to use self-organized bead structures to isolate circulating tumor cells using lab-on-chip technologies. Typically blood flows past microposts functionalized with antibodies for circulating tumor cells. Creating these microposts with interacting magnetic beads makes it possible to tune the geometry in size, position and shape. We developed a simulation tool that combines micromagnetics and discrete particle dynamics, in order to design micropost arrays made of interacting beads. The simulation takes into account the viscous drag of the blood flow, magnetostatic interactions between the magnetic beads and gradient forces from external aligned magnets. We developed a particle-particle particle-mesh method for effective computation of the magnetic force and torque acting on the particles.

  12. A facile method for the preparation of monodisperse beads with uniform pore sizes for cell culture.

    PubMed

    Moon, Seung-Kwan; Oh, Myeong-Jin; Paik, Dong-Hyun; Ryu, Tae-Kyung; Park, Kyeongsoon; Kim, Sung-Eun; Park, Jong-Hoon; Kim, Jung-Hyun; Choi, Sung-Wook

    2013-03-12

    This paper describes a facile method for the preparation of porous gelatin beads with uniform pore sizes using a simple fluidic device and their application as supporting materials for cell culture. An aqueous gelatin droplet containing many uniform toluene droplets, produced in the fluidic device, is dropped into liquid nitrogen for instant freezing and the small toluene droplets evolve into pores in the gelatin beads after removal of toluene and then freeze-drying. The porous gelatin beads exhibit a uniform pore size and monodisperse diameter as well as large open pores at the surface. Fluorescence microscopy images of fibroblast-loaded gelatin beads confirm the attachment and proliferation of the cells throughout the porous gelatin beads. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Montmorillonite-Alginate Composites as a Drug delivery System: Intercalation and In vitro Release of Diclofenac sodium

    PubMed Central

    Kevadiya, B. D.; Patel, H. A.; Joshi, G. V.; Abdi, S. H. R.; Bajaj, H. C.

    2010-01-01

    Diclofenac sodium and alginate was intercalated into montmorillonite to form uniform sized beads by gelation method. The structure and surface morphology of the synthesized composite beads were characterized by powdered X-ray diffraction, Fourier transform infrared spectroscopy, thermo gravimetric analysis and scanning electron microscopy. Diclofenac release kinetics of the composite in simulated intestinal fluid medium (pH 7.4) and effect of montmorillonite content on the in vitro release of diclofenac from diclofenac-montmorillonite-alginate composites bead was investigated by UV/Vis spectrophotometer. Diclofenac encapsulation efficiency in the montmorillonite-alginate composites bead increases with an increase in the montmorillonite content. The control release of diclofenac from diclofenac-montmorillonite-alginate composites beads was observed to be better as compared to diclofenac-alginate beads. PMID:21969745

  14. The Use of Index-Matched Beads in Optical Particle Counters

    PubMed Central

    Hu, Zhishang; Ripple, Dean C

    2014-01-01

    In this paper, we demonstrate the use of 2-pyridinemethanol (2P) aqueous solutions as a refractive index matching liquid. The high refractive index and low viscosity of 2P-water mixtures enables refractive index matching of beads that cannot be index matched with glycerol-water or sucrose-water solutions, such as silica beads that have the refractive index of bulk fused silica or of polymethylmethacrylate beads. Suspensions of beads in a nearly index-matching liquid are a useful tool to understand the response of particle counting instruments to particles of low optical contrast, such as aggregated protein particles. Data from flow imaging and light obscuration instruments are presented for bead diameters ranging from 6 µm to 69 µm, in a matrix liquid spanning the point of matched refractive index. PMID:26601049

  15. Micro-Raman spectroscopy and μ-XRF in the investigation of ancient glass beads from the archaeological sites, eastern Taiwan

    NASA Astrophysics Data System (ADS)

    San Liou, Ying; Liu, Yi Chang

    2017-04-01

    Ancient glass beads with different colors, shapes, and stylistics unearthed from the archaeological sites of eastern Taiwan, dating back to approximately 1850-310 BP, have been investigated. It is generally known that glass bead is alien to invade into Taiwan along with metal ware, glass, agate, etc. since the Metal Age of Taiwan. Nevertheless, souring provenance and trade routes still remain controversial. Micro-Raman spectroscopy and μ-XRF have been applied on fifty-six ancient glass beads to reveal the mineralogical and chemical compositions and to help decipher the raw materials used and souring provenance. Micro-Raman measurements indicate the presence of hematite, zincite, siderite, sphalerite, lead tin yellow type II, quartz, feldspar, anatase, rutite, ankerite, graphite, calcite, etc. Among them, hematite, zincite, siderite, sphalerite, lead tin yellow type II, and rutile were found to be colorants/opacifiers. Moreover, crystalline phases such as lead tin yellow type II (PbSn1-xSixO3), zincite (ZnO), tricalcium diphosphate (Ca2(PO4)2), sphalerite ((Zn, Fe)S) and ankerite (Ca(Fe, Mg, Mn)(CO3)2) were detected in ancient glass beads unearthed from Taiwan for the first time. The chemical results obtained by μXRF show SiO2, Al2O3, Na2O, K2O, MgO, CaO, and PbO as the most abundant oxides. Na2O, K2O, Al2O3, MgO, and PbO could be the main/minor fluxes and colorants. In general, results of mineralogical and chemical analyses are compatible. According to chemical results, ancient glass beads can be classified as mineral soda alumina glass (m-Na-Al glass), soda plant ash glass (v-Na-Ca glass), lead silicate glass, and some less well known types. Mineral soda alumina and soda plant ash glass beads, as well as lead silicate glass beads are generally believed to be the distinct phases of production and exchange in Southeast Asia and China, respectively. In terms of chronology of glass bead, beads excavated from sites of 1850-930 BP are mineral soda alumina glass (m-Na-Al glass) and soda plant ash glass (v-Na-Ca glass). On the other hand, beads from sites of <930 BP are belonging to lead silicate glass. It is indicated that the souring provenance of ancient beads of eastern Taiwan is probably a multiple sources, i.e., in earlier time, glass beads were brought into Taiwan through the maritime exchange and/or trade activities between Taiwan and Southeast Asia; at the later period, lead silicate glass beads were imported from China. However, some mineral soda alumina and soda plant ash glass beads were found in a later period, it might be attributed to glass beads reuse or trade route between Taiwan and Southeast Asia is successive since ca. 1850 BP.

  16. Functionally Graded Adhesives for Composite Joints

    NASA Technical Reports Server (NTRS)

    Stapleton, Scott E.; Waas, Anthony M.; Arnold, Steven M.

    2012-01-01

    Adhesives with functionally graded material properties are being considered for use in adhesively bonded joints to reduce the peel stress concentrations located near adherend discontinuities. Several practical concerns impede the actual use of such adhesives. These include increased manufacturing complications, alterations to the grading due to adhesive flow during manufacturing, and whether changing the loading conditions significantly impact the effectiveness of the grading. An analytical study is conducted to address these three concerns. An enhanced joint finite element, which uses an analytical formulation to obtain exact shape functions, is used to model the joint. Furthermore, proof of concept testing is conducted to show the potential advantages of functionally graded adhesives. In this study, grading is achieved by strategically placing glass beads within the adhesive layer at different densities along the joint.

  17. Jeffamine Derivatized TentaGel Beads and PDMS Microbead Cassettes for Ultra-high Throughput in situ Releasable Solution-Phase Cell-based Screening of OBOC Combinatorial Small Molecule Libraries

    PubMed Central

    Townsend, Jared B.; Shaheen, Farzana; Liu, Ruiwu; Lam, Kit S.

    2011-01-01

    A method to efficiently immobilize and partition large quantities of microbeads in an array format in microfabricated polydimethylsiloxane (PDMS) cassette for high-throughput in situ releasable solution-phase cell-based screening of one-bead-one-compound (OBOC) combinatorial libraries is described. Commercially available Jeffamine triamine T-403 (∼440 Da) was derivatized such that two of its amino groups were protected by Fmoc and the remaining amino group capped with succinic anhydride to generate a carboxyl group. This resulting tri-functional hydrophilic polymer was then sequentially coupled two times to the outer layer of topologically segregated bilayer TentaGel (TG) beads with solid phase peptide synthesis chemistry, resulting in beads with increased loading capacity, hydrophilicity and porosity at the outer layer. We have found that such bead configuration can facilitate ultra high-throughput in situ releasable solution-phase screening of OBOC libraries. An encoded releasable OBOC small molecule library was constructed on Jeffamine derivatized TG beads with library compounds tethered to the outer layer via a disulfide linker and coding tags in the interior of the beads. Compound-beads could be efficiently loaded (5-10 minutes) into a 5 cm diameter Petri dish containing a 10,000-well PDMS microbead cassette, such that over 90% of the microwells were each filled with only one compound-bead. Jurkat T-lymphoid cancer cells suspended in Matrigel® were then layered over the microbead cassette to immobilize the compound-beads. After 24 hours of incubation at 37°C, dithiothreitol was added to trigger the release of library compounds. Forty-eight hours later, MTT reporter assay was used to identify regions of reduced cell viability surrounding each positive bead. From a total of about 20,000 beads screened, 3 positive beads were detected and physically isolated for decoding. A strong consensus motif was identified for these three positive compounds. These compounds were re-synthesized and found to be cytotoxic (IC50 50-150 μM) against two T-lymphoma cell lines and less so against the MDA-MB 231 breast cancer cell line. This novel ultra high-throughput OBOC releasable method can potentially be adapted to many existing 96- or 384-well solution-phase cell-based or biochemical assays. PMID:20593859

  18. Chloride Cotransporters as a Molecular Mechanism underlying Spreading Depolarization-Induced Dendritic Beading.

    PubMed

    Steffensen, Annette B; Sword, Jeremy; Croom, Deborah; Kirov, Sergei A; MacAulay, Nanna

    2015-09-02

    Spreading depolarizations (SDs) are waves of sustained neuronal and glial depolarization that propagate massive disruptions of ion gradients through the brain. SD is associated with migraine aura and recently recognized as a novel mechanism of injury in stroke and brain trauma patients. SD leads to neuronal swelling as assessed in real time with two-photon laser scanning microscopy (2PLSM). Pyramidal neurons do not express aquaporins and thus display low inherent water permeability, yet SD rapidly induces focal swelling (beading) along the dendritic shaft by unidentified molecular mechanisms. To address this issue, we induced SD in murine hippocampal slices by focal KCl microinjection and visualized the ensuing beading of dendrites expressing EGFP by 2PLSM. We confirmed that dendritic beading failed to arise during large (100 mOsm) hyposmotic challenges, underscoring that neuronal swelling does not occur as a simple osmotic event. SD-induced dendritic beading was not prevented by pharmacological interference with the cytoskeleton, supporting the notion that dendritic beading may result entirely from excessive water influx. Dendritic beading was strictly dependent on the presence of Cl(-), and, accordingly, combined blockade of Cl(-)-coupled transporters led to a significant reduction in dendritic beading without interfering with SD. Furthermore, our in vivo data showed a strong inhibition of dendritic beading during pharmacological blockage of these cotransporters. We propose that SD-induced dendritic beading takes place as a consequence of the altered driving forces and thus activity for these cotransporters, which by transport of water during their translocation mechanism may generate dendritic beading independently of osmotic forces. Spreading depolarization occurs during pathological conditions such as stroke, brain injury, and migraine and is characterized as a wave of massive ion translocation between intracellular and extracellular space in association with recurrent transient focal swelling (beading) of dendrites. Numerous ion channels have been demonstrated to be involved in generation and propagation of spreading depolarization, but the molecular machinery responsible for the dendritic beading has remained elusive. Using real-time in vitro and in vivo two-photon laser scanning microscopy, we have identified the transport mechanisms involved in the detrimental focal swelling of dendrites. These findings have clear clinical significance because they may point to a new class of pharmacological targets for prevention of neuronal swelling that consequently will serve as neuroprotective agents. Copyright © 2015 the authors 0270-6474/15/3512172-16$15.00/0.

  19. Optimization of propranolol HCl release kinetics from press coated sustained release tablets.

    PubMed

    Ali, Adel Ahmed; Ali, Ahmed Mahmoud

    2013-01-01

    Press-coated sustained release tablets offer a valuable, cheap and easy manufacture alternative to the highly expensive, multi-step manufacture and filling of coated beads. In this study, propranolol HCl press-coated tablets were prepared using hydroxylpropylmethylcellulose (HPMC) as tablet coating material together with carbopol 971P and compressol as release modifiers. The prepared formulations were optimized for zero-order release using artificial neural network program (INForm, Intelligensys Ltd, North Yorkshire, UK). Typical zero-order release kinetics with extended release profile for more than 12 h was obtained. The most important variables considered by the program in optimizing formulations were type and proportion of polymer mixture in the coat layer and distribution ratio of drug between core and coat. The key elements found were; incorporation of 31-38 % of the drug in the coat, fixing the amount of polymer in coat to be not less than 50 % of coat layer. Optimum zero-order release kinetics (linear regression r2 = 0.997 and Peppas model n value > 0.80) were obtained when 2.5-10 % carbopol and 25-42.5% compressol were incorporated into the 50 % HPMC coat layer.

  20. Combinative Particle Size Reduction Technologies for the Production of Drug Nanocrystals

    PubMed Central

    Salazar, Jaime; Müller, Rainer H.; Möschwitzer, Jan P.

    2014-01-01

    Nanosizing is a suitable method to enhance the dissolution rate and therefore the bioavailability of poorly soluble drugs. The success of the particle size reduction processes depends on critical factors such as the employed technology, equipment, and drug physicochemical properties. High pressure homogenization and wet bead milling are standard comminution techniques that have been already employed to successfully formulate poorly soluble drugs and bring them to market. However, these techniques have limitations in their particle size reduction performance, such as long production times and the necessity of employing a micronized drug as the starting material. This review article discusses the development of combinative methods, such as the NANOEDGE, H 96, H 69, H 42, and CT technologies. These processes were developed to improve the particle size reduction effectiveness of the standard techniques. These novel technologies can combine bottom-up and/or top-down techniques in a two-step process. The combinative processes lead in general to improved particle size reduction effectiveness. Faster production of drug nanocrystals and smaller final mean particle sizes are among the main advantages. The combinative particle size reduction technologies are very useful formulation tools, and they will continue acquiring importance for the production of drug nanocrystals. PMID:26556191

  1. Retro-reflection of glass beads for traffic road stripe paints

    NASA Astrophysics Data System (ADS)

    Grosges, T.

    2008-06-01

    The retro-reflection of light by glass beads injected in road stripes is studied experimentally and theoretically. The complete contribution of the retro-reflected intensity is modelled by taking into account the glass beads and the paint stripes. The efficiency of such a technique is evaluated for various compositions and densities of glass beads injected in paints, including the paint meniscus contributions.

  2. The role of silica colloids on facilitated cesium transport through glass bead columns and modeling

    NASA Astrophysics Data System (ADS)

    Noell, Alan L.; Thompson, Joseph L.; Corapcioglu, M. Yavuz; Triay, Inés R.

    1998-05-01

    Groundwater colloids can act as a vector which enhances the migration of contaminants. While sorbed to mobile colloids, contaminants can be held in the aqueous phase which prevents them from interacting with immobile aquifer surfaces. In this study, an idealized laboratory set-up was used to examine the influence of amorphous silica colloids on the transport of cesium. Synthetic groundwater and saturated glass bead columns were used to minimize the presence of natural colloidal material. The columns were assembled in replicate, some packed with 150-210 μm glass bead and others packed with 355-420 μm glass beads. The colloids used in these experiments were 100 nm amorphous silica colloids from Nissan Chemical Company. In the absence of these colloids, the retardation factor for cesium was 8.0 in the 150-210 μm glass bead columns and 3.6 in the 355-420 μm glass bead columns. The influence of anthropogenic colloids was tested by injecting 0.09 pore volume slugs of an equilibrated suspension of cesium and colloids into the colloid-free columns. Although there was little noticeable facilitation in the smaller glass bead columns, there was a slight reduction in the retardation of cesium in the larger glass bead columns. This was attributed to cesium having less of a retention time in the larger glass bead columns. When cesium was injected into columns with a constant flux of colloids, the retardation of cesium was reduced by 14-32% in the 150-210 μm glass bead columns and by 38-51% in the 355-420 μm glass bead columns. A model based on Corapcioglu and Jiang (1993) [Corapcioglu, M.Y., Jiang, S., 1993. Colloid-facilitated groundwater contaminant transport, Water Resour. Res., 29 (7) 2215-2226] was compared with the experimental elution data. When equilibrium sorption expressions were used and the flux of colloids through the glass bead columns was constant, the colloid facilitated transport of cesium was able to be described using an effective retardation coefficient. Fully kinetic simulations, however, more accurately described the colloid facilitated transport of cesium.

  3. The impact of school water, sanitation, and hygiene improvements on infectious disease using serum antibody detection.

    PubMed

    Chard, Anna N; Trinies, Victoria; Moss, Delynn M; Chang, Howard H; Doumbia, Seydou; Lammie, Patrick J; Freeman, Matthew C

    2018-04-01

    Evidence from recent studies assessing the impact of school water, sanitation and hygiene (WASH) interventions on child health has been mixed. Self-reports of disease are subject to bias, and few WASH impact evaluations employ objective health measures to assess reductions in disease and exposure to pathogens. We utilized antibody responses from dried blood spots (DBS) to measure the impact of a school WASH intervention on infectious disease among pupils in Mali. We randomly selected 21 beneficiary primary schools and their 21 matched comparison schools participating in a matched-control trial of a comprehensive school-based WASH intervention in Mali. DBS were collected from 20 randomly selected pupils in each school (n = 807). We analyzed eluted IgG from the DBS using a Luminex multiplex bead assay to 28 antigens from 17 different pathogens. Factor analysis identified three distinct latent variables representing vector-transmitted disease (driven primarily by dengue), food/water-transmitted enteric disease (driven primarily by Escherichia coli and Vibrio cholerae), and person-to-person transmitted enteric disease (driven primarily by norovirus). Data were analyzed using a linear latent variable model. Antibody evidence of food/water-transmitted enteric disease (change in latent variable mean (β) = -0.24; 95% CI: -0.53, -0.13) and person-to-person transmitted enteric disease (β = -0.17; 95% CI: -0.42, -0.04) was lower among pupils attending beneficiary schools. There was no difference in antibody evidence of vector-transmitted disease (β = 0.11; 95% CI: -0.05, 0.33). Evidence of enteric disease was lower among pupils attending schools benefitting from school WASH improvements than students attending comparison schools. These findings support results from the parent study, which also found reduced incidence of self-reported diarrhea among pupils of beneficiary schools. DBS collection was feasible in this resource-poor field setting and provided objective evidence of disease at a low cost per antigen analyzed, making it an effective measurement tool for the WASH field. The trial was registered at ClinicalTrials.gov (NCT01787058).

  4. The impact of school water, sanitation, and hygiene improvements on infectious disease using serum antibody detection

    PubMed Central

    Trinies, Victoria; Doumbia, Seydou; Lammie, Patrick J.; Freeman, Matthew C.

    2018-01-01

    Background Evidence from recent studies assessing the impact of school water, sanitation and hygiene (WASH) interventions on child health has been mixed. Self-reports of disease are subject to bias, and few WASH impact evaluations employ objective health measures to assess reductions in disease and exposure to pathogens. We utilized antibody responses from dried blood spots (DBS) to measure the impact of a school WASH intervention on infectious disease among pupils in Mali. Methodology/Principal findings We randomly selected 21 beneficiary primary schools and their 21 matched comparison schools participating in a matched-control trial of a comprehensive school-based WASH intervention in Mali. DBS were collected from 20 randomly selected pupils in each school (n = 807). We analyzed eluted IgG from the DBS using a Luminex multiplex bead assay to 28 antigens from 17 different pathogens. Factor analysis identified three distinct latent variables representing vector-transmitted disease (driven primarily by dengue), food/water-transmitted enteric disease (driven primarily by Escherichia coli and Vibrio cholerae), and person-to-person transmitted enteric disease (driven primarily by norovirus). Data were analyzed using a linear latent variable model. Antibody evidence of food/water-transmitted enteric disease (change in latent variable mean (β) = -0.24; 95% CI: -0.53, -0.13) and person-to-person transmitted enteric disease (β = -0.17; 95% CI: -0.42, -0.04) was lower among pupils attending beneficiary schools. There was no difference in antibody evidence of vector-transmitted disease (β = 0.11; 95% CI: -0.05, 0.33). Conclusions/Significance Evidence of enteric disease was lower among pupils attending schools benefitting from school WASH improvements than students attending comparison schools. These findings support results from the parent study, which also found reduced incidence of self-reported diarrhea among pupils of beneficiary schools. DBS collection was feasible in this resource-poor field setting and provided objective evidence of disease at a low cost per antigen analyzed, making it an effective measurement tool for the WASH field. Trial registration The trial was registered at ClinicalTrials.gov (NCT01787058) PMID:29659574

  5. Effects of absorption enhancers in chloroquine suppository formulations: I. In vitro release characteristics.

    PubMed

    Onyeji, C O; Adebayo, A S; Babalola, C P

    1999-12-01

    The need to develop chloroquine suppository formulations that yield optimal bioavailability of the drug has been emphasized. This study demonstrates the effects of incorporation of known absorption-enhancing agents (nonionic surfactants and sodium salicylate) on the in vitro release characteristics of chloroquine from polyethylene glycol (1000:4000, 75:25%, w/w) suppositories. The release rates were determined using a modification of the continuous flow bead-bed dissolution apparatus for suppositories. Results showed that the extent of drug release from suppositories containing any of three surfactants (Tween 20, Tween 80 and Brij 35) was 100%, whereas 88% release was obtained with control formulation (without enhancer) (P<0.05). However, Tween 20 was more effective than Brij 35 and Tween 80 in improving the drug release rate. There was a concentration-dependent effect with Tween 20, and 4% (w/w) of this surfactant was associated with the highest increase in the rate of drug release from the suppositories. Sodium salicylate at a concentration of 25% (w/w) also significantly enhanced the drug release rate, but a higher concentration of the adjuvant markedly reduced both the rate and extent of drug release. Combined incorporation of Tween 20 and sodium salicylate did not significantly modify (P0.05) the rate of drug release when compared to the effect of the more effective single agent. Due to their effects in improving the drug release profiles coupled with their intrinsic absorption-promoting properties, it is suggested that incorporation of 4% (w/w) Tween 20 and/or 25% (w/w) sodium salicylate in the composite polyethylene glycol chloroquine suppository formulations, may result in enhancement of rectal absorption of the drug. This necessitates an in vivo validation.

  6. Methylphenidate and dexmethylphenidate formulations for children with attention-deficit/hyperactivity disorder.

    PubMed

    Sugrue, David; Bogner, Robin; Ehret, Megan J

    2014-07-15

    Current literature on the safety and efficacy of various intermediate- and long-acting preparations of methylphenidate and dexmethylphenidate for pediatric attention-deficit/hyperactivity disorder (ADHD) is reviewed. The efficacy of methylphenidate in controlling ADHD symptoms is firmly established. Given the drug's relatively short half-life in pediatric patients (about 2.5 hours), a number of intermediate- and long-acting products have been developed; these extended-release methylphenidate products provide the same efficacy as immediate-release (IR) formulations, with the convenience of less frequent dosing. Intermediate-acting methylphenidate preparations have effects lasting as long as 8 hours, but peak concentrations are not attained for up to 5 hours, and many patients may require twice-daily dosing. Long-acting methylphenidate products developed to address these challenges include a controlled-release tablet and bimodal-delivery capsules containing mixtures of IR and extended-release beads (durations of effect, 8-12 hours). Options for patients with difficulty swallowing tablets or capsules include a once-daily transdermal delivery system and a once-daily liquid formulation. Dexmethylphenidate (the more pharmacologically active d-isomer of racemic methylphenidate) can provide efficacy comparable to that of IR methylphenidate at half the dose; an extended-release form of dexmethylphenidate can provide less fluctuation in peak and trough concentrations than the IR form. Methylphenidate and dexmethylphenidate products in capsule form can be opened and sprinkled on applesauce. The various formulations of IR and intermediate- and extended-release methylphenidate and dexmethylphenidate can be useful options in satisfying patients' individual needs in the management of ADHD. All are equally efficacious in controlling ADHD symptoms. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  7. Intranasal delivery of Norwalk virus-like particles formulated in an in-situ gelling, dry powder vaccine

    PubMed Central

    Velasquez, Lissette S.; Shira, Samantha; Berta, Alice N.; Kilbourne, Jacquelyn; Medi, Babu M.; Tizard, Ian; Ni, Yawei; Arntzen, Charles J.; Herbst-Kralovetz, Melissa M.

