WorldWideScience

Sample records for delivery basket functionality

  1. Assembling Appliances Standards from a Basket of Functions

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    Siderious, Hans-Paul; Meier, Alan

    2014-08-11

    Rapid innovation in product design challenges the current methodology for setting standards and labels, especially for electronics, software and networking. Major problems include defining the product, measuring its energy consumption, and choosing the appropriate metric and level for the standard. Most governments have tried to solve these problems by defining ever more specific product subcategories, along with their corresponding test methods and metrics. An alternative approach would treat each energy-using product as something that delivers a basket of functions. Then separate standards would be constructed for the individual functions that can be defined, tested, and evaluated. Case studies of thermostats, displays and network equipment are presented to illustrate the problems with the classical approach for setting standards and indicate the merits and drawbacks of the alternative. The functional approach appears best suited to products whose primary purpose is processing information and that have multiple functions.

  2. Trapping of organophosphorus chemical nerve agents in water with amino acid functionalized baskets.

    Science.gov (United States)

    Ruan, Yian; Dalkiliç, Erdin; Peterson, Paul W; Pandit, Aroh; Dastan, Arif; Brown, Jason D; Polen, Shane M; Hadad, Christopher M; Badjić, Jovica D

    2014-04-07

    We prepared eleven amino-acid functionalized baskets and used (1) H NMR spectroscopy to quantify their affinity for entrapping dimethyl methylphosphonate (DMMP, 118 Å(3) ) in aqueous phosphate buffer at pH=7.0±0.1; note that DMMP guest is akin in size to chemical nerve agent sarin (132 Å(3) ). The binding interaction (Ka ) was found to vary with the size of substituent groups at the basket's rim. In particular, the degree of branching at the first carbon of each substituent had the greatest effect on the host-guest interaction, as described with the Verloop's B1 steric parameter. The branching at the remote carbons, however, did not perturb the encapsulation, which is important for guiding the design of more effective hosts and catalysts in future.

  3. Twisted baskets.

    Science.gov (United States)

    Hermann, Keith; Pratumyot, Yaowalak; Polen, Shane; Hardin, Alex M; Dalkilic, Erdin; Dastan, Arif; Badjić, Jovica D

    2015-02-23

    A preparative procedure for obtaining a pair of twisted molecular baskets, each comprising a chiral framework with either right ((P)-1syn) or left ((M)-1syn) sense of twist and six ester groups at the rim has been developed and optimized. The racemic (P/M)-1syn can be obtained in three synthetic steps from accessible starting materials. The resolution of (P/M)-1syn is accomplished by its transesterification with (1R,2S,5R)-(-)-menthol in the presence of a Ti(IV) catalyst to give diastereomeric 8(P) and 8(M). It was found that dendritic-like cavitands 8(P) and 8(M), in CD2Cl2, undergo self-inclusion ((1)H NMR spectroscopy) with a menthol moiety occupying the cavity of each host. Importantly, the degree of inclusion of the menthol group was ((1)H NMR spectroscopy) found to be greater in the case of 8(P) than 8(M). Accordingly, it is suggested that different folding characteristic of 8(P) and 8(M) ought to affect the physicochemical characteristics of the hosts to permit their effective separation by column chromatography. The absolute configuration of 8(P)/8(M), encompassing right- and left-handed "cups", was determined with the exciton chirality method and also verified in silico (DFT: B3LYP/TZVP). Finally, the twisted baskets are strongly fluorescent due to three naphthalene chromophores, having a high fluorescence quantum yield within the rigid framework of 8(P)/8(M).

  4. Neuronal Dystroglycan Is Necessary for Formation and Maintenance of Functional CCK-Positive Basket Cell Terminals on Pyramidal Cells.

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    Früh, Simon; Romanos, Jennifer; Panzanelli, Patrizia; Bürgisser, Daniela; Tyagarajan, Shiva K; Campbell, Kevin P; Santello, Mirko; Fritschy, Jean-Marc

    2016-10-05

    Distinct types of GABAergic interneurons target different subcellular domains of pyramidal cells, thereby shaping pyramidal cell activity patterns. Whether the presynaptic heterogeneity of GABAergic innervation is mirrored by specific postsynaptic factors is largely unexplored. Here we show that dystroglycan, a protein responsible for the majority of congenital muscular dystrophies when dysfunctional, has a function at postsynaptic sites restricted to a subset of GABAergic interneurons. Conditional deletion of Dag1, encoding dystroglycan, in pyramidal cells caused loss of CCK-positive basket cell terminals in hippocampus and neocortex. PV-positive basket cell terminals were unaffected in mutant mice, demonstrating interneuron subtype-specific function of dystroglycan. Loss of dystroglycan in pyramidal cells had little influence on clustering of other GABAergic postsynaptic proteins and of glutamatergic synaptic proteins. CCK-positive terminals were not established at P21 in the absence of dystroglycan and were markedly reduced when dystroglycan was ablated in adult mice, suggesting a role for dystroglycan in both formation and maintenance of CCK-positive terminals. The necessity of neuronal dystroglycan for functional innervation by CCK-positive basket cell axon terminals was confirmed by reduced frequency of inhibitory events in pyramidal cells of dystroglycan-deficient mice and further corroborated by the inefficiency of carbachol to increase IPSC frequency in these cells. Finally, neurexin binding seems dispensable for dystroglycan function because knock-in mice expressing binding-deficient T190M dystroglycan displayed normal CCK-positive terminals. Together, we describe a novel function of dystroglycan in interneuron subtype-specific trans-synaptic signaling, revealing correlation of presynaptic and postsynaptic molecular diversity.

  5. Tapping Ancient Roots: Plaited Paper Baskets

    Science.gov (United States)

    Patrick, Jane

    2011-01-01

    With ancient roots, basket making has been practiced since the earliest civilizations, and according to textile experts, probably pre-dates pottery. This is partly conjecture since few baskets remain. It is through evidence found in clay impressions that the earliest baskets reveal themselves. Basically, basketry construction is like flat weaving.…

  6. Bounds for Asian basket options

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    Deelstra, Griselda; Diallo, Ibrahima; Vanmaele, Michèle

    2008-09-01

    In this paper we propose pricing bounds for European-style discrete arithmetic Asian basket options in a Black and Scholes framework. We start from methods used for basket options and Asian options. First, we use the general approach for deriving upper and lower bounds for stop-loss premia of sums of non-independent random variables as in Kaas et al. [Upper and lower bounds for sums of random variables, Insurance Math. Econom. 27 (2000) 151-168] or Dhaene et al. [The concept of comonotonicity in actuarial science and finance: theory, Insurance Math. Econom. 31(1) (2002) 3-33]. We generalize the methods in Deelstra et al. [Pricing of arithmetic basket options by conditioning, Insurance Math. Econom. 34 (2004) 55-57] and Vanmaele et al. [Bounds for the price of discrete sampled arithmetic Asian options, J. Comput. Appl. Math. 185(1) (2006) 51-90]. Afterwards we show how to derive an analytical closed-form expression for a lower bound in the non-comonotonic case. Finally, we derive upper bounds for Asian basket options by applying techniques as in Thompson [Fast narrow bounds on the value of Asian options, Working Paper, University of Cambridge, 1999] and Lord [Partially exact and bounded approximations for arithmetic Asian options, J. Comput. Finance 10 (2) (2006) 1-52]. Numerical results are included and on the basis of our numerical tests, we explain which method we recommend depending on moneyness and time-to-maturity.

  7. Biogenesis, delivery, and function of extracellular RNA

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    James G. Patton

    2015-08-01

    Full Text Available The Extracellular RNA (exRNA Communication Consortium was launched by the National Institutes of Health to focus on the extent to which RNA might function in a non-cell-autonomous manner. With the availability of increasingly sensitive tools, small amounts of RNA can be detected in serum, plasma, and other bodily fluids. The exact mechanism(s by which RNA can be secreted from cells and the mechanisms for the delivery and uptake by recipient cells remain to be determined. This review will summarize current knowledge about the biogenesis and delivery of exRNA and outline projects seeking to understand the functional impact of exRNA.

  8. Laparoscopic retrieval of impacted Dormia basket

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    Manash Ranjan Sahoo

    2017-01-01

    Full Text Available For choledocholithiasis, endoscopic management is the first line of treatment. Both Dormia basket and balloon catheter are used to retrieve common bile duct (CBD stones. Here we present a case of impaction of the Dormia basket during an endoscopic procedure. The patient was managed through laparoscopic choledochotomy, and the basket was found to be impacted with a common bile stone of size 18 mm. The stone was disengaged from the basket and, by holding the tip of the basket, was removed through one of the laparoscopic ports.

  9. Thulium fiber laser damage to Nitinol stone baskets

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    Wilson, Christopher R.; Hardy, Luke A.; Irby, Pierce B.; Fried, Nathaniel M.

    2015-02-01

    Our laboratory is studying the experimental Thulium fiber laser (TFL) as an alternative lithotripter to clinical gold standard Holmium:YAG laser. Safety studies characterizing undesirable Holmium laser-induced damage to Nitinol stone baskets have been previously reported. Similarly, this study characterizes TFL induced stone basket damage. A TFL beam with pulse energy of 35 mJ, pulse duration of 500 μs, and pulse rates of 50-500 Hz was delivered through 100-μm-core optical fibers, to a standard 1.9-Fr Nitinol stone basket wire. Stone basket damage was graded as a function of pulse rate, number of pulses, and working distance. Nitinol wire damage decreased with working distance and was non-existent at distances greater than 1.0 mm. In contact mode, 500 pulses delivered at pulse rates >= 200 Hz (Nitinol wires. The Thulium fiber laser, operated in low pulse energy and high pulse rate mode, may provide a greater safety margin than standard Holmium laser for lithotripsy, as evidenced by shorter non-contact working distances for stone basket damage than previously reported with Holmium laser.

  10. Assembly and Folding of Twisted Baskets in Organic Solvents.

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    Pratumyot, Yaowalak; Chen, Shigui; Hu, Lei; Polen, Shane M; Hadad, Christopher M; Badjić, Jovica D

    2016-09-02

    A synthetic method for obtaining enantiopure and twisted baskets of type (P)-3 is described. These chiral cavitands were found to fold quinoline gates, at the rim of their twisted platform, in acetonitrile and give molecular capsules that assemble into large unilamellar vesicles. In a less polar dichloromethane, however, cup-shaped (P)-3 packed into vesicles but with the quinoline gates in an unfolded orientation. The ability of twisted baskets to form functional nanostructured materials could be of interest for building stereoselective sensors and catalysts.

  11. Blending Multiple Genres in Theme Baskets.

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    Richison, Jeannine D.; Hernandez, Anita C.; Carter, Marcia

    2002-01-01

    Proposes using "theme baskets" as a progression of texts to scaffold core literature. Defines the theme basket as a combination of several approaches: using a thematic approach to teaching literature; using children's books in secondary classrooms; coupling young adult books with the classics; and capitalizing on young adults'…

  12. Impact of Mode of Delivery on Female Postpartum Sexual Functioning: Spontaneous Vaginal Delivery and Operative Vaginal Delivery vs. Cesarean Section.

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    Barbara, Giussy; Pifarotti, Paola; Facchin, Federica; Cortinovis, Ivan; Dridi, Dhohua; Ronchetti, Camilla; Calzolari, Luca; Vercellini, Paolo

    2016-03-01

    Several studies have explored the association between modes of delivery and postpartum female sexual functioning, although with inconsistent findings. To investigate the impact of mode of delivery on female postpartum sexual functioning by comparing spontaneous vaginal delivery, operative vaginal delivery, and cesarean section. One hundred thirty-two primiparous women who had a spontaneous vaginal delivery, 45 who had an operative vaginal delivery, and 92 who underwent a cesarean section were included in the study (N = 269). Postpartum sexual functioning was evaluated 6 months after childbirth using the Female Sexual Function Index. Time to resumption of sexual intercourse, postpartum depression, and current breastfeeding also were assessed 6 months after delivery. Female Sexual Function Index total and domain scores and time to resumption of sexual intercourse at 6 months after childbirth. Women who underwent an operative vaginal delivery had poorer scores on arousal, lubrication, orgasm, and global sexual functioning compared with the cesarean section group and lower orgasm scores compared with the spontaneous vaginal delivery group (P < .05). The mode of delivery did not significantly affect time to resumption of sexual intercourse. Women who were currently breastfeeding had lower lubrication, more pain at intercourse, and longer time to resumption of sexual activity. Operative vaginal delivery might be associated with poorer sexual functioning, but no conclusions can be drawn from this study regarding the impact of pelvic floor trauma (perineal laceration or episiotomy) on sexual functioning because of the high rate of episiotomies. Overall, obstetric algorithms currently in use should be refined to decrease further the risk of operative vaginal delivery. Copyright © 2016. Published by Elsevier Inc.

  13. Comparative Study of Molecular Basket Sorbents Consisting of Polyallylamine and Polyethylenimine Functionalized SBA-15 for CO2 Capture from Flue Gas.

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    Wang, Xiaoxing; Wang, Dongxiang; Song, Chunshan

    2017-09-20

    Polyallylamine (PAA)-based molecular basket sorbents (MBS) have been studied for CO2 capture in comparison with polyethylenimine (PEI)-based MBS. The characterizations showed that PAA (Mn=15,000) is more rigid and has more steric hindrance inside SBA-15 pores than PEI due mainly to its different polymer structure. The effects of temperature and PAA loadings on the CO2 capacity of PAA/SBA-15 were examined by TGA using 100% CO2 gas stream and compared to PEI/SBA-15. The capacity increased with temperature and the optimum capacity of 88 mg-CO2/g-sorb was obtained at 140 C for PAA(50)/SBA-15; while the optimum temperature was 75 and 90 C for PEI-I(50)/SBA-15 (PEI-I, Mn=423) and PEI-II(50)/SBA-15 (PEI-II, Mn=25,000), respectively. The capacity initially increased with the increase of PAA loading and then dropped at high amine contents, due to the increased diffusion barrier. The highest CO2 capacity of 109 mg-CO2/g-sorb was obtained at PAA loading of 65 wt%, while PAA(50)/SBA-15 gave the best amine efficiency of 0.23 mol-CO2/mol-N. The effect of moisture was examined in the fixed-bed flow system with simulated flue gas containing 15% CO2 and 4.5% O2 in N2, which showed that the presence of moisture significantly enhanced CO2 sorption over PAA(50)/SBA-15 and greatly improved its cyclic stability and regenerability. Compared to PEI/SBA-15, PAA/SBA-15 possesses a better thermal stability and higher resistance to oxidative degradation, however its CO2 sorption rate was much slower. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Sterilization of single-use helical stone baskets: an experimental study

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    Cely Barreto da Silva

    2011-03-01

    Full Text Available Objectives: To experimentally evaluate the efficacy of a standard sterilization protocol employed during reuse of disposable helical stone baskets. Methods: Study performed on 20 helical stone baskets: 10 were used in the initial validation process, contaminated with Escherichia coli ATCC 25922 and imprinted on Müeller-Hinton media; 10 catheters were contaminated with Geobacillus stearothermophilus ATCC 7953, processed, inoculated in TSB and incubated in a water bath at a temperature of 55ºC. Bacterial growth was evaluated after 1, 3, 5 and 7 days. After sterilization, stone baskets were also opened and closed 40 times to check for functional problems. All plastic and basket parts were carefully checked for damages. Results: After the 72-hour incubation period, there was growth of E. coli ATCC 25922 in 100% of imprints. After the sterilization process and up to 7 days incubation period on a blood agar plate, there was no growth of G. stearothermophilus ATCC 7953 or any other bacteria. There were no functional problems or damage to baskets after the sterilization process. Conclusion: The ethylene oxide system is efficacious and safe for sterilization of disposable helical stone baskets. However, further clinical studies are required and should provide more safety information.