    2011-01-01

    The development of a vaccine to prevent norovirus infections has been focused on immunization at a mucosal surface, but has been limited by the low immunogenicity of self-assembling Norwalk virus-like particles (NV VLPs) delivered enterically or at nasal surfaces. Nasal immunization, which offers the advantage of ease of immunization, faces obstacles imposed by the normal process of mucociliary clearance, which limits residence time of applied antigens. Herein, we describe the use of a dry powder formulation (GelVac) of an inert in-situ gelling polysaccharide (GelSite) extracted from Aloe vera for nasal delivery of NV VLP antigen. Powder formulations, with or without NV VLP antigen, were similar in structure in dry form or when rehydrated in simulated nasal fluids. Immunogenicity of the dry powder VLP formulation was compared to equivalent antigen/adjuvant liquid formulations in animals. For the GelVac powder, we observed superior NV-specific serum and mucosal (aerodigestive and reproductive tracts) antibody responses relative to liquid formulations. Incorporation of TLR7 agonist gardiquimod in dry powder formulations did not enhance antibody responses, although its inclusion in liquid formulations did enhance VLP immunogenicity irrespective of the presence or absence of GelSite. We interpret these data as showing that GelSite-based dry powder formulations 1.) stabilize the immunogenic structural properties of VLPs and 2.) induce systemic and mucosal antibody titers which are equal or greater than those achieved by VLPs plus adjuvant in a liquid formulation. We conclude that in-situ gelation of the GelVac dry powder formulation at nasal mucosal surfaces delays mucociliary clearance and thereby prolongs VLP antigen exposure to immune effector sites. PMID:21640778

  8. Arsenic and fluoride removal from contaminated drinking water with Haix-Fe-Zr and Haix-Zr resin beads.

    PubMed

    Phillips, Debra H; Sen Gupta, Bhaskar; Mukhopadhyay, Soumyadeep; Sen Gupta, Arup K

    2018-06-01

    The objective of the study was to carry-out batch tests to examine the effectiveness of Haix-Fe-Zr and Haix-Zr resin beads in the removal of As(III), As(V) and F - from groundwater with a similar geochemistry to a site where a community-based drinking water plant has been installed in West Bengal, India. The groundwater was spiked separately with ∼200 μg/L As(III) and As(V) and 5 mg/L F - . Haix-Zr resin beads were more effective than Haix-Fe-Zr resin beads in removing As(III) and As(V). Haix-Zr resin beads showed higher removal of As(V) compared to As(III). Haix-Zr resin beads removed As(V) below the WHO (10 μg/L) drinking water standards at 8.79 μg/L after 4 h of shaking, while As(III) was reduced to 7.72 μg/L after 8 h of shaking. Haix-Fe-Zr resin beads were more effective in removing F - from the spiked groundwater compared to Haix-Zr resin beads. Concentrations of F - decreased from 6.27 mg/L to 1.26 mg/L, which is below the WHO drinking water standards (1.5 mg/L) for F - , after 15 min of shaking with Haix-Fe-Zr resin beads. After 20 min of shaking in groundwater treated with Haix-Zr resin beads, F - concentrations decreased from 6.27 mg/L to 1.43 mg/L. In the removal of As(III), As(V), and F - from the groundwater, Haix-Fe-Zr and Haix-Zr resin beads fit the parabolic diffusion equation (PDE) suggesting that adsorption of these contaminants was consistent with inter-particle diffusion. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Bacterial polyester inclusions engineered to display vaccine candidate antigens for use as a novel class of safe and efficient vaccine delivery agents.

    PubMed

    Parlane, Natalie A; Wedlock, D Neil; Buddle, Bryce M; Rehm, Bernd H A

    2009-12-01

    Bioengineered bacterial polyester inclusions have the potential to be used as a vaccine delivery system. The biopolyester beads were engineered to display a fusion protein of the polyester synthase PhaC and the two key antigens involved in immune response to the infectious agent that causes tuberculosis, Mycobacterium tuberculosis, notably antigen 85A (Ag85A) and the 6-kDa early secreted antigenic target (ESAT-6) from Mycobacterium tuberculosis. Polyester beads displaying the respective fusion protein at a high density were successfully produced (henceforth called Ag85A-ESAT-6 beads) by recombinant Escherichia coli. The ability of the Ag85A-ESAT-6 beads to enhance mouse immunity to the displayed antigens was investigated. The beads were not toxic to the animals, as determined by weight gain and absence of lesions at the inoculation site in immunized animals. In vivo injection of the Ag85A-ESAT-6 beads in mice induced significant humoral and cell-mediated immune responses to both Ag85A and ESAT-6. Vaccination with Ag85A-ESAT-6 beads was efficient at stimulating immunity on their own, and this ability was enhanced by administration of the beads in an oil-in-water emulsion. In addition, vaccination with the Ag85A-ESAT-6 beads induced significantly stronger humoral and cell-mediated immune responses than vaccination with an equivalent dose of the fusion protein Ag85A-ESAT-6 alone. The immune response induced by the beads was of a mixed Th1/Th2 nature, as assessed from the induction of the cytokine gamma interferon (Th1 immune response) and increased levels of immunoglobulin G1 (Th2 immune response). Hence, engineered biopolyester beads displaying foreign antigens represent a new class of versatile, safe, and biocompatible vaccines.

  10. Controlled release of D-glucose from starch granules containing 29% free D-glucose and Eudragit L100-55 as a binding and coating agent.

    PubMed

    Kim, Yeon-Kye; Mukerjea, Rupendra; Robyt, John F

    2010-05-27

    Waxy maize starch (100% amylopectin) granules were modified by reaction of the granules with glucoamylase in a minimum amount of water to give 29% (w/w) D-glucose inside the granules [Kim, Y.-K.; Robyt, J. F. Carbohydr. Res.1999, 318, 129-134]. These granules were made into beads by dropping an ethanol slurry of starch and different amounts of Eudragit L100-55 in a constant ratio of 100:1 from a pipette onto Whatman 3MM filter paper. The starch beads were air dried and then repeatedly sprayed 0-12 times with 2.0% (w/v) Eudragit L100-55 in ethanol, with drying between each spraying, to coat the surface of the starch beads, giving different amounts of Eudragit L100-55 coating. Seven different kinds of beads, with different amounts of Eudragit L100-55 binding and coating agent, were obtained. The rates of release of D-glucose into water from the seven kinds of beads were inversely proportional to the amount of binding and coating agent. Bead type I, which was without any binding and coating gave a fast 100% release of D-glucose in 30 min. Beads II and III also gave a fast 100% release in 60 min and 90 min, respectively. Bead IV gave a near linear release of 97% D-glucose in 150 min; Bead V gave a 50% release in 120 min followed by the remaining 50% in 60 min; and Beads VI and VII gave a slow release of 10% and 4%, respectively, from 0 to 120 min, followed by a rapid 100% release from 120 to 180 min. (c) 2010 Elsevier Ltd. All rights reserved.

  11. A novel alginate-encapsulated system to study biological response to critical-sized wear particles of UHMWPE loaded with alendronate sodium.

    PubMed

    Liu, Yumei; Shi, Feng; Bo, Lin; Zhi, Wei; Weng, Jie; Qu, Shuxin

    2017-10-01

    The aim of this study was to develop a novel alginate-encapsulated system (Alg beads) to investigate the cell response to critical-sized wear particles of ultra-high molecular weight polyethylene loaded with alendronate sodium (UHMWPE-ALN), one of the most effective drugs to treat bone resorption in clinic. The extrusion method was used to prepare Alg beads encapsulating rat calvarial osteoblasts (RCOs) and critical-sized UHMWPE-ALN wear particles with spherical morphology and uniform size. The morphology, permeability and stability of Alg beads were characterized. The proliferation, ALP activity, cell apoptosis and distribution of live/dead RCOs co-cultured with wear particles in Alg beads were evaluated. RCOs and critical-sized UHMWPE-ALN wear particles distributed evenly and contacted efficiently in Alg beads. Alg beads were both permeable to trypsin and BSA, while the smaller the molecular was, the larger the diffuse was. The proliferation of RCOs in Alg beads increased with time, which indicated that Alg beads provided suitable conditions for cell culture. The long-term stability of Alg beads indicated the possibility for the longer time of co-cultured cells with wear particles. Critical-sized UHMWPE-ALN and UHMWPE wear particles both inhibited the proliferation and differentiation of RCOs, and induced the apoptosis of RCOs encapsulated in Alg beads. However, these effects could be significantly alleviated by the ALN released from the critical-sized UHMWPE-ALN wear particles. The present results suggested that this novel-developed co-culture system was feasible to evaluate the cell response to critical-sized UHMWPE-ALN wear particles for a longer time. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Operational parameters and their influence on particle-side mass transfer resistance in a packed bed bioreactor.

    PubMed

    Hussain, Amir; Kangwa, Martin; Yumnam, Nivedita; Fernandez-Lahore, Marcelo

    2015-12-01

    The influence of internal mass transfer on productivity as well as the performance of packed bed bioreactor was determined by varying a number of parameters; chitosan coating, flow rate, glucose concentration and particle size. Saccharomyces cerevisiae cells were immobilized in chitosan and non-chitosan coated alginate beads to demonstrate the effect on particle side mass transfer on substrate consumption time, lag phase and ethanol production. The results indicate that chitosan coating, beads size, glucose concentration and flow rate have a significant effect on lag phase duration. The duration of lag phase for different size of beads (0.8, 2 and 4 mm) decreases by increasing flow rate and by decreasing the size of beads. Moreover, longer lag phase were found at higher glucose medium concentration and also with chitosan coated beads. It was observed that by increasing flow rates; lag phase and glucose consumption time decreased. The reason is due to the reduction of external (fluid side) mass transfer as a result of increase in flow rate as glucose is easily transported to the surface of the beads. Varying the size of beads is an additional factor: as it reduces the internal (particle side) mass transfer by reducing the size of beads. The reason behind this is the distance for reactants to reach active site of catalyst (cells) and the thickness of fluid created layer around alginate beads is reduced. The optimum combination of parameters consisting of smaller beads size (0.8 mm), higher flow rate of 90 ml/min and glucose concentration of 10 g/l were found to be the maximum condition for ethanol production.

  13. Chemical and Colloidal Stability of Carboxylated Core-Shell Magnetite Nanoparticles Designed for Biomedical Applications

    PubMed Central

    Szekeres, Márta; Tóth, Ildikó Y.; Illés, Erzsébet; Hajdú, Angéla; Zupkó, István; Farkas, Katalin; Oszlánczi, Gábor; Tiszlavicz, László; Tombácz, Etelka

    2013-01-01

    Despite the large efforts to prepare super paramagnetic iron oxide nanoparticles (MNPs) for biomedical applications, the number of FDA or EMA approved formulations is few. It is not known commonly that the approved formulations in many instances have already been withdrawn or discontinued by the producers; at present, hardly any approved formulations are produced and marketed. Literature survey reveals that there is a lack for a commonly accepted physicochemical practice in designing and qualifying formulations before they enter in vitro and in vivo biological testing. Such a standard procedure would exclude inadequate formulations from clinical trials thus improving their outcome. Here we present a straightforward route to assess eligibility of carboxylated MNPs for biomedical tests applied for a series of our core-shell products, i.e., citric acid, gallic acid, poly(acrylic acid) and poly(acrylic acid-co-maleic acid) coated MNPs. The discussion is based on physicochemical studies (carboxylate adsorption/desorption, FTIR-ATR, iron dissolution, zeta potential, particle size, coagulation kinetics and magnetization measurements) and involves in vitro and in vivo tests. Our procedure can serve as an example to construct adequate physico-chemical selection strategies for preparation of other types of core-shell nanoparticles as well. PMID:23857054

  14. Flow-orthogonal bead oscillation in a microfluidic chip with a magnetic anisotropic flux-guide array.

    PubMed

    van Pelt, Stijn; Derks, Roy; Matteucci, Marco; Hansen, Mikkel Fougt; Dietzel, Andreas

    2011-04-01

    A new concept for the manipulation of superparamagnetic beads inside a microfluidic chip is presented in this paper. The concept allows for bead actuation orthogonal to the flow direction inside a microchannel. Basic manipulation functionalities were studied by means of finite element simulations and results were oval-shaped steady state oscillations with bead velocities up to 500 μm/s. The width of the trajectory could be controlled by prescribing external field rotation. Successful verification experiments were performed on a prototype chip fabricated with excimer laser ablation in polycarbonate and electroforming of nickel flux-guides. Bead velocities up to 450 μm/s were measured in a 75 μm wide channel. By prescribing the currents in the external quadrupole magnet, the shape of the bead trajectory could be controlled.

  15. Oxytetracycline removal from water by novel microbial embedding gel beads

    NASA Astrophysics Data System (ADS)

    Wu, Nan; Pan, Peng; Zeng, Ming; Wang, Wei; Xu, Chenshan; Zhang, Zongpeng; Liu, Xinyuan; Wang, Yichao

    2018-01-01

    As a common antibiotic in aquatic environment, excessive oxytetracycline (OTC) is urgent to be removed due to its great biological toxicity. Compared with the traditional activated sludge, microbial embedding can enhance the treating efficiency. In this study, novel microbial embedding gel beads were produced with the additional agent of cyclodextrin (CD). Results show that CD could increase the mass transfer of OTC into gel beads, possibly because of its strong affinity for organic matters. In terms of OTC biodegradation, gel beads with CD were comparable to gel beads without CD, while the former’s sucrose removal efficiency was higher than the latter. The biodegradation of OTC only occurred in the presence of sucrose. The respiration test also confirmed these findings. Overall, the produced novel gel beads modified with CD could improve the removal performance of OTC.

  16. Functional analysis of alpha5beta1 integrin and lipid rafts in invasion of epithelial cells by Porphyromonas gingivalis using fluorescent beads coated with bacterial membrane vesicles.

    PubMed

    Tsuda, Kayoko; Furuta, Nobumichi; Inaba, Hiroaki; Kawai, Shinji; Hanada, Kentaro; Yoshimori, Tamotsu; Amano, Atsuo

    2008-01-01

    Porphyromonas gingivalis, a periodontal pathogen, was previously suggested to exploit alpha5beta1 integrin and lipid rafts to invade host cells. However, it is unknown if the functional roles of these host components are distinct from one another during bacterial invasion. In the present study, we analyzed the mechanisms underlying P. gingivalis invasion, using fluorescent beads coated with bacterial membrane vesicles (MV beads). Cholesterol depletion reagents including methyl-beta-cyclodextrin (MbetaCD) drastically inhibited the entry of MV beads into epithelial cells, while they were less effective on bead adhesion to the cells. Bead entry was also abolished in CHO cells deficient in sphingolipids, components of lipid rafts, whereas adhesion was negligibly influenced. Following MbetaCD treatment, downstream events leading to actin polymerization were abolished; however, alpha5beta1 integrin was recruited to beads attached to the cell surface. Dominant-negative Rho GTPase Rac1 abolished cellular engulfment of the beads, whereas dominant-negative Cdc42 did not. Following cellular interaction with the beads, Rac1 was found to be translocated to the lipid rafts fraction, which was inhibited by MbetaCD. These results suggest that alpha5beta1 integrin, independent of lipid rafts, promotes P. gingivalis adhesion to epithelial cells, while the subsequent uptake process requires lipid raft components for actin organization, with Rho GTPase Rac1.

  17. Removal of phthalate esters from aqueous solutions by chitosan bead.

    PubMed

    Chen, Chih-Yu; Chung, Ying-Chien

    2006-01-01

    Removal of phthalate esters (PAEs) by chitosan bead in aqueous solution was studied. The adsorption isotherms of PAEs by chitosan bead were well described by Freundlich isotherm equations. Results of kinetic experiments indicated that diheptyl phthalate (DHpP) had the highest adsorption capacity (1.52 mg/g) among six PAEs in our research. PAE adsorption efficiency by chitosan bead was examined in both batch and continuous systems, and DHpP attained 74.9% recovery efficiency from chitosan bead by shaking with an equal volume mixture of methanol and water. The recovered chitosan bead was reusable as an adsorbent. The influences of temperature, pH, Ca+2, and NaCl on PAE adsorption were also evaluated to determine performance in different water environments (e.g., groundwater, surface water, and sea water). The results showed that PAE adsorption decreased as temperature increased. From pH experiments it appeared that pH 8.0 was optimal for adsorption. The effect of Ca+2 showed that adsorption efficiency did not change by increasing the concentrations of Ca+2 until 400 mg/L. NaCl coexistence showed an insignificant effect on PAE adsorption. Furthermore, the chitosan bead was also applied to treating the discharge of a plastics plant, and the treatment results resembled those of a laboratory continuous system. This is the first report to use chitosan bead as an adsorbent to adsorb phthalate esters from aqueous solution. These results indicate that the application of chitosan bead is feasible in the aqueous environments of Taiwan.

  18. Osteogenic differentiation of human mesenchymal stem cells in mineralized alginate matrices.

    PubMed

    Westhrin, Marita; Xie, Minli; Olderøy, Magnus Ø; Sikorski, Pawel; Strand, Berit L; Standal, Therese

    2015-01-01

    Mineralized biomaterials are promising for use in bone tissue engineering. Culturing osteogenic cells in such materials will potentially generate biological bone grafts that may even further augment bone healing. Here, we studied osteogenic differentiation of human mesenchymal stem cells (MSC) in an alginate hydrogel system where the cells were co-immobilized with alkaline phosphatase (ALP) for gradual mineralization of the microenvironment. MSC were embedded in unmodified alginate beads and alginate beads mineralized with ALP to generate a polymer/hydroxyapatite scaffold mimicking the composition of bone. The initial scaffold mineralization induced further mineralization of the beads with nanosized particles, and scanning electron micrographs demonstrated presence of collagen in the mineralized and unmineralized alginate beads cultured in osteogenic medium. Cells in both types of beads sustained high viability and metabolic activity for the duration of the study (21 days) as evaluated by live/dead staining and alamar blue assay. MSC in beads induced to differentiate in osteogenic direction expressed higher mRNA levels of osteoblast-specific genes (RUNX2, COL1AI, SP7, BGLAP) than MSC in traditional cell cultures. Furthermore, cells differentiated in beads expressed both sclerostin (SOST) and dental matrix protein-1 (DMP1), markers for late osteoblasts/osteocytes. In conclusion, Both ALP-modified and unmodified alginate beads provide an environment that enhance osteogenic differentiation compared with traditional 2D culture. Also, the ALP-modified alginate beads showed profound mineralization and thus have the potential to serve as a bone substitute in tissue engineering.

  19. In vitro evaluation of antibiotic diffusion from antibiotic-impregnated biodegradable beads and polymethylmethacrylate beads.

    PubMed Central

    Mader, J T; Calhoun, J; Cobos, J

    1997-01-01

    Antibiotic-impregnated beads are used in the dead bone space following debridement surgery to deliver local, high concentrations of antibiotics. Polymethylmethacrylate (PMMA), 2,000-molecular-weight (MW) polylactic acid (PLA), Poly(DL-lactide)-coglycolide (PL:CG; 90:10, 80:20, and 70:30), and the combination 2,000-MW PLA-70:20 PL:CG were individually mixed with clindamycin, tobramycin, or vancomycin. Beads were placed in 1 ml of phosphate-buffered saline (PBS) and incubated at 37 degrees C. The PBS was changed daily, and the removed PBS samples were stored at -70 degrees C until the antibiotic in each sample was determined by microbiological disk diffusion assay. Nondissolving PMMA beads with tobramycin and clindamycin had concentrations well above breakpoint sensitivity concentrations (i.e., the antibiotic concentrations at the transition point between bacterial killing and resistance to the antibiotic) for more than 90 days, but vancomycin concentrations dropped by day 12. ALl PLA, PL:CG, and the 2,000-MW PLA-70:30 PL:CG biodegradable beads release high concentrations of all the antibiotics in vitro for the period of time needed to treat bone infections (i.e., 4 to 8 weeks). Antibiotic-loaded PLA and PL:CG beads have the advantage of better antibiotic elution and the ability to biodegradable (thereby averting the need for secondary surgery for bead removal) compared to the PMMA beads presently used in the clinical setting. PMID:9021200

  20. Digital analysis of the expression levels of multiple colorectal cancer-related genes by multiplexed digital-PCR coupled with hydrogel bead-array.

    PubMed

    Qi, Zongtai; Ma, Yinjiao; Deng, Lili; Wu, Haiping; Zhou, Guohua; Kajiyama, Tomoharu; Kambara, Hideki

    2011-06-07

    To digitally analyze expression levels of multiple genes in one reaction, we proposed a method termed as 'MDHB' (Multiplexed Digital-PCR coupled with Hydrogel Bead-array). The template for bead-based emulsion PCR (emPCR) was prepared by reverse transcription using sequence-tagged primers. The beads recovered from emPCR were immobilized with hydrogel to form a single-bead layer on a chip, and then decoded by gene-specific probe hybridization and Cy3-dUTP based primer extension reaction. The specificity of probe hybridization was improved by using electrophoresis to remove mismatched probes on the bead's surface. The number of positive beads reflects the abundance of expressed genes; the expression levels of target genes were normalized to a housekeeping gene and expressed as the number ratio of green beads to red beads. The discrimination limit of MDHB is 0.1% (i.e., one target molecule from 1000 background molecules), and the sensitivity of the method is below 100 cells when using the β-actin gene as the detection target. We have successfully employed MDHB to detect the relative expression levels of four colorectal cancer (CRC)-related genes (c-myc, COX-2, MMP7, and DPEP1) in 8 tissue samples and 9 stool samples from CRC patients, giving the detection rates of 100% and 77%, respectively. The results suggest that MDHB could be a potential tool for early non-invasive diagnosis of CRC.

  1. Digital detection of multiple minority mutants and expression levels of multiple colorectal cancer-related genes using digital-PCR coupled with bead-array.

    PubMed

    Huang, Huan; Li, Shuo; Sun, Lizhou; Zhou, Guohua

    2015-01-01

    To simultaneously analyze mutations and expression levels of multiple genes on one detection platform, we proposed a method termed "multiplex ligation-dependent probe amplification-digital amplification coupled with hydrogel bead-array" (MLPA-DABA) and applied it to diagnose colorectal cancer (CRC). CRC cells and tissues were sampled to extract nucleic acid, perform MLPA with sequence-tagged probes, perform digital emulsion polymerase chain reaction (PCR), and produce a hydrogel bead-array to immobilize beads and form a single bead layer on the array. After hybridization with fluorescent probes, the number of colored beads, which reflects the abundance of expressed genes and the mutation rate, was counted for diagnosis. Only red or green beads occurred on the chips in the mixed samples, indicating the success of single-molecule PCR. When a one-source sample was analyzed using mixed MLPA probes, beads of only one color occurred, suggesting the high specificity of the method in analyzing CRC mutation and gene expression. In gene expression analysis of a CRC tissue from one CRC patient, the mutant percentage was 3.1%, and the expression levels of CRC-related genes were much higher than those of normal tissue. The highly sensitive MLPA-DABA succeeds in the relative quantification of mutations and gene expressions of exfoliated cells in stool samples of CRC patients on the same chip platform. MLPA-DABA coupled with hydrogel bead-array is a promising method in the non-invasive diagnosis of CRC.