  15. Two-Basket Approach and Emission Metrics

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    Tanaka, K.; Schmale, J.; von Schneidemesser, E.

    2013-12-01

    Cutting the emissions of Short-Lived Climate-Forcing Air Pollutants (SLCPs) gains increasing global attention as a mitigation policy option because of direct benefits for climate and co-benefits such as improvements in air quality. Including SLCPs as target components to abate within a single basket (e.g. the Kyoto Protocol) would, however, face issues with regard to: i) additional assumptions that are required to compare SLCP emissions and CO2 emissions within a basket in terms of climatic effects, especially because of the difference in lifetimes, ii) the accountability of non-climatic effects in the emission trading between SLCPs and CO2. The idea of a two-basket approach was originally proposed as a climatic analogue to the Montreal Protocol dealing with ozone depleting substances (Jackson 2009; Daniel et al. 2012; Smith et al. 2013). In a two-basket approach, emissions are allowed to be traded within a basket but not across the baskets. While this approach potentially ensures scientifically supported emission trading (e.g. (Smith et al. 2013)), this approach leaves open the important issue of how to determine the relative weight between two baskets. Determining the weight cannot be answered by science alone, as the question involves a value judgment as stressed in metric studies (e.g. (Tanaka et al. 2010; Tanaka et al. 2013)). We discuss emission metrics in the context of a two-basket approach and present policy implications of such an approach. In a two-basket approach, the weight between two baskets needs to be determined a priori or exogenously. Here, an opportunity arises to present synergetic policy options targeted at mitigating climate change and air pollution simultaneously. In other words, this could be a strategy to encourage policymakers to consider cross-cutting issues. Under a two-basket climate policy, policymakers would be exposed to questions such as: - What type of damages caused by climate change does one choose to avoid? - To what extent

  16. Efficient least-squares basket-weaving

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    Winkel, B.; Flöer, L.; Kraus, A.

    2012-11-01

    We report on a novel method to solve the basket-weaving problem. Basket-weaving is a technique that is used to remove scan-line patterns from single-dish radio maps. The new approach applies linear least-squares and works on gridded maps from arbitrarily sampled data, which greatly improves computational efficiency and robustness. It also allows masking of bad data, which is useful for cases where radio frequency interference is present in the data. We evaluate the algorithms using simulations and real data obtained with the Effelsberg 100-m telescope.

  17. Efficient least-squares basket-weaving

    CERN Document Server

    Winkel, B; Kraus, A

    2012-01-01

    We report on a novel method to solve the basket-weaving problem. Basket-weaving is a technique that is used to remove scan-line patterns from single-dish radio maps. The new approach applies linear least-squares and works on gridded maps from arbitrarily sampled data, which greatly improves computational efficiency and robustness. It also allows masking of bad data, which is useful for cases where radio frequency interference is present in the data. We evaluate the algorithms using simulations and real data obtained with the Effelsberg 100-m telescope.

  18. Functional RNA delivery targeted to dendritic cells by synthetic nanoparticles.

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    McCullough, Kenneth C; Bassi, Isabelle; Démoulins, Thomas; Thomann-Harwood, Lisa J; Ruggli, Nicolas

    2012-09-01

    Dendritic cells (DCs) are essential to many aspects of immune defense development and regulation. They provide important targets for prophylactic and therapeutic delivery. While protein delivery has had considerable success, RNA delivery is still expanding. Delivering RNA molecules for RNAi has shown particular success and there are reports on successful delivery of mRNA. Central, therein, is the application of cationic entities. Following endocytosis of the delivery vehicle for the RNA, cationic entities should promote vesicular membrane perturbation, facilitating cytosolic release. The present review explains the diversity of DC function in immune response development and control. Promotion of delivered RNA cytosolic release is discussed, relating to immunoprophylactic and therapeutic potential, and DC endocytic machinery is reviewed, showing how DC endocytic pathways influence the handling of internalized material. The potential advantages for application of replicating RNA are presented and discussed, in consideration of their value and development in the near future.

  19. A Tisket, A Tasket--Out of the Editor's Basket

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    Williams, Kathryn R.

    2001-05-01

    In September 1940, the Journal introduced Out of the Editor's Basket for short items of interest: excerpts from letters, pamphlets, newspapers, and periodicals. By 1950, however, the Editor's Basket had evolved into a bulletin board for descriptions of new products and services, and it now contains almost exclusively press releases about recently marketed items. Now over 60 years old, the Editor's Basket still provides interesting tidbits for the Journal's broad readership.

  20. Design Enhancement of CANDU S/F Storage Basket

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    Choi, Woo Seok; Seo, Ki Seog [Korea Atomic Energy Research Innstitute, Daejeon (Korea, Republic of); Park, Wan Gyu [Korea Hydro and Nuclear Power Co. Ltd., Gyungju (Korea, Republic of)

    2012-06-15

    Necessity of demonstration test to evaluate the structural integrity of a basket for accident conditions arose during license approval procedure for the WSPP's dry storage facility named MACSTOR/KN-400. A drop test facility for demonstration was constructed in KAERI site and demonstration tests for basket drop were conducted. As the upper welding region of a loaded basket was collided with a dropped basket during the drop test, the welding in this region was fractured and leakage happened after the drop test. The enhancement of basket design was needed since the existing basket design was not able to satisfy the performance requirement. The directions for design modification were determined and six enhanced designs were derived based on these directions. Structural analyses and specimen tests for each enhanced design were conducted. By evaluating structural analysis results and test results, one among six enhanced designs was decided as a final design for revision. The final design was the one to reduce the height of central post of a basket and to decrease the impact velocity with a dropped basket. Test basket models were fabricated with accordance with the final enhanced design. Additional demonstration test was performed for this test model and all the performance requirements were satisfied.

  1. Russian Nesting Doll Complexes of Molecular Baskets and Zinc Containing TPA Ligands.

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    Zhiquan, Lei; Polen, Shane; Hadad, Christopher M; RajanBabu, T V; Badjić, Jovica D

    2016-07-06

    In this study, we examined the structural and electronic complementarities of convex 1-Zn(II), comprising functionalized tris(2-pyridylmethyl)amine (TPA) ligand, and concave baskets 2 and 3, having glycine and (S)-alanine amino acids at the rim. With the assistance of (1)H NMR spectroscopy and mass spectrometry, we found that basket 2 would entrap 1-Zn(II) in water to give equimolar 1-Zn⊂2in complex (K = (2.0 ± 0.2) × 10(3) M(-1)) resembling Russian nesting dolls. Moreover, C3 symmetric and enantiopure basket 3, containing (S)-alanine groups at the rim, was found to transfer its static chirality to entrapped 1-Zn(II) and, via intermolecular ionic contacts, twist the ligand's pyridine rings into a left-handed (M) propeller (circular dichroism spectroscopy). With molecular baskets embodying the second coordination sphere about metal-containing TPAs, the here described findings should be useful for extending the catalytic function and chiral discrimination capability of TPAs.

  2. Mesoporous-Silica-Functionalized Nanoparticles for Drug Delivery.

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    Giret, Simon; Wong Chi Man, Michel; Carcel, Carole

    2015-09-28

    The ever-growing interest for finding efficient and reliable methods for treatment of diseases has set a precedent for the design and synthesis of new functional hybrid materials, namely porous nanoparticles, for controlled drug delivery. Mesoporous silica nanoparticles (MSNPs) represent one of the most promising nanocarriers for drug delivery as they possess interesting chemical and physical properties, thermal and mechanical stabilities, and are biocompatibile. In particular, their easily functionalizable surface allows a large number of property modifications further improving their efficiency in this field. This Concept article deals with the advances on the novel methods of functionalizing MSNPs, inside or outside the pores, as well as within the walls, to produce efficient and smart drug carriers for therapy.

  3. Carboxylic acid-functionalized SBA-15 nanorods for gemcitabine delivery

    Energy Technology Data Exchange (ETDEWEB)

    Bahrami, Zohreh; Badiei, Alireza, E-mail: abadiei@khayam.ut.ac.ir [University of Tehran, School of Chemistry, College of Science (Iran, Islamic Republic of); Ziarani, Ghodsi Mohammadi [Alzahra University, Research Laboratory of Pharmaceutical (Iran, Islamic Republic of)

    2015-03-15

    The present study deals with the functionalization of mesoporous silica nanoparticles as drug delivery systems. Mono, di, and tri amino-functionalized SBA-15 nanorods were synthesized by post-grafting method using (3-aminopropyl) triethoxysilane, N-(2-aminoethyl-)3- aminopropyltrimethoxysilane, and 3-[2-(2-aminoethylamino) ethylamino] propyl trimethoxysilane, respectively. The carboxylic acid derivatives of the amino-functionalized samples were obtained using succinic anhydride. Tminopropyltrimethoxysilanehe obtained modified materials were investigated as matrixes for the anticancer drug (gemcitabine) delivery. The prepared samples were characterized by SAXS, N{sub 2} adsorption/desorption, SEM, transmission electron microscopy, thermogravimetric analysis, and FTIR and UV spectroscopies. The adsorption and release properties of all samples were studied. It was revealed that the adsorption capacity and release behavior of gemcitabine were highly dependent on the type of the introduced functional groups. The carboxylic acid-modified samples have higher loading content, due to the strong interaction with gemcitabine. The maximum content of deposited drug in the modified SBA-15 nanorods is close to 40 wt%. It was found that the surface functionalization leads toward significant decrease of the drug release rate. The carboxylic acid-functionalized samples have slower release rate in contrast with the amino-functionalized samples.

  4. Carboxylic acid-functionalized SBA-15 nanorods for gemcitabine delivery

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    Bahrami, Zohreh; Badiei, Alireza; Ziarani, Ghodsi Mohammadi

    2015-03-01

    The present study deals with the functionalization of mesoporous silica nanoparticles as drug delivery systems. Mono, di, and tri amino-functionalized SBA-15 nanorods were synthesized by post-grafting method using (3-aminopropyl) triethoxysilane, N-(2-aminoethyl-)3- aminopropyltrimethoxysilane, and 3-[2-(2-aminoethylamino) ethylamino] propyl trimethoxysilane, respectively. The carboxylic acid derivatives of the amino-functionalized samples were obtained using succinic anhydride. Tminopropyltrimethoxysilanehe obtained modified materials were investigated as matrixes for the anticancer drug (gemcitabine) delivery. The prepared samples were characterized by SAXS, N2 adsorption/desorption, SEM, transmission electron microscopy, thermogravimetric analysis, and FTIR and UV spectroscopies. The adsorption and release properties of all samples were studied. It was revealed that the adsorption capacity and release behavior of gemcitabine were highly dependent on the type of the introduced functional groups. The carboxylic acid-modified samples have higher loading content, due to the strong interaction with gemcitabine. The maximum content of deposited drug in the modified SBA-15 nanorods is close to 40 wt%. It was found that the surface functionalization leads toward significant decrease of the drug release rate. The carboxylic acid-functionalized samples have slower release rate in contrast with the amino-functionalized samples.

  5. SiRNA delivery with functionalized carbon nanotubes.

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    Varkouhi, Amir Khashayar; Foillard, Stéphanie; Lammers, Twan; Schiffelers, Raymond M; Doris, Eric; Hennink, Wim E; Storm, Gert

    2011-09-20

    Carbon nanotubes (CNTs) have been studied for drug, antigen and nucleic acid delivery both in vitro and in vivo. Due to their nano-needle structure, they are supposed to cross the plasma membrane and enter directly into the cytoplasm likely upon an endocytosis-independent mechanism without inducing cell death. In this study, two cationically functionalized CNTs (CNT-PEI and CNT-pyridinium) were investigated for siRNA delivery. Both functionalized CNTs complexed siRNA and showed 10-30% silencing activity and a cytotoxicity of 10-60%. However, in terms of reduced toxicity or increased silencing activity, CNT-PEI and CNT-pyridinium did not show an added value over PEI and other standard transfection systems. Probably, the type of functionalization of carbon nanotubes might be a key parameter to obtain an efficient and non-cytotoxic CNT-based delivery system. Nevertheless, in view of the present results and importantly also of the non-degradability of CNTs, preference should currently be given to designing biodegradable carriers which mimic the needle structure of CNTs.

  6. Liposome-based Formulation for Intracellular Delivery of Functional Proteins

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    Benoît Chatin

    2015-01-01

    Full Text Available The intracellular delivery of biologically active protein represents an important emerging strategy for both fundamental and therapeutic applications. Here, we optimized in vitro delivery of two functional proteins, the β-galactosidase (β-gal enzyme and the anti-cytokeratin8 (K8 antibody, using liposome-based formulation. The guanidinium-cholesterol cationic lipid bis (guanidinium-tren-cholesterol (BGTC (bis (guanidinium-tren-cholesterol combined to the colipid dioleoyl phosphatidylethanolamine (DOPE (dioleoyl phosphatidylethanolamine was shown to efficiently deliver the β-gal intracellularly without compromising its activity. The lipid/protein molar ratio, protein amount, and culture medium were demonstrated to be key parameters affecting delivery efficiency. The protein itself is an essential factor requiring selection of the appropriate cationic lipid as illustrated by low K8 binding activity of the anti-K8 antibody using guanidinium-based liposome. Optimization of various lipids led to the identification of the aminoglycoside lipid dioleyl succinyl paromomycin (DOSP associated with the imidazole-based helper lipid MM27 as a potent delivery system for K8 antibody, achieving delivery in 67% of HeLa cells. Cryo-transmission electron microscopy showed that the structure of supramolecular assemblies BGTC:DOPE/β-gal and DOSP:MM27/K8 were different depending on liposome types and lipid/protein molar ratio. Finally, we observed that K8 treatment with DOSP:MM27/K8 rescues the cyclic adenosine monophosphate (cAMP-dependent chloride efflux in F508del-CFTR expressing cells, providing a new tool for the study of channelopathies.

  7. Effect of functionalization on drug delivery potential of carbon nanotubes.

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    Sharma, Sonam; Mehra, Neelesh Kumar; Jain, Keerti; Jain, Narendra Kumar

    2016-12-01

    The main aim of the present investigation was to explore the effect of functionalization on drug delivery potential of carbon nanotubes (CNTs) and to compare the in vitro and in vivo cancer targeting potential of doxorubicin HCL (DOX)-loaded ox-/multi-walled CNTs (MWCNTs), DOX-loaded PEG-MWCNTs and DOX-loaded FA-PEG-MWCNTs. The DOX/PEG-FA-MWCNTs showed enhanced cytotoxicity and were most preferentially taken up by the cancerous cells. The obtained results also support the extended resistance time and sustained release profile of drug-loaded surface-engineered MWCNTs. Overall, we concluded that the developed MWCNTs nanoformulations have higher cancer targeting potential.

  8. The Effect of Mode of Delivery on Postpartum Sexual Functioning in Primiparous Women

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    Fatemeh Dabiri

    2014-07-01

    Full Text Available Objective: To evaluate the effect of mode of delivery on postpartum sexual functioning in primiparous women. Methods: In this cross-sectional descriptive study, 150 primiparous women in postpartum period, who attended the family planning or vaccination clinics, were enrolled for the study. Eighty-one had vaginal delivery with episiotomy and 69 had experienced cesarean section. Sexual function was evaluated by the Female Sexual Function Index within 3 and 6 months postpartum. Results: About 29% in vaginal delivery group and 37% in cesarean delivery group had resumed their sexual intercourses four weeks after delivery (p=0.280.There were no significant differences between mode of delivery and sexual functioning, including desire, arousal, lubrication, orgasm, satisfaction and pain. Conclusion: The present study showed that postpartum sexual functioning was not associated with the type of delivery.

  9. The Effect of Mode of Delivery on Postpartum Sexual Functioning in Primiparous Women

    Science.gov (United States)

    Dabiri, Fatemeh; Yabandeh, Asieh Pormehr; Shahi, Arefeh; Kamjoo, Azita; Teshnizi, Saeed Hosseini

    2014-01-01

    Objective To evaluate the effect of mode of delivery on postpartum sexual functioning in primiparous women. Methods In this cross-sectional descriptive study, 150 primiparous women in postpartum period, who attended the family planning or vaccination clinics, were enrolled for the study. Eighty-one had vaginal delivery with episiotomy and 69 had experienced cesarean section. Sexual function was evaluated by the Female Sexual Function Index within 3 and 6 months postpartum. Results About 29% in vaginal delivery group and 37% in cesarean delivery group had resumed their sexual intercourses four weeks after delivery (p=0.280).There were no significant differences between mode of delivery and sexual functioning, including desire, arousal, lubrication, orgasm, satisfaction and pain. Conclusion The present study showed that postpartum sexual functioning was not associated with the type of delivery. PMID:25170409

  10. Diamine Functionalized Cubic Mesoporous Silica for Ibuprofen Controlled Delivery.

    Science.gov (United States)

    Sivaguru, J; Selvaraj, M; Ravi, S; Park, H; Song, C W; Chun, H H; Ha, C-S

    2015-07-01

    A diamine functionalized cubic mesostructured KIT-6 (N-KIT-6) has been prepared by post-synthetic method using calcined mesoporous KIT-6 with a diamine source, i.e., N-'[3-(tri methoxysilyl)- propyl]'ethylenediamine. The KIT-6 mesoporous silica used for N-KIT-6 was synthesized under weak acidic hydrothermal method using bitemplates, viz., Pluronic P123 and 1-butanol. The synthesized mesoporous materials, KIT-6 and N-KIT-6, have been characterized by the relevant instrumental techniques such as SAXS, N2 sorption isotherm, FT-IR, SEM, TEM and TGA to prove the standard mesoporous materials with the identification of diamine groups. The characterized mesoporous materials, KIT-6 and N-KIT-6, have been extensively used in the potential application of controlled drug delivery, where ibuprofen (IBU) employed as a model drug. The rate of IBU adsorption and release was monitored by UV vis-spectrometer. On the basis of the experimental results of controlled drug delivery system, the results of IBU adsorption and releasing rate in N-KIT-6 are higher than those of KIT-6 because of the higher hydrophobic nature as well as rich basic sites on the surface of inner pore wall silica.

  11. Tunable drug delivery using chemoselective functionalization of hydrogels.

    Science.gov (United States)

    Mauri, Emanuele; Rossi, Filippo; Sacchetti, Alessandro

    2016-04-01

    In the last decades interests on cleavable linkers are growing due to the need to develop controlled drug delivery systems in biochemical and therapeutic applications. The synthesis of hydrogels as devices capable to maintain the drug level within a desired range for a long and sustained period of time is a leading strategy for this aim. However with respect to the good results obtained with antibodies and peptides there are a lot of problems related to the quick and uncontrolled diffusion of small molecules through hydrogel pores. In this work, we propose the functionalization of polyethylene glycol (PEG) chains with two different pH-sensitive linkers, ester and hydrazone, and their application as building blocks of microwave-assisted hydrogels for controlled delivery of small hydrophilic drugs. As drug mimetic we used Rhodamine B, a harmless fluorophore with steric hindrance and reactive groups similar to many small hydrophilic drugs. At physiological and low basic conditions, the cleavability of ester and hydrazone spacer evidenced the possibility to delay the release of drugs from the scaffold compared to hydrogels where drug was entrapped within the network only due to its steric hindrance. The obtained release profiles were compared, underlining the opportunity to tune the release rate using the synthesized hydrogels.

  12. Homing to nest baskets by wild female mallards

    Science.gov (United States)

    Doty, H.A.; Lee, F.B.

    1974-01-01

    A high rate of homing to nest baskets by adult female mallards (Anas platyrhynchos) was observed in prairie potholes of North Dakota. One hundred and thirteen female mallards were caught on nest baskets, banded, and marked with nasal saddles. Forty-six percent homed at least once to nest baskets in the marshes where they were previously captured. Two-thirds of the returnees were observed in the same baskets where they had been caught. The observed rate of homing by previously successful nesters (52 percent) was significantly (P old ducklings that hatched in nest baskets were recaptured as nesting adults in baskets. Five of these hens returned to their natal marshes, and two others were found within 2 km of their natal marshes. Band recovery data indicated that 91 percent of the hunting mortality occurred within 10 km of the banding locations. Information on estimated rate of annual survival and the observed rate of homing suggests that nearly all surviving marked adults returned to within 10 km of the marshes where they were banded.

  13. Controlling fungal biofilms with functional drug delivery denture biomaterials.

    Science.gov (United States)

    Wen, Jianchuan; Jiang, Fuguang; Yeh, Chih-Ko; Sun, Yuyu

    2016-04-01

    Candida-associated denture stomatitis (CADS), caused by colonization and biofilm-formation of Candida species on denture surfaces, is a significant clinical concern. We show here that modification of conventional denture materials with functional groups can significantly increase drug binding capacity and control drug release rate of the resulting denture materials for potentially managing CADS. In our approach, poly(methyl methacrylate) (PMMA)-based denture resins were surface grafted with three kinds of polymers, poly(1-vinyl-2-pyrrolidinone) (PNVP), poly(methacrylic acid) (PMAA), and poly(2-hydroxyethyl methacrylate) (PHEMA), through plasma-initiated grafting polymerization. With a grafting yield as low as 2 wt%, the three classes of new functionalized denture materials showed significantly higher drug binding capacities toward miconazole, a widely used antifungal drug, than the original PMMA denture resin control, leading to sustained drug release and potent biofilm-controlling effects against Candida. Among the three classes of functionalized denture materials, PNVP-grafted resin provided the highest miconazole binding capability and the most powerful antifungal and biofilm-controlling activities. Drug binding mechanisms were studied. These results demonstrated the importance of specific interactions between drug molecules and functional groups on biomaterials, shedding lights on future design of CADS-managing denture materials and other related devices for controlled drug delivery.

  14. Chemical functionalization of hyaluronic acid for drug delivery applications

    Energy Technology Data Exchange (ETDEWEB)

    Vasi, Ana-Maria [“Gheorghe Asachi” Technical University of Iasi, Faculty of Chemical Engineering and Environmental Protection, 73 Prof. dr. docent Dimitrie Mangeron Street, 700050 Iasi (Romania); Popa, Marcel Ionel, E-mail: mipopa@ch.tuiasi.ro [“Gheorghe Asachi” Technical University of Iasi, Faculty of Chemical Engineering and Environmental Protection, 73 Prof. dr. docent Dimitrie Mangeron Street, 700050 Iasi (Romania); Butnaru, Maria [“Grigore T. Popa” University of Medicine Pharmacy, Faculty of Medical Bioengineering, 9-13 Kogalniceanu Street, 700454 Iasi (Romania); Dodi, Gianina [“Gheorghe Asachi” Technical University of Iasi, Faculty of Chemical Engineering and Environmental Protection, 73 Prof. dr. docent Dimitrie Mangeron Street, 700050 Iasi (Romania); SCIENT — Research Center for Instrumental Analysis, S.C. CROMATEC PLUS, 18 Sos. Cotroceni, 060114 Bucharest (Romania); Verestiuc, Liliana [“Grigore T. Popa” University of Medicine Pharmacy, Faculty of Medical Bioengineering, 9-13 Kogalniceanu Street, 700454 Iasi (Romania)

    2014-05-01

    Functionalized hyaluronic acid (HA) derivatives were obtained by ring opening mechanism of maleic anhydride (MA). FTIR and H{sup 1} NMR spectroscopy were used to confirm the chemical linkage of MA on the hyaluronic acid chains. Thermal analysis (TG-DTG and DSC) and GPC data for the new products revealed the formation of new functional groups, without significant changes in molecular weight and thermal stability. New gels based on hyaluronic acid modified derivatives were obtained by acrylic acid copolymerization in the presence of a redox initiation system. The resulted circular and interconnected pores of the gels were visualized by SEM. The release profiles of an ophthalmic model drug, pilocarpine from tested gels were studied in simulated media. Evaluation of the cytotoxicity and cell proliferation properties indicates the potential of the new systems to be used in contact with biological media in drug delivery applications. - Highlights: • New functionalized hyaluronic acid was prepared by ring opening of maleic anhydride. • Gels with circular pores based on acrylic acid copolymerization were formulated. • In vitro drug loading/release profile was evaluated in simulated ophthalmic media. • The cytotoxicity indicates the potential of derivatives to be used in vivo.

  15. Influence of nutrient delivery on gut structure and function.

    Science.gov (United States)

    Bragg, L E; Thompson, J S; Rikkers, L F

    1991-01-01

    Food is an important stimulus for the growth of gastrointestinal mucosa. Gut structure is influenced by the route of nutrient administration, dietary composition and the availability of specific nutrients. The alterations in intestinal structure and function that occur when enteral nutrition is withheld suggests that the ingestion of food results in physiologic responses that are responsible for the maintenance of gut mass during the fed state. The mechanism of mucosal suppression that occurs during starvation, stress, and total parenteral nutrition is not completely understood but may involve the absence of luminal substrates, decreased pancreaticobiliary secretions and alterations in the endocrine or paracrine events that normally accompany eating, digestion, and absorption. Enterocytes prefer glutamine and ketone bodies as oxidative fuels, whereas colonocytes utilize short chain fatty acids. Although enteral delivery of nutrients is the preferred route for maintenance of intestinal mass, provision of specific nutrients and hormonal stimulation during parenteral alimentation has been shown to be important in maintaining mucosal structure and function. If not adequately maintained, the intestine becomes susceptible to a variety of injuries which may result in impaired ability to digest and absorb nutrients and loss of mucosal barrier function.

  16. Distinct and synergistic feedforward inhibition of pyramidal cells by basket and bistratified interneurons

    Directory of Open Access Journals (Sweden)

    Michele eFerrante

    2015-11-01

    Full Text Available Feedforward inhibition (FFI enables pyramidal cells in area CA1 of the hippocampus (CA1PCs to remain easily excitable while faithfully representing a broad range of excitatory inputs without quickly saturating. Despite the cortical ubiquity of FFI, its specific function is not completely understood. FFI in CA1PCs is mediated by two physiologically and morphologically distinct GABAergic interneurons: fast-spiking, perisomatic-targeting basket cells and regular-spiking, dendritic-targeting bistratified cells. These two FFI pathways might create layer-specific computational sub-domains within the same CA1PC, but teasing apart their specific contributions remains experimentally challenging. We implemented a biophysically realistic model of CA1PCs using 40 digitally reconstructed morphologies and constraining synaptic numbers, locations, amplitude, and kinetics with available experimental data. First, we validated the model by reproducing the known combined basket and bistratified FFI of CA1PCs at the population level. We then analyzed how the two interneuron types independently affected the CA1PC spike probability and timing as a function of inhibitory strength. Separate FFI by basket and bistratified respectively modulated CA1PC threshold and gain. Concomitant FFI by both interneuron types synergistically extended the dynamic range of CA1PCs by buffering their spiking response to excitatory stimulation. These results suggest testable hypotheses on the precise effects of GABAergic diversity on cortical computation.

  17. Dual-cavity basket promotes encapsulation in water in an allosteric fashion.

    Science.gov (United States)

    Chen, Shigui; Yamasaki, Makoto; Polen, Shane; Gallucci, Judith; Hadad, Christopher M; Badjić, Jovica D

    2015-09-30

    We prepared dual-cavity basket 1 to carry six (S)-alanine residues at the entrance of its two juxtaposed cavities (289 Å(3)). With the assistance of (1)H NMR spectroscopy and calorimetry, we found that 1 could trap a single molecule of 4 (K1 = 1.45 ± 0.40 × 10(4) M(-1), ITC), akin in size (241 Å(3)) and polar characteristics to nerve agent VX (289 Å(3)). The results of density functional theory calculations (DFT, M06-2X/6-31G*) and experiments ((1)H NMR spectroscopy) suggest that the negative homotropic allosterism arises from the guest forming C-H···π contacts with all three of the aromatic walls of the occupied basket's cavity. In response, the other cavity increases its size and turns rigid to prevent the formation of the ternary complex. A smaller guest 6 (180 Å(3)), akin in size and polar characteristics to soman (186 Å(3)), was also found to bind to dual-cavity 1, although giving both binary [1⊂6] and ternary [1⊂62] complexes (K1 = 7910 M(-1) and K2 = 2374 M(-1), (1)H NMR spectroscopy). In this case, the computational and experimental ((1)H NMR spectroscopy) results suggest that only two aromatic walls of the occupied basket's cavity form C-H···π contacts with the guest to render the singly occupied host flexible enough to undergo additional structural changes necessary for receiving another guest molecule. The structural adaptivity of dual-cavity baskets of type 1 is unique and important for designing multivalent hosts capable of effectively sequestering targeted guests in an allosteric manner to give stable supramolecular polymers.

  18. Light activated liposomes: Functionality and prospects in ocular drug delivery.

    Science.gov (United States)

    Lajunen, Tatu; Nurmi, Riikka; Kontturi, Leena; Viitala, Lauri; Yliperttula, Marjo; Murtomäki, Lasse; Urtti, Arto

    2016-12-28

    Ocular drug delivery, especially to the retina and choroid, is a major challenge in drug development. Liposome technology may be useful in ophthalmology in enabling new routes of delivery, prolongation of drug action and intracellular drug delivery, but drug release from the liposomes should be controlled. For that purpose, light activation may be an approach to release drug at specified time and site in the eye. Technical advances have been made in the field of light activated drug release, particularly indocyanine green loaded liposomes are a promising approach with safe materials and effective light triggered release of small and large molecules. This review discusses the liposomal drug delivery with light activated systems in the context of ophthalmic drug delivery challenges.

  19. Alendronate functionalized mesoporous hydroxyapatite nanoparticles for drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Li, Dongdong, E-mail: lidongchem@sina.cn [State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China); Zhu, Yuntao; Liang, Zhiqiang [State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Changchun 130012 (China)

    2013-06-01

    Highlights: ► The synthesized mesoporous hydroxyapatite has nanostructure and bioactivity. ► The materials have high surface area and amino group. ► The materials show higher drug loading and slower release rate than pure HAP. - Abstract: Mesoporous nanosized hydroxyapatite (HAP) functionalized by alendronate (ALN) was synthesized using cationic surfactant CTAB as template. The structural, morphological and textural properties were fully characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR) and N{sub 2} adsorption/desorption. Then the obtained materials were performed as drug delivery carriers using ibuprofen (IBU) as a model drug to investigate their drug storage/release properties in simulated body fluid (SBF). The materials showed relatively slower release rate compared with HAP due to the ionic interaction between -NH{sub 3}{sup +} on the matrix and -COO{sup −}belongs to IBU. The system provides a new concept for improving the drug loading or slowing down the release rate.