  2. Osteogenic Differentiation of Human Mesenchymal Stem Cells in Mineralized Alginate Matrices

    PubMed Central

    Westhrin, Marita; Xie, Minli; Olderøy, Magnus Ø.; Sikorski, Pawel

    2015-01-01

    Mineralized biomaterials are promising for use in bone tissue engineering. Culturing osteogenic cells in such materials will potentially generate biological bone grafts that may even further augment bone healing. Here, we studied osteogenic differentiation of human mesenchymal stem cells (MSC) in an alginate hydrogel system where the cells were co-immobilized with alkaline phosphatase (ALP) for gradual mineralization of the microenvironment. MSC were embedded in unmodified alginate beads and alginate beads mineralized with ALP to generate a polymer/hydroxyapatite scaffold mimicking the composition of bone. The initial scaffold mineralization induced further mineralization of the beads with nanosized particles, and scanning electron micrographs demonstrated presence of collagen in the mineralized and unmineralized alginate beads cultured in osteogenic medium. Cells in both types of beads sustained high viability and metabolic activity for the duration of the study (21 days) as evaluated by live/dead staining and alamar blue assay. MSC in beads induced to differentiate in osteogenic direction expressed higher mRNA levels of osteoblast-specific genes (RUNX2, COL1AI, SP7, BGLAP) than MSC in traditional cell cultures. Furthermore, cells differentiated in beads expressed both sclerostin (SOST) and dental matrix protein-1 (DMP1), markers for late osteoblasts/osteocytes. In conclusion, Both ALP-modified and unmodified alginate beads provide an environment that enhance osteogenic differentiation compared with traditional 2D culture. Also, the ALP-modified alginate beads showed profound mineralization and thus have the potential to serve as a bone substitute in tissue engineering. PMID:25769043

  3. Chitosan Enriched Three-Dimensional Matrix Reduces Inflammatory and Catabolic Mediators Production by Human Chondrocytes

    PubMed Central

    Oprenyeszk, Frederic; Sanchez, Christelle; Dubuc, Jean-Emile; Maquet, Véronique; Henrist, Catherine; Compère, Philippe; Henrotin, Yves

    2015-01-01

    This in vitro study investigated the metabolism of human osteoarthritic (OA) chondrocytes encapsulated in a spherical matrix enriched of chitosan. Human OA chondrocytes were encapsulated and cultured for 28 days either in chitosan-alginate beads or in alginate beads. The beads were formed by slowly passing dropwise either the chitosan 0.6%–alginate 1.2% or the alginate 1.2% solution through a syringe into a 102 mM CaCl2 solution. Beads were analyzed histologically after 28 days. Interleukin (IL)-6 and -8, prostaglandin (PG) E2, matrix metalloproteinases (MMPs), hyaluronan and aggrecan were quantified directly in the culture supernatant by specific ELISA and nitric oxide (NO) by using a colorimetric method based on the Griess reaction. Hematoxylin and eosin staining showed that chitosan was homogeneously distributed through the matrix and was in direct contact with chondrocytes. The production of IL-6, IL-8 and MMP-3 by chondrocytes significantly decreased in chitosan-alginate beads compared to alginate beads. PGE2 and NO decreased also significantly but only during the first three days of culture. Hyaluronan and aggrecan production tended to increase in chitosan-alginate beads after 28 days of culture. Chitosan-alginate beads reduced the production of inflammatory and catabolic mediators by OA chondrocytes and tended to stimulate the synthesis of cartilage matrix components. These particular effects indicate that chitosan-alginate beads are an interesting scaffold for chondrocytes encapsulation before transplantation to repair cartilage defects. PMID:26020773

  4. Optical diamagnetic biosensor for immunocomplexes on beads

    NASA Astrophysics Data System (ADS)

    Norina, Svetlana B.

    2000-12-01

    In the present work, diamagnetic separation parameters for the porous beads are studied using optical video recording microscopy. The possible direct amount determination of single or double macromolecular layers immobilized in the meshes of the porous beads is demonstrated for the concentrations' range used in heterogenic immunotest and the affinity chromatography, where the direct rapid detection of ligands within sorbent particles is known to be the actual task. A gradient diamagnetic biosensor is described as suitable for rapid quantitative detection of single or double macromolecular layers in porous nonmagnetic beads. Measurements of capture traveling time or accumulation radius in gradient magnetic field have shown that it is possible to determine 0.20 mg/ml of macromolecular amount within several seconds. The portative devices were made on the base of the fabre optic technique to detect accumulation radius of collected beads in two gradient magnetic positions: diamagnetic and paramagnetic zones of magnetized wire with 55 μm in diameter and to registrate with a lot of fabre wires having 30 μm in diameters. The successive procedures of the present method can be described by: the obtaining of agarose immuno-beads, the incubation of beads with the ligand sample or the injection of sample through affinity mini-column, the submerging of the loaded beads into the glass cell containing Ni-wire or the narrow gap of magnetic poles; the computational obtaining of immuno- parameters; binding constants, accumulation radius. Several biotechnological applications of the biosensor are presented on sorbent beads, human lymphocytes.

  5. Role of cholesterol on the transfection barriers of cationic lipid/DNA complexes

    NASA Astrophysics Data System (ADS)

    Pozzi, Daniela; Cardarelli, Francesco; Salomone, Fabrizio; Marchini, Cristina; Amenitsch, Heinz; Barbera, Giorgia La; Caracciolo, Giulio

    2014-08-01

    Most lipid formulations need cholesterol for efficient transfection, but the precise motivation remains unclear. Here, we have investigated the effect of cholesterol on the transfection efficiency (TE) of cationic liposomes made of 1,2-dioleoyl-3-trimethylammonium-propane and dioleoylphosphocholine in Chinese hamster ovary cells. The transfection mechanisms of cholesterol-containing lipoplexes have been investigated by TE, synchrotron small angle X-ray scattering, and laser scanning confocal microscopy experiments. We prove that cholesterol-containing lipoplexes enter the cells using different endocytosis pathways. Formulations with high cholesterol content efficiently escape from endosomes and exhibit a lamellar-nonlamellar phase transition in mixture with biomembrane mimicking lipid formulations. This might explain both the DNA release ability and the high transfection efficiency. These studies highlight the enrichment in cholesterol as a decisive factor for transfection and will contribute to the rational design of lipid nanocarriers with superior TE.

  6. In vitro stability, potency, and dissolution of duloxetine enteric-coated pellets after exposure to applesauce, apple juice, and chocolate pudding.

    PubMed

    Wells, Kevin A; Losin, William G

    2008-07-01

    Difficulty swallowing is a common problem in the clinical setting, particularly in elderly patients, and can significantly affect an individual's ability to maintain a proper level of nutrition. The purpose of this in vitro study was to determine if mixing duloxetine enteric-coated pellets in food substances is an acceptable alternative method for administering this oral formulation to patients with swallowing difficulties. To determine whether administration in food substances with varying pH values (applesauce and apple juice, pH = approximately 3.5; chocolate pudding, pH = approximately 5.5-6.0) affects the enteric coating of the formulation, duloxetine pellets (ie, the contents of a 20-mg duloxetine capsule) were exposed to applesauce, apple juice, and chocolate pudding at room temperature and tested in triplicate for potency and impurities; for dissolution, 6 replicates were tested. To assess product stability and integrity of the enteric coating, potency, impurities, and dissolution tests of the pellets were conducted and compared with pellets not exposed to food. The duloxetine pellets were extracted from the food material using a solution of 0.1 normal (N) hydrochloric acid (HCl) prepared from concentrated HCl (commercially available) and deionized water. For the potency and impurities tests, a 40:60 solution of acetonitrile and pH 8.0 phosphate buffer was used as the sample solvent to extract the active pharmaceutical ingredient from the formulation to prepare the samples for testing. The amount of active pharmaceutical ingredient released (in vitro dissolution) from the pellets after exposure to the food substances was determined using 2 media solutions, 0.1 N HCl followed by pH 6.8 phosphate buffer. Applesauce and chocolate pudding were selected as vehicles for oral administration, while apple juice was intended to be used as a wash for a nasogastric tube. Mean (SD) potency results for the 20-mg capsule strength were 20.256 (0.066), 20.222 (0.163), and 19.961 (0.668) mg/capsule for the comparator not exposed to food, the sample exposed to applesauce, and the sample exposed to apple juice, respectively. However, exposure to chocolate pudding altered the integrity of the pellet's enteric coating (mean [SD] potency results, 17.780 [1.605] mg/capsule). Results of impurities testing suggested that none of the test foods caused significant degradation of the drug product. Mean dissolution results found that after 2 hours in 0.1 N HCl, < or = 1% of duloxetine was released from the comparator and pellets exposed to applesauce and apple juice. However, the mean dissolution profile of the sample exposed to pudding reported near-total release (90%) after 2 hours in 0.1 N HCl during the gastric challenge portion of the dissolution test. Results from this study found that the enteric coating of duloxetine pellets mixed with applesauce or apple juice was not negatively affected. The pellets were stable at room temperature for < or = 2 hours and should quantitatively allow delivery of the full capsule dose, provided that the pellet integrity is maintained (ie, not crushed, chewed, or otherwise broken). Therefore, mixing duloxetine pellets with applesauce or apple juice appears to be an acceptable vehicle for administration. However, exposing the pellets to chocolate pudding damaged the pellets' enteric coating, suggesting that pudding may be an unacceptable vehicle for administration.

  7. THE STUDENT AND CAMPUS CLIMATES OF LEARNING. NEW DIMENSIONS IN HIGHER EDUCATION, NUMBER 18.

    ERIC Educational Resources Information Center

    FREEDMAN, MERVIN B.

    CURRENT BELIEFS ABOUT THE EXTENT OF THE INFLUENCE OF COLLEGE EXPERIENCE WERE SURVEYED BY A REVIEW OF REPORTED RESEARCH. THE PRINCIPAL CONCLUSIONS FORMULATED BY THE AUTHOR FROM THE LITERATURE STUDIED WERE (1) THE OUTCOME OF COLLEGE EDUCATION IS LIKELY TO BE A COMPROMISE BETWEEN THE CHARACTERISTICS OF ENTERING FRESHMEN AND THE IDEALS OF LIBERAL…

  8. Preparation of Silk Sericin/Lignin Blend Beads for the Removal of Hexavalent Chromium Ions.

    PubMed

    Kwak, Hyo Won; Shin, Munju; Yun, Haesung; Lee, Ki Hoon

    2016-09-02

    In the present study, novel adsorbents having high adsorption capability and reusability were prepared using agricultural by-products: silk sericin and lignin. Silk sericin and lignin blend beads were successfully prepared using simple coagulation methods for the removal of hexavalent chromium (Cr(VI)) from aqueous solution. A 1 M lithium chloride (LiCl)/dimethyl sulfoxide (DMSO) solvent system successfully dissolved both sericin and lignin and had sufficient viscosity for bead preparation. Compared to the conventional sericin bead adsorbent, sericin/lignin blend beads showed higher Cr(VI) adsorption capacity. The amount of lignin added to the adsorbent greatly affected the adsorption capacity of the beads, and a 50:50 sericin/lignin blend ratio was optimal. Adsorption behavior followed the Freundlich isotherm, which means the adsorption of Cr(VI) occurred on the heterogeneous surface. Cr(VI) adsorption capability increased with temperature because of thermodynamic-kinetic effects. In addition, over 90% of Cr(VI) ions were recovered from the Cr(VI) adsorbed sericin/lignin beads in a 1 M NaOH solution. The adsorption-desorption recycling process was stable for more than seven cycles, and the recycling efficiency was 82%. It is expected that the sericin/lignin beads could be successfully applied in wastewater remediation especially for hazardous Cr(VI) ions in industrial wastewater.

  9. Preparation of Silk Sericin/Lignin Blend Beads for the Removal of Hexavalent Chromium Ions

    PubMed Central

    Kwak, Hyo Won; Shin, Munju; Yun, Haesung; Lee, Ki Hoon

    2016-01-01

    In the present study, novel adsorbents having high adsorption capability and reusability were prepared using agricultural by-products: silk sericin and lignin. Silk sericin and lignin blend beads were successfully prepared using simple coagulation methods for the removal of hexavalent chromium (Cr(VI)) from aqueous solution. A 1 M lithium chloride (LiCl)/dimethyl sulfoxide (DMSO) solvent system successfully dissolved both sericin and lignin and had sufficient viscosity for bead preparation. Compared to the conventional sericin bead adsorbent, sericin/lignin blend beads showed higher Cr(VI) adsorption capacity. The amount of lignin added to the adsorbent greatly affected the adsorption capacity of the beads, and a 50:50 sericin/lignin blend ratio was optimal. Adsorption behavior followed the Freundlich isotherm, which means the adsorption of Cr(VI) occurred on the heterogeneous surface. Cr(VI) adsorption capability increased with temperature because of thermodynamic-kinetic effects. In addition, over 90% of Cr(VI) ions were recovered from the Cr(VI) adsorbed sericin/lignin beads in a 1 M NaOH solution. The adsorption-desorption recycling process was stable for more than seven cycles, and the recycling efficiency was 82%. It is expected that the sericin/lignin beads could be successfully applied in wastewater remediation especially for hazardous Cr(VI) ions in industrial wastewater. PMID:27598142

  10. Transfer of Fas (CD95) protein from the cell surface to the surface of polystyrene beads coated with anti-Fas antibody clone CH-11

    PubMed Central

    Sawai, H.; Domae, N.

    2010-01-01

    Mouse monoclonal anti-Fas (CD95) antibody clone CH-11 has been widely used in research on apoptosis. CH-11 has the ability to bind to Fas protein on cell surface and induce apoptosis. Here, we used polystyrene beads coated with CH-11 to investigate the role of lipid rafts in Fas-mediated apoptosis in SKW6.4 cells. Unexpectedly, by treatment of the cells with CH-11-coated beads Fas protein was detached from cell surface and transferred to the surface of CH-11-coated beads. Western blot analysis showed that Fas protein containing both extracellular and intracellular domains was attached to the beads. Fas protein was not transferred from the cells to the surface of the beads coated with other anti-Fas antibodies or Fas ligand. Similar phenomenon was observed in Jurkat T cells. Furthermore, CH-11-induced apoptosis was suppressed by pretreatment with CH-11-coated beads in Jurkat cells. These results suggest that CH-11 might possess distinct properties on Fas protein compared with other anti-Fas antibodies or Fas ligand, and also suggest that caution should be needed to use polystyrene beads coated with antibodies such as CH-11. PMID:20353915

  11. Quality assurance for sperm concentration using latex beads.

    PubMed

    Peters, A J; Zaneveld, L J; Jeyendran, R S

    1993-10-01

    To provide a simple, universally applicable method of quality assurance for sperm counting, thereby reducing intercounting chamber variation. By using a known concentration of latex beads, the sperm:bead ratio can be used to calculate the actual sperm count. The mean sperm and bead counts were determined in both a Spot-lite hemocytometer (Baxter Diagnostics, McGaw Park, IL) and a Makler chamber (Polymedco Inc., Yorktown, NY) from 21 different ejaculates mixed with a known concentration of beads. The hemocytometer chamber was used as the standard counting chamber because it consistently yielded a low variation in sperm count. The adjusted sperm concentration of the Makler chamber was calculated using the following formula [hemocytometer beads]/[Makler beads] x [Makler sperm]. Observed mean +/- SD sperm counts were significantly different between the hemocytometer chamber (110.6 +/- 66.2 x 10(6)/mL) and Makler chamber (173.3 +/- 103.5 x 10(6)/mL). However, calculated Makler chamber sperm counts (118.1 +/- 76.1 x 10(6)/mL) was not statistically different from observed hemocytometer sperm counts. This novel approach to sperm counting using a known concentration of latex beads as a reference material can be used to reduce variation in sperm counting between observers, counting chambers, and possibly computerized sperm analyzers.

  12. Impact of Microplastic Beads and Fibers on Waterflea (Ceriodaphnia dubia) Survival, Growth, and Reproduction: Implications of Single and Mixture Exposures.

    PubMed

    Ziajahromi, Shima; Kumar, Anupama; Neale, Peta A; Leusch, Frederic D L

    2017-11-21

    There is limited knowledge regarding the adverse effects of wastewater-derived microplastics, particularly fibers, on aquatic biota. In this study, we examined the acute (48 h) and chronic (8 d) effects of microplastic polyester fibers and polyethylene (PE) beads on freshwater zooplankton Ceriodaphnia dubia. We also assessed the acute response of C. dubia to a binary mixture of microplastic beads and fibers for the first time. Acute exposure to fibers and PE beads both showed a dose-dependent effect on survival. An equitoxic binary mixture of beads and fibers resulted in a toxic unit of 1.85 indicating less than additive effects. Chronic exposure to lower concentrations did not significantly affect survival of C. dubia, but a dose-dependent effect on growth and reproduction was observed. Fibers showed greater adverse effects than PE beads. While ingestion of fibers was not observed, scanning electron microscopy showed carapace and antenna deformities after exposure to fibers, with no deformities observed after exposure to PE beads. While much of the current research has focused on microplastic beads, our study shows that microplastic fibers pose a greater risk to C. dubia, with reduced reproductive output observed at concentrations within an order of magnitude of reported environmental levels.

  13. Alginate and Algal-Based Beads for the Sorption of Metal Cations: Cu(II) and Pb(II)

    PubMed Central

    Wang, Shengye; Vincent, Thierry; Faur, Catherine; Guibal, Eric

    2016-01-01

    Alginate and algal-biomass (Laminaria digitata) beads were prepared by homogeneous Ca ionotropic gelation. In addition, glutaraldehyde-crosslinked poly (ethyleneimine) (PEI) was incorporated into algal beads. The three sorbents were characterized by scanning electron microscopy (SEM) coupled with energy dispersive X-ray analysis (EDX): the sorption occurs in the whole mass of the sorbents. Sorption experiments were conducted to evaluate the impact of pH, sorption isotherms, and uptake kinetics. A special attention was paid to the effect of drying (air-drying vs. freeze-drying) on the mass transfer properties. For alginate, freeze drying is required for maintaining the porosity of the hydrogel, while for algal-based sorbents the swelling of the material minimizes the impact of the drying procedure. The maximum sorption capacities observed from experiments were 415, 296 and 218 mg Pb g−1 and 112, 77 and 67 mg Cu g−1 for alginate, algal and algal/PEI beads respectively. Though the sorption capacities of algal-beads decreased slightly (compared to alginate beads), the greener and cheaper one-pot synthesis of algal beads makes this sorbent more competitive for environmental applications. PEI in algal beads decreases the sorption properties in the case of the sorption of metal cations under selected experimental conditions. PMID:27598128

  14. On-bead antibody-small molecule conjugation using high-capacity magnetic beads.

    PubMed

    Nath, Nidhi; Godat, Becky; Benink, Hélène; Urh, Marjeta

    2015-11-01

    Antibodies labeled with small molecules such as fluorophore, biotin or drugs play an important role in various areas of biological research, drug discovery and diagnostics. However, the majority of current methods for labeling antibodies is solution-based and has several limitations including the need for purified antibodies at high concentrations and multiple buffer exchange steps. In this study, a method (on-bead conjugation) is described that addresses these limitations by combining antibody purification and conjugation in a single workflow. This method uses high capacity-magnetic Protein A or Protein G beads to capture antibodies directly from cell media followed by conjugation with small molecules and elution of conjugated antibodies from the beads. High-capacity magnetic antibody capture beads are key to this method and were developed by combining porous and hydrophilic cellulose beads with oriented immobilization of Protein A and Protein G using HaloTag technology. With a variety of fluorophores it is shown that the on-bead conjugation method is compatible with both thiol- and amine-based chemistry. This method enables simple and rapid processing of multiple samples in parallel with high-efficiency antibody recovery. It is further shown that recovered antibodies are functional and compatible with downstream applications. Copyright © 2015. Published by Elsevier B.V.

  15. Nanoparticle flotation collectors: mechanisms behind a new technology.

    PubMed

    Yang, Songtao; Pelton, Robert; Raegen, Adam; Montgomery, Miles; Dalnoki-Veress, Kari

    2011-09-06

    This is the first report describing a new technology where hydrophobic nanoparticles adsorb onto much larger, hydrophilic mineral particle surfaces to facilitate attachment to air bubbles in flotation. The adsorption of 46 nm cationic polystyrene nanoparticles onto 43 μm diameter glass beads, a mineral model, facilitates virtually complete removal of the beads by flotation. As little as 5% coverage of the bead surfaces with nanoparticles promotes high flotation efficiencies. The maximum force required to pull a glass bead from an air bubble interface into the aqueous phase was measured by micromechanics. The pull-off force was 1.9 μN for glass beads coated with nanoparticles, compared to 0.0086 μN for clean beads. The pull-off forces were modeled using Scheludko's classical expression. We propose that the bubble/bead contact area may not be dry (completely dewetted). Instead, for hydrophobic nanoparticles sitting on a hydrophilic surface, it is possible that only the nanoparticles penetrate the air/water interface to form a three-phase contact line. We present a new model for pull-off forces for such a wet contact patch between the bead and the air bubble. Contact angle measurements of both nanoparticle coated glass and smooth films from dissolved nanoparticles were performed to support the modeling. © 2011 American Chemical Society

  16. BeadArray Expression Analysis Using Bioconductor

    PubMed Central

    Ritchie, Matthew E.; Dunning, Mark J.; Smith, Mike L.; Shi, Wei; Lynch, Andy G.

    2011-01-01

    Illumina whole-genome expression BeadArrays are a popular choice in gene profiling studies. Aside from the vendor-provided software tools for analyzing BeadArray expression data (GenomeStudio/BeadStudio), there exists a comprehensive set of open-source analysis tools in the Bioconductor project, many of which have been tailored to exploit the unique properties of this platform. In this article, we explore a number of these software packages and demonstrate how to perform a complete analysis of BeadArray data in various formats. The key steps of importing data, performing quality assessments, preprocessing, and annotation in the common setting of assessing differential expression in designed experiments will be covered. PMID:22144879

  17. Development and evaluation of spherical molecularly imprinted polymer beads.

    PubMed

    Kempe, Henrik; Kempe, Maria

    2006-06-01

    The majority of studies on molecularly imprinted polymers has until now been carried out on irregularly shaped particles prepared by grinding of polymer monoliths. The preparation procedures are time- and labor-consuming and produce particles of wide size distributions. To answer the need for fast and straightforward routes to spherical molecularly imprinted polymer beads, we have developed a method comprising the formation of droplets of pre-polymerization solution directly in mineral oil by vigorous mixing followed by transformation of the droplets into solid spherical beads by photoinduced free-radical polymerization. No detergents or stabilizers were required for the droplet formation. Factors influencing the bead synthesis have been investigated and are detailed here. The beads were evaluated in parallel with corresponding irregularly shaped particles prepared from polymer monoliths. Conditions for the synthesis of propranolol-imprinted poly(methacrylic acid-co-trimethylolpropane trimethacrylate) beads in the size range of 1-100 microm in almost quantitative yield are described. The beads were applied as the recognition element in a 96-well plate format radioligand assay of propranolol in human serum.

  18. Two-bead polarizable water models combined with a two-bead multipole force field (TMFF) for coarse-grained simulation of proteins.

    PubMed

    Li, Min; Zhang, John Z H

    2017-03-08

    The development of polarizable water models at coarse-grained (CG) levels is of much importance to CG molecular dynamics simulations of large biomolecular systems. In this work, we combined the newly developed two-bead multipole force field (TMFF) for proteins with the two-bead polarizable water models to carry out CG molecular dynamics simulations for benchmark proteins. In our simulations, two different two-bead polarizable water models are employed, the RTPW model representing five water molecules by Riniker et al. and the LTPW model representing four water molecules. The LTPW model is developed in this study based on the Martini three-bead polarizable water model. Our simulation results showed that the combination of TMFF with the LTPW model significantly stabilizes the protein's native structure in CG simulations, while the use of the RTPW model gives better agreement with all-atom simulations in predicting the residue-level fluctuation dynamics. Overall, the TMFF coupled with the two-bead polarizable water models enables one to perform an efficient and reliable CG dynamics study of the structural and functional properties of large biomolecules.

  19. Insights on novel particulate self-assembled drug delivery beads based on partial inclusion complexes between triglycerides and cyclodextrins.

    PubMed

    Aburahma, Mona Hassan

    2016-09-01

    Most of the newly designed drug molecules are lipophilic in nature and often encounter erratic absorption and low bioavailability after oral administration. Finding ways to enhance the absorption and bioavailability of these lipophilic drugs is one of the major challenges that face pharmaceutical industry nowadays. In view of that, the purpose of this review is to shed some light on a novel particulate self-assembling system named "beads" than can act as a safe carrier for delivering lipophilic drugs. The beads are prepared simply by mixing oils with cyclodextrin (CD) aqueous solution in mild conditions. A unique interaction between oil components and CD molecules occurs to form in situ surface-active complexes which are prerequisites for beads formation. This review mainly focuses on the fundamentals of beads preparation through reviewing present, yet scarce, literature. The key methods used for beads characterization are discussed in details. Also, the potential mechanisms by which beads increase the bioavailability of lipophilic drugs are illustrated. Finally, the related research areas that needs to be addressed in future for optimizing this promising delivery system are briefly outlined.

  20. Dynamic trajectory analysis of superparamagnetic beads driven by on-chip micromagnets

    PubMed Central

    Abedini-Nassab, Roozbeh; Lim, Byeonghwa; Yang, Ye; Howdyshell, Marci; Sooryakumar, Ratnasingham; Yellen, Benjamin B.