  20. Regulation of Parvalbumin Basket cell plasticity in rule learning.

    Science.gov (United States)

    Caroni, Pico

    2015-04-24

    Local inhibitory Parvalbumin (PV)-expressing Basket cell networks shift to one of two possible opposite configurations depending on whether behavioral learning involves acquisition of new information or consolidation of validated rules. This reflects the existence of PV Basket cell subpopulations with distinct schedules of neurogenesis, output target neurons and roles in learning. Plasticity of hippocampal early-born PV neurons is recruited in rule consolidation, whereas plasticity of late-born PV neurons is recruited in new information acquisition. This involves regulation of early-born PV neuron plasticity specifically through excitation, and of late-born PV neuron plasticity specifically through inhibition. Therefore, opposite learning requirements are implemented by distinct local networks involving PV Basket cell subpopulations specifically regulated through inhibition or excitation.

  1. Damage of Stone Baskets by Endourologic Lithotripters: A Laboratory Study of 5 Lithotripters and 4 Basket Types

    Directory of Open Access Journals (Sweden)

    Jens Cordes

    2013-01-01

    Full Text Available Background. In some cases, the ureteral stone is simultaneously stabilized by a stone basket when endourologic lithotripsy is performed. This stabilization can be either on purpose or by accident. By accident means that an impaction in the ureter occurs by an extraction of a stone with a basket. A stabilization on purpose means to avoid a retropulsion of the stone into the kidney during lithotripsy. At this part of the operation, stone baskets have been frequently damaged. This severing of wires can lead to ureteral trauma because of hook formation. Material and Methods. In a laboratory setting, the time and the pulse numbers were measured until breaking the wires from four different nitinol stone baskets by using five different lithotripsy devices. The endpoint was gross visibledamage to the wire and loss of electric conduction. Results. The Ho:YAG laser and the ultrasonic device were able to destroy almost all the wires. The ballistic devices and the electrohydraulic device were able to destroy thin wires. Conclusion. The operating surgeon should know the risk of damagefor every lithotripter. The Ho:YAG-laser and the ultrasonic device should be classified as dangerous for the basket wire with all adverse effects to the patient.

  2. Construction of a Basket of Diversified Portfolios, via Quantum Annealing, to Aid in Cardinality Constratined Portfolio Optimization

    OpenAIRE

    Kolar, Emilija; Seyedin, Ehsan

    2014-01-01

    In this project, we propose and investigate a new approach for solving portfolio optimization problems (POP) with cardinality constraints using an evolutionary algorithm based on the distribution of diversified baskets (EADDB).The Diversified basket is the basket of portfolios each of which obtains one of the lowest risks. The distribution of the diversified basket indicates the probability of having each asset in the diversified basket. Finding the diversified basket is an NP-hard problem, a...

  3. Production Functions for Water Delivery Systems: Analysis and Estimation Using Dual Cost Function and Implicit Price Specifications

    Science.gov (United States)

    Teeples, Ronald; Glyer, David

    1987-05-01

    Both policy and technical analysis of water delivery systems have been based on cost functions that are inconsistent with or are incomplete representations of the neoclassical production functions of economics. We present a full-featured production function model of water delivery which can be estimated from a multiproduct, dual cost function. The model features implicit prices for own-water inputs and is implemented as a jointly estimated system of input share equations and a translog cost function. Likelihood ratio tests are performed showing that a minimally constrained, full-featured production function is a necessary specification of the water delivery operations in our sample. This, plus the model's highly efficient and economically correct parameter estimates, confirms the usefulness of a production function approach to modeling the economic activities of water delivery systems.

  4. Multi-basket approaches to climate and environmental policies

    Science.gov (United States)

    Tanaka, Katsumasa

    2014-05-01

    Short-lived climate pollutants (SLCPs) such as methane (CH4) and black carbon (BC) receive increasing attention because emission abatements of most of these substances not only reduce air pollution but also slow down the global warming. Cutting the emissions of carbon dioxide (CO2), a long-lived gas in contrast, is of primary importance to mitigate the global climate change as well as to stop ocean acidification. To keep abreast of such multiple challenges in a flexible and cost-effective manner, emission caps can be specified in terms of a reference gas (e.g., CO2) and emissions of different components can be converted according to emission metrics. However, under a current one-basket approach (used continuously in the Kyoto Protocol), which allows trading for all the components, any emission metrics may not be scientifically acceptable due to their diverse atmospheric lifetimes among many other reasons. Here we question whether an emerging multi-basket approach, which groups substances based on their atmospheric lifetimes and permits trading for components within each basket, is more robust in guiding us to achieve multiple policy targets and more useful to maintain the balance between SLCP and CO2 abatements with relatively small additional costs. In a wider context a multi-basket approach may simplify the dialogue among stakeholders and underpin a parallel pursuit of multiple climate and environmental challenges that our society faces.

  5. Functionalized bimodal mesoporous silicas as carriers for controlled aspirin delivery

    Science.gov (United States)

    Gao, Lin; Sun, Jihong; Li, Yuzhen

    2011-08-01

    The bimodal mesoporous silica modified with 3-aminopropyltriethoxysilane was performed as the aspirin carrier. The samples' structure, drug loading and release profiles were characterized with X-ray diffraction, scanning electron microscopy, N 2 adsorption and desorption, Fourier transform infrared spectroscopy, TG analysis, elemental analysis and UV-spectrophotometer. For further exploring the effects of the bimodal mesopores on the drug delivery behavior, the unimodal mesoporous material MCM-41 was also modified as the aspirin carrier. Meantime, Korsmeyer-Peppas equation ft= ktn was employed to analyze the dissolution data in details. It is indicated that the bimodal mesopores are beneficial for unrestricted drug molecules diffusing and therefore lead to a higher loading and faster releasing than that of MCM-41. The results show that the aspirin delivery properties are influenced considerably by the mesoporous matrix, whereas the large pore of bimodal mesoporous silica is the key point for the improved controlled-release properties.

  6. Natural polysaccharide functionalized gold nanoparticles as biocompatible drug delivery carrier.

    Science.gov (United States)

    Pooja, Deep; Panyaram, Sravani; Kulhari, Hitesh; Reddy, Bharathi; Rachamalla, Shyam S; Sistla, Ramakrishna

    2015-09-01

    Biocompatibility is one of the major concerns with inorganic nanoparticles for their applications as drug delivery system. Natural compounds such as sugars, hydrocolloids and plant extracts have shown potential for the green synthesis of biocompatible gold nanoparticles. In this study, we report the synthesis of gum karaya (GK) stabilized gold nanoparticles (GKNP) and the application of prepared nanoparticles in the delivery of anticancer drugs. GKNP were characterized using different analytical techniques. GKNP exhibited high biocompatibility during cell survival study against CHO normal ovary cells and A549 human non-small cell lung cancer cells and during hemolytic toxicity studies. Gemcitabine hydrochloride (GEM), an anticancer drug, was loaded on the surface of nanoparticles with 19.2% drug loading efficiency. GEM loaded nanoparticles (GEM-GNP) showed better inhibition of growth of cancer cells in anti-proliferation and clonogenic assays than native GEM. This effect was correlated with higher reactive oxygen species generation by GEM-GNP in A549 cells than native GEM. In summary, GK has significant potential in the synthesis of biocompatible gold nanoparticles that could be used as prospective drug delivery carrier for anticancer drugs.

  7. Functional nanostructures for effective delivery of small interfering RNA therapeutics.

    Science.gov (United States)

    Hong, Cheol Am; Nam, Yoon Sung

    2014-01-01

    Small interfering RNA (siRNA) has proved to be a powerful tool for target-specific gene silencing via RNA interference (RNAi). Its ability to control targeted gene expression gives new hope to gene therapy as a treatment for cancers and genetic diseases. However, siRNA shows poor pharmacological properties, such as low serum stability, off-targeting, and innate immune responses, which present a significant challenge for clinical applications. In addition, siRNA cannot cross the cell membrane for RNAi activity because of its anionic property and stiff structure. Therefore, the development of a safe, stable, and efficient system for the delivery of siRNA therapeutics into the cytoplasm of targeted cells is crucial. Several nanoparticle platforms for siRNA delivery have been developed to overcome the major hurdles facing the therapeutic uses of siRNA. This review covers a broad spectrum of non-viral siRNA delivery systems developed for enhanced cellular uptake and targeted gene silencing in vitro and in vivo and discusses their characteristics and opportunities for clinical applications of therapeutic siRNA.

  8. A 3-fold "butterfly valve" in command of the encapsulation's kinetic stability. Molecular baskets at work.

    Science.gov (United States)

    Wang, Bao-Yu; Bao, Xiaoguang; Yan, Zhiqing; Maslak, Veselin; Hadad, Christopher M; Badjić, Jovica D

    2008-11-12

    Molecular basket 1, composed of a semirigid tris-norbornadiene framework and three revolving pyridine-based gates at the rim, has been built to "dynamically" enclose space and as such regulate molecular encapsulation. The gates were shown to fold via intramolecular hydrogen bonding and thereby form a C3nu symmetrical receptor: the 1H NMR resonance for the amide N-H protons of the pyridine gates appeared downfield (delta= 10.98 ppm), and the N-H vibrational stretch (IR) was observed at 3176 cm(-1). Accordingly, density functional theory (DFT, B3LYP) investigations revealed for the closed conformers of 1 to be energetically the most stable and dominant. The gearing of the pyridine "gates", about their axis, led to the interconversion of two dynamic enantiomers 1A and 1B comprising the clockwise and counterclockwise seam of intramolecular hydrogen bonds. Dynamic 1H NMR spectroscopic measurements and line-shape simulations suggested that the energy barrier of 10.0 kcal/mol (DeltaG++(A/B), 298 K) is required for the 1A/B interconversion, when CCl4 occupies the cavity of 1. Likewise, the activation free energy for CCl4 departing the basket was found to be 13.1 kcal/mol (DeltaG++, 298 K), whereas the thermodynamic stability of 1:CCl4 complex was -2.7 kcal/mol (DeltaGdegrees, 298 K). In view of that, CCl4 (but also (CH3)3CBr) was proposed to escape from, and a molecule of solvent to enter, the basket when the gates rotate about their axis: the exit of CCl4 requires the activation energy of 12.7 kcal/mol (DeltaG++(A/B) + DeltaGdegrees), similar to the experimentally found 13.1 kcal/mol (DeltaG++).

  9. Vulnerability of Bread-Baskets to Weather Shocks

    Science.gov (United States)

    Gerber, J. S.; Ray, D. K.; West, P. C.; Foley, J. A.

    2013-12-01

    Many analyses of food security consider broad trends in food supply (crop production, crop use) and demand (changing diets, population growth.) However, if past shocks to the food system due to weather events (i.e. droughts) were to repeat themselves today, the resulting famines could be far more serious due to increased concentration of grain production in vulnerable bread-baskets, and decreased resilience of global and regional food systems (i.e. lower stocks, dependence on fewer crops). The present research project takes advantage of high-resolution historical weather datasets to assess probabilities of historically observed droughts repeating themselves in one or more of today's bread-basket regions. Using recently developed relationships between weather and crop yield, we consider the likelihood of region-wide crop failures under current conditions, and also under various climate scenarios.

  10. Basket Option Pricing Using GP-GPU Hardware Acceleration

    KAUST Repository

    Douglas, Craig C.

    2010-08-01

    We introduce a basket option pricing problem arisen in financial mathematics. We discretized the problem based on the alternating direction implicit (ADI) method and parallel cyclic reduction is applied to solve the set of tridiagonal matrices generated by the ADI method. To reduce the computational time of the problem, a general purpose graphics processing units (GP-GPU) environment is considered. Numerical results confirm the convergence and efficiency of the proposed method. © 2010 IEEE.

  11. STS-103 crew practice emergency egress in the slidewire basket

    Science.gov (United States)

    1999-01-01

    In the slidewire basket on Launch Pad 39B, STS-103 Mission Specialist C. Michael Foale (Ph.D.) gets ready to pull the lever, which will release the basket. With Foale are fellow crew members Mission Specialists Claude Nicollier of Switzerland and John M. Grunsfeld (Ph.D.). The baskets are part of the emergency egress system for persons in the Shuttle vehicle or on the Rotating Service Structure. Seven slidewires extend from the orbiter access arm, with a netted, flatbottom basket suspended from each wire. The STS-103 crew are taking part in Terminal Countdown Demonstration Test (TCDT) activities in preparation for launch. The other crew members taking part are Commander Curtis L. Brown Jr., Pilot Scott J. Kelly, and Mission Specialists Steven L. Smith, and Jean-Frangois Clervoy of France. Clervoy and Nicollier are with the European Space Agency. The TCDT provides the crew with the emergency egress training, opportunities to inspect their mission payloads in the orbiter's payload bay, and simulated countdown exercises. STS-103 is a 'call-up' mission due to the need to replace and repair portions of the Hubble Space Telescope, including the gyroscopes that allow the telescope to point at stars, galaxies and planets. The STS-103 crew will be replacing a Fine Guidance Sensor, an older computer with a new enhanced model, an older data tape recorder with a solid-state digital recorder, a failed spare transmitter with a new one, and degraded insulation on the telescope with new thermal insulation. The crew will also install a Battery Voltage/Temperature Improvement Kit to protect the spacecraft batteries from overcharging and overheating when the telescope goes into a safe mode. Four EVA's are planned to make the necessary repairs and replacements on the telescope. The mission is targeted for launch Dec. 6 at 2:37 a.m. EST.

  12. Price Paradox and Strategic Choice of "Vegetable Basket" in China

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    By using the analysis method of game theory,this paper analyzes the phenomenon of price paradox of "vegetable basket" in China and its reason as follows:the price paradox of "vegetable basket" in China is that if the vegetable is cheap,it will harm farmers,and if the vegetable is expensive,it will harm people;high-cost logistics,low negotiation status of vegetable growers and cooperation predicament are responsible for price paradox.Based on the theoretical basis of strategic choice-theory of intermediaries,it indicates that the intermediaries can realize effective transaction and save transaction cost.The strategic choice of solving price paradox of "vegetable basket" is put forward as follows:support vegetable growers’ cooperatives,reduce transaction cost and raise the negotiation status of vegetable growers;develop the model of connection of agricultural products and supermarkets,and reduce the cost of transport and distribution;innovate upon intermediaries and develop the third-party logistics.

  13. Surface-functionalized electrospun nanofibers for tissue engineering and drug delivery.

    Science.gov (United States)

    Yoo, Hyuk Sang; Kim, Taek Gyoung; Park, Tae Gwan

    2009-10-05

    Electrospun nanofibers with a high surface area to volume ratio have received much attention because of their potential applications for biomedical devices, tissue engineering scaffolds, and drug delivery carriers. In order to develop electrospun nanofibers as useful nanobiomaterials, surfaces of electrospun nanofibers have been chemically functionalized for achieving sustained delivery through physical adsorption of diverse bioactive molecules. Surface modification of nanofibers includes plasma treatment, wet chemical method, surface graft polymerization, and co-electrospinning of surface active agents and polymers. A variety of bioactive molecules including anti-cancer drugs, enzymes, cytokines, and polysaccharides were entrapped within the interior or physically immobilized on the surface for controlled drug delivery. Surfaces of electrospun nanofibers were also chemically modified with immobilizing cell specific bioactive ligands to enhance cell adhesion, proliferation, and differentiation by mimicking morphology and biological functions of extracellular matrix. This review summarizes surface modification strategies of electrospun polymeric nanofibers for controlled drug delivery and tissue engineering.