    2015-01-01

    We investigate the non-linear dynamics of superparamagnetic beads moving around the periphery of patterned magnetic disks in the presence of an in-plane rotating magnetic field. Three different dynamical regimes are observed in experiments, including (1) phase-locked motion at low driving frequencies, (2) phase-slipping motion above the first critical frequency fc1, and (3) phase-insulated motion above the second critical frequency fc2. Experiments with Janus particles were used to confirm that the beads move by sliding rather than rolling. The rest of the experiments were conducted on spherical, isotropic magnetic beads, in which automated particle position tracking algorithms were used to analyze the bead dynamics. Experimental results in the phase-locked and phase-slipping regimes correlate well with numerical simulations. Additional assumptions are required to predict the onset of the phase-insulated regime, in which the beads are trapped in closed orbits; however, the origin of the phase-insulated state appears to result from local magnetization defects. These results indicate that these three dynamical states are universal properties of bead motion in non-uniform oscillators. PMID:26648596

  1. Water dynamics in the digestive tract of the freshwater rainbow trout during the processing of a single meal.

    PubMed

    Bucking, Carol; Wood, Chris M

    2006-05-01

    The temporal effects of feeding and digestion on chyme composition, specifically water and solid content, and net fluxes across the gastrointestinal tract, as well as plasma parameters, were examined in freshwater rainbow trout. A single meal of commercial dry pellets, incorporating ballotini beads as inert reference markers, was employed. Plasma Na+ levels increased by 15-20% at 2 h post-feeding, where Cl- levels did not change. Plasma osmolality was well regulated despite an initial chyme osmolality (775 mOsm) 2.8-fold higher than that in the blood plasma. Chyme osmolality throughout the gastrointestinal tract remained significantly higher than plasma osmolality for the duration of the 72 h period. Solid material was absorbed along the entire intestinal tract, although not in the stomach, necessitating the incorporation of an inert marker. A similar temporal pattern of transit between the ballotini beads (solid phase marker) and 3[H]-PEG 4000 (fluid phase marker), provided support for the use of ballotini beads. Large additions of water to the chyme were seen in the stomach, the largest occurring within 2 h following feeding (7.1+/-1.4 ml kg(-1)), and amounted to approximately 16 ml kg(-1) over the first 12 h. As the chyme entered the anterior intestine, a further large water secretion (3.5+/-0.5 ml kg(-1)) was seen. Thereafter the water fluxes into the chyme of the anterior intestine decreased steadily over time, but remained positive, whereas the mid-intestine exhibited net absorption of water at all time points, and the posterior intestine demonstrated little water handling at any time. The endogenous water that was secreted into the anterior intestine was absorbed along the tract, which showed a net water flux close to zero. However, assuming that the water secreted into the stomach was endogenous in nature, the processing of a single meal resulted in net loss of endogenous water (0.24 ml kg(-1) h(-1)) to the environment, a beneficial consequence of the osmotic challenge offered by the food for a freshwater hyperosmotic regulator.

  2. Calibration beads containing luminescent lanthanide ion complexes

    EPA Science Inventory

    The reliability of lanthanide luminescence measurements, by both flow cytometry and digital microscopy, will be enhanced by the availability of narrow-band emitting lanthanide calibration beads. These beads can also be used to characterize spectrographic instruments, including mi...

  3. Observation and Kinematic Description of Long Actin Tracks Induced by Spherical Beads

    PubMed Central

    Kang, Hyeran; Perlmutter, David S.; Shenoy, Vivek B.; Tang, Jay X.

    2010-01-01

    We report an in vitro study comparing the growth of long actin tails induced by spherical beads coated with the verprolin central acidic domain of the polymerization enzyme N-WASP to that induced by Listeria monocytogenes in similar cellular extracts. The tracks behind the beads show characteristic differences in shape and curvature from those left by the bacteria, which have an elongated shape and a similar polymerization-inducing enzyme distributed only on the rear surface of the cell. The experimental tracks are simulated using a generalized kinematic model, which incorporates three modes of bead rotation with respect to the tail. The results show that the trajectories of spherical beads are mechanically deterministic rather than random, as suggested by stochastic models. Assessment of the bead rotation and its mechanistic basis offers insights into the biological function of actin-based motility. PMID:21044576

  4. Hollow polydimethylsiloxane beads with a porous structure for cell encapsulation.

    PubMed

    Oh, Myeong-Jin; Ryu, Tae-Kyoung; Choi, S-W

    2013-11-01

    Based on a water-in-oil-in-water emulsion system, porous and hollow polydimethylsiloxane (PDMS) beads containing cells using a simple fluidic device with three flow channels are fabricated. Poly(ethylene glycol) (PEG) in the PDMS oil phase is served as a porogen for pore development. The feasibility of the porous PDMS beads prepared with different PEG concentrations (10, 20, and 30 wt%) for cell encapsulation in terms of pore size, protein diffusion, and cell proliferation inside the PDMS beads is evaluated. The PDMS beads prepared with PEG 30 wt% are exhibited a highly porous structure and facilitated fast diffusion of protein from the core domain to the outer phase, eventually leading to enhanced cell proliferation. The results clearly indicate that hollow PDMS beads with a porous structure could provide a favorable microenvironment for cell survival due to the large porous structure. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Microinjection - a tool to study gravitropism

    NASA Astrophysics Data System (ADS)

    Scherp, P.; Hasenstein, K. H.

    2003-05-01

    Despite extensive studies on plant gravitropism this phenomenon is still poorly understood. The separation of gravity sensing, signal transduction and response is a common concept but especially the mechanism of gravisensing remains unclear. This paper focuses on microinjection as powerful tool to investigate gravisensing in plants. We describe the microinjection of magnetic beads in rhizoids of the green alga Chara and related subsequent manipulation of the gravisensing system. After injection, an external magnet can control the movement of the magnetic beads. We demonstrate successful injection of magnetic beads into rhizoids and describe a multitude of experiments that can be carried out to investigate gravitropism in Chara rhizoids. In addition to examining mechanical properties, bead microinjection is also useful for probing the function of the cytoskeleton by coating beads with drugs that interfere with the cytoskeleton. The injection of fluorescently labeled beads or probes may reveal the involvement of the cytoskeleton during gravistimulation and response in living cells.

  6. Increased Growth of the Microalga Chlorella vulgaris when Coimmobilized and Cocultured in Alginate Beads with the Plant-Growth-Promoting Bacterium Azospirillum brasilense†

    PubMed Central

    Gonzalez, Luz E.; Bashan, Yoav

    2000-01-01

    Coimmobilization of the freshwater microalga Chlorella vulgaris and the plant-growth-promoting bacterium Azospirillum brasilense in small alginate beads resulted in a significantly increased growth of the microalga. Dry and fresh weight, total number of cells, size of the microalgal clusters (colonies) within the bead, number of microalgal cells per cluster, and the levels of microalgal pigments significantly increased. Light microscopy revealed that both microorganisms colonized the same cavities inside the beads, though the microalgae tended to concentrate in the more aerated periphery while the bacteria colonized the entire bead. The effect of indole-3-acetic acid addition to microalgal culture prior to immobilization of microorganisms in alginate beads partially imitated the effect of A. brasilense. We propose that coimmobilization of microalgae and plant-growth-promoting bacteria is an effective means of increasing microalgal populations within confined environments. PMID:10742237

  7. An integrated microfluidic cell for detection, manipulation, and sorting of single micron-sized magnetic beads

    NASA Astrophysics Data System (ADS)

    Jiang, Z.; Llandro, J.; Mitrelias, T.; Bland, J. A. C.

    2006-04-01

    A lab-on-a-chip integrated microfluidic cell has been developed for magnetic biosensing, which is comprised of anisotropic magnetoresistance (AMR) sensors optimized for the detection of single magnetic beads and electrodes to manipulate and sort the beads, integrated into a microfluidic channel. The device is designed to read out the real-time signal from 9 μm diameter magnetic beads moving over AMR sensors patterned into 18×4.5 μm rectangles and 10 μm diameter rings and arranged in Wheatstone bridges. The beads are moved over the sensors along a 75×75 μm wide channel patterned in SU8. Beads of different magnetic moments can be sorted through a magnetostatic sorting gate into different branches of the microfluidic channel using a magnetic field gradient applied by lithographically defined 120 nm thick Cu striplines carrying 0.2 A current.

  8. Development of modified release 3D printed tablets (printlets) with pharmaceutical excipients using additive manufacturing.

    PubMed

    Goyanes, Alvaro; Fina, Fabrizio; Martorana, Annalisa; Sedough, Daniel; Gaisford, Simon; Basit, Abdul W

    2017-07-15

    The aim of this study was to manufacture 3D printed tablets (printlets) from enteric polymers by single filament fused deposition modeling (FDM) 3D printing (3DP). Hot melt extrusion was used to generate paracetamol-loaded filaments from three different grades of the pharmaceutical excipient hypromellose acetate succinate (HPMCAS), grades LG, MG and HG. One-step 3DP was used to process these filaments into enteric printlets incorporating up to 50% drug loading with two different infill percentages (20 and 100%). X-ray Micro Computed Tomography (Micro-CT) analysis revealed that printlets with 20% infill had cavities in the core compared to 100% infill, and that the density of the 50% drug loading printlets was higher than the equivalent formulations loaded with 5% drug. In biorelevant bicarbonate dissolution media, drug release from the printlets was dependent on the polymer composition, drug loading and the internal structure of the formulations. All HPMCAS-based printlets showed delayed drug release properties, and in the intestinal conditions, drug release was faster from the printlets prepared with polymers with a lower pH-threshold: HPMCAS LG > HPMCAS MG > HPMCAS HG. These results confirm that FDM 3D printing makes it possible not only to manufacture delayed release printlets without the need for an outer enteric coating, but it is also feasible to adapt the release profile in response to the personal characteristics of the patient, realizing the full potential of additive manufacturing in the development of personalised dose medicines. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Real option valuation of a decremental regulation service provided by electricity storage.

    PubMed

    Szabó, Dávid Zoltán; Martyr, Randall

    2017-08-13

    This paper is a quantitative study of a reserve contract for real-time balancing of a power system. Under this contract, the owner of a storage device, such as a battery, helps smooth fluctuations in electricity demand and supply by using the device to increase electricity consumption. The battery owner must be able to provide immediate physical cover, and should therefore have sufficient storage available in the battery before entering the contract. Accordingly, the following problem can be formulated for the battery owner: determine the optimal time to enter the contract and, if necessary, the optimal time to discharge electricity before entering the contract. This problem is formulated as one of optimal stopping, and is solved explicitly in terms of the model parameters and instantaneous values of the power system imbalance. The optimal operational strategies thus obtained ensure that the battery owner has positive expected economic profit from the contract. Furthermore, they provide explicit conditions under which the optimal discharge time is consistent with the overall objective of power system balancing. This paper also carries out a preliminary investigation of the 'lifetime value' aggregated from an infinite sequence of these balancing reserve contracts. This lifetime value, which can be viewed as a single project valuation of the battery, is shown to be positive and bounded. Therefore, in the long run such reserve contracts can be beneficial to commercial operators of electricity storage, while reducing some of the financial and operational risks in power system balancing.This article is part of the themed issue 'Energy management: flexibility, risk and optimization'. © 2017 The Author(s).

  10. Delayed release film coating applications on oral solid dosage forms of proton pump inhibitors: case studies.

    PubMed

    Missaghi, Shahrzad; Young, Cara; Fegely, Kurt; Rajabi-Siahboomi, Ali R

    2010-02-01

    Formulation of proton pump inhibitors (PPIs) into oral solid dosage forms is challenging because the drug molecules are acid-labile. The aim of this study is to evaluate different formulation strategies (monolithic and multiparticulates) for three PPI drugs, that is, rabeprazole sodium, lansoprazole, and esomeprazole magnesium, using delayed release film coating applications. The core tablets of rabeprazole sodium were prepared using organic wet granulation method. Multiparticulates of lansoprazole and esomeprazole magnesium were prepared through drug layering of sugar spheres, using powder layering and suspension layering methods, respectively. Tablets and drug-layered multiparticulates were seal-coated, followed by delayed release film coating application, using Acryl-EZE(R), aqueous acrylic enteric system. Multiparticulates were then filled into capsules. The final dosage forms were evaluated for physical properties, as well as in vitro dissolution testing in both compendial acid phase, 0.1N HCl (pH 1.2), and intermediate pH, acetate buffer (pH 4.5), followed by phosphate buffer, pH 6.8. The stability of the delayed release dosage forms was evaluated upon storage in accelerated conditions [40 degrees C/75% relative humidity] for 3 months. All dosage forms demonstrated excellent enteric protection in the acid phase, followed by rapid release in their respective buffer media. Moreover, the delayed release dosage forms remained stable under accelerated stability conditions for 3 months. Results showed that Acryl-EZE enteric coating systems provide excellent performance in both media (0.1N HCl and acetate buffer pH 4.5) for monolithic and multiparticulate dosage forms.

  11. Treating inertia in passive microbead rheology.

    PubMed

    Indei, Tsutomu; Schieber, Jay D; Córdoba, Andrés; Pilyugina, Ekaterina

    2012-02-01

    The dynamic modulus G(*) of a viscoelastic medium is often measured by following the trajectory of a small bead subject to Brownian motion in a method called "passive microbead rheology." This equivalence between the positional autocorrelation function of the tracer bead and G(*) is assumed via the generalized Stokes-Einstein relation (GSER). However, inertia of both bead and medium are neglected in the GSER so that the analysis based on the GSER is not valid at high frequency where inertia is important. In this paper we show how to treat both contributions to inertia properly in one-bead passive microrheological analysis. A Maxwell fluid is studied as the simplest example of a viscoelastic fluid to resolve some apparent paradoxes of eliminating inertia. In the original GSER, the mean-square displacement (MSD) of the tracer bead does not satisfy the correct initial condition. If bead inertia is considered, the proper initial condition is realized, thereby indicating an importance of including inertia, but the MSD oscillates at a time regime smaller than the relaxation time of the fluid. This behavior is rather different from the original result of the GSER and what is observed. What is more, the discrepancy from the GSER result becomes worse with decreasing bead mass, and there is an anomalous gap between the MSD derived by naïvely taking the zero-mass limit in the equation of motion and the MSD for finite bead mass as indicated by McKinley et al. [J. Rheol. 53, 1487 (2009)]. In this paper we show what is necessary to take the zero-mass limit of the bead safely and correctly without causing either the inertial oscillation or the anomalous gap, while obtaining the proper initial condition. The presence of a very small purely viscous element can be used to eliminate bead inertia safely once included in the GSER. We also show that if the medium contains relaxation times outside the window where the single-mode Maxwell behavior is observed, the oscillation can be attenuated inside the window. This attenuation is realized even in the absence of a purely viscous element. Finally, fluid inertia also affects the bead autocorrelation through the Basset force and the fluid dragged around with the bead. We show that the Basset force plays the same role as the purely viscous element in high-frequency regime, and the oscillation of MSD is suppressed if fluid density and bead density are comparable. © 2012 American Physical Society

  12. Microcinematographic analysis of tethered Leptospira illini.

    PubMed Central

    Charon, N W; Daughtry, G R; McCuskey, R S; Franz, G N

    1984-01-01

    A model of Leptospira motility was recently proposed. One element of the model states that in translating cells the anterior spiral-shaped end gyrates counterclockwise and the posterior hook-shaped end gyrates clockwise. We tested these predictions by analyzing cells tethered to a glass surface. Leptospira illini was incubated with antibody-coated latex beads (Ab-beads). These beads adhered to the cells, and subsequently some cells became attached to either the slide or the cover glass via the Ab-beads. As previously reported, these cells rapidly moved back and forth across the surface of the beads. In addition, a general trend was observed: cells tethered to the cover glass rotated clockwise around the Ab-bead; cells tethered to the slide rotated counterclockwise around the Ab-bead. A computer-aided microcinematographic analysis of tethered cells indicated that the direction of rotation of cells around the Ab-bead was a function of both the surface of attachment and the shape of the cell ends. The results can best be explained by assuming that the gyrating ends interact with the glass surface to cause rotation around the Ab-beads. The analysis obtained indicates that the hook- and spiral-shaped ends rotate in the directions predicted by the model. In addition, the tethered cell assay permitted detection of rapid, coordinated reversals of the cell ends, e.g., cells rapidly switched from a hook-spiral configuration to a spiral-hook configuration. These results suggest the existance of a mechanism which coordinates the shape of the cell ends of L. illini. Images PMID:6501226

  13. Sorption Properties of Aerogel in Liquid Nitrogen

    NASA Technical Reports Server (NTRS)

    Johnson, Wesley L.

    2006-01-01

    Aerogel products are now available as insulation materials of the future. The Cryogenics Test Laboratory at the NASA Kennedy Space Center is developing aerogel-based thermal insulation systems for space launch applications. Aerogel beads (Cabot Nanogel ) and aerogel blankets (Aspen Aerogels Spaceloft ) have outstanding ambient pressure thermal performance that makes them useful for applications where sealing is not possible. Aerogel beads are open-celled silicone dioxide and have tiny pores that run throughout the body of the bead. It has also recently been discovered that aerogel beads can be used as a filtering device for aqueous compounds at room temperature. With their hydrophobic covering, the beads absorb any non-polar substance and they can be chemically altered to absorb hot gases. The combination of the absorption and cryogenic insulating properties of aerogel beads have never been studied together. For future cryogenic insulation applications, it is crucial to know how the beads react while immersed in cryogenic liquids, most notably liquid nitrogen. Aerogel beads in loose-fill situation and aerogel blankets with composite fiber structure have been tested for absorption properties. Depending on the type of aerogel used and the preparation, preliminary results show the material can absorb up to seven times its own weight of liquid nitrogen, corresponding to a volumetric ratio of 0.70 (unit volume nitrogen per unit volume aerogel). These tests allow for an estimate on how much insulation is needed in certain situations. The theory behind the different processes of sorption is necessary for a better understanding of the preparation of the beads before they are used in an insulation system.

  14. Digital Detection of Multiple Minority Mutants and Expression Levels of Multiple Colorectal Cancer-Related Genes Using Digital-PCR Coupled with Bead-Array

    PubMed Central

    Huang, Huan; Li, Shuo; Sun, Lizhou; Zhou, Guohua

    2015-01-01

    To simultaneously analyze mutations and expression levels of multiple genes on one detection platform, we proposed a method termed “multiplex ligation-dependent probe amplification–digital amplification coupled with hydrogel bead-array” (MLPA–DABA) and applied it to diagnose colorectal cancer (CRC). CRC cells and tissues were sampled to extract nucleic acid, perform MLPA with sequence-tagged probes, perform digital emulsion polymerase chain reaction (PCR), and produce a hydrogel bead-array to immobilize beads and form a single bead layer on the array. After hybridization with fluorescent probes, the number of colored beads, which reflects the abundance of expressed genes and the mutation rate, was counted for diagnosis. Only red or green beads occurred on the chips in the mixed samples, indicating the success of single-molecule PCR. When a one-source sample was analyzed using mixed MLPA probes, beads of only one color occurred, suggesting the high specificity of the method in analyzing CRC mutation and gene expression. In gene expression analysis of a CRC tissue from one CRC patient, the mutant percentage was 3.1%, and the expression levels of CRC-related genes were much higher than those of normal tissue. The highly sensitive MLPA–DABA succeeds in the relative quantification of mutations and gene expressions of exfoliated cells in stool samples of CRC patients on the same chip platform. MLPA–DABA coupled with hydrogel bead-array is a promising method in the non-invasive diagnosis of CRC. PMID:25880764

  15. Relative toxicities of pure propylene and ethylene glycol and formulated deicers on plant species

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    DuFresne, D.L.; Pillard, D.A.

    1994-12-31

    Propylene and ethylene glycol deicers are commonly used at airports in the US and other countries to remove and retard the accumulation of snow and ice on aircraft. Deicers may not only enter water bodies without treatment, due to excessive storm-related flow, but also may expose terrestrial organisms to high concentrations through surface runoff. Most available toxicity data are for aquatic vertebrates and invertebrate species; this study examined effects on terrestrial and aquatic plants. Terrestrial plant species included both a monocot (rye grass, Lolium perenne) and a dicot (lettuce, Lactuca saliva). Aquatic species included a single cell alga (Selenastrum capricomutum),more » and an aquatic macrophyte (duckweed, Lemna minor). Glycol deicers were obtained in the formulated mixtures used on aircraft. Pure ethylene and propylene glycol were obtained from Sigma{reg_sign}. Parameters measured included germination, root and shoot length, survival, and growth. Formulated deicers, like those used at airports, were generally more toxic than pure chemicals, based on glycol concentration. This greater toxicity of formulated deicers is consistent with results of tests using animal species.« less

  16. Filtering of windborne particles by a natural windbreak

    NASA Astrophysics Data System (ADS)

    Bouvet, Thomas; Loubet, Benjamin; Wilson, John D.; Tuzet, Andree

    2007-06-01

    New measurements of the transport and deposition of artificial heavy particles (glass beads) to a thick ‘shelterbelt’ of maize (width/height ratio W/ H ≈ 1.6) are used to test numerical simulations with a Lagrangian stochastic trajectory model driven by the flow field from a RANS (Reynolds-averaged, Navier-Stokes) wind and turbulence model. We illustrate the ambiguity inherent in applying to such a thick windbreak the pre-existing (Raupach et al. 2001; Atmos. Environ. 35, 3373-3383) ‘thin windbreak’ theory of particle filtering by vegetation, and show that the present description, while much more laborious, provides a reasonably satisfactory account of what was measured. A sizeable fraction of the particle flux entering the shelterbelt across its upstream face is lifted out of its volume by the mean updraft induced by the deceleration of the flow in the near-upstream and entry region, and these particles thereby escape deposition in the windbreak.

  17. Study of The Effect of Draw-bead Geometry on Stretch Flange Formability

    NASA Astrophysics Data System (ADS)

    Orlov, O. S.; Winkler, S. L.; Worswick, M. J.; Lloyd, D. J.; Finn, M. J.

    2004-06-01

    A fully instrumented stretch flange press equipped with a back-up punch and draw-beads near the specimen cutout area is simulated. The utilization of different draw-bead geometries is examined numerically to determine the restraining forces, strains and amount of damage generated in stretch flanges during forming. Simulations of the forming process are conducted for 1mm AA5182 sheets with circular cutouts. The damage evolution with the deformed specimens is investigated using the explicit dynamic finite element code, LS-DYNA, with a modified Gurson-based material model. It was found that double draw-beads can provide the same amount of restraining force as single draw-beads, but at reduced levels of damage.

  18. Local Antibiotic Delivery by a Bioabsorbable Gel Is Superior to PMMA Bead Depot in Reducing Infection in an Open Fracture Model

    DTIC Science & Technology

    2014-06-01

    be achieved in the wound while avoiding the side effects and cost of systemic administration. Beads molded from polymethylmethacrylate cement are... polymethylmethacrylate antibiotic beads is less effective because this method has to rely on diffusion of the antibiotic from the high concentration close...antibiotics in clinical use is polymethylmethacrylate (PMMA) blended with antibiotics and molded into beads.6–8 There are, however, disadvantages

  19. Continuous microwave regeneration apparatus for absorption media

    DOEpatents

    Smith, Douglas D.

    1999-01-01

    A method and apparatus for continuously drying and regenerating ceramic beads for use in process gas moisture drying operations such as glove boxes. A microwave energy source is coupled to a process chamber to internally heat the ceramic beads and vaporize moisture contained therein. In a preferred embodiment, the moisture laden ceramic beads are conveyed toward the microwave source by a screw mechanism. The regenerated beads flow down outside of the screw mechanism and are available to absorb additional moisture.

  20. Hot Forging of a Cladded Component by Automated GMAW Process

    NASA Astrophysics Data System (ADS)

    Rafiq, Muhammad; Langlois, Laurent; Bigot, Régis

    2011-01-01

    Weld cladding is employed to improve the service life of engineering components by increasing corrosion and wear resistance and reducing the cost. The acceptable multi-bead cladding layer depends on single bead geometry. Hence, in first step, the relationship between input process parameters and the single bead geometry is studied and in second step a comprehensive study on multi bead clad layer deposition is carried out. This paper highlights an experimental study carried out to get single layer cladding deposited by automated Gas Metal Arc Welding (GMAW) process and to find the possibility of hot forming of the cladded work piece to get the final hot formed improved structure. GMAW is an arc welding process that uses an arc between a consumable electrode and the welding pool with an external shielding gas and the cladding is done by alongside deposition of weld beads. The experiments for single bead were conducted by varying the three main process parameters wire feed rate, arc voltage and welding speed while keeping other parameters like nozzle to work distance, shielding gas and its flow rate and torch angle constant. The effect of bead spacing and torch orientation on the cladding quality of single layer from the results of single bead deposition was studied. Effect of the dilution rate and nominal energy on the cladded layer hot bending quality was also performed at different temperatures.

  1. Fabrication and characterization of superporous cellulose bead for high-speed protein chromatography.

    PubMed

    Wang, Dong-Mei; Hao, Gang; Shi, Qing-Hong; Sun, Yan

    2007-03-30

    Novel superporous cellulose (SC) matrix has been fabricated by water-in-oil emulsification-thermal regeneration using granules of calcium carbonate as porogenic agents. As a control, microporous cellulose (MC) bead was fabricated in the absence of calcium carbonate. Simultaneously, double cross-linking was applied to enhance the mechanical strength of the particles. The photographs by scanning electron microscopy of the SC bead illustrated that there were more "craters" of several microns scattering on the surface of the beads. It led to a higher water content and effective porosity of the SC medium. The two beads were then modified with diethylaminoethyl (DEAE) group to prepare anion exchangers. The dynamic uptake results of bovine serum albumin (BSA) exhibited that the pore diffusivity of BSA in the DEAE-SC bead was two to three times larger than that in the DEAE-MC bead. In addition, the column packed with the DEAE-SC showed lower backpressure, higher column efficiency and dynamic binding capacity than the column packed with the DEAE-MC at a flow rate range of 150-900cm/h. Moreover, the column efficiency of the DEAE-SC column was independent of flow velocity up to a flow rate of 1200cm/h. All the results exhibited the superior characteristics of the SC bead as a potential medium for high-speed protein chromatography.

  2. Ecohydraulics of Strings and Beads in Bedrock Rivers

    NASA Astrophysics Data System (ADS)

    Wohl, E.

    2016-12-01

    Twenty years ago, Jack Stanford and others described rivers in bedrock canyons as resembling beads on a string when viewed in planform. The beads are relatively wide, low gradient river segments with floodplains, whereas the strings are the intervening steep, narrow river segments with minimal floodplain development. This pattern of longitudinal variations in channel and valley morphology along bedrock canyon rivers is very common, from small channels to major rivers such as the Colorado. Basic understanding of river ecosystems, as well as limited studies, indicates that the beads are more retentive and biologically productive. Although both strings and beads can provide habitat for diverse organisms, strings are more likely to serve as migration corridors, whereas beads provide spawning and nursery habitat, facilitate lateral (channel-floodplain) and vertical (channel-hyporheic) exchanges and associated habitat diversity, and retain dissolved and particulate organic matter. Recognition of the different characteristics and functions of strings and beads can be used to identify their spatial distribution along a river or within a river network and the hydraulically driven processes that sustain channel form, water quality, and biota within strings and beads. Diverse modeling approaches can then be used to quantify the fluxes of water and sediment needed to maintain these hydraulically driven processes. This conceptual framework is illustrated using examples from mountain streams in the Southern Rockies and canyon rivers in the southwestern United States.

  3. Micromagnet arrays for on-chip focusing, switching, and separation of superparamagnetic beads and single cells.

    PubMed

    Rampini, S; Kilinc, D; Li, P; Monteil, C; Gandhi, D; Lee, G U

    2015-08-21

    Nonlinear magnetophoresis (NLM) is a novel approach for on-chip transport and separation of superparamagnetic (SPM) beads, based on a travelling magnetic field wave generated by the combination of a micromagnet array (MMA) and an applied rotating magnetic field. Here, we present two novel MMA designs that allow SPM beads to be focused, sorted, and separated on-chip. Converging MMAs were used to rapidly collect the SPM beads from a large region of the chip and focus them into synchronised lines. We characterise the collection efficiency of the devices and demonstrate that they can facilitate on-chip analysis of populations of SPM beads using a single-point optical detector. The diverging MMAs were used to control the transport of the beads and to separate them based on their size. The separation efficiency of these devices was determined by the orientation of the magnetisation of the micromagnets relative to the external magnetic field and the size of the beads and relative to that of micromagnets. By controlling these parameters and the rotation of the external magnetic field we demonstrated the controlled transport of SPM bead-labelled single MDA-MB-231 cells. The use of these novel MMAs promises to allow magnetically-labelled cells to be efficiently isolated and then manipulated on-chip for analysis with high-resolution chemical and physical techniques.

  4. Geochemical features of glass beads excavated from the Iron Age archaeological sites, Eastern Taiwan

    NASA Astrophysics Data System (ADS)

    Yang, H.

    2016-12-01

    The uses of metallic artifacts began 2500-2000 years ago in Taiwan; in the meanwhile glass beads have also been as a common ornament by the prehistoric people. Glass, as the earliest artificial ornament, is made by a mixture of quartz sands and flux which were heated to more than one thousand Celsius degrees. Therefore, the production processes, raw material provenance and exchange systems could be revealed by the chemical compositions of glass artifacts. The chemical composition of glass beads studies from four archaeological sites (PL, PN, CHL and TL sites) in early Iron Age are reported in this study. By the producing in drawn method and limited ranges of colors with various hue, all the studied glass beads here should be classified as Indo-Pacific glass beads. As these ancient glass beads are unique and precious, a non-destructive analytical method is always considered at the initial stage. Therefore, we use the best known and most widely-used of the surface analytical techniques SEM/EDX to get the surface and quantitative elemental information of glass beads. According to the analytical results, the PL and PN glass beads all belong to potassium silica glass and those coexisting with so-called Kueishan sherds excavated from CHL and TL sites should be classified as sodium-calcium glass which is the most general composition of Indo-Pacific glass beads. Not only the different flux using between potassium and sodium glass, the variation in the aluminum contents between potassium and sodium glass also exhibits different provenances of glass-making raw materials. As lack of glass-making remains in Taiwan, these ancient glass beads were considered as a precious and trading artifact to Taiwan from overseas and introduced into prehistoric societies via various sources and paths. Although the trading/exchange routes of ancient glass beads are still debatable, we find that compositional analyses can help answer such questions as what types of glass were used for their manufacture and with separate traditions and hope the results can give us some insight into the potential beadmaking sites and in addition to establish the exchange networks of prehistoric people.

  5. Pancreatic enzyme replacement therapy for people with cystic fibrosis.

    PubMed

    Somaraju, Usha Rani; Solis-Moya, Arturo

    2014-10-13

    Most people with cystic fibrosis (80% to 90%) need pancreatic enzyme replacement therapy to prevent malnutrition. Enzyme preparations need to be taken whenever food is taken, and the dose needs to be adjusted according to the food consumed. A systematic review on the efficacy and safety of pancreatic enzyme replacement therapy is needed to guide clinical practice, as there is variability between centres with respect to assessment of pancreatic function, time of commencing treatment, dose and choice of supplements. To evaluate the efficacy and safety of pancreatic enzyme replacement therapy in children and adults with cystic fibrosis and to compare the efficacy and safety of different formulations of this therapy and their appropriateness in different age groups. Also, to compare the effects of pancreatic enzyme replacement therapy in cystic fibrosis according to different diagnostic subgroups (e.g. different ages at introduction of therapy and different categories of pancreatic function). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 14 August 2014.We also searched an ongoing trials website and the websites of the pharmaceutical companies who manufacture pancreatic enzyme replacements for any additional trials. Most recent search: 12 May 2014. Randomised and quasi-randomised controlled trials in people of any age, with cystic fibrosis and receiving pancreatic enzyme replacement therapy, at any dosage and in any formulation, for a period of not less than four weeks, compared to placebo or other pancreatic enzyme replacement therapy preparations. Two authors independently assessed trials and extracted outcome data. They also assessed the risk of bias of the trials included in the review. One parallel trial and 11 cross-over trials of children and adults with cystic fibrosis were included in the review. The number of participants in each trial varied between 14 and 129 with a total of 426 participants included in the review. All the included trials were for a duration of four weeks. The included trials had mostly an unclear risk of bias from the randomisation process as the details of this were not given; they also mostly had a high risk of attrition bias and reporting bias.We could not combine data from all the trials as they compared different formulations. Findings from individual studies provided insufficient evidence to determine the size and precision of the effects of different formulations. Ten studies reported information on the review's primary outcome (nutritional status); however, we were only able to combine data from two small cross-over studies (n = 41). The estimated gain in body weight was imprecise, 0.32 kg (95% confidence interval -0.03 to 0.67, P = 0.07). Combined data from the same studies gave statistically significant results favouring enteric-coated microspheres over enteric-coated tablets for our secondary outcomes stool frequency, abdominal pain and fecal fat excretion. Data from another single small cross-over study also favoured enteric-coated microspheres over non-enteric-coated tablets with adjuvant cimetidine in terms of stool frequency. There is limited evidence of benefit from enteric-coated microspheres when compared to non-enteric coated pancreatic enzyme preparations up to one month. In the only comparison where we could combine any data, the fact that these were cross-over studies is likely to underestimate the level of inconsistency between the results of the studies due to over-inflation of confidence intervals from the individual studies.There is no evidence on the long-term effectiveness and risks associated with pancreatic enzyme replacement therapy. There is also no evidence on the relative dosages of enzymes needed for people with different levels of severity of pancreatic insufficiency, optimum time to start treatment and variations based on differences in meals and meal sizes. There is a need for a properly designed trial that can answer these questions.

  6. Optimization of Enzyme Co-Immobilization with Sodium Alginate and Glutaraldehyde-Activated Chitosan Beads.

    PubMed

    Gür, Sinem Diken; İdil, Neslihan; Aksöz, Nilüfer

    2018-02-01

    In this study, two different materials-alginate and glutaraldehyde-activated chitosan beads-were used for the co-immobilization of α-amylase, protease, and pectinase. Firstly, optimization of multienzyme immobilization with Na alginate beads was carried out. Optimum Na alginate and CaCl 2 concentration were found to be 2.5% and 0.1 M, respectively, and optimal enzyme loading ratio was determined as 2:1:0.02 for pectinase, protease, and α-amylase, respectively. Next, the immobilization of multiple enzymes on glutaraldehyde-activated chitosan beads was optimized (3% chitosan concentration, 0.25% glutaraldehyde with 3 h of activation and 3 h of coupling time). While co-immobilization was successfully performed with both materials, the specific activities of enzymes were found to be higher for the enzymes co-immobilized with glutaraldehyde-activated chitosan beads. In this process, glutaraldehyde was acting as a spacer arm. SEM and FTIR were used for the characterization of activated chitosan beads. Moreover, pectinase and α-amylase enzymes immobilized with chitosan beads were also found to have higher activity than their free forms. Three different enzymes were co-immobilized with these two materials for the first time in this study.

  7. OBT analysis method using polyethylene beads for limited quantities of animal tissue.

    PubMed

    Kim, S B; Stuart, M

    2015-08-01

    This study presents a polyethylene beads method for OBT determination in animal tissues and animal products for cases where the amount of water recovered by combustion is limited by sample size or quantity. In the method, the amount of water recovered after combustion is enhanced by adding tritium-free polyethylene beads to the sample prior to combustion in an oxygen bomb. The method reduces process time by allowing the combustion water to be easily collected with a pipette. Sufficient water recovery was achieved using the polyethylene beads method when 2 g of dry animal tissue or animal product were combusted with 2 g of polyethylene beads. Correction factors, which account for the dilution due to the combustion water of the beads, are provided for beef, chicken, pork, fish and clams, as well as egg, milk and cheese. The method was tested by comparing its OBT results with those of the conventional method using animal samples collected on the Chalk River Laboratories (CRL) site. The results determined that the polyethylene beads method added no more than 25% uncertainty when appropriate correction factors are used. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  8. Wearable glass beads for in vivo dosimetry of total skin electron irradiation treatments

    NASA Astrophysics Data System (ADS)

    Nabankema, S. K.; Jafari, S. M.; Peet, S. C.; Binny, D.; Sylvander, S. R.; Crowe, S. B.

    2017-11-01

    Glass beads have recently been proposed for use as radiation therapy dosimeters. Glass beads have a number of characteristics that make them suitable for in vivo skin dose measurements, including an ability to be worn on a string, and therefore avoid possible patient discomfort that may result from the use of adhesives. In this study, their use for in vivo dose measurements in total skin electron irradiation treatments has been tested. First, the dosimetric properties of cylindrical beads with a 3 mm diameter were characterised using electron fields produced by a linear accelerator. The mean individual bead reproducibility was demonstrated to be within 3%; and a batch variation of 7% was observed. The beads were shown to have a linear dose response, and both dose rate and beam energy independence, within the measurement uncertainty. Phantom measurements were then performed for a total skin electron irradiation beam arrangement, and results compared against optically stimulated luminescent dosimeters at five anatomical sites. For a majority of measurement locations, agreement within 3% was observed between the two dosimetry techniques, demonstrating the feasibility of glass beads as in vivo dosimeters for total skin electron irradiation; though further investigation may be needed to minimise uncertainty in results.

  9. Facile preparation and characterization of pH sensitive Mt/CMC nanocomposite hydrogel beads for propranolol controlled release.

    PubMed

    Farhadnejad, Hassan; Mortazavi, Seyed Alireza; Erfan, Mohammad; Darbasizadeh, Behzad; Motasadizadeh, Hamidreza; Fatahi, Yousef

    2018-05-01

    The main aim of the present study was to design pH-sensitive nanocomposite hydrogel beads, based on carboxymethyl cellulose (CMC) and montmorillonite (Mt)-propranolol (PPN) nanohybrid, and evaluate whether the prepared nanocomposite beads could potentially be used as oral drug delivery systems. PPN-as a model drug-was intercalated into the interlayer space of Mt clay mineral via the ion exchange procedure. The resultant nanohybrid (Mt-PPN) was applied to fabricate nanocomposite hydrogel beads by association with carboxymethyl cellulose. The characterization of test samples was performed using different techniques: X-Ray Diffraction (XRD), IR spectroscopy (FT-IR), thermal gravity analysis (TGA), and scanning electron microscopy (SEM). The drug encapsulation efficiency was evaluated by UV-vis spectroscopy, and was found to be high for Mt/CMC beads. In vitro drug release test was performed in the simulated gastrointestinal conditions to evaluate the efficiency of Mt-PPN/CMC nanocomposite beads as a controlled-release drug carrier. The drug release profiles indicated that the Mt-PPN/CMC nanocomposite beads had high stability against stomach acid and a sustained- and controlled-release profile for PPN under the simulated intestinal conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Hydrodynamic Torques and Rotations of Superparamagnetic Bead Dimers

    NASA Astrophysics Data System (ADS)

    Pease, Christopher; Etheridge, J.; Wijesinghe, H. S.; Pierce, C. J.; Prikockis, M. V.; Sooryakumar, R.

    Chains of micro-magnetic particles are often rotated with external magnetic fields for many lab-on-a-chip technologies such as transporting beads or mixing fluids. These applications benefit from faster responses of the actuated particles. In a rotating magnetic field, the magnetization of superparamagnetic beads, created from embedded magnetic nano-particles within a polymer matrix, is largely characterized by induced dipoles mip along the direction of the field. In addition there is often a weak dipole mop that orients out-of-phase with the external rotating field. On a two-bead dimer, the simplest chain of beads, mop contributes a torque Γm in addition to the torque from mip. For dimers with beads unbound to each other, mop rotates individual beads which generate an additional hydrodynamic torque on the dimer. Whereas, mop directly torques bound dimers. Our results show that Γm significantly alters the average frequency-dependent dimer rotation rate for both bound and unbound monomers and, when mop exceeds a critical value, increases the maximum dimer rotation frequency. Models that include magnetic and hydrodynamics torques provide good agreement with the experimental findings over a range of field frequencies.

  11. Use of micrometric latex beads to improve the porosity of hydroxyapatite obtained by chemical coprecipitation method

    NASA Astrophysics Data System (ADS)

    Webler, G. D.; Rodrigues, W. C.; Silva, A. E. S.; Silva, A. O. S.; Fonseca, E. J. S.; Degenhardt, M. F. S.; Oliveira, C. L. P.; Otubo, L.; Barros Filho, D. A.

    2018-04-01

    Hydroxyapatite is one of the most important biomaterials whose application mainly extends to implants and drug delivery. This work will discuss the changes in the pore size distribution of hydroxyapatite when there are latex beads present during the synthesis. These changes were monitored using different techniques: small angle X-ray scattering, X-ray diffraction, thermal gravimetrical analysis, N2 adsorption, scanning and transmission electron microscopy. Latex beads and hydroxyapatite form a single nanocomposite with well-distinguished inorganic and organic phases. Latex bead removal in the temperature range of 300-600 °C did not modify the original crystalline structure of hydroxyapatite. However, the latex beads favored an increase in the adsorption capacity of mesopores at temperatures higher than their glassy transition (Tg). The main result of this research work consists on the increase of surface area and pore size distribution obtained after the removal of latex beads template. Latex beads have been used in a different approach changing the porosity of hydroxyapatite scaffolds not only introducing new routes for cell integration but also broadening the pore size distribution which can result in a more high efficiency for drug release in living cells.

  12. Artocarpus heterophyllus L. seed starch-blended gellan gum mucoadhesive beads of metformin HCl.

    PubMed

    Nayak, Amit Kumar; Pal, Dilipkumar; Santra, Kousik

    2014-04-01

    Jackfruit (Artocarpus heterophyllus Lam., family: Moraceae) seed starch (JFSS)-gellan gum (GG) mucoadhesive beads containing metformin HCl were developed through ionotropic gelation technique. The effect of GG to JFSS ratio and CaCl2 concentration on the drug encapsulation efficiency (DEE, %) and cumulative drug release at 10h (R10h, %) was optimized and analyzed using response surface methodology based on 3(2) factorial design. The optimized JFSS-GG beads containing metformin HCl showed DEE of 92.67±4.46%, R10h of 61.30±2.37%, and mean diameter of 1.67±0.27 mm. The optimized beads showed pH-dependent swelling and mucoadhesivity with the goat intestinal mucosa. The in vitro drug release from all these JFSS-GG beads containing metformin HCl was followed zero-order pattern (R(2)=0.9907-0.9975) with super case-II transport mechanism over a period of 10 h. The beads were also characterized by SEM and FTIR. The optimized JFSS-GG beads containing metformin HCl exhibited significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Hierarchical Theoretical Methods for Understanding and Predicting Anisotropic Thermal Transport Release in Rocket Propellant Formulations

    DTIC Science & Technology

    2016-12-08

    mesoscopic models of interfaces and interphases, and microstructure-resolved representative volume element simulations. Atomic simulations were...title and subtitle with volume number and part number, if applicable. On classified documents, enter the title classification in parentheses. 5a...careful prediction of the pressure- volume -temperature equation of state, pressure- and temperature-dependent crystal and liquid thermal and transport

  14. A novel once daily microparticulate dosage form comprising lansoprazole to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease: preparation, pharmacokinetic and pharmacodynamic evaluation.

    PubMed

    Alai, Milind; Lin, Wen Jen

    2013-01-01

    The objective of this study was to formulate and evaluate the lansoprazole (LPZ)-loaded microparticles to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease (GERD). The microparticulate delivery system was prepared by solvent evaporation method using Eudragit RS100 as a matrix polymer followed by enteric coated with Eudragit S100 and hydroxypropyl methylcellulose phthalate HP55 using spray drying method. The enteric coated microparticles were stable in gastric pH condition. In vivo pharmacokinetic and pharmacodynamic studies in male Wistar rats demonstrated that enteric coated microparticles sustained release of LPZ and promoted ulcer healing activity. In other words, the microparticulate dosage form provided effective drug concentration for a longer period as compared to conventional extended release dosage form, and showed sufficient anti-acid secretion activity to treat acid related disorders including the enrichment of nocturnal acid breakthrough event based on a once daily administration.

  15. Proposal for a new practicable categorization system for food for special medical purposes - Enteral nutritional products.

    PubMed

    Stippler, Dietmar; Bode, Volker; Fischer, Magnus; Kollex, Katrin; Rohde, Evelyn; Tisowsky, Berta; Künstner, Jana; Pahne, Norbert

    2015-12-01

    Changes in the EU regulation on food for specific groups (FSG) [1] and within the German social law [2] combined with various definitions in the legal and the scientific background led to the need for development of a categorization system for "Food for special medical purposes" (FSMP) for enteral use [3]. The system was developed by an interdisciplinary working group of two German industry associations, which represent the leading manufacturers and distributors of FSMP in Europe. It aims to minimize the misunderstandings surrounding the different definitions used in relation to enteral nutritional products and incorporate the latest scientific knowledge and medical guidelines [4]. The new proposal consists of a table which shows the product categories and briefly the definitions of the used terms. The text contains the relevant definitions of terms often used within the field of enteral nutrition. This provides health care professionals with support and the decision making process for the prescription and use of such products. Additionally it also benefits the responsible authorities to formulate new directives, which are user-friendly and reflect the latest knowledge in medical nutrition. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Crosslinked, porous, polyacrylate beads

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Yen, Shiao-Ping Siao (Inventor); Dreyer, William J. (Inventor)

    1976-01-01

    Uniformly-shaped, porous, round beads are prepared by the co-polymerization of an acrylic monomer and a cross-linking agent in the presence of 0.05 to 5% by weight of an aqueous soluble polymer such as polyethylene oxide. Cross-linking proceeds at high temperature above about 50.degree.C or at a lower temperature with irradiation. Beads of even shape and even size distribution of less than 2 micron diameter are formed. The beads will find use as adsorbents in chromatography and as markers for studies of cell surface receptors.

  17. Crosslinked, porous, polyacrylate beads

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Yen, Shiao-Ping S. (Inventor); Dreyer, William J. (Inventor)

    1977-01-01

    Uniformly-shaped, porous, round beads are prepared by the co-polymerization of an acrylic monomer and a cross-linking agent in the presence of 0.05 to 5% by weight of an aqueous soluble polymer such as polyethylene oxide. Cross-linking proceeds at high temperature above about 50.degree. C or at a lower temperature with irradiation. Beads of even shape and even size distribution of less than 2 micron diameter are formed. The beads will find use as adsorbents in chromatography and as markers for studies of cell surface receptors.

  18. Measurement of retroreflection by glass beads for road marking

    NASA Astrophysics Data System (ADS)

    Ivanov, L. A.; Kiesewetter, D. V.; Kiselev, N. N.; Malyugin, V. I.; Slugin, V. A.

    2006-04-01

    The parameters of retroreflection of the monolayer of glass beads of the different size and quality in paint for road marking are measured. The new method of simultaneous measurement of the size and coefficient of retroreflection of separate beads is offered. The system of the statistical characteristics of optical quality is introduced. The measurements for different dimensional fractions are carried out. The capability of estimation of influencing of defects of glass beads on retro reflecting properties of the materials is shown.

  19. Small, porous polyacrylate beads

    NASA Technical Reports Server (NTRS)

    Yen, Shiao-Ping Siao (Inventor); Rembaum, Alan (Inventor); Dreyer, William J. (Inventor)

    1976-01-01

    Uniformly-shaped, porous, round beads are prepared by the co-polymerization of an acrylic monomer and a cross-linking agent in the presence of 0.05 to 5% by weight of an aqueous soluble polymer such as polyethylene oxide. Cross-linking proceeds at high temperature above about 50.degree.C or at a lower temperature with irradiation. Beads of even shape and even size distribution of less than 2 micron diameter are formed. The beads will find use as adsorbents in chromatography and as markers for studies of cell surface receptors.

  20. Polymeric Beads for Organic Coatings

    DTIC Science & Technology

    1982-10-31

    Clear Solid Polymeric Beads A solid polymeric bead is comprised of a sol id mass of polymerized unsaturated polyester/styrene resin mixture . 2. lear...than the current unsaturated polyester resin . For example, a bead male from acrylic resin could be more trans- - parent, more durable and provide more...0.44 Isopropyl Alcohol I 11.26 I 1 .73 60% Wt. Alkyd Resin - Volume I 251.26 i 30.52 " Sol ids 51% 1 I Anti.-Skinning Agent I 0.90 I 0.12 Mineral

  1. Evaluation of in vitro serial antibiotic elution from meropenem-impregnated polymethylmethacrylate beads after ethylene oxide gas and autoclave sterilization.