  14. Long-term changes in sexual functions following complicated pregnancies and deliveries

    Directory of Open Access Journals (Sweden)

    Ali Özler

    2013-12-01

    Full Text Available Objective: The aim of this study is to evaluate the effects of complicated pregnancy and delivery (P/D on sexual functions and to determine possible risk factors that affect sexual functions. Methods: Women, who have the history of severe preeclampsia, placenta previa totalis, abruption placentae or postpartum uterine atonia, comprised the study group. The control group was comprised the women matched for age, parity, mode of delivery, vocation, the level of income and education status. Their fear of getting pregnant again and fear of death in the most recent delivery were measured by questionnaires. The Arizona Sexual Experience Scale was used to assess the sexual functions. We compared sexual functions of the women with and without suffering from complicated P/D. Results: Fear of death during the last delivery and fear of getting pregnant again were significantly more intense in the study group (p=0.002 and p<0.001, respectively. The rates of volunteers detected sexual dysfunction in the study and control groups were 55.1% and 38.7%, respectively (p=0.081. Fear of death during the last delivery was found to be significant risk factors for sexual dysfunction (odds ratio [OR] = 1.653; 95% CI = 1.131-2.415; p=0.009. Conclusion: In conclusion, sexual dysfunction rate of women with a history of complicated pregnancy and delivery, was almost equal that of women with a history of health pregnancy and delivery. Fear of death during the last delivery was found to be most important risk factor for sexual dysfunction. J Clin Exp Invest 2013; 4 (4: 429-435

  15. Regulation of the Hippocampal Network by VGLUT3-Positive CCK- GABAergic Basket Cells

    Directory of Open Access Journals (Sweden)

    Caroline Fasano

    2017-05-01

    Full Text Available Hippocampal interneurons release the inhibitory transmitter GABA to regulate excitation, rhythm generation and synaptic plasticity. A subpopulation of GABAergic basket cells co-expresses the GABA/glycine vesicular transporters (VIAAT and the atypical type III vesicular glutamate transporter (VGLUT3; therefore, these cells have the ability to signal with both GABA and glutamate. GABAergic transmission by basket cells has been extensively characterized but nothing is known about the functional implications of VGLUT3-dependent glutamate released by these cells. Here, using VGLUT3-null mice we observed that the loss of VGLUT3 results in a metaplastic shift in synaptic plasticity at Shaeffer’s collaterals – CA1 synapses and an altered theta oscillation. These changes were paralleled by the loss of a VGLUT3-dependent inhibition of GABAergic current in CA1 pyramidal layer. Therefore presynaptic type III metabotropic could be activated by glutamate released from VGLUT3-positive interneurons. This putative presynaptic heterologous feedback mechanism inhibits local GABAergic tone and regulates the hippocampal neuronal network.

  16. Functionalized mesoporous silica nanoparticles for oral delivery of budesonide

    Energy Technology Data Exchange (ETDEWEB)

    Yoncheva, K., E-mail: krassi.yoncheva@gmail.com [Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia (Bulgaria); Popova, M. [Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Sofia (Bulgaria); Szegedi, A.; Mihaly, J. [Institute of Nanochemistry and Catalysis, Chemical Research Center, Hungarian Academy of Sciences, Pusztaszeri út. 59-67, 1025 Budapest (Hungary); Tzankov, B.; Lambov, N.; Konstantinov, S.; Tzankova, V. [Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia (Bulgaria); Pessina, F.; Valoti, M. [Dipartimento di Scienze della Vita, Universita di Siena, via Aldo Moro 2, Siena (Italy)

    2014-03-15

    Non-functionalized and amino-functionalized mesoporous silica nanoparticle were loaded with anti-inflammatory drug budesonide and additionally post-coated with bioadhesive polymer (carbopol). TEM images showed spherical shape of the nanoparticles and slightly higher polydispersity after coating with carbopol. Nitrogen physisorption and thermogravimetic analysis revealed that more efficient loading and incorporation into the pores of nanoparticles was achieved with the amino-functionalized silica carrier. Infrared spectra indicated that the post-coating of these nanoparticles with carbopol led to the formation of bond between amino groups of the functionalized carrier and carboxyl groups of carbopol. The combination of amino-functionalization of the carrier with the post-coating of the nanoparticles sustained budesonide release. Further, an in vitro model of inflammatory bowel disease showed that the cytoprotective effect of budesonide loaded in the post-coated silica nanoparticles on damaged HT-29 cells was more pronounced compared to the cytoprotection obtained with pure budesonide. -- Graphical abstract: Silica mesoporous MCM-41 particles were amino-functionalized, loaded with budesonide and post-coated with bioadhesive polymer (carbopol) in order to achieve prolonged residence of anti-inflammatory drug in GIT. Highlights: • Higher drug loading in amino-functionalized mesoporous silica. • Amino-functionalization and post-coating of the nanoparticles sustained drug release. • Achievement of higher cytoprotective effect with drug loaded into the nanoparticles.

  17. Functional food microstructures for macronutrient release and delivery.

    Science.gov (United States)

    Norton, J E; Gonzalez Espinosa, Y; Watson, R L; Spyropoulos, F; Norton, I T

    2015-03-01

    There is a need to understand the role of fat, protein and carbohydrate in human health, and also how foods containing and/or structured using these macronutrients can be designed so that they can have a positive impact on health. This may include a reduction in fat, salt or sugar, the protection and targeted release of micronutrients or active ingredients from/to particular parts of the digestive system, improvement of gastrointestinal health or satiety enhancing properties. Such foods can be designed with various macro- and microstructures that will impact on macronutrient release and delivery. These include simple and double emulsions, the use of Pickering particles and shells, nanoparticles, liposomes, gelled networks, fluid gels and gel particles, foams, self-assembled structures, and encapsulated systems. In order to design foods that deliver these benefits understanding of how these structures behave in the gastrointestinal tract is also required, which should involve utilising both in vitro and in vivo studies. This review aims to draw together research in these areas, by focusing on the current state of the art, but also exciting possibilities for future research and food development.

  18. The Impact of Timing and Dose of Rehabilitation Delivery on Functional Recovery of Stroke Patients

    Directory of Open Access Journals (Sweden)

    Hsiu-Chen Huang

    2009-05-01

    Conclusion: There is a dose-dependent effect of rehabilitation on functional improvement of stroke patients for the first 6 months post-stroke, and earlier delivery of rehabilitation has lasting effects on the functional recovery of stroke patients up to 1 year.

  19. Impact of the mode of delivery on female sexual function after childbirth.

    Science.gov (United States)

    Eid, M A; Sayed, A; Abdel-Rehim, R; Mostafa, T

    2015-01-01

    This cohort study aimed to assess the effect of the mode of delivery on female sexual function (FSF) after childbirth. Out of 256 primiparous women, 200 subjects that completed the study were divided into two groups; women that delivered vaginally and women that had elective cesarean section (CS). They were subjected to a translated version of female sexual function index (FSFI) questionnaire evaluating desire, lubrication, orgasm, satisfaction, pain both antenatally and 12 weeks postpartum. The mean FSFI total score of the two investigated groups demonstrated nonsignificant difference 12 weeks after delivery compared with these scores antenatally. Women that delivered vaginally demonstrated significant decreases in the scores of desire, arousal and lubrication domains 12 weeks after delivery compared with these scores antenatally where other scores demonstrated nonsignificant differences. Women that delivered by CS demonstrated a significant difference in desire domain 12 weeks after delivery compared with these scores antenatally where other scores demonstrated nonsignificant differences. It is concluded that the mode of delivery has nonsignificant effect on the FSF 12 weeks after childbirth. Specifically, vaginal delivery is associated with significant decrease in the desire, arousal and lubrication domains where elective CS is associated with significant decrease in the desire domain.

  20. Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Feng Jiang

    2015-10-01

    Full Text Available Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX, are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems.

  1. Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems.

    Science.gov (United States)

    Jiang, Feng; Liu, Biao; Lu, Jun; Li, Fangfei; Li, Defang; Liang, Chao; Dang, Lei; Liu, Jin; He, Bing; Badshah, Shaikh Atik; Lu, Cheng; He, Xiaojuan; Guo, Baosheng; Zhang, Xiao-Bing; Tan, Weihong; Lu, Aiping; Zhang, Ge

    2015-01-01

    Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems.

  2. Basket call option pricing for CCVG using sparse grids

    KAUST Repository

    Crocce, Fabian

    2016-01-06

    The use of processes with jumps to overcome the shortcomings of the classical Black and Scholes when modelling stock prices has became very popular. One of the best-known models is the Common Clock Variance Gamma model (CCVG), introduced by Madan and Seneta in the 1990 [3]. We propose a method to price European basket call options modelled by the CCVG. The method could be extended to other model obtained by the subordination of a multidimensional Brownian motion and to more general options. To simplify the expositions we consider calls under the CCVG.

  3. STS-110 Pilot Frick and Commander Bloomfield in slidewire basket

    Science.gov (United States)

    2002-01-01

    KENNEDY SPACE CENTER, FLA. -- STS-110 Pilot Stephen N. Frick and Commander Michael J. Bloomfield climb into the slidewire basket, part of emergency egress equipment on the launch pad.. The crew is taking part in Terminal Countdown Demonstration Test activities, which also include a simulated launch countdown, held at KSC prior to each Space Shuttle flight. Scheduled for launch April 4, the 11-day mission will feature Shuttle Atlantis docking with the International Space Station (ISS) and delivering the S0 truss, the centerpiece-segment of the primary truss structure that will eventually extend over 300 feet.

  4. Monomeric Chiral and Achiral Basket-Handle Porphyrins: Synthesis, Structural Features, and Arrested Tautomerism.

    Science.gov (United States)

    Gehrold, Andreas C; Bruhn, Torsten; Schneider, Heidi; Radius, Udo; Bringmann, Gerhard

    2015-12-18

    Chiral and achiral basket-handle porphyrins (BHPs) with different p-xylene straps and peripheral solubilizing groups were synthesized using a previously established synthetic approach. Subsequent modification, functionalization, and metalation of the tetrapyrrolic macrocycle yielded more than 80 BHPs. The chiral representatives were resolved into their enantiomers, whose absolute configurations were determined by comparison of their ECD spectra with other experimental or quantum chemically calculated spectra. NMR studies and coupled-cluster calculations proved that the free base BHPs, although highly symmetric, exhibited the phenomenon of "arrested tautomerism". Comparison of the solid-state structures of three metalated BHPs offered detailed insight into their three-dimensional shape. Finally, directly linked dimeric porphyrins with a BHP subunit were synthesized from functionalized BHPs to prove their value as synthetic building blocks.

  5. Polymer functionalized single walled carbon nanotubes mediated drug delivery of gliotoxin in cancer cells.

    Science.gov (United States)

    Bhatnagar, Ira; Venkatesan, Jayachandran; Kiml, Se-Kwon

    2014-01-01

    During recent years, significant development has been achieved in carbon nanotube conjugated with polymer system for drug delivery system (DDS). In the present study, we have prepared functionalized single walled carbon nanotube conjugated with chitooligosaccharide (f-SWNT-COS) as a Drug Delivery System. In addition, drug Gliotoxin (GTX) and targeting molecules (Lysozyme, p53 and Folic acid) have been incorporated into f-SWNT-COS. f-SWNTs-COS-GTX-p53, f-SWNTs-COS-GTX-lysozyme, f-SWNTs-COS-GTX-FA have been physiochemically characterized for DDS. FT-IR, SEM and TEM analysis confirmed the formation of chemical interaction and polymer coating. FT-IR result clearly confirmed the interaction between f-SWNT and COS. The effective drug release was monitored against cervical cancer (HeLa) cells and Breast Cancer (MCF-7) cells and it was found that all the three drug delivery systems showed significant cytotoxicity. f-SWNTs-COS-GTX-p53 delivery vehicle and its effective cytotoxicity on HeLa cells was further checked with fluorescent activated cell sorter analysis. Our results suggest that the f-SWNTs-COS-GTX-p53 is the most effective delivery vehicle with a controlled release and enhanced cytotoxicity rendered through apoptosis in human cervical cancer (HeLa) cells. These systems can further be used for the delivery of other commercially available anti cancer drugs as well.

  6. Functional Analysis and Treatment of Rumination Using Fixed-Time Delivery of a Flavor Spray

    Science.gov (United States)

    Wilder, David A.; Register, Martisa; Register, Stanley; Bajagic, Vedrana; Neidert, Pamela L.

    2009-01-01

    A functional analysis suggested that rumination exhibited by an adult with autism was maintained by automatic reinforcement. Next, a preference assessment with three flavor sprays (i.e., flavored sprays used by dieters) showed that apple pie spray was most preferred. Finally, the effects of fixed-time delivery of the apple pie spray on levels of…

  7. Intracellular delivery of a membrane-impermeable enzyme in active form using functionalized gold nanoparticles.

    Science.gov (United States)

    Ghosh, Partha; Yang, Xiaochao; Arvizo, Rochelle; Zhu, Zheng-Jiang; Agasti, Sarit S; Mo, Zhihong; Rotello, Vincent M

    2010-03-03

    Gold nanoparticles were coated with a short peptide to promote intracellular delivery of membrane-impermeable proteins. Through microscopy and enzyme assays, we demonstrated the particles were able to transport functional enzymes into a variety of cell lines. Significantly, the transported proteins were able to escape from endosomes. Moreover, these particles showed no apparent cytotoxicity.

  8. Anatomical and functional changes in the lower urinary tract following spontaneous vaginal delivery

    NARCIS (Netherlands)

    Wijma, J; Potters, AEW; de Wolf, BTHM; Tinga, DJ; Aarnoudse, JG

    Objective To assess the incidence of urinary incontinence in pregnancy and after spontaneous vaginal delivery and its relation with changes in the static and dynamic function of the pelvic floor. Design The second part of a prospective longitudinal study. Setting University Hospital Groningen and

  9. Mapping Access to Community-Developed Healthy Food Baskets Including Cost and Availability

    Science.gov (United States)

    Ginn, Alison; Majumdar, Anne; Carr, Marimba; Eastwood, Ginny; Menger, Beth

    2016-01-01

    Background: Food security is a topical issue but one that can be difficult to measure. Objective: To develop a community-approved food basket tool and use this to investigate the availability and affordability of a healthy diet in a multicultural urban setting. Design: A 7-day healthy food basket (HFB) containing 96 foods for six household types…

  10. Drop Test of the Candu Spent Fuel Storage Basket in MACSTOR/KN-400

    Energy Technology Data Exchange (ETDEWEB)

    Choi, W.S.; Jeon, J.Y.; Seo, K.S. [KAERI, 1045 Daedeokdaero, Yuseong, Daejeon, 305-353 (Korea, Republic of); Park, J.E.; Yoo, G.S.; Park, W.G. [Korea Hydro Nuclear Power - KHNP (Korea, Republic of)

    2009-06-15

    The MACSTOR/KN-400 of Wolsung power plant in Korea is a dry interim storage facilities. There are 400 long slender cylinders in MACSTOR/KN-400. In one cylinder, ten baskets where Candu spent fuels are loaded are stacked and stored. For this MACSTOR/KN-400 facilities, analyses and tests for the hypothetical accident conditions that might happen during moving and storing baskets into a cylinder were performed. The hypothetical accident conditions to be considered are two cases. One is the case of basket dropping onto the bottom plate of a cylinder. The other is the case of basket dropping onto the other basket top plate stored in the cylinder. For the drop analyses, the case of hanging cylinder and the case of cylinder on the unyielding target surface were considered. Based on the dropping analysis, testing condition was determined as the latter case that is for the cylinder on the target surface. In a basket, 60 dummy fuel bundles are loaded which have the same weight of real spent fuel bundles. On the external surface of the basket, 8 strain gauges and 4 accelerometers were attached for the data acquisition. In order to measure the velocity when a basket impacts, three different devices were utilized. And the impact velocity results were compared and cross-checked. After the dropping tests, helium leak tests were conducted to evaluate the leakage rate. (authors)

  11. Tribological investigation of a functional medical textile with lubricating drug-delivery finishing.

    Science.gov (United States)

    Gerhardt, L-C; Lottenbach, R; Rossi, R M; Derler, S

    2013-08-01

    Textile-based drug delivery systems have a high potential for innovative medical and gerontechnological applications. In this study, the tribological behaviour and lubrication properties of a novel textile with drug delivery function/finishing was investigated by means of friction experiments that simulated cyclic dynamic contacts with skin under dry and wet conditions. The textile drug delivery system is based on a loadable biopolymer dressing on a polyester (PES) woven fabric. The fabrics were finished with low (LC) and highly cross-linked (HC) polysaccharide dressings and investigated in the unloaded condition as well as loaded with phytotherapeutic substances. The mechanical resistance and possible abrasion of the functional coatings on the textile substrate were assessed by friction measurements and scanning electron microscopical analyses. Under dry contact conditions, all investigated fabrics (PES substrate alone and textiles with loaded and unloaded dressings) showed generally low friction coefficients (0.20-0.26). Under wet conditions, the measured friction coefficients were typically higher (0.34-0.51) by a factor of 1.5-2. In the wet condition, both loaded drug delivery textiles exhibited 7-29% lower friction (0.34-0.41) than the PES fabric with unloaded dressings (0.42-0.51), indicating pronounced lubrication effects. The lubrication effects as well as the abrasion resistance of the studied textiles with drug delivery function depended on the degree of dilution of the phytotherapeutic substances. Lubricating formulations of textile-based drug delivery systems which reduce friction against the skin might be promising candidates for advanced medical textile finishes in connection with skin care and wound (decubitus ulcer) prevention.

  12. Flexible shape-memory scaffold for minimally invasive delivery of functional tissues

    Science.gov (United States)

    Montgomery, Miles; Ahadian, Samad; Davenport Huyer, Locke; Lo Rito, Mauro; Civitarese, Robert A.; Vanderlaan, Rachel D.; Wu, Jun; Reis, Lewis A.; Momen, Abdul; Akbari, Saeed; Pahnke, Aric; Li, Ren-Ke; Caldarone, Christopher A.; Radisic, Milica

    2017-10-01

    Despite great progress in engineering functional tissues for organ repair, including the heart, an invasive surgical approach is still required for their implantation. Here, we designed an elastic and microfabricated scaffold using a biodegradable polymer (poly(octamethylene maleate (anhydride) citrate)) for functional tissue delivery via injection. The scaffold’s shape memory was due to the microfabricated lattice design. Scaffolds and cardiac patches (1 cm × 1 cm) were delivered through an orifice as small as 1 mm, recovering their initial shape following injection without affecting cardiomyocyte viability and function. In a subcutaneous syngeneic rat model, injection of cardiac patches was equivalent to open surgery when comparing vascularization, macrophage recruitment and cell survival. The patches significantly improved cardiac function following myocardial infarction in a rat, compared with the untreated controls. Successful minimally invasive delivery of human cell-derived patches to the epicardium, aorta and liver in a large-animal (porcine) model was achieved.

  13. The Relationship between Mode of Delivery and Sexual Function in Nulliparous Women

    Directory of Open Access Journals (Sweden)

    Aytay Alesheikh

    2016-07-01

    Full Text Available Background & aim: Sexual activity is one of the most important aspects of a marital life. Childbirth is also a major event in the life of women, and the period of postpartum is a time of emotional upheaval. Since women believe that vaginal delivery could negatively affect their sexual function after childbirth, they tend to give birth through caesarean section. Therefore, this study aimed to evaluate the relationship between mode of delivery and sexual function in nulliparous women referred to healthcare centers in Mashhad, Iran. Methods: This correlational study was conducted on 450 nulliparous women, divided into two groups of vaginal delivery and cesarean section in 2014. Suubjects were selected via multistage sampling. Data collection tools included Female Sexual Function Index (FSFI, Depression, Anxiety and Stress scale (DASS-21, and Cassidy social support scale. Data was analyzed in SPSS version 16 using Spearman correlation coefficient and Mann-Whitney test, T-test, ANOVA, and Kruskal-Wallis. Moreover, general linear model was used to control confounding variables, and P-value of less than 0.05 was considered statistically significant. Results: Independent t-test results indicated that mean scores of sexual function in two groups of the study were 26.11±4.36 and 26.38±4.41, respectively, which revealed no statistically significant difference between the groups (P=0.509. Conclusion: No significant difference was observed between the vaginal delivery and caesarean section groups regarding sexual function. Therefore, it seems that cesarean section does not necessarily lead to pleasing sexual relationships in postpartum period compared to vaginal delivery.

  14. Self-assembled lecithin/chitosan nanoparticles for oral insulin delivery: preparation and functional evaluation

    OpenAIRE

    Liu LY; Zhou CP; Xia XJ; Liu YL

    2016-01-01

    Liyao Liu, Cuiping Zhou, Xuejun Xia, Yuling Liu State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China Purpose: Here, we investigated the formation and functional properties of self-assembled lecithin/chitos...

  15. Delivery of small interfering RNAs in human cervical cancer cells by polyethylenimine-functionalized carbon nanotubes

    OpenAIRE

    Huang, Yuan-Pin; Lin, I-Jou; Chen, Chih-Chen; Hsu, Yi-Chiang; Chang, Chi-Chang; Lee, Mon-Juan

    2013-01-01

    Carbon nanotubes are capable of penetrating the cell membrane and are widely considered as potential carriers for gene or drug delivery. Because the C-C and C=C bonds in carbon nanotubes are nonpolar, functionalization is required for carbon nanotubes to interact with genes or drugs as well as to improve their biocompatibility. In this study, polyethylenimine (PEI)-functionalized single-wall (PEI-NH-SWNTs) and multiwall carbon nanotubes (PEI-NH-MWNTs) were produced by direct amination method....

  16. Quantitative ultrastructural analysis of basket and axo-axonic cell terminals in the mouse hippocampus.

    Science.gov (United States)

    Takács, Virág T; Szőnyi, András; Freund, Tamás F; Nyiri, Gábor; Gulyás, Attila I

    2015-03-01

    Three functionally different populations of perisomatic interneurons establish GABAergic synapses on hippocampal pyramidal cells: parvalbumin (PV)-containing basket cells, type 1 cannabinoid receptor (CB1)-positive basket cells both of which target somata, and PV-positive axo-axonic cells that innervate axon initial segments. Using electron microscopic reconstructions, we estimated that a pyramidal cell body receives synapses from about 60 and 140 synaptic terminals in the CA1 and CA3 area, respectively. About 60 % of these terminals were PV positive, whereas 35-40 % of them were CB1 positive. Only about 1 % (CA1) and 4 % (CA3) of the somatic boutons were negative for both markers. Using fluorescent labeling, we showed that most of the CB1-positive terminals expressed vesicular glutamate transporter 3. Reconstruction of somatic boutons revealed that although their volumes are similar, CB1-positive boutons are more flat and the total volume of their mitochondria was smaller than that of PV-positive boutons. Both types of boutons contain dense-core vesicles and frequently formed multiple release sites on their targets and innervated an additional soma or dendrite as well. PV-positive boutons possessed small, macular synapses; whereas the total synaptic area of CB1-positive boutons was larger and formed multiple irregular-shaped synapses. Axo-axonic boutons were smaller than somatic boutons, had only one synapse and their ultrastructural parameters were closer to those of PV-positive somatic boutons. Our results represent the first quantitative measurement-using a highly reliable method-of the contribution of different cell types to the perisomatic innervation of pyramidal neurons, and may help to explain functional differences in their output properties.

  17. A targeted drug delivery system based on dopamine functionalized nano graphene oxide

    Science.gov (United States)

    Masoudipour, Elham; Kashanian, Soheila; Maleki, Nasim

    2017-01-01

    The cellular targeting property of a biocompatible drug delivery system can widely increase the therapeutic effect against various diseases. Here, we report a dopamine conjugated nano graphene oxide (DA-nGO) carrier for cellular delivery of the anticancer drug, Methotrexate (MTX) into DA receptor positive human breast adenocarcinoma cell line. The material was characterized using scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy and UV-vis spectroscopy. Furthermore, the antineoplastic action of MTX loaded DA-nGO against DA receptor positive and negative cell lines were explored. The results presented in this article demonstrated that the application of DA functionalized GO as a targeting drug carrier can improve the drug delivery efficacy for DA receptor positive cancer cell lines and promise future designing of carrier conjugates based on it.

  18. From structures to functions: insights into exosomes as promising drug delivery vehicles.

    Science.gov (United States)

    Ren, Jinghua; He, Wenshan; Zheng, Lifen; Duan, Hongwei

    2016-05-24

    Exosomes are small membrane vesicles secreted by most cell types, and appear ubiquitously in cell culture supernatants and body fluids. Increasing evidence supports that exosomes play important roles in intercellular communication, both locally and systemically, by transporting their contents such as proteins, lipids and RNAs between cells. Of particular interest for controlled drug delivery is that cell-derived exosomes offer the possibilities of overcoming biological barriers, thereby allowing the incorporated gene and drug to reach targeted tissue, which have been considerable challenges for synthetic carriers. Great research efforts have been dedicated to developing exosome-based drug delivery systems for the treatment of inflammatory diseases, degenerative disorders and cancer. In this review, we will describe the structural and functional properties of exosomes and emphasize current advances in the therapeutic applications of exosomes as drug delivery vehicles, followed by a discussion on current challenges and future perspectives.

  19. Functionalized layered double hydroxide nanoparticles conjugated with disulfide-linked polycation brushes for advanced gene delivery.

    Science.gov (United States)

    Hu, H; Xiu, K M; Xu, S L; Yang, W T; Xu, F J

    2013-06-19

    Layered double hydroxides (LDHs) have aroused great attention as potential nanosized drug delivery carriers, but independent inorganic LDH wrapped with DNA shows very low transfection efficiency. To manipulate and control the surface properties of LDH nanoparticles is of crucial importance in the designing of LDH-based drug carriers. In this work, surface-initiated atom transfer radical polymerization (ATRP) of 2-(dimethylamino)ethyl methacrylate (DMAEMA) is employed to tailor the functionality of LDH surfaces in a well-controlled manner and produce a series of well-defined novel gene delivery vectors (termed as LDH-PDs), where a flexible three-step method was first developed to introduce the ATRP initiation sites containing disulfide bonds onto LDH surfaces. In comparison the pristine LDH particles, the resultant LDH-PDs exhibited better ability to condense plasmid DNA (pDNA) and much higher levels to delivery genes in different cell lines including COS7 and HepG2 cell lines. Moreover, the LDH-PDs also could largely enhance cellular uptake. This present study demonstrates that functionalization of bioinorganic LDH with flexible polycation brushes is an effective means to produce new LDH-based gene delivery systems.

  20. Electrophysiological heterogeneity of fast-spiking interneurons: chandelier versus basket cells.

    Directory of Open Access Journals (Sweden)

    Nadezhda V Povysheva

    Full Text Available In the prefrontal cortex, parvalbumin-positive inhibitory neurons play a prominent role in the neural circuitry that subserves working memory, and alterations in these neurons contribute to the pathophysiology of schizophrenia. Two morphologically distinct classes of parvalbumin neurons that target the perisomatic region of pyramidal neurons, chandelier cells (ChCs and basket cells (BCs, are generally thought to have the same "fast-spiking" phenotype, which is characterized by a short action potential and high frequency firing without adaptation. However, findings from studies in different species suggest that certain electrophysiological membrane properties might differ between these two cell classes. In this study, we assessed the physiological heterogeneity of fast-spiking interneurons as a function of two factors: species (macaque monkey vs. rat and morphology (chandelier vs. basket. We showed previously that electrophysiological membrane properties of BCs differ between these two species. Here, for the first time, we report differences in ChCs membrane properties between monkey and rat. We also found that a number of membrane properties differentiate ChCs from BCs. Some of these differences were species-independent (e.g., fast and medium afterhyperpolarization, firing frequency, and depolarizing sag, whereas the differences in the first spike latency between ChCs and BCs were species-specific. Our findings indicate that different combinations of electrophysiological membrane properties distinguish ChCs from BCs in rodents and primates. Such electrophysiological differences between ChCs and BCs likely contribute to their distinctive roles in cortical circuitry in each species.

  1. The impact of mode of delivery on the sexual function of primiparous women: a prospective study.

    Science.gov (United States)

    Kahramanoglu, Ilker; Baktiroglu, Merve; Hamzaoglu, Kubra; Kahramanoglu, Ozge; Verit, Fatma Ferda; Yucel, Oguz

    2017-04-01

    The purpose of this study was to evaluate the impact of mode of delivery on the sexual function of women using the Female Sexual Function Index (FSFI). This was a prospective study of 452 nulliparous women, comparing their sexual function before and after birth. A Turkish version of the FSFI questionnaire was administered within the first 8 weeks of pregnancy, at 3 and 6 months postpartum in a face-to-face manner and subsequently at the 12th month and 24th month over the telephone. Age, BMI, education level, house income, duration of marriage, birthweight, and feeding at each time point were similar between group 1 [vaginal birth and mediolateral episiotomy (MLE)] and group 2 [caesarean section (CS)]. In the postpartum period, there were 265 and 138 participants at 3rd month, 216 and 121 participants at 6th month, 189 and 111 participants at 12th month, and 133 and 85 participants at 24th month in group 1 and 2, respectively. The FSFI total scores decreased at 3 and 6 months postpartum in both groups (27.3 to 23.1 in group 1 and 27.5 to 25 in group 2; p delivery scores in both groups. Compared with the caesarean group, the vaginal birth with MLE group had lower satisfaction and higher pain levels at 3 months postpartum (p delivery, sexual function 6 months after childbirth is similar to that in pre-pregnancy.

  2. Development and characterization of porous functionalized collagen scaffolds for delivery of FGF-2

    OpenAIRE

    Pokholenko Ia. O.; Chetyrkina M. D.; Dubey L. V.; Dubey I. Ya.; Moshynets O. V.; Sheludko E. V.; Shpylova S. P.; Degtiarova M. I.; Kordium V. A.

    2014-01-01

    Aim. To develop the porous functionalized collagen scaffold for the delivery of FGF-2 and studying its properties in vitro and in vivo. Methods. Porous collagen scaffolds were prepared by freeze- drying collagen I solutions containing the polymer developed on the basis of cross-linked modified heparin. The scaffolds have been analyzed by SEM, AFM and SCLM. The angiogenic activity of these scaffolds loaded with FGF-2 was tested in a CAM assay. Results. The data obtained by SEM and SCLM analysi...