    PubMed

    Báez, L A; Langston, C; Givaruangsawat, S; McLaughlin, R

    2011-01-01

    To determine the elution properties of meropenem and to compare the elutions of meropenem-impregnated polymethylmethacrylate (PMMA) beads without sterilization (P-M-C) to those sterilized with steam (P-M-A) and ethylene oxide gas (P-M-EO). A commercial bead mould was used to produce four groups of beads: one group without antibiotic (negative control), and three groups of meropenem-impregnated beads: P-M-C, P-M-A, and P-M-EO. The beads were placed in a phosphate buffered solution and eluent samples were collected. Concentrations of the antibiotic in eluent samples from the two sterilized groups and the control beads were determined using a microbiological assay at 1, 3, 6 and 12 hours and at 1, 2, 3, 6, 9, 12, 15, 18, 22, 26, and 30 days. The microbiological assay resulted in no zone of inhibition at all time periods for the P-M-A samples and the samples of PMMA without antimicrobial. The meropenem concentration on the eluent remained above 4 mcg/ml for 15 days in the P-M-C group and until day 18 for P-M-EO group. There was no statistical difference in AUC0-∞ (p<0.318), however significance did occur for MRT (p<0.005) when comparing P-M-C and P-M-EO with the later being higher. The meropenem incorporated in the PMMA beads eluted effectively and gradually decreased after the 24 hour peak, but remained above the concentration level of 4 mcg/ml for 15 days in the P-M-C group and until day 18 for P-M-EO group. Ethylene oxide does not adversely affect meropenem's elution from PMMA beads.

  2. Plasma membrane isolation using immobilized concanavalin A magnetic beads.

    PubMed

    Lee, Yu-Chen; Srajer Gajdosik, Martina; Josic, Djuro; Lin, Sue-Hwa

    2012-01-01

    Isolation of highly purified plasma membranes is the key step in constructing the plasma membrane proteome. Traditional plasma membrane isolation method takes advantage of the differential density of organelles. While differential centrifugation methods are sufficient to enrich for plasma membranes, the procedure is lengthy and results in low recovery of the membrane fraction. Importantly, there is significant contamination of the plasma membranes with other organelles. The traditional agarose affinity matrix is suitable for isolating proteins but has limitation in separating organelles due to the density of agarose. Immobilization of affinity ligands to magnetic beads allows separation of affinity matrix from organelles through magnets and could be developed for the isolation of organelles. We have developed a simple method for isolating plasma membranes using lectin concanavalin A (ConA) magnetic beads. ConA is immobilized onto magnetic beads by binding biotinylated ConA to streptavidin magnetic beads. The ConA magnetic beads are used to bind glycosylated proteins present in the membranes. The bound membranes are solubilized from the magnetic beads with a detergent containing the competing sugar alpha methyl mannoside. In this study, we describe the procedure of isolating rat liver plasma membranes using sucrose density gradient centrifugation as described by Neville. We then further purify the membrane fraction by using ConA magnetic beads. After this purification step, main liver plasma membrane proteins, especially the highly glycosylated ones and proteins containing transmembrane domains could be identified by LC-ESI-MS/MS. While not described here, the magnetic bead method can also be used to isolate plasma membranes from cell lysates. This membrane purification method should expedite the cataloging of plasma membrane proteome.

  3. Feasibility of using glass-bead thermoluminescent dosimeters for radiotherapy treatment plan verification.

    PubMed

    Jafari, Shakardokht M; Jordan, Tom J; Distefano, Gail; Bradley, David A; Spyrou, Nicholas M; Nisbet, Andrew; Clark, Catharine H

    2015-01-01

    To investigate the feasibility of using glass beads as novel thermoluminescent dosemeters (TLDs) for radiotherapy treatment plan verification. Commercially available glass beads with a size of 1-mm thickness and 2-mm diameter were characterized as TLDs. Five clinical treatment plans including a conventional larynx, a conformal prostate, an intensity-modulated radiotherapy (IMRT) prostate and two stereotactic body radiation therapy (SBRT) lung plans were transferred onto a CT scan of a water-equivalent phantom (Solid Water(®), Gammex, Middleton, WI) and the dose distribution recalculated. The number of monitor units was maintained from the clinical plan and delivered accordingly. The doses determined by the glass beads were compared with those measured by a graphite-walled ionization chamber, and the respective expected doses were determined by the treatment-planning system (TPS) calculation. The mean percentage difference between measured dose with the glass beads and TPS was found to be 0.3%, -0.1%, 0.4%, 1.8% and 1.7% for the conventional larynx, conformal prostate, IMRT prostate and each of the SBRT delivery techniques, respectively. The percentage difference between measured dose with the ionization chamber and glass bead was found to be -1.2%, -1.4%, -0.1%, -0.9% and 2.4% for the above-mentioned plans, respectively. The results of measured doses with the glass beads and ionization chamber in comparison with expected doses from the TPS were analysed using a two-sided paired t-test, and there was no significant difference at p < 0.05. It is feasible to use glass-bead TLDs as dosemeters in a range of clinical plan verifications. Commercial glass beads are utilized as low-cost novel TLDs for treatment-plan verification.

  4. Effect of pH and polypropylene beads in hybrid water treatment process of alumina ceramic microfiltration and PP beads with air back-flushing and UV irradiation.

    PubMed

    Park, Jin Yong; Song, Seunghwa

    2017-07-07

    For advanced water treatment, effects of pH and pure polypropylene (PP) beads packing concentration on membrane fouling and treatment efficiency were observed in a hybrid process of alumina ceramic microfiltration (MF; pore size 0.1 μm) and pure PP beads. Instead of natural organic matters and fine inorganic particles in natural water source, a quantity of humic acid (HA) and kaolin was dissolved in distilled water. The synthetic feed flowed inside the MF membrane, and the permeated water contacted the PP beads fluidized in the gap of the membrane and the acryl module case with outside UV irradiation. Periodic air back-flushing was performed to control membrane fouling during 10 s per 10 min. The membrane fouling resistance (R f ) was the maximum at 30 g/L of PP bead concentration. Finally, the maximum total permeated volume (V T ) was acquired at 5 g/L of PP beads, because flux maintained higher all through the operation. The treatment efficiency of turbidity was almost constant, independent of PP bead concentration; however, that of dissolved organic materials (DOM) showed the maximal at 50 g/L of PP beads. The R f increased as increasing feed pH from 5 to 9; however, the maximum V T was acquired at pH 6. It means that the membrane fouling could be inhibited at low acid condition. The treatment efficiency of turbidity increased a little, and that of DOM increased from 73.6 to 75.7% as increasing pH from 5 to 9.

  5. Metal Oxide Assisted Preparation of Core-Shell Beads with Dense Metal-Organic Framework Coatings for the Enhanced Extraction of Organic Pollutants.

    PubMed

    Del Rio, Mateo; Palomino Cabello, Carlos; Gonzalez, Veronica; Maya, Fernando; Parra, Jose B; Cerdà, Victor; Turnes Palomino, Gemma

    2016-08-08

    Dense and homogeneous metal-organic framework (MOF) coatings on functional bead surfaces are easily prepared by using intermediate sacrificial metal oxide coatings containing the metal precursor of the MOF. Polystyrene (PS) beads are coated with a ZnO layer to give ZnO@PS core-shell beads. The ZnO@PS beads are reactive in the presence of 2-methylimidazole to transform part of the ZnO coating into a porous zeolitic imidazolate framework-8 (ZIF-8) external shell positioned above the internal ZnO precursor shell. The obtained ZIF-8@ZnO@PS beads can be easily packed in column format for flow-through applications, such as the solid-phase extraction of trace priority-listed environmental pollutants. The prepared material shows an excellent permeance to flow when packed as a column to give high enrichment factors, facile regeneration, and excellent reusability for the extraction of the pollutant bisphenol A. It also shows an outstanding performance for the simultaneous enrichment of mixtures of endocrine disrupting chemicals (bisphenol A, 4-tert-octylphenol and 4-n-nonylphenol), facilitating their analysis when present at very low levels (<1 μg L(-1) ) in drinking waters. For the extraction of the pollutant bisphenol A, the prepared ZIF-8@ZnO@PS beads also show a superior extraction and preconcentration capacity to that of the PS beads used as precursors and the composite materials obtained by the direct growth of ZIF-8 on the surface of the PS beads in the absence of metal oxide intermediate coatings. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Characterization of long-term elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate beads in vitro by two distinct sample collection methods.

    PubMed

    Tulipan, Rachel J; Phillips, Heidi; Garrett, Laura D; Dirikolu, Levent; Mitchell, Mark A

    2017-05-01

    OBJECTIVE To characterize long-term elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate (CI-CSH) beads in vitro by comparing 2 distinct sample collection methods designed to mimic 2 in vivo environments. SAMPLES 162 CI-CSH beads containing 4.6 mg of carboplatin (2.4 mg of platinum/bead). PROCEDURES For method 1, which mimicked an in vivo environment with rapid and complete fluid exchange, each of 3 plastic 10-mL conical tubes contained 3 CI-CSH beads and 5 mL of PBS solution. Eluent samples were obtained by evacuation of all fluid at 1, 2, 3, 6, 9, and 12 hours and 1, 2, 3, 6, 9, 12, 15, 18, 22, 26, and 30 days. Five milliliters of fresh PBS solution was then added to each tube. For method 2, which mimicked an in vivo environment with no fluid exchange, each of 51 tubes (ie, 3 tubes/17 sample collection times) contained 3 CI-CSH beads and 5 mL of PBS solution. Eluent samples were obtained from the assigned tubes for each time point. All samples were analyzed for platinum content by inductively coupled plasma-mass spectrometry. RESULTS Platinum was released from CI-CSH beads for 22 to 30 days. Significant differences were found in platinum concentration and percentage of platinum eluted from CI-CSH beads over time for each method. Platinum concentrations and elution percentages in method 2 samples were significantly higher than those of method 1 samples, except for the first hour measurements. CONCLUSIONS AND CLINICAL RELEVANCE Sample collection methods 1 and 2 may provide estimates of the minimum and maximum platinum release, respectively, from CI-CSH beads in vivo.

  7. Design criteria for developing low-resource magnetic bead assays using surface tension valves

    PubMed Central

    Adams, Nicholas M.; Creecy, Amy E.; Majors, Catherine E.; Wariso, Bathsheba A.; Short, Philip A.; Wright, David W.; Haselton, Frederick R.

    2013-01-01

    Many assays for biological sample processing and diagnostics are not suitable for use in settings that lack laboratory resources. We have recently described a simple, self-contained format based on magnetic beads for extracting infectious disease biomarkers from complex biological samples, which significantly reduces the time, expertise, and infrastructure required. This self-contained format has the potential to facilitate the application of other laboratory-based sample processing assays in low-resource settings. The technology is enabled by immiscible fluid barriers, or surface tension valves, which stably separate adjacent processing solutions within millimeter-diameter tubing and simultaneously permit the transit of magnetic beads across the interfaces. In this report, we identify the physical parameters of the materials that maximize fluid stability and bead transport and minimize solution carryover. We found that fluid stability is maximized with ≤0.8 mm i.d. tubing, valve fluids of similar density to the adjacent solutions, and tubing with ≤20 dyn/cm surface energy. Maximizing bead transport was achieved using ≥2.4 mm i.d. tubing, mineral oil valve fluid, and a mass of 1-3 mg beads. The amount of solution carryover across a surface tension valve was minimized using ≤0.2 mg of beads, tubing with ≤20 dyn/cm surface energy, and air separators. The most favorable parameter space for valve stability and bead transport was identified by combining our experimental results into a single plot using two dimensionless numbers. A strategy is presented for developing additional self-contained assays based on magnetic beads and surface tension valves for low-resource diagnostic applications. PMID:24403996

  8. Long-term biocompatibility, imaging appearance and tissue effects associated with delivery of a novel radiopaque embolization bead for image-guided therapy.

    PubMed

    Sharma, Karun V; Bascal, Zainab; Kilpatrick, Hugh; Ashrafi, Koorosh; Willis, Sean L; Dreher, Matthew R; Lewis, Andrew L

    2016-10-01

    The objective of this study was to undertake a comprehensive long-term biocompatibility and imaging assessment of a new intrinsically radiopaque bead (LC Bead LUMI™) for use in transarterial embolization. The sterilized device and its extracts were subjected to the raft of ISO10993 biocompatibility tests that demonstrated safety with respect to cytotoxicity, mutagenicity, blood contact, irritation, sensitization, systemic toxicity and tissue reaction. Intra-arterial administration was performed in a swine model of hepatic arterial embolization in which 0.22-1 mL of sedimented bead volume was administered to the targeted lobe(s) of the liver. The beads could be visualized during the embolization procedure with fluoroscopy, DSA and single X-ray snapshot imaging modalities. CT imaging was performed before and 1 h after embolization and then again at 7, 14, 30 and 90 days. LC Bead LUMI™ could be clearly visualized in the hepatic arteries with or without administration of IV contrast and appeared more dense than soluble contrast agent. The CT density of the beads did not deteriorate during the 90 day evaluation period. The beads embolized predictably and effectively, resulting in areas devoid of contrast enhancement on CT imaging suggesting ischaemia-induced necrosis nearby the sites of occlusion. Instances of off target embolization were easily detected on imaging and confirmed pathologically. Histopathology revealed a classic foreign body response at 14 days, which resolved over time leading to fibrosis and eventual integration of the beads into the tissue, demonstrating excellent long-term tissue compatibility. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  9. Evaluation of local toxic effects and outcomes for dogs undergoing marginal tumor excision with intralesional cisplatin-impregnated bead placement for treatment of soft tissue sarcomas: 62 cases (2009-2012).

    PubMed

    Bergman, Noelle S; Urie, Bridget K; Pardo, Anthony D; Newman, Rebecca G

    2016-05-15

    OBJECTIVE To evaluate outcomes for dogs following marginal tumor excision and intralesional placement of cisplatin-impregnated beads for the treatment of cutaneous or subcutaneous soft tissue sarcomas (STSs) and assess local toxic effects of cisplatin-impregnated beads in these patients. DESIGN Retrospective case series. ANIMALS 62 client-owned dogs. PROCEDURES Medical records were reviewed to identify dogs with STSs treated with marginal excision and intralesional placement of cisplatin-impregnated beads. Patient signalment; tumor location, type, and grade; dates of tumor resection and bead placement; number of beads placed; and concurrent treatments were recorded. Data regarding toxicosis at the bead site (up to the time of suture removal) and tumor recurrence were collected; variables of interest were evaluated for associations with these outcomes, and systemic adverse effects (if any) were recorded. RESULTS 24 of 51 (47%) evaluated dogs had toxicosis at bead placement sites (classified as mild [n = 12] or moderate [10] in most). Fifteen of 51 (29%) tumors recurred. Median disease-free interval was not reached for dogs with grade 1 and 2 STSs, whereas that for dogs with grade 3 STSs was 148 days. Disease-free survival rates of dogs with grade 1 and 2 tumors at 1, 2, and 3 years were 88%, 75%, and 64%, respectively. One dog was treated for presumptive systemic toxicosis but recovered with medical treatment. CONCLUSIONS AND CLINICAL RELEVANCE Cisplatin-impregnated beads were generally well tolerated; good results were achieved for dogs with grade 1 or 2 STSs. Prospective, controlled studies are needed to determine efficacy of this treatment for preventing recurrence of marginally excised STSs in dogs.

  10. Parental experiences with a hospital-based bead programme for children with congenital heart disease.

    PubMed

    Wilson, Valerie; Chando, Shingisai

    2015-02-01

    To present survey findings on parental experiences with a hospital-based bead programme for children with congenital heart disease. The Heart Beads programme commenced at a paediatric hospital in Australia in 2008. Children enrolled in the programme are awarded a distinctive bead for every procedure/treatment they have while in hospital. A previous evaluation study on the programme revealed that the beads are therapeutic for the child and parents; however, due to a small sample size, the results were representative of the experiences of a small number of families who participated in the programme. This was an evaluation study which employed a nonexperimental descriptive design. Surveys were mailed to all eligible families who enrolled in the programme. Data collection occurred between July-December 2012. Questions on parental experiences with the Heart Beads programme were divided into three categories: understanding, acknowledgement and quality. Descriptive statistics were obtained and analysed. One hundred and sixty-two mothers and 136 fathers responded to the survey. Heart Beads assisted mothers (83%) and fathers (80%) with understanding their child's condition and helped them with communication (mothers 80%, fathers 58%). The majority of fathers felt that their experience was acknowledged by nursing staff (64%) and medical staff (62%), while mothers indicated a higher response from nurses (76%) compared to medical staff (67%). Overall, parents rated the programme positively; however, there was some concern that children at times missed out on beads. Understanding how mothers and fathers experience the programme differently can guide staff in their communication with parents and inform future initiatives. The Heart Beads help nurses understand how parents are experiencing care and ways in which they can provide support and acknowledgement of the parent's experience. © 2014 John Wiley & Sons Ltd.

  11. Development of an in situ magnetic beads based RT-PCR method for electrochemiluminescent detection of rotavirus

    NASA Astrophysics Data System (ADS)

    Zhan, Fangfang; Zhou, Xiaoming

    2012-12-01

    Rotaviruses are double-stranded RNA viruses belonging to the family of enteric pathogens. It is a major cause of diarrhoeal disease in infants and young children worldwide. Consequently, rapid and accurate detection of rotaviruses is of great importance in controlling and preventing food- and waterborne diseases and outbreaks. Reverse transcription-polymerase chain reaction (RT-PCR) is a reliable method that possesses high specificity and sensitivity. It has been widely used to detection of viruses. Electrochemiluminescence (ECL) can be considered as an important and powerful tool in analytical and clinical application with high sensitivity, excellent specificity, and low cost. Here we have developed a method for the detection of rotavirus by combining in situ magnetic beads (MBs) based RT-PCR with ECL. RT of rotavirus RNA was carried out in a traditional way and the resulting cDNA was directly amplified on MBs. Forward primers were covalently bounded to MBs and reverse primers were labeled with tris-(2, 2'-bipyridyl) ruthenium (TBR). During the PCR cycling, the TBR labeled products were directly loaded and enriched on the surface of MBs. Then the MBs-TBR complexes could be analyzed by a magnetic ECL platform without any post-modification or post-incubation which avoid some laborious manual operations and achieve rapid yet sensitive detection. In this study, rotavirus from fecal specimens was successfully detected within 2 h, and the limit of detection was estimated to be 104copies/μL. This novel in situ MBs based RT-PCR with ECL detection method can be used for pathogen detection in food safety field and clinical diagnosis.

  12. Intrusion dynamics of particle plumes in stratified water with weak crossflow: Application to deep ocean blowouts

    NASA Astrophysics Data System (ADS)

    Wang, Dayang; Adams, E. Eric

    2016-06-01

    We present an experimental study of particle plumes in ambient stratification and a mild current. In an inverted framework, the results describe the fate of oil droplets released from a deep ocean blowout. A continuous stream of dense glass beads was released from a carriage towed in a salt-stratified tank. Nondimensional particle slip velocity UN ranged from 0.1 to 1.9, and particles with UN ≤ 0.5 were observed to enter the intrusion layer. The spatial distributions of beads, collected on a bottom sled towed with the source, present a Gaussian distribution in the transverse direction and a skewed distribution in the along-current direction. Dimensions of the distributions increase with decreasing UN. The spreading relations can be used as input to far-field models describing subsequent transport of particles or, in an inverted framework, oil droplets. The average particle settling velocity, Uave, was found to exceed the individual particle slip velocity, Us, which is attributed to the initial plume velocity near the point of release. Additionally, smaller particles exhibit a "group" or "secondary plume" effect as they exit the intrusion as a swarm. The secondary effect becomes more prominent as UN decreases, and might help explain observations from the 2000 Deep Spill field experiment where oil was found to surface more rapidly than predicted based on Us. An analytical model predicting the particle deposition patterns was validated against experimental measurements, and used to estimate near-field oil transport under the Deepwater Horizon spill conditions, with/without chemical dispersants.

  13. Formulation of D-brane Dynamics

    NASA Astrophysics Data System (ADS)

    Evans, Thomas

    2012-03-01

    It is the purpose of this paper (within the context of STS rules & guidelines ``research report'') to formulate a statistical-mechanical form of D-brane dynamics. We consider first the path integral formulation of quantum mechanics, and extend this to a path-integral formulation of D-brane mechanics, summing over all the possible path integral sectors of R-R, NS charged states. We then investigate this generalization utilizing a path-integral formulation summing over all the possible path integral sectors of R-R charged states, calculated from the mean probability tree-level amplitude of type I, IIA, and IIB strings, serving as a generalization of all strings described by D-branes. We utilize this generalization to study black holes in regimes where the initial D-brane system is legitimate, and further this generalization to look at information loss near regions of nonlocality on a non-ordinary event horizon. We see here that in these specific regimes, we can calculate a path integral formulation, as describing D0-brane mechanics, tracing the dissipation of entropy throughout the event horizon. This is used to study the information paradox, and to propose a resolution between the phenomena and the correct and expected quantum mechanical description. This is done as our path integral throughout entropy entering the event horizon effectively and correctly encodes the initial state in subtle correlations in the Hawking radiation.

  14. Negative dielectrophoresis spectroscopy for rare analyte quantification in biological samples

    NASA Astrophysics Data System (ADS)

    Kirmani, Syed Abdul Mannan; Gudagunti, Fleming Dackson; Velmanickam, Logeeshan; Nawarathna, Dharmakeerthi; Lima, Ivan T., Jr.

    2017-03-01

    We propose the use of negative dielectrophoresis (DEP) spectroscopy as a technique to improve the detection limit of rare analytes in biological samples. We observe a significant dependence of the negative DEP force on functionalized polystyrene beads at the edges of interdigitated electrodes with respect to the frequency of the electric field. We measured this velocity of repulsion for 0% and 0.8% conjugation of avidin with biotin functionalized polystyrene beads with our automated software through real-time image processing that monitors the Rayleigh scattering from the beads. A significant difference in the velocity of the beads was observed in the presence of as little as 80 molecules of avidin per biotin functionalized bead. This technology can be applied in the detection and quantification of rare analytes that can be useful in the diagnosis and the treatment of diseases, such as cancer and myocardial infarction, with the use of polystyrene beads functionalized with antibodies for the target biomarkers.

  15. Microinjection--a tool to study gravitropism.

    PubMed

    Scherp, P; Hasenstein, K H

    2003-01-01

    Despite extensive studies on plant gravitropism this phenomenon is still poorly understood. The separation of gravity sensing, signal transduction and response is a common concept but especially the mechanism of gravisensing remains unclear. This paper focuses on microinjection as powerful tool to investigate gravisensing in plants. We describe the microinjection of magnetic beads in rhizoids of the green alga Chara and related subsequent manipulation of the gravisensing system. After injection, an external magnet can control the movement of the magnetic beads. We demonstrate successful injection of magnetic beads into rhizoids and describe a multitude of experiments that can be carried out to investigate gravitropism in Chara rhizoids. In addition to examining mechanical properties, bead microinjection is also useful for probing the function of the cytoskeleton by coating beads with drugs that interfere with the cytoskeleton. The injection of fluorescently labeled beads or probes may reveal the involvement of the cytoskeleton during gravistimulation and response in living cells. c2003 COSPAR. Published by Elsevier Ltd. All rights reserved.

  16. Static antibiotic spacers augmented by calcium sulphate impregnated beads in revision TKA: Surgical technique and review of literature.

    PubMed

    Risitano, Salvatore; Sabatini, Luigi; Atzori, Francesco; Massè, Alessandro; Indelli, Pier Francesco

    2018-06-01

    Periprosthetic joint infection (PJI) is a serious complication in total knee arthroplasty (TKA) and represents one of the most common causes of revision. The challenge for surgeons treating an infected TKA is to quickly obtain an infection-free joint in order to re-implant, when possible, a new TKA. Recent literature confirms the role of local antibiotic-loaded beads as a strong bactericidal, allowing higher antibiotic elution when compared with antibiotic loaded spacers only. Unfortunately, classical Polymethylmethacrylate (PMMA) beads might allow bacteria adhesion, secondary development of antibiotic resistance and eventually surgical removal once antibiotics have eluted. This article describes a novel surgical technique using static, custom-made antibiotic loaded spacers augmented by calcium sulphate antibiotic-impregnated beads to improve the success rate of revision TKA in a setting of PJI. The use of calcium sulphate beads has several potential benefits, including a longer sustained local antibiotic release when compared with classical PMMA beads and, being resorbable, not requiring accessory surgical interventions.