  3. Carboxyl group (-CO2 H) functionalized coordination polymer nanoparticles as efficient platforms for drug delivery.

    Science.gov (United States)

    Novio, Fernando; Lorenzo, Julia; Nador, Fabiana; Wnuk, Karolina; Ruiz-Molina, Daniel

    2014-11-17

    Functionalization of nanoparticles can significantly influence their properties and potential applications. Although researchers can now functionalize metal, metal oxide, and organic polymer nanoparticles with a high degree of precision, controlled surface functionalization of nanoscale coordination polymer particles (CPPs) has remained a significant challenge. The lack of methodology is perhaps one of the greatest roadblocks to the advancement of CPPs into high added-value drug delivery applications. Here, we report having achieved this goal through a stepwise formation and functionalization protocol. We fabricated robust nanoparticles with enhanced thermal and colloidal stabilities by incorporation of carboxyl groups and these surface carboxyl groups could be subsequently functionalized through well-known peptide coupling reactions. The set of chemistries that we employed as proof-of-concept enabled a plethora of new functional improvements for the application of CPPs as drug delivery carriers, including enhanced colloidal stabilities and the incorporation of additional functional groups such as polyethylene glycol (PEG) or fluorescent dyes that enabled tracking of their cellular uptake. Finally, we ascertained the cytotoxicity of the new CPP nanoparticles loaded with camptothecin to human breast adenocarcinoma (MCF-7). Efflux measurements show that the encapsulation of camptothecin enhances the potency of the drug 6.5-fold and increases the drug retention within the cell.

  4. STUDY ON ALCOHOLIC FERMENTATION IN A STATIONARY BASKET BIOREACTOR WITH IMMOBILIZED YEAST CELLS

    Directory of Open Access Journals (Sweden)

    Dan Caşcaval

    2011-02-01

    Full Text Available The use of a stationary basket bioreactor with immobilized S. cerevisiae cells indicated the possibility to extend the number of alcoholic fermentation cycles that can be carried out with the same biocatalysts to over nine. Although the rates of glucose consumption and ethanol production were lower than those recorded for the mobile beds of immobilized yeast cells, the mechanical lysis of the biocatalysts is avoided in the case of basket bed. Due to the substrate and product accumulation inside the basket bed, the fermentation process can be improved by washing out the biocatalysts bed over two or four cycles.

  5. Experience with certifying borated stainless steel as a shipping cask basket material

    Energy Technology Data Exchange (ETDEWEB)

    Abbott, D.G. (EG and G Idaho, Inc., Idaho Falls, ID (USA)); Nickell, R.E. (Applied Science and Technology, Inc., Poway, CA (USA))

    1990-01-01

    The original cask designs for a cask demonstration project featured fuel baskets constructed of borated stainless steel (bss) as a structural material. The project is intended to demonstrate casks that can be used for both shipping and storing spent nuclear fuel assemblies. The baskets were intended to maintain the fuel assemblies in a subcritical array for both normal and accident conditions. The Nuclear Regulatory Commission, however, judged bss to be unacceptable as a structural material. The cask designs were subsequently modified. The knowledge gained during this cask demonstration project may be applicable to development of bss as a basket material in future cask design. 6 refs., 2 figs., 2 tabs.

  6. Experience with certifying borated stainless steel as a shipping cask basket material

    Energy Technology Data Exchange (ETDEWEB)

    Abbott, D.G. [Idaho National Engineering Lab., Idaho Falls, ID (United States); Nickell, R.E. [Applied Science and Technology, Poway, CA (United States)

    1990-10-01

    This paper discusses the original cask designs for a cask demonstration project that has featured fuel baskets constructed of borated stainless steel (bss) as a structural material. The project is intended to demonstrate casks that can be used for both shipping and storing spent nuclear fuel assemblies. The baskets were intended to maintain the fuel assemblies in a subcritical array for both normal and accident conditions. The Nuclear Regulatory Commission, judged bss to be unacceptable as a structural material. The cask designs were subsequently modified. The knowledge gained during this cask demonstration project may be applicable to development of bss as a basket material in future cask design.

  7. Molecular design and nanoparticle-mediated intracellular delivery of functional proteins to target cellular pathways

    Science.gov (United States)

    Shah, Dhiral Ashwin

    Intracellular delivery of specific proteins and peptides represents a novel method to influence stem cells for gain-of-function and loss-of-function. Signaling control is vital in stem cells, wherein intricate control of and interplay among critical pathways directs the fate of these cells into either self-renewal or differentiation. The most common route to manipulate cellular function involves the introduction of genetic material such as full-length genes and shRNA into the cell to generate (or prevent formation of) the target protein, and thereby ultimately alter cell function. However, viral-mediated gene delivery may result in relatively slow expression of proteins and prevalence of oncogene insertion into the cell, which can alter cell function in an unpredictable fashion, and non-viral delivery may lead to low efficiency of genetic delivery. For example, the latter case plagues the generation of induced pluripotent stem cells (iPSCs) and hinders their use for in vivo applications. Alternatively, introducing proteins into cells that specifically recognize and influence target proteins, can result in immediate deactivation or activation of key signaling pathways within the cell. In this work, we demonstrate the cellular delivery of functional proteins attached to hydrophobically modified silica (SiNP) nanoparticles to manipulate specifically targeted cell signaling proteins. In the Wnt signaling pathway, we have targeted the phosphorylation activity of glycogen synthase kinase-3beta (GSK-3beta) by designing a chimeric protein and delivering it in neural stem cells. Confocal imaging indicates that the SiNP-chimeric protein conjugates were efficiently delivered to the cytosol of human embryonic kidney cells and rat neural stem cells, presumably via endocytosis. This uptake impacted the Wnt signaling cascade, indicated by the elevation of beta-catenin levels, and increased transcription of Wnt target genes, such as c-MYC. The results presented here suggest that

  8. A Review on Characterizations and Biocompatibility of Functionalized Carbon Nanotubes in Drug Delivery Design

    Directory of Open Access Journals (Sweden)

    Julia M. Tan

    2014-01-01

    Full Text Available The revolutionary development of functionalized carbon nanotubes (f-CNTs for applications in nanomedicine has emerged as one of the most interesting fields, which has increased exponentially in recent years. This is due to their appealing physical and chemical properties, as well as their unique architecture. After a brief introduction on the physicochemical properties of carbon nanotubes (CNTs, we described several functionalization methods for the surface modification of CNTs, with the aim to facilitate their solubility in physiological aqueous environment. This review focuses on recent advances in drug delivery design based on f-CNTs with an emphasis on the determination of various parameters involved and characterization methods used in order to achieve higher therapeutic efficacy of targeted drug delivery. In particular, we will highlight a variety of different analytical techniques which can be used to characterize the elemental composition, chemical structure, and functional groups introduced onto the CNTs after surface modification. We also review the current progress of available in vitro biocompatibility assays based on f-CNTs and then discuss their toxicological profile and biodistribution for advanced drug delivery.

  9. Functional hydrogel contact lens for drug delivery in the application of oculopathy therapy.

    Science.gov (United States)

    Hu, Xiaohong; Tan, Huaping; Hao, Lingyun

    2016-12-01

    Although hydrogel contact lens has attracted increasingly concerns as delivery carriers in the field of oculopathy therapy, traditional hydrogel does not show excellent drug encapsulated and controlled properties due to simple hydrophilic polymer chain lacking extra interaction with drug molecule. Herein, functional hydrogels were synthesized in this research to delivery ophthalmic drug for oculopathy therapy. Functional monomer of mono-GMA-β-CD and functional crosslinker of MA-β-CD were incorporated into hydrogel by copolymerization. For hydrogels, equilibrium swelling ratio and contact angle was influenced by mono-GMA-β-CD ratio and MA-β-CD ratio, respectively. All hydrogels exhibited similar water loss behavior and good transparency. Hydrogels had rheological characteristic of typical elastomer. Viscoelasticity and surface morphology of hydrogel were also affected by mono-GMA-β-CD ratio and MA-β-CD ratio. In the aspect of properties, functional hydrogel containing β-CD domain exhibited better protein resistance capacity and significantly higher equilibrium encapsulated drug amount than traditional hydrogel. Besides the performance, drug release behavior of drug encapsulated hydrogel was adjusted by both mono-GMA-β-CD ratio and MA-β-CD ratio. Preliminary in vivo evaluation revealed that functional hydrogel contact lens had better effect and efficacy on lowering intraocular tension than commercial eye drop. It is inferred from all results that functional contact lens has a bright prospect in the application of oculopathy therapy.

  10. Pluronic F127 nanomicelles engineered with nuclear localized functionality for targeted drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yong-Yong; Li, Lan; Dong, Hai-Qing, E-mail: inano_donghq@tongji.edu.cn; Cai, Xiao-Jun; Ren, Tian-Bin, E-mail: rentianbin@yeah.net

    2013-07-01

    PKKKRKV (Pro-Lys-Lys-Lys-Arg-Lys-Val, PV7), a seven amino acid peptide, has emerged as one of the primary nuclear localization signals that can be targeted into cell nucleus via the nuclear import machinery. Taking advantage of chemical diversity and biological activities of this short peptide sequence, in this study, Pluronic F127 nanomicelles engineered with nuclear localized functionality were successfully developed for intracellular drug delivery. These nanomicelles with the size ∼ 100 nm were self-assembled from F127 polymer that was flanked with two PV7 sequences at its both terminal ends. Hydrophobic anticancer drug doxorubicin (DOX) with inherent fluorescence was chosen as the model drug, which was found to be efficiently encapsulated into nanomicelles with the encapsulation efficiency at 72.68%. In comparison with the non-functionalized namomicelles, the microscopic observation reveals that PV7 functionalized nanomicelles display a higher cellular uptake, especially into the nucleus of HepG2 cells, due to the nuclear localization signal effects. Both cytotoxicity and apoptosis studies show that the DOX-loaded nanomicelles were more potent than drug nanomicelles without nuclear targeting functionality. It was thus concluded that PV7 functionalized nanomicelles could be a potentially alternative vehicle for nuclear targeting drug delivery. - Highlights: ► A new nuclear targeted drug delivery system based on micelles is developed. ► This micellar system features a core-shell structure with the size peaked at 100 nm. ► PV7, a short peptide sequence, is adopted as a nuclear targeting ligand. ► PV7 functionalized drug loaded micelles are more potent in killing tumor cells.

  11. Applications of functional carbon nanomaterials from hydrogen storage to drug delivery

    Science.gov (United States)

    Leonard, Ashley Dawn

    This dissertation describes the modification and functionalization of single-walled carbon nanotubes (SWCNTs). These SWCNTs were then investigated for their use in medical applications and for the storage of hydrogen. A technique was developed that leads to highly customized, individually suspended aqueous solutions of SWCNTs. These newly generated water-soluble SWCNTs were then functionalized further in water, thereby permitting the second functionalization addends to be chemically sensitive functional groups, for example drugs, that would not withstand the strongly acidic conditions of the first functionalization. The radical scavenging properties of nanovectors derived from SWCNTs were investigated and it was found that even the poorest SWCNT nanovector studied was nearly 40 times more effective at scavenging radicals than dendrite-fullerene DF-1, which has been shown to be a radioprotective to zebrafish via an antioxidant niechanism. This was used as the base to investigate using SWCNTs as protectors and mitigators of radiation exposure. SWCNTs were then explored for their use as drug delivery agents, in particular, the water insoluble chemotherapy drug, paclitaxel. SWCNTs showed promising in vivo and in vitro efficacy in the delivery of paclitaxel. Toxicity and biodistribution studies of the SWCNTs as drug delivery agents were performed in vivo using SWCNTs functionalized with radiolabeled indium. It was found that SWCNTs could be used for hydrogen storage by chemically crosslinking 3-dimensional frameworks of SWCNT fibers. These frameworks were shown to physisorb twice as much hydrogen, at low pressures, with respect to their surface areas, than typical macroporous carbon materials. This makes these SWCNT frameworks attractive materials for the development of a hydrogen vehicle fuel tank.

  12. Bacillus-shape design of polymer based drug delivery systems with janus-faced function for synergistic targeted drug delivery and more effective cancer therapy.

    Science.gov (United States)

    Cui, Fei; Lin, Jinyan; Li, Yang; Li, Yanxiu; Wu, Hongjie; Yu, Fei; Jia, Mengmeng; Yang, Xiangrui; Wu, Shichao; Xie, Liya; Ye, Shefang; Luo, Fanghong; Hou, Zhenqing

    2015-04-01

    The particle shape of the drug delivery systems had a strong impact on their in vitro and in vivo performance, but there was limited availability of techniques to produce the specific shaped drug carriers. In this article, the novel methotrexate (MTX) decorated MPEG-PLA nanobacillus (MPEG-PLA-MTX NB) was prepared by the self-assembly technique followed by the extrusion through SPG membrane with high N2 pressure for targeted drug delivery, in which Janus-like MTX was not only used as a specific anticancer drug but could also be served as a tumor-targeting ligand. The MPEG-PLA-MTX NBs demonstrated much higher in vitro and in vivo targeting efficiency compared to the MPEG-PLA-MTX nanospheres (MPEG-PLA-MTX NSs) and MPEG-PLA nanospheres (MPEG-PLA NSs). In addition, the MPEG-PLA-MTX NBs also displayed much more excellent in vitro and in vivo antitumor activity than the MPEG-PLA-MTX NSs and free MTX injection. To our knowledge, this work provided the first example of the integration of the shape design (which mediated an early phase tumor accumulation and a late-phase cell internalization) and Janus-faced function (which mediated an early phase active targeting effect and a late-phase anticancer effect) on the basis of nanoscaled drug delivery systems. The highly convergent and cooperative drug delivery strategy opens the door to more drug delivery systems with new shapes and functions for cancer therapy.

  13. UPAYA PENINGKATAN KARAKTER SISWA SMA DALAM PERMAINAN BOLA BASKET MELALUI MODEL TPSR

    Directory of Open Access Journals (Sweden)

    Titis Nurina

    2014-04-01

    Full Text Available Pembelajaran pendidikan jasmani dalam model TPSR lebih menekankan pada kondisi siswa dan pendekatannya juga berorientasi kepada aktualisasi diri dan rekonstruksi sosial siswa di dalam pembelajaran permainan bola basket. Penelitian ini bertujuan untuk meningkatkan karakter tanggung jawab, kerja sama, dan percaya diri siswa putri kelas XI IPS 2 SMA Muhammadiyah 3 Yogyakarta dengan model TPSR dalam pembelajaran permainan bola basket. Penelitian ini menggunakan metode penelitian tindakan kelas yang dilaksanakan dalam dua siklus. Subjek dalam penelitian adalah seluruh siswa putri kelas XI IPS 2 SMA Muhammadiyah 3 yang berjumlah sembilan siswa. Analisis data menggunakan analisis diskriptif, kualitatif, dan kuantitatif. Hasil penelitian menunjukkan bahwa model pembelajaran TPSR dapat meningkatkan karakter tanggung jawab dan kerja sama dalam pembel-ajaran permainan bola basket yang berdampak pada kepercayaan diri siswa putri kelas XI IPS 2 SMA Muhammadiyah 3 Yogyakarta yang dapat dilihat dari peningkatan nilai keterampilan psikomotor, kognitif, dan afektif siswa. Kata Kunci: TPSR, karakter, permainan bola basket

  14. On the Basket Stinkhorn Mushroom Phallus merulinus (Phallaceae in Mangalore, Karnataka, India

    Directory of Open Access Journals (Sweden)

    K.R. Sridhar

    2013-03-01

    Full Text Available The Basket Stinkhorm Mushroom Phallus merulinus is reported from the monocot debris of Mangalore University Arbortum. Its occurrence, growth and characteristics are compared with other Phallus spp.