  17. Effect of lecithin and starch on alginate-encapsulated probiotic bacteria.

    PubMed

    Donthidi, A R; Tester, R F; Aidoo, K E

    2010-01-01

    The effect of lecithin and starch on viability of alginate encapsulated probiotics was determined at different temperatures. Probiotic organisms (1% v/v>10Log CFU ml(-1)) were encapsulated using alginate (2% w/v), gelatinized starches (2% w/v) and lecithin (0-4% w/v) and stored in sealed containers at 4, 23 and 37 degrees C (to simulate shelf storage conditions). Incorporation of lecithin improved the entrapment efficiency (p < 0.05) and the viability of encapsulated bacteria (p = 0.02). Encapsulated Lactobacillus, Bifidobacterium species and Lactococcus lactis in lecithin containing freeze-dried beads had good survival stability (above 6Log CFU ml(-1)) at 23 degrees C for 12 weeks. The bacteria in the beads showed 6Log survival by the end of 2 weeks at 37 degrees C. Encapsulated L. casei in the alginate beads containing lecithin were also more stable in the yoghurt than the beads without lecithin. SEM analysis of the beads showed an irregular surface for the beads without lecithin.

  18. Microporous novolac-derived carbon beads/sulfur hybrid cathode for lithium-sulfur batteries

    NASA Astrophysics Data System (ADS)

    Choudhury, Soumyadip; Krüner, Benjamin; Massuti-Ballester, Pau; Tolosa, Aura; Prehal, Christian; Grobelsek, Ingrid; Paris, Oskar; Borchardt, Lars; Presser, Volker

    2017-07-01

    Novolac-derived nanoporous carbon beads were used as conductive matrix for lithium-sulfur battery cathodes. We employed a facile self-emulsifying synthesis to obtain sub-micrometer novolac-derived carbon beads with nanopores. After pyrolysis, the carbon beads showed already a specific surface area of 640 m2 g-1 which was increased to 2080 m2 g-1 after physical activation. The non-activated and the activated carbon beads represent nanoporous carbon with a medium and a high surface area, respectively. This allows us to assess the influence of the porosity on the electrochemical performance of lithium-sulfur battery cathodes. The carbon/sulfur hybrids were obtained from two different approaches of sulfur infiltration: melt-infusion of sulfur (annealing) and in situ formation of sulfur from sodium thiosulfate. The best performance (∼880 mAh gsulfur-1 at low charge rate; 5th cycle) and high performance stability (>600 mAh gsulfur-1 after 100 cycles) were found for the activated carbon beads when using melt infusion of sulfur.

  19. Selective accumulation of harmful compounds by the DNA-inorganic hybrid-immobilized glass bead.

    PubMed

    Yamada, Masanori; Hamai, Akari

    2009-08-11

    Previously, we reported the DNA-inorganic hybrid material including double-stranded DNA by mixing the aqueous DNA solution and silane coupling reagents. Here, we immobilized the DNA-inorganic hybrid material onto the glass bead and prepared the DNA-immobilized glass bead column. The DNA-immobilized glass beads were stable in water and the amount of eluted DNA from the DNA-glass beads did not change for more than 1 week. Additionally, this DNA-immobilized column selectively accumulated the harmful compounds with the planar structure, such as dioxin- and polychlorinated biphenyl (PCB)-derivatives, and these accumulation percentages were 50-70%. Furthermore, the DNA-immobilized glass bead was recycled nine times by the application of ethanol solution and the accumulative ratio was maintained at more than 60% and did not appear to be decreasing. Therefore, these DNA-columns might have a potential for the selective removal and separation of DNA-intercalating molecules and harmful compounds with the planar structure from experimental or industrial drainages.

  20. Calcium gluconate as cross-linker improves survival and shelf life of encapsulated and dried Metarhizium brunneum and Saccharomyces cerevisiae for the application as biological control agents.

    PubMed

    Humbert, Pascal; Przyklenk, Michael; Vemmer, Marina; Patel, Anant V

    2017-02-01

    Calcium chloride (CC) is the most common cross-linker for the encapsulation of biocontrol microorganisms in alginate beads. The aim of this study was to evaluate if calcium gluconate (CG) can replace CC as cross-linker and at the same time improve viability after drying and rehydration, hygroscopic properties, shelf life and nutrient supply. Hence, the biocontrol fungi Metarhizium brunneum and Saccharomyces cerevisiae were encapsulated in Ca-alginate beads supplemented with starch. Beads were dried and maximum survival was found in beads cross-linked with CG. Beads prepared with CG showed lower hygroscopic properties, but a higher shelf life for encapsulated fungi. Moreover, we demonstrated that gluconate has a nutritive effect on encapsulated fungi, leading to increased mycelium growth of M. brunneum and to enhanced CO 2 release from beads containing Saccharomyces cerevisiae. The application of CG as cross-linker will pave the way towards increasing drying survival and shelf life of various, especially drying-sensitive microbes.

  1. Characterisation of bare and tannase-loaded calcium alginate beads by microscopic, thermogravimetric, FTIR and XRD analyses.

    PubMed

    Larosa, Claudio; Salerno, Marco; de Lima, Juliana Silva; Merijs Meri, Remo; da Silva, Milena Fernandes; de Carvalho, Luiz Bezerra; Converti, Attilio

    2018-08-01

    Incorporating enzymes into calcium alginate beads is an effective method to immobilise them and to preserve, at the same time, their catalytic activity. Sodium alginate was mixed with Aspergillus ficuum tannase in aqueous solution, and tannase-loaded calcium alginate beads were prepared using a simple droplet-based microfluidic system. Extensive experimental analysis was carried out to characterise the samples. Microscopic imaging revealed morphological differences between the surfaces of bare alginate matrix and tannase-loaded alginate beads. Thermal analysis allowed assessing the hydration contents of alginate and revealed the presence of tannase entrapped in the loaded beads, which was confirmed by vibrational spectroscopy. X-ray diffraction allowed us to conclude that alginate of tannase-loaded beads is not crystalline, which would make them suitable as carriers for possible controlled release. Moreover, they could be used in food applications to improve tea quality or clarify juices. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Microinjection--a tool to study gravitropism

    NASA Technical Reports Server (NTRS)

    Scherp, P.; Hasenstein, K. H.

    2003-01-01

    Despite extensive studies on plant gravitropism this phenomenon is still poorly understood. The separation of gravity sensing, signal transduction and response is a common concept but especially the mechanism of gravisensing remains unclear. This paper focuses on microinjection as powerful tool to investigate gravisensing in plants. We describe the microinjection of magnetic beads in rhizoids of the green alga Chara and related subsequent manipulation of the gravisensing system. After injection, an external magnet can control the movement of the magnetic beads. We demonstrate successful injection of magnetic beads into rhizoids and describe a multitude of experiments that can be carried out to investigate gravitropism in Chara rhizoids. In addition to examining mechanical properties, bead microinjection is also useful for probing the function of the cytoskeleton by coating beads with drugs that interfere with the cytoskeleton. The injection of fluorescently labeled beads or probes may reveal the involvement of the cytoskeleton during gravistimulation and response in living cells. c2003 COSPAR. Published by Elsevier Ltd. All rights reserved.

  3. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wahyuni, Wulan Tri, E-mail: wulantriws@gmail.com; Department of Chemistry, FMIPA, Universitas Indonesia, Kampus UI Depok; Ivandini, Tribidasari A.

    Biomolecule modified magnetic beads has been widely used in separation and sensing process. This study used streptavidin modified magnetic beads to immobilize biotin modified zanamivir. Biotin-streptavidin affinity facilitates immobilization of zanamivir on magnetic beads. Then interaction of zanamivir and neuraminidase was adopted as basic for enzyme detection. Detection of neuraminidase was performed at gold modified BDD using cyclic voltammetry technique. The measurement was carried out based on alteration of electrochemical signals of working electrode as neuraminidase response. The result showed that zanamivir was successfully immobilized on magnetic beads. The optimum amount of magnetic beads for zanamivir immobilization was 120 ug.more » Linear responses of neuraminidase were detected in concentration range of 0-15 mU. Detection limit (LOD) of measurement was 2.32 mU (R2 = 0.959) with precision as % RSD of 1.41%. Measurement of neuraminidase on magnetic beads could be also performed in the presence of mucin matrix. The linearity range was 0-8 mU with LOD of 0.64 mU (R2 = 0.950) and % RSD of 7.25%.« less

  4. Viscosity of dilute suspensions of rigid bead arrays at low shear: accounting for the variation in hydrodynamic stress over the bead surfaces.

    PubMed

    Allison, Stuart A; Pei, Hongxia

    2009-06-11

    In this work, we examine the viscosity of a dilute suspension of irregularly shaped particles at low shear. A particle is modeled as a rigid array of nonoverlapping beads of variable size and geometry. Starting from a boundary element formalism, approximate account is taken of the variation in hydrodynamic stress over the surface of the individual beads. For a touching dimer of two identical beads, the predicted viscosity is lower than the exact value by 5.2%. The methodology is then applied to several other model systems including tetramers of variable conformation and linear strings of touching beads. An analysis is also carried out of the viscosity and translational diffusion of several dilute amino acids and diglycine in water. It is concluded that continuum hydrodynamic modeling with stick boundary conditions is unable to account for the experimental viscosity and diffusion data simultaneously. A model intermediate between "stick" and "slip" could possibly reconcile theory and experiment.

  5. Disintegration of Nannochloropsis sp. cells in an improved turbine bead mill.

    PubMed

    Pan, Zhidong; Huang, Ying; Wang, Yanmin; Wu, Zhiwei

    2017-12-01

    The Nannochloropsis sp. cells in aqueous solution were disintegrated in an improved bead mill with turbine agitator. The disintegration rates of cell samples disrupted under various operating parameters (i.e., circumferential speed, bead size, disintegration time, and cell concentration) were analyzed. An experimental strategy to optimize the parameters affecting the cell disintegration process was proposed. The results show that Nannochloropsis sp. cells can be effectively disintegrated in the turbine stirred bead mill under the optimum condition (i.e., circumferential speed of 2.3m/s, concentration of 15vol.%, disintegration time of 40min and bead size of 0.3-0.4mm). The disintegration mechanism was discussed via the selection and breakage functions from population balance modelling. It is revealed that the impact and compression effects of stirring beads are more effective for the disruption of coarser fraction of cells, and the shear effect dominates the production of finer fractions of disintegrated cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Spot Surface Labeling of Magnetic Microbeads and Application in Biological Force Measurements

    NASA Astrophysics Data System (ADS)

    Estes, Ashley; O'Brien, E. Tim; Hill, David; Superfine, Richard

    2006-11-01

    Biological force measurements on single molecules and macromolecular structures often use microbeads for the application of force. These techniques are often complicated by multiple attachments and nonspecific binding. In one set of experiments, we are applying a magnetic force microscope that allows us to pull on magnetic beads attached to ciliated human bronchial epithelial cells. These experiments provide a means to measure the stall force of cilia and understand how cilia propel fluids. However, because we are using beads with diameters of one and 2.8 microns, and the diameter of human airway cilia is approximately 200 nm, we cannot be assured that the bead is bound to a single cilium. To address this, we have developed a sputter coating technique to block the biotin binding capability of the streptavidin labeled bead over its entire surface except for a small spot. These beads may also have applications in other biological experiments such as DNA force experiments in which binding of a single target to an individual bead is critical.

  7. Design, formulation and evaluation of Aloe vera chewing gum

    PubMed Central

    Aslani, Abolfazl; Ghannadi, Alireza; Raddanipour, Razieh

    2015-01-01

    Background: Aloe vera has antioxidant, antiinflammatory, healing, antiseptic, anticancer and antidiabetic effects. The aim of the present study was to design and evaluate the formulation of Aloe vera chewing gum with an appropriate taste and quality with the indications for healing oral wounds, such as lichen planus, mouth sores caused by cancer chemotherapy and mouth abscesses as well as reducing mouth dryness caused by chemotherapy. Materials and Methods: In Aloe vera powder, the carbohydrate content was determined according to mannose and phenolic compounds in terms of gallic acid. Aloe vera powder, sugar, liquid glucose, glycerin, sweeteners and different flavors were added to the soft gum bases. In Aloe vera chewing gum formulation, 10% of dried Aloe vera extract entered the gum base. Then the chewing gum was cut into pieces of suitable sizes. Weight uniformity, content uniformity, the organoleptic properties evaluation, releasing the active ingredient in the phosphate buffer (pH, 6.8) and taste evaluation were examined by Latin square method. Results: One gram of Aloe vera powder contained 5.16 ± 0.25 mg/g of phenolic compounds and 104.63 ± 4.72 mg/g of carbohydrates. After making 16 Aloe vera chewing gum formulations, the F16 formulation was selected as the best formulation according to its physicochemical and organoleptic properties. In fact F16 formulation has suitable hardness, lack of adhesion to the tooth and appropriate size and taste; and after 30 min, it released more than 90% of its drug content. Conclusion: After assessments made, the F16 formulation with maltitol, aspartame and sugar sweeteners was selected as the best formulation. Among various flavors used, peppermint flavor which had the most acceptance between consumers was selected. PMID:26605214

  8. Sodium bicarbonate-gelled chitosan beads as mechanically stable carriers for the covalent immobilization of enzymes.

    PubMed

    Wahba, Marwa I

    2018-03-01

    The poor mechanical stability of chitosan has long impeded its industrial utilization as an immobilization carrier. In this study, the mechanical properties of chitosan beads were greatly improved through utilizing the slow rate of the sodium bicarbonate-induced chitosan gelation and combining it with the chemical cross-linking action of glutaraldehyde (GA). The GA-treated sodium bicarbonate-gelled chitosan beads exhibited much better mechanical properties and up to 2.45-fold higher observed activity of the immobilized enzyme (β-D-galactosidase (β-gal)) when compared to the GA-treated sodium tripolyphosphate (TPP)-gelled chitosan beads. The differences between the sodium bicarbonate-gelled and the TPP-gelled chitosan beads were proven visually and also via scanning electron microscopy, elemental analysis, and differential scanning calorimetry. Moreover, the optimum pH, the optimum temperature, the apparent K m , and the apparent V max of the β-gals immobilized onto the two aforementioned types of chitosan beads were determined and compared. A reusability study was also performed. This study proved the superiority of the sodium bicarbonate-gelled chitosan beads as they retained 72.22 ± 4.57% of their initial observed activity during the 13 th reusability cycle whereas the TPP-gelled beads lost their activity during the first four reusability cycles, owing to their fragmentation. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:347-361, 2018. © 2017 American Institute of Chemical Engineers.

  9. A prototype of injector to control and to detect the release of magnetic beads within the constraints of multibifurcation magnetic resonance navigation procedures.

    PubMed

    Bigot, Alexandre; Soulez, Gilles; Martel, Sylvain

    2017-01-01

    An injector equipped with a bead capture and a bead detection system is presented. In the context of magnetic resonance navigation (MRN), in which MRI gradients are used to steer intravascular therapeutic carriers, fast and reliable injection is essential. In this paper, we present a prototype of injector to control and to detect the release of magnetic beads. The injector relies on two distinct subsystems: (1) the capture subsystem, which creates local magnetic force to stop the flow of magnetic beads; and (2) the detection subsystem, which detects flowing beads and generates a trigger signal to start MRI gradient pulses. Both systems rely on small microcoils wound on the tubing. Five-turn microcoils show the best compromise between size and performance. Less than 5 mW of power is required to capture 0.8-mm beads moving in a flow above 5 mL min -1 or when a gradient above 200 mT m -1 is applied. The detection system is not sensitive to noise and detects every 0.8-mm bead in flow rates up to 14 mL m -1 . The prototype of injector shows performance above the requirements inherent to magnetic resonance navigation. This system is a step toward in vivo multibifurcation MRN. Magn Reson Med 77:444-452, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Microfluidic magnetic bead conveyor belt.

    PubMed

    van Pelt, Stijn; Frijns, Arjan; den Toonder, Jaap

    2017-11-07

    Magnetic beads play an important role in the miniaturization of clinical diagnostics systems. In lab-on-chip platforms, beads can be made to link to a target species and can then be used for the manipulation and detection of this species. Current bead actuation systems utilize complex on-chip coil systems that offer low field strengths and little versatility. We demonstrate a novel system based on an external rotating magnetic field and on-chip soft-magnetic structures to focus the field locally. These structures were designed and optimized using finite element simulations in order to create a number of local flux density maxima. These maxima, to which the magnetic beads are attracted, move over the chip surface in a continuous way together with the rotation of the external field, resulting in a mechanism similar to that of a conveyor belt. A prototype was fabricated using PDMS molding techniques mixed with iron powder for the magnetic structures. In the subsequent experiments, a quadrupole electromagnet was used to create the rotating external field. We observed that beads formed agglomerates that rolled over the chip surface, just above the magnetic structures. Field rotation frequencies between 0.1-50 Hz were tested resulting in magnetic bead speeds of over 1 mm s -1 for the highest frequency. With this, we have shown that our novel concept works, combining a simple design and simple operation with a powerful and versatile method for bead actuation. This makes it a promising method for further research and utilization in lab-on-chip systems.

  11. A direct comparison of the performance of ground, beaded and silica-grafted MIPs in HPLC and turbulent flow chromatography applications.

    PubMed

    Fairhurst, Robert E; Chassaing, Christophe; Venn, Richard F; Mayes, Andrew G

    2004-12-15

    Spherical molecularly imprinted polymers (MIPs) specific to the beta-blocker propranolol have been synthesised using two different approaches and compared to traditional ground monolithic MIPs in HPLC and TFC applications. TFC is a LC technique used for rapid extraction of compounds directly from complex matrices. It can be easily coupled to HPLC and MS for automation of an extraction/analysis procedure. Spherical MIP beads were produced using a suspension polymerisation technique and silica/MIP composite beads by grafting MIP to spherical silica particles using a surface-bound initiator species. Synthesis of both beaded and silica-grafted MIPs was more practical than using the traditional grinding method and yields of spherical particles of the required size between 80 and 100% were routinely achieved. Under HPLC conditions, beaded and ground MIP materials showed a degree of chiral separation for all of the nine beta-blockers tested. The beaded MIP, however, showed much better flow properties and peak shape than the ground material. Silica-grafted MIP showed some separation in five of the drugs and a large improvement in peak shape and analysis times compared with both ground and beaded MIPs. The materials prepared were also used in extraction columns for Turbulent Flow Chromatography (TFC). Although no imprinting effect was observed under typical TFC conditions, beaded polymer materials showed promise for use as TFC extraction columns due to the good flow properties and clean extracts obtained.

  12. Perfect count: a novel approach for the single platform enumeration of absolute CD4+ T-lymphocytes.

    PubMed

    Storie, Ian; Sawle, Alex; Goodfellow, Karen; Whitby, Liam; Granger, Vivian; Ward, Rosalie Y; Peel, Janet; Smart, Theresa; Reilly, John T; Barnett, David

    2004-01-01

    The derivation of reliable CD4(+) T lymphocyte counts is vital for the monitoring of disease progression and therapeutic effectiveness in HIV(+) individuals. Flow cytometry has emerged as the method of choice for CD4(+) T lymphocyte enumeration, with single-platform technology, coupled with reference counting beads, fast becoming the "gold standard." However, although single-platform, bead-based, sample acquisition requires the ratio of beads to cells to remain unchanged, there is no available method, until recently, to monitor this. Perfect Count beads have been developed to address this issue and to incorporate two bead populations, with different densities, to allow the detection of inadequate mixing. Comparison of the relative proportions of both beads with the manufacture's defined limits enables an internal QC check during sample acquisition. In this study, we have compared CD4(+) T lymphocyte counts, obtained from 104 HIV(+) patients, using TruCount beads with MultiSet software (defined as the predicated method) and the new Perfect Count beads, incorporating an in house sequential gating strategy. We have demonstrated an excellent degree of correlation between the predicate method and the Perfect Count system (r(2) = 0.9955; Bland Altman bias +27 CD4(+) T lymphocytes/microl). The Perfect Count system is a robust method for performing single platform absolute counts and has the added advantage of having internal QC checks. Such an approach enables the operator to identify potential problems during sample preparation, acquisition and analysis. Copyright 2003 Wiley-Liss, Inc.

  13. Opportunities for bead-based multiplex assays in veterinary diagnostic laboratories

    USDA-ARS?s Scientific Manuscript database

    Bead based multiplex assays (BBMA) also referred to as Luminex, MultiAnalyte Profiling or cytometric bead array (CBA) assays, are applicable for high throughput, simultaneous detection of multiple analytes in solution (from several, up to 50-500 analytes within a single, small sample volume). Curren...

  14. Evaluation of the Seismic Characterision of Select Engineered Nanoparticles in Saturated Glass Beads

    EPA Science Inventory

    A laboratory testing apparatus was developed for the study of seismic body wave propagation through nanoparticles dispersed in pore fluid that is essentially saturating glass beads. First, the responses of water-saturated glass bead specimens were studied to establish baseline si...

  15. Freeforming objects with low-binder slurry

    DOEpatents

    Cesarano, III, Joseph; Calvert, Paul D.

    2000-01-01

    In a rapid prototyping system, a part is formed by depositing a bead of slurry that has a sufficient high concentration of particles to be pseudoplastic and almost no organic binders. After deposition the bead is heated to drive off sufficient liquid to cause the bead to become dilatant.

  16. Development of novel indole-3-aldehyde loaded gastro-resistant spray-dried microparticles for post-biotic small intestine local delivery.

    PubMed

    Puccetti, Matteo; Giovagnoli, Stefano; Zelante, Teresa; Romani, Luigina; Ricci, Maurizio

    2018-04-28

    Considering the recent evidences on the therapeutic potential of post-biotics, this study was focused on two mains goals: i) to develop an enteric microparticle (MP) formulation for intestinal localized delivery of Indole-3-aldehyde (3-IAld) (a microbial-derived metabolite produced by the host's lactobacilli during the catabolic pathway of tryptophan); ii) to provide support to the employment of spray-drying as innovative one-step manufacturing technique for enteric products. For this purpose, special attention was taken in the knowledge of the influence of equipment setup and feedstock properties on MP enteric behaviour. Eudragit® S100 and L100 and ethyl cellulose were used as wall materials and NaOH and ethanol solutions as solvent systems. 3-IAld loading was maintained at 10% w/w. As postulated, feedstock properties influenced spray-drying regime. In addition, they prevailed over other spray-drying process factors in determining MP enteric behavior. Albeit the high buckling regime that produced crumped particles, gastro-resistance was obtained by spray-drying 2:1 Eudragit® S100:L100 with 30% w/w ethyl cellulose (EC) in ethanol solution. These results support the use of spray-drying as a method for manufacturing gastro-resistant MP. The obtained 3-IAld loaded enteric MP will be useful to investigate novel post-biotic-based treatments in different therapeutic areas. Copyright © 2018. Published by Elsevier Inc.

  17. Design and evaluation of enteric-coated tablets for rifampicin and isoniazid combinations.

    PubMed

    Wang, Yongjun; Liu, Hongzhuo; Liu, Kai; Sun, Jin; He, Zhonggui

    2013-01-01

    In order to improve the bioavailability of rifampicin (RIF) from rifampicin and isoniazid (INH) combination formulations, the physicochemical characteristics of RIF, stability of RIF in different pH buffers in the presence of INH, as well as the effect of particle size of RIF materials on the dissolution rate were investigated. On the basis of the above examinations, enteric-coated tablets for RIF and INH combinations were designed and prepared. RIF showed low solubility and high apparent distribution coefficient in the intestinal pH (pH 4.0-7.4). With the decrease in pH, the degradation of RIF increase and the presence of INH deepen the degradation. Enteric-coated tablets were prepared after grinding the RIF materials by dry granulation technique. The pharmacokinetics of RIF and INH of self-made enteric-coated tablets in dogs were studied by comparing with the reference tablets. The AUC(0-48) of RIF in both reference and test tablets were 304.77 ± 42.27 and 353.79 ± 31.63 µg·h·mL(-1), respectively. The AUC(0-48) of INH in both reference and test tablets were 17.14 ± 8.59 and 19.62 ± 10.57 µg·h·mL(-1), respectively. Enteric-coated tablets may minimize the decomposition of RIF in gastrointestinal tract and improve the bioavailability.

  18. 75 FR 73159 - Continental Tire North America, Inc., Receipt of Petition for Decision of Inconsequential...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-29

    ... is located in an area that is not more than one-fourth of the distance from the bead to the shoulder... the bead and a point one-half the distance from the bead to the shoulder of the tire, on at least one...

  19. EMP Design Guidelines for Naval Ship Systems

    DTIC Science & Technology

    1975-08-22

    le xc Ci .ube irret i Type FXC it LA 38 Beads 4 * 1 svj- I * 1 1 \\ Measured 3( )0 Beads V i i V 30 Bead 1 s...ATTN: R. W. Rostrom RCA Corporation Government & Commercial Systems Astro Electronics Division P. 0. Box 800 Princeton, New Jersey 08540 ATTN

  20. Method for freeforming objects with low-binder slurry

    DOEpatents

    Cesarano, III, Joseph; Calvert, Paul D.

    2002-01-01

    In a rapid prototyping system, a part is formed by depositing a bead of slurry that has a sufficient high concentration of particles to be pseudoplastic and almost no organic binders. After deposition the bead is heated to drive off sufficient liquid to cause the bead to become dilatant.

  1. Nutrient requirements and other factors involved in the culture of human kidney cells on microcarrier beads

    NASA Technical Reports Server (NTRS)

    Lewis, Marian L.; Morrison, Dennis R.

    1987-01-01

    The culture of human kidney cells on microcarrier beads in the Bioprocessing Laboratory at the Johnson Space Center is described. These were the first series of studies performed before and during 1983 to determine optimum conditions, including medium type, bead type and density. The composition of several medium types and the molecular weights of some common culture medium supplements and cellular proteins are included. The microgravity cell-to-bead attachment experiment performed on Space Transportation System Flight 8 is described.

  2. Metallic Bead Detection by Using Eddy-Current Probe with SV-GMR Sensor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yamada, S.; Chomsuwan, K.; Hagino, T.

    2005-04-09

    The progress of the ECT probe with micro magnetic sensor becomes possible to apply to various applications. The detection of micro metallic bead used for electric packaging has been reported in this paper. We proposed micro ECT probes with meander coil as exciter and spin-valve giant magneto-resistance (SV-GMR) as receiver. Micro metallic bead(solder ball) with the diameter of 0.25 to 0.76 mm is used as a measuring object. We discuss the detection and alignment of metallic bead by using ECT technique.

  3. Note: A quartz cell with Pt single crystal bead electrode for electrochemical scanning tunneling microscope measurements.

    PubMed

    Xia, Zhigang; Wang, Jihao; Hou, Yubin; Lu, Qingyou

    2014-09-01

    In this paper, we provide and demonstrate a design of a unique cell with Pt single crystal bead electrode for electrochemical scanning tunneling microscope (ECSTM) measurements. The active metal Pt electrode can be protected from air contamination during the preparation process. The transparency of the cell allows the tip and bead to be aligned by direct observation. Based on this, a new and effective alignment method is introduced. The high-quality bead preparations through this new cell have been confirmed by the ECSTM images of Pt (111).

  4. Single molecule actuation and detection on a lab-on-a-chip magnetoresistive platform

    NASA Astrophysics Data System (ADS)

    Chaves, R. C.; Bensimon, D.; Freitas, P. P.

    2011-03-01

    On-chip magnetic tweezers based on current loops were integrated with magnetoresistive sensors. Magnetic forces up to 1.0±0.3pN are produced to actuate on DNA anchored to the surface of a flow cell and labeled with micrometer-sized magnetic beads. The levitation of the beads stretches the immobilized DNA. The relative position of the magnetic beads is monitored using spin-valve sensors. A bead vertical displacement resolution of 60nm is derived for DNA molecular motor activity in a tweezer steady current regime.

  5. Single Cell Detection with Driven Magnetic Beads

    NASA Astrophysics Data System (ADS)

    McNaughton, B. H.; Agayan, R. R.; Stoica, V. A.; Clarke, R.; Kopelman, R.

    Shifts in the nonlinear rotational frequency of magnetic beads (microspheres) offer a new and dynamic approach for the detection of single cells. We present the first demonstration of this capability by measuring the changes in the nonlinear rotational frequency of magnetic beads driven by an external magnetic field. The presence of an Escherichia coli bacterium on the surface of a 2.0 μm magnetic bead affects the drag of the system, thus changing the nonlinear rotation rate. Measurement of this rotational frequency is straight-forward utilizing standard microscopy techniques.

  6. “Nanofiltration” Enabled by Super-Absorbent Polymer Beads for Concentrating Microorganisms in Water Samples

    NASA Astrophysics Data System (ADS)

    Xie, Xing; Bahnemann, Janina; Wang, Siwen; Yang, Yang; Hoffmann, Michael R.

    2016-02-01

    Detection and quantification of pathogens in water is critical for the protection of human health and for drinking water safety and security. When the pathogen concentrations are low, large sample volumes (several liters) are needed to achieve reliable quantitative results. However, most microbial identification methods utilize relatively small sample volumes. As a consequence, a concentration step is often required to detect pathogens in natural waters. Herein, we introduce a novel water sample concentration method based on superabsorbent polymer (SAP) beads. When SAP beads swell with water, small molecules can be sorbed within the beads, but larger particles are excluded and, thus, concentrated in the residual non-sorbed water. To illustrate this approach, millimeter-sized poly(acrylamide-co-itaconic acid) (P(AM-co-IA)) beads are synthesized and successfully applied to concentrate water samples containing two model microorganisms: Escherichia coli and bacteriophage MS2. Experimental results indicate that the size of the water channel within water swollen P(AM-co-IA) hydrogel beads is on the order of several nanometers. The millimeter size coupled with a negative surface charge of the beads are shown to be critical in order to achieve high levels of concentration. This new concentration procedure is very fast, effective, scalable, and low-cost with no need for complex instrumentation.

  7. Raman signatures of the modern pigment (Zn,Cd)S1-xSex and glass matrix of a red bead from Magoro Hill, an archaeological site in Limpopo Province, South Africa, recalibrate the settlement chronology

    NASA Astrophysics Data System (ADS)

    Prinsloo, Linda C.; Boeyens, Jan C. A.; van der Ryst, Maria M.; Webb, Geoffrey

    2012-09-01

    Two glass trade beads, one red and one yellow, retrieved from a secure archaeological context on Magoro Hill, an erstwhile Venda stronghold in South Africa's Limpopo Province, were analyzed with Raman and photoluminescence spectroscopy. Raman spectroscopy identified the pigment coloring the yellow bead as lead tin yellow Type II and the glass as a typical soda-lime-silica glass. Both pigments and glass type were in use over a long time span and therefore the bead cannot be used as a temporal marker. The pigment coloring the red bead, on the other hand, was identified as nano-(Zn,Cd)S1-xSex mixed crystals, a pigment that was only widely used in the early 20th century. This date casts doubt on local oral tradition that associates the brick-built structure from which the beads were recovered with Manzinzinzi, a Venda chief who, according to contemporary documentary accounts, had already passed away in the 1880s. The more recent date for the red bead resolves the apparent discord between the oral and written records, suggesting that the building was probably erected and/or occupied by one of Manzinzinzi's successors.

  8. PHOS-Select Iron Affinity beads enrich peptides for detection of organophosphorus adducts on albumin

    PubMed Central

    Jiang, Wei; Dubrovskii, Yaroslav A; Podolskaya, Ekaterina P; Murashko, Ekaterina A; Babakov, Vladimir; Nachon, Florian; Masson, Patrick; Schopfer, Lawrence M; Lockridge, Oksana

    2013-01-01

    Albumin is covalently modified by organophosphorus toxicants (OP) on tyrosine 411, but less than 1% of albumin is modified in humans by lethal OP doses that inhibit 95% of plasma butyrylcholinesterase. A method that enriches OP-modified albumin peptides could aid analysis of low dose exposures. Soman or chlorpyrifos oxon treated human plasma was digested with pepsin. Albumin peptides were enriched by binding to Fe3+ beads at pH 11 and eluted with pH 2.6 buffer. Similarly, mouse and guinea pig albumin modified by chlorpyrifos oxon were digested with pepsin and enriched by binding to Fe3+ beads. Peptides were identified by MALDI-TOF/TOF mass spectrometry. PHOS-select Iron Affinity beads specifically enriched albumin peptides VRY411TKKVPQVST and LVRY411TKKVPQVST in a pepsin digest of human plasma. The unmodified as well as OP-modified peptides bound to the beads. The binding capacity of 500 μl beads was the pepsin digest of 2.1 μL human plasma. The limit of detection was 0.2% of OP-modified albumin peptide in 0.43 μL plasma. Enrichment of OP-modified albumin peptides by binding to Fe3+ beads is a method with potential application to diagnosis of OP pesticide and nerve agent exposure in humans, mice, and guinea pigs. PMID:24187955

  9. Rapid Detection of Enterobacter Sakazakii in milk Powder using amino modified chitosan immunomagnetic beads.

    PubMed

    Zhu, Yinglian; Wang, Dongfeng

    2016-12-01

    Chitosan immunomagnetic beads (CIBs) were first prepared through converting hydroxyl groups of natural polymer material-chitosan into amino groups using epichlorohydrin and ethylenediamine as modification agent and then coupling with polyclonal antibodies of Enterobacter sakazakii using glutaraldehyde as cross-linking agent. The beads before coupling with antibodies were characterized by magnetic property measurement, FTIR, SEM and XRD technologies. In the assay a natural polysaccharide-chitosan, which has good biological and chemical properties such as non-toxicity, biocompatibility and high chemical reactivity was first used for synthesis of immunomagnetic beads. The detection method first established in this paper that combined the beads with chromogenic medium together to rapid detect E. sakazakii in milk powder could greatly improve the detection specificity and working efficiency. The beads exhibited a maximum capturing capacity of 1×10 6 cfu/g with the detection sensitivity of 4cfu/g. The results demonstrate that the assay is a straightforward, specific and sensitive alternative for rapid detection of E.sakazakii in food matrix. The total analysis time was as little as about 25h, which greatly shorten the detection time. The method can provides new ideas not only to preparation technique of immunomagnetic beads but to imunne detection technique in food safety. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Multiple pathogen biomarker detection using an encoded bead array in droplet PCR.

    PubMed

    Periyannan Rajeswari, Prem Kumar; Soderberg, Lovisa M; Yacoub, Alia; Leijon, Mikael; Andersson Svahn, Helene; Joensson, Haakan N

    2017-08-01

    We present a droplet PCR workflow for detection of multiple pathogen DNA biomarkers using fluorescent color-coded Luminex® beads. This strategy enables encoding of multiple singleplex droplet PCRs using a commercially available bead set of several hundred distinguishable fluorescence codes. This workflow provides scalability beyond the limited number offered by fluorescent detection probes such as TaqMan probes, commonly used in current multiplex droplet PCRs. The workflow was validated for three different Luminex bead sets coupled to target specific capture oligos to detect hybridization of three microorganisms infecting poultry: avian influenza, infectious laryngotracheitis virus and Campylobacter jejuni. In this assay, the target DNA was amplified with fluorescently labeled primers by PCR in parallel in monodisperse picoliter droplets, to avoid amplification bias. The color codes of the Luminex detection beads allowed concurrent and accurate classification of the different bead sets used in this assay. The hybridization assay detected target DNA of all three microorganisms with high specificity, from samples with average target concentration of a single DNA template molecule per droplet. This workflow demonstrates the possibility of increasing the droplet PCR assay detection panel to detect large numbers of targets in parallel, utilizing the scalability offered by the color-coded Luminex detection beads. Copyright © 2017. Published by Elsevier B.V.

  11. Microparticle sampling by electrowetting-actuated droplet sweeping.

    PubMed

    Zhao, Yuejun; Cho, Sung Kwon

    2006-01-01

    This paper describes a new microparticle sampler where particles can be efficiently swept from a solid surface and sampled into a liquid medium using moving droplets actuated by the electrowetting principle. We successfully demonstrate that super hydrophilic (2 microm and 7.9 microm diameter glass beads of about 14 degrees contact angle), intermediate hydrophilic (7.5 microm diameter polystyrene beads of about 70 degrees contact angle), and super hydrophobic (7.9 microm diameter Teflon-coated glass beads and 3 microm size PTFE particles of over 110 degrees contact angles) particles on a solid surface are picked up by electrowetting-actuated moving droplets. For the glass beads as well as the polystyrene beads, the sampling efficiencies are over 93%, in particular over 98% for the 7.9 microm glass beads. For the PTFE particles, however, the sampling efficiency is measured at around 70%, relatively lower than that of the glass and polystyrene beads. This is due mainly to the non-uniformity in particle size and the particle hydrophobicity. In this case, the collected particles staying (adsorbing) on the air-to-water interface hinder the droplet from advancing. This particle sampler requires an extremely small amount of liquid volume (about 500 nanoliters) and will thus be highly compatible and easily integrated with lab-on-a-chip systems for follow-up biological/chemical analyses.

  12. Organization of microbeads in Leidenfrost drops.

    PubMed

    Maquet, Laurent; Colinet, Pierre; Dorbolo, Stéphane

    2014-06-21

    We investigated the organization of micrometric hydrophilic beads (glass or basalt) immersed in Leidenfrost drops. Starting from a large volume of water compared to the volume of the beads, while the liquid evaporates, we observed that the grains are eventually trapped at the interface of the droplet and accumulate. At a moment, the grains entirely cover the droplet. We measured the surface area at this moment as a function of the total mass of particles inserted in the droplet. We concluded that the grains form a monolayer around the droplet assuming (i) that the packing of the beads at the surface is a random close packing and (ii) that the initial surface of the drop is larger than the maximum surface that the beads can cover. Regarding the evaporation dynamics, the beads are found to reduce the evaporation rate of the drop. The slowdown of the evaporation is interpreted as being the consequence of the dewetting of the particles located at the droplet interface which makes the effective surface of evaporation smaller. As a matter of fact, contact angles of the beads with the water deduced from the evaporation rates are consistent with contact angles of beads directly measured at a flat air-water interface of water in a container.

  13. Preparation and testing of a tetra-amine copper(II) chitosan bead system for enhanced phosphate remediation.

    PubMed

    Kumar, Ilango Aswin; Viswanathan, Natrayasamy

    2018-03-01

    A tetra-amine copper(II) chitosan bead system (TAC@CS composite beads) was developed by grafting tetra-amine copper(II) (TAC) with chitosan (CS) and utilized for phosphate removal. The prepared TAC@CS composite beads possess enhanced phosphate sorption capacity (SC) of 41.42 ± 0.071 mg/g than copper grafted chitosan (Cu@CS) composite, TAC and chitosan which were found to be 37.01 ± 0.803, 33.20 ± 0.650 and 7.24 ± 0.059 mg/g respectively. In batch mode, various adsorption influencing parameters like contact time, initial phosphate concentration, solution pH, co-anions and temperature were optimized for maximum phosphate sorption. The prepared adsorbents were characterized by FTIR, XRD, UV-Visible, SEM and EDAX analysis. The adsorption isotherms and thermodynamic parameters of the adsorbent were studied. The feasible phosphate uptake mechanism of TAC@CS biocomposite beads was reported. The reusability studies of TAC@CS composite beads were carried out using NaOH as elutant. The suitability of TAC@CS composite beads at field conditions was tested with phosphate contaminated field water samples collected from nearby areas of Dindigul district. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. "Nanofiltration" Enabled by Super-Absorbent Polymer Beads for Concentrating Microorganisms in Water Samples.

    PubMed

    Xie, Xing; Bahnemann, Janina; Wang, Siwen; Yang, Yang; Hoffmann, Michael R

    2016-02-15

    Detection and quantification of pathogens in water is critical for the protection of human health and for drinking water safety and security. When the pathogen concentrations are low, large sample volumes (several liters) are needed to achieve reliable quantitative results. However, most microbial identification methods utilize relatively small sample volumes. As a consequence, a concentration step is often required to detect pathogens in natural waters. Herein, we introduce a novel water sample concentration method based on superabsorbent polymer (SAP) beads. When SAP beads swell with water, small molecules can be sorbed within the beads, but larger particles are excluded and, thus, concentrated in the residual non-sorbed water. To illustrate this approach, millimeter-sized poly(acrylamide-co-itaconic acid) (P(AM-co-IA)) beads are synthesized and successfully applied to concentrate water samples containing two model microorganisms: Escherichia coli and bacteriophage MS2. Experimental results indicate that the size of the water channel within water swollen P(AM-co-IA) hydrogel beads is on the order of several nanometers. The millimeter size coupled with a negative surface charge of the beads are shown to be critical in order to achieve high levels of concentration. This new concentration procedure is very fast, effective, scalable, and low-cost with no need for complex instrumentation.

  15. Structuring and calorie control of bakery products by templating batter with ultra melt-resistant food-grade hydrogel beads.

    PubMed

    Thompson, Benjamin R; Horozov, Tommy S; Stoyanov, Simeon D; Paunov, Vesselin N

    2017-08-01

    We report the use of a temperature insensitive, food-grade hydrogel to reduce the caloric density of pancakes that were prepared at temperatures much higher than the boiling point of water. This cheap, facile method utilises a mixed agar-methylcellulose hydrogel, which was blended to produce a slurry of hydrogel microbeads. The pancake batter was mixed with a controlled volume percentage of slurry of hydrogel beads and cooked. From bomb calorimetry experiments, the composites were found to have a reduced caloric density that reflects the volume percentage of hydrogel beads mixed with the batter. Using this procedure, we were able to reduce the caloric density of pancakes by up to 23 ± 3% when the volume percentage of hydrogel beads initially used was 25%. The method is not limited to pancakes and could potentially be applied to various other food products. The structure and morphology of the freeze-dried pancakes and pancake-hydrogel composites were investigated and pores of a similar size to the hydrogel beads were found, confirming that the gel beads maintained their structure during the cooking process. There is scope for further development of this method by the encapsulation of nutritionally beneficial or flavour enhancing ingredients within the hydrogel beads.

  16. Graphene oxide/alginate beads as adsorbents: Influence of the load and the drying method on their physicochemical-mechanical properties and adsorptive performance.

    PubMed

    Platero, Emiliano; Fernandez, Maria Emilia; Bonelli, Pablo Ricardo; Cukierman, Ana Lea

    2017-04-01

    Graphene oxide/alginate beads were prepared from lab-synthesized graphene oxide, varying its content within the beads (0.05, 0.125, and 0.25wt.%). Ethanol-drying and lyophilization were compared as drying methods to obtain suitable adsorbents which were later tested to the removal of a model organic molecule (methylene blue). The morphological and textural properties of all the beads were characterized by scanning electron microscopy and N 2 adsorption/desorption isotherms at -196°C, respectively. Limited porosity was obtained for all cases (S BET <60m 2 /g). Uniaxial compression tests were performed to assess the mechanical properties of the beads. Ethanol-dried ones exhibited higher Young's elasticity modulus (E=192kPa) than the lyophilized samples (twice at 0.25wt.% graphene oxide loading), which disclosed breakage points at lower deformation percentages. Adsorption experiments were conducted and dye adsorption isotherms were obtained for the beads with the best removal performance. The experimental data were better fitted by the Langmuir model. The highest maximum adsorption capacity (4.25mmol/g) was obtained for the lyophilized beads with the highest graphene oxide content. Mechanical properties were found to be affected also by the dye adsorption. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Blood Compatibility of Sulfonated Cladophora Nanocellulose Beads.

    PubMed

    Rocha, Igor; Lindh, Jonas; Hong, Jaan; Strømme, Maria; Mihranyan, Albert; Ferraz, Natalia

    2018-03-07

    Sulfonated cellulose beads were prepared by oxidation of Cladophora nanocellulose to 2,3-dialdehyde cellulose followed by sulfonation using bisulfite. The physicochemical properties of the sulfonated beads, i.e., high surface area, high degree of oxidation, spherical shape, and the possibility of tailoring the porosity, make them interesting candidates for the development of immunosorbent platforms, including their application in extracorporeal blood treatments. A desired property for materials used in such applications is blood compatibility; therefore in the present work, we investigate the hemocompatibility of the sulfonated cellulose beads using an in vitro whole blood model. Complement system activation (C3a and sC5b-9 levels), coagulation activation (thrombin-antithrombin (TAT) levels) and hemolysis were evaluated after whole blood contact with the sulfonated beads and the results were compared with the values obtained with the unmodified Cladophora nanocellulose. Results showed that neither of the cellulosic materials presented hemolytic activity. A marked decrease in TAT levels was observed after blood contact with the sulfonated beads, compared with Cladophora nanocellulose. However, the chemical modification did not promote an improvement in Cladophora nanocellulose hemocompatibility in terms of complement system activation. Even though the sulfonated beads presented a significant reduction in pro-coagulant activity compared with the unmodified material, further modification strategies need to be investigated to control the complement activation by the cellulosic materials.

  18. “Nanofiltration” Enabled by Super-Absorbent Polymer Beads for Concentrating Microorganisms in Water Samples

    PubMed Central

    Xie, Xing; Bahnemann, Janina; Wang, Siwen; Yang, Yang; Hoffmann, Michael R.

    2016-01-01

    Detection and quantification of pathogens in water is critical for the protection of human health and for drinking water safety and security. When the pathogen concentrations are low, large sample volumes (several liters) are needed to achieve reliable quantitative results. However, most microbial identification methods utilize relatively small sample volumes. As a consequence, a concentration step is often required to detect pathogens in natural waters. Herein, we introduce a novel water sample concentration method based on superabsorbent polymer (SAP) beads. When SAP beads swell with water, small molecules can be sorbed within the beads, but larger particles are excluded and, thus, concentrated in the residual non-sorbed water. To illustrate this approach, millimeter-sized poly(acrylamide-co-itaconic acid) (P(AM-co-IA)) beads are synthesized and successfully applied to concentrate water samples containing two model microorganisms: Escherichia coli and bacteriophage MS2. Experimental results indicate that the size of the water channel within water swollen P(AM-co-IA) hydrogel beads is on the order of several nanometers. The millimeter size coupled with a negative surface charge of the beads are shown to be critical in order to achieve high levels of concentration. This new concentration procedure is very fast, effective, scalable, and low-cost with no need for complex instrumentation. PMID:26876979

  19. Alginate-caseinate composites: Molecular interactions and characterization of cross-linked beads for the delivery of anticandidals.

    PubMed

    Khlibsuwan, Rapee; Khunkitti, Watcharee; Pongjanyakul, Thaned

    2018-04-19

    Polysaccharide-protein composites offer potential utility for the delivery of drugs. The objectives of this work were to investigate the molecular interactions between sodium alginate (SA) and sodium caseinate (SC) in dispersions and films and to characterize calcium alginate (CA) beads mixed with SC for the delivery of fluconazole (FZ) and clotrimazole (CZ). The results demonstrated that SA could interact with SC, which caused a viscosity synergism in the dispersions. Hydrogen bonding between the carboxyl or hydroxyl groups of SA and the amide groups of SC led to the formation of soluble complexes that could reinforce the CA beads prepared by calcium cross-linking. The SC-CA beads provided higher drug entrapment efficiency, lower water uptake and erosion, and slower drug release than for the CA beads. The loaded FZ was an amorphous form, but CZ crystals were embedded in the bead matrix due to the low water solubility of this drug. However, SC micellization could enhance the water solubility and efficacy of CZ against Candida albicans. This finding indicates that SA can interact with SC via hydrogen bonding to form complexes and that the anticandidal-loaded SC-CA beads can be used as drug delivery systems and drug reservoirs in tablets for oral candidiasis. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. A new dimension in retrograde flow: centripetal movement of engulfed particles.

    PubMed Central

    Caspi, A; Yeger, O; Grosheva, I; Bershadsky, A D; Elbaum, M

    2001-01-01

    Centripetal motion of surface-adherent particles is a classic experimental system for studying surface dynamics on a eukaryotic cell. To investigate bead migration over the entire cell surface, we have developed an experimental assay using multinuclear giant fibroblasts, which provide expanded length scales and an unambiguous frame of reference. Beads coated by adhesion ligands concanavalin A or fibronectin are placed in specific locations on the cell using optical tweezers, and their subsequent motion is tracked over time. The adhesion, as well as velocity and directionality of their movement, expose distinct regions of the cytoplasm and membrane. Beads placed on the peripheral lamella initiate centripetal motion, whereas beads placed on the central part of the cell attach to a stationary cortex and do not move. Careful examination by complementary three-dimensional methods shows that the motion of a bead placed on the cell periphery takes place after engulfment into the cytoplasm, whereas stationary beads, placed near the cell center, are not engulfed. These results demonstrate that centripetal motion of adhering particles may occur inside as well as outside the cell. Inhibition of actomyosin activity is used to explore requirements for engulfment and aspects of the bead movement. Centripetal movement of adherent particles seems to depend on mechanisms distinct from those driving overall cell contractility. PMID:11566772

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