  15. Pluronic F127 nanomicelles engineered with nuclear localized functionality for targeted drug delivery.

    Science.gov (United States)

    Li, Yong-Yong; Li, Lan; Dong, Hai-Qing; Cai, Xiao-Jun; Ren, Tian-Bin

    2013-07-01

    PKKKRKV (Pro-Lys-Lys-Lys-Arg-Lys-Val, PV7), a seven amino acid peptide, has emerged as one of the primary nuclear localization signals that can be targeted into cell nucleus via the nuclear import machinery. Taking advantage of chemical diversity and biological activities of this short peptide sequence, in this study, Pluronic F127 nanomicelles engineered with nuclear localized functionality were successfully developed for intracellular drug delivery. These nanomicelles with the size ~100 nm were self-assembled from F127 polymer that was flanked with two PV7 sequences at its both terminal ends. Hydrophobic anticancer drug doxorubicin (DOX) with inherent fluorescence was chosen as the model drug, which was found to be efficiently encapsulated into nanomicelles with the encapsulation efficiency at 72.68%. In comparison with the non-functionalized namomicelles, the microscopic observation reveals that PV7 functionalized nanomicelles display a higher cellular uptake, especially into the nucleus of HepG2 cells, due to the nuclear localization signal effects. Both cytotoxicity and apoptosis studies show that the DOX-loaded nanomicelles were more potent than drug nanomicelles without nuclear targeting functionality. It was thus concluded that PV7 functionalized nanomicelles could be a potentially alternative vehicle for nuclear targeting drug delivery.

  16. Impaction of a lithotripsy basket during endoscopic lithotomy of a common bile duct stone

    Institute of Scientific and Technical Information of China (English)

    Nobutada; Fukino; Takatsugu; Oida; Atsushi; Kawasaki; Kenji; Mimatsu; Youichi; Kuboi; Hisao; Kano; Sadao; Amano

    2010-01-01

    The treatments for common bile duct (CBD) stones are being continually developed. Impaction of the lithotripsy basket during endoscopic removal of CBD stones was seen in 5.9% patients. We report the case of a 66-yearold woman who underwent surgery for the removal of an impacted biliary basket. She was admitted to our hospital with a complaint of right upper abdominal pain. Magnetic resonance cholangiopancreatography revealed a CBD stone (20 mm × 15 mm). We diagnosed her with choledocholithiasis and performe...

  17. Market Basket Analysis for a Supermarket based on Frequent Itemset Mining

    Directory of Open Access Journals (Sweden)

    Loraine Charlet Annie M.C.

    2012-09-01

    Full Text Available Market basket analysis is an important component of analytical system in retail organizations to determine the placement of goods, designing sales promotions for different segments of customers to improve customer satisfaction and hence the profit of the supermarket. These issues for a leading supermarket are addressed here using frequent itemset mining. The frequent itemsets are mined from the market basket database using the efficient K-Apriori algorithm and then the association rules are generated.

  18. Discovering market basket patterns using hierarchical association rules

    Directory of Open Access Journals (Sweden)

    Marijana Zekić-Sušac

    2015-10-01

    Full Text Available Association rules are a data mining method for discovering patterns of frequent item sets, such as products in a store that are frequently purchased at the same time by a customer (market basket analysis. A number of interestingness measures for association rules have been developed to date, but research has shown that there a dominant measure does not exist. Authors have mostly used objective measures, whereas subjective measures have rarely been investigated. This paper aims to combine objective measures such as support, confidence and lift with a subjective approach based on human expert selection in order to extract interesting rules from a real dataset collected from a large Croatian retail chain. Hierarchical association rules were used to enhance the efficiency of the extraction rule. The results show that rules that are more interesting were extracted using the hierarchical method, and that a hybrid approach of combining objective and subjective measures succeeds in extracting certain unexpected and actionable rules. The research can be useful for retail and marketing managers in planning marketing strategies, as well as for researchers investigating this field.

  19. Canasta Básica de Alimentos Basic Food Basket

    Directory of Open Access Journals (Sweden)

    Cecilia Antún

    2010-06-01

    Full Text Available En abril de 2009 se conformó en la Asociación Argentina de Dietistas y Nutricionistas Dietistas el Grupo de Estudio sobre Soberanía Alimentaria, constituido por un grupo de licenciados en nutrición con interés en el tema. Como primer objetivo, el Grupo se propuso estudiar tres temas: "el Derecho a la Alimentación", "la Producción y Disponibilidad de alimentos en Argentina" y "la Canasta Básica de Alimentos". En el presente artículo se expone un resumen de los avances en el tercer tema mencionado.In April 2009, the Argentina Association of Dietitians and Nutritionists-Dietitians formed the Study Group on Food Sovereignty, made up of graduates in Nutrition having an interest in the subject. As a first objective, the Group decided to study three subjects: "The Right to Food", "Production and Availability of Food in Argentina" and "Basic Food Basket." This article is a summary of the progress made on the third subject mentioned.

  20. Why Do Agricultural Producers Exhibit at Bread Basket?

    Directory of Open Access Journals (Sweden)

    M. Havlíková

    2015-12-01

    Full Text Available A literature survey proved that trade shows are important marketing tools, enabling sellers to present and test new products, to monitor their competitors, and to establish personal contacts with customers. The paper extends the current research of trade shows by analyzing exhibitors ́ motives for exhibiting. The research is conducted for a traditional international agricultural fair - Bread Basket. Exhibitors, including animal production exhibitors, crop production exhibitors and agriculture technology exhibitors, were offered a list of potential motives for exhibiting and were asked to indicate their agreement (disagreement on a 5-point Likert scale. Subsequently, a factor analysis revealed four key factors for exhibiting, including searching for information and company development, product development, focus on company surroundings and new market possibilities. Finally, exhibitors were surveyed again in order to choose one of these factors to be the most important one for exhibiting. Logistic regression revealed how the specific variables (NACE classification, year of establishment and frequency of exhibitin g influence the selected factors.

  1. Evaluation of copper for divider subassembly in MCO Mark IA and Mark IV scrap fuel baskets

    Energy Technology Data Exchange (ETDEWEB)

    Graves, C.E.

    1997-09-29

    The K Basin Spent Nuclear Fuel (SNF) Project Multi-Canister Overpack (MCO) subprojection eludes the design and fabrication of a canister that will be used to confine, contain, and maintain fuel in a critically safe array to enable its removal from the K Basins, vacuum drying, transport, staging, hot conditioning, and interim storage (Goldinann 1997). Each MCO consists of a shell, shield plug, fuel baskets (Mark IA or Mark IV), and other incidental equipment. The Mark IA intact and scrap fuel baskets are a safety class item for criticality control and components necessary for criticality control will be constructed from 304L stainless steel. It is proposed that a copper divider subassembly be used in both Mark IA and Mark IV scrap baskets to increase the safety basis margin during cold vacuum drying. The use of copper would increase the heat conducted away from hot areas in the baskets out to the wall of the MCO by both radiative and conductive heat transfer means. Thus copper subassembly will likely be a safety significant component of the scrap fuel baskets. This report examines the structural, cost and corrosion consequences associated with using a copper subassembly in the stainless steel MCO scrap fuel baskets.

  2. Local circuitry involving parvalbumin-positive basket cells in the CA2 region of the hippocampus.

    Science.gov (United States)

    Mercer, Audrey; Eastlake, Karen; Trigg, Hayley L; Thomson, Alex M

    2012-01-01

    There is a growing recognition that the CA2 region of the hippocampus has its own distinctive properties, inputs, and pathologies. The dendritic and axonal patterns of some interneurons in this region are also strikingly different from those described previously in CA1 and CA3. The local circuitry in this region, however, had yet to be studied in detail. Accordingly, using dual intracellular recordings and biocytin-filling, excitatory and inhibitory connections involving CA2 parvalbumin-positive basket cells were characterized for the first time. CA2 basket cells targeted neighboring pyramidal cells and received excitatory inputs from them. CA2 basket cells that resembled those in CA1 with a fast spiking behavior and dendritic tree confined to the region of origin received depressing excitatory postsynaptic potentials (EPSPs). In contrast, unlike CA1 basket cells but like CA1 Oriens-Lacunosum Moleculare (OLM) cells, the majority of CA2 basket cells had horizontally oriented dendrites in Stratum Oriens (SO), which extended into all three CA subfields, had an adapting firing pattern, presented a "sag" in their voltage responses to hyperpolarizing current injection, and received facilitating EPSPs. The expression of I(h) did not influence the EPSP time courses and paired pulse ratios (PPR). Estimates of the probability of release (p) for the depressing and facilitating EPSPs were correlated with the PPR. Connections with low probabilities of release had higher PPR. Quantal amplitude (q) for the facilitating connections was larger than q at depressing inputs onto fast spiking basket cells.

  3. Perisomatic GABAergic synapses of basket cells effectively control principal neuron activity in amygdala networks

    Science.gov (United States)

    Veres, Judit M; Nagy, Gergő A; Hájos, Norbert

    2017-01-01

    Efficient control of principal neuron firing by basket cells is critical for information processing in cortical microcircuits, however, the relative contribution of their perisomatic and dendritic synapses to spike inhibition is still unknown. Using in vitro electrophysiological paired recordings we reveal that in the mouse basal amygdala cholecystokinin- and parvalbumin-containing basket cells provide equally potent control of principal neuron spiking. We performed pharmacological manipulations, light and electron microscopic investigations to show that, although basket cells innervate the entire somato-denditic membrane surface of principal neurons, the spike controlling effect is achieved primarily via the minority of synapses targeting the perisomatic region. As the innervation patterns of individual basket cells on their different postsynaptic partners show high variability, the impact of inhibitory control accomplished by single basket cells is also variable. Our results show that both basket cell types can powerfully regulate the activity in amygdala networks predominantly via their perisomatic synapses. DOI: http://dx.doi.org/10.7554/eLife.20721.001 PMID:28060701

  4. Functionalized carbon nanomaterials: exploring the interactions with Caco-2 cells for potential oral drug delivery

    Directory of Open Access Journals (Sweden)

    Coyuco JC

    2011-10-01

    Full Text Available Jurja C Coyuco, Yuanjie Liu, Bee-Jen Tan, Gigi NC ChiuDepartment of Pharmacy, Faculty of Science, National University of Singapore, SingaporeAbstract: Although carbon nanomaterials (CNMs have been increasingly studied for their biomedical applications, there is limited research on these novel materials for oral drug delivery. As such, this study aimed to explore the potential of CNMs in oral drug delivery, and the objectives were to evaluate CNM cytotoxicity and their abilities to modulate paracellular transport and the P-glycoprotein (P-gp efflux pump. Three types of functionalized CNMs were studied, including polyhydroxy small-gap fullerenes (OH-fullerenes, carboxylic acid functionalized single-walled carbon nanotubes (fSWCNT-COOH and poly(ethylene glycol functionalized single-walled carbon nanotubes (fSWCNT-PEG, using the well-established Caco-2 cell monolayer to represent the intestinal epithelium. All three CNMs had minimum cytotoxicity on Caco-2 cells, as demonstrated through lactose dehydrogenase release and 3-(4,5-dimethyliazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assays. Of the three CNMs, fSWCNT-COOH significantly reduced transepithelial electrical resistance and enhanced transport of Lucifer Yellow across the Caco-2 monolayer. Confocal fluorescence microscopy showed that fSWCNT-COOH treated cells had the highest perturbation in the distribution of ZO-1, a protein marker of tight junction, suggesting that fSWCNT-COOH could enhance paracellular permeability via disruption of tight junctions. This modulating effect of fSWCNT-COOH can be reversed over time. Furthermore, cellular accumulation of the P-gp substrate, rhodamine-123, was significantly increased in cells treated with fSWCNT-COOH, suggestive of P-gp inhibition. Of note, fSWCNT-PEG could increase rhodamine-123 accumulation without modifying the tight junction. Collectively, these results suggest that the functionalized CNMs could be useful as modulators for oral drug

  5. Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery.

    Science.gov (United States)

    Chu, Derrick M; Ma, Jun; Prince, Amanda L; Antony, Kathleen M; Seferovic, Maxim D; Aagaard, Kjersti M

    2017-03-01

    Human microbial communities are characterized by their taxonomic, metagenomic and metabolic diversity, which varies by distinct body sites and influences human physiology. However, when and how microbial communities within each body niche acquire unique taxonomical and functional signatures in early life remains underexplored. We thus sought to determine the taxonomic composition and potential metabolic function of the neonatal and early infant microbiota across multiple body sites and assess the effect of the mode of delivery and its potential confounders or modifiers. A cohort of pregnant women in their early third trimester (n = 81) were prospectively enrolled for longitudinal sampling through 6 weeks after delivery, and a second matched cross-sectional cohort (n = 81) was additionally recruited for sampling once at the time of delivery. Samples across multiple body sites, including stool, oral gingiva, nares, skin and vagina were collected for each maternal-infant dyad. Whole-genome shotgun sequencing and sequencing analysis of the gene encoding the 16S rRNA were performed to interrogate the composition and function of the neonatal and maternal microbiota. We found that the neonatal microbiota and its associated functional pathways were relatively homogeneous across all body sites at delivery, with the notable exception of the neonatal meconium. However, by 6 weeks after delivery, the infant microbiota structure and function had substantially expanded and diversified, with the body site serving as the primary determinant of the composition of the bacterial community and its functional capacity. Although minor variations in the neonatal (immediately at birth) microbiota community structure were associated with the cesarean mode of delivery in some body sites (oral gingiva, nares and skin; R(2) = 0.038), this was not true for neonatal stool (meconium; Mann-Whitney P > 0.05), and there was no observable difference in community function regardless of delivery mode

  6. Mass producible and biocompatible microneedle patch and functional verification of its usefulness for transdermal drug delivery.

    Science.gov (United States)

    Jin, Chun Yan; Han, Man Hee; Lee, Seung S; Choi, Yo Han

    2009-12-01

    The key issues in the development of a microneedle patch as a tool for transdermal drug delivery are safety and delivery performance in addition to economical production. In this paper, novel fabrication methods for an inexpensive microneedle patch made of biocompatible polymer are reported, along with functional verifications for the fabricated microneedle patch through animal models. We combined the merits of in-line microneedles, i.e., easy and economical production, with the superior performance of two-dimensionally arrayed microneedles. One-dimensionally fabricated microneedles were assembled to make two-dimensionally arrayed patches to attain our goal. First, we fabricated strips with one-dimensionally arrayed microneedles through deep X-ray lithography on polymethylmethacrylate or another negative photoresist, SU-8, with sharply reduced exposure time. Second, we assembled microneedle strips to make two-dimensionally arrayed microneedles, which we utilized further for fabrication of molding masters. Finally, we prepared microneedle patches made of polycarbonate by hot embossing with these masters. We then demonstrated the actual delivery of exogenous materials through application on skin via animal experiments, and we found no detectable side effects such as inflammation or allergic reactions at the site of application.

  7. Polymeric nanohybrids and functionalized carbon nanotubes as drug delivery carriers for cancer therapy.

    Science.gov (United States)

    Prakash, Satya; Malhotra, Meenakshi; Shao, Wei; Tomaro-Duchesneau, Catherine; Abbasi, Sana

    2011-11-01

    The scope of nanotechnology to develop target specific carriers to achieve higher therapeutic efficacy is gaining importance in the pharmaceutical and other industries. Specifically, the emergence of nanohybrid materials is posed to edge over chemotherapy and radiation therapy as cancer therapeutics. This is primarily because nanohybrid materials engage controlled production parameters in the making of engineered particles with specific size, shape, and other essential properties. It is widely expressed that these materials will significantly contribute to the next generation of medical care technology and pharmaceuticals in areas of disease diagnosis, disease prevention and many other treatment procedures. This review focuses on the currently used nanohybrid materials, polymeric nanoparticles and nanotubes, which show great potential as effective drug delivery systems for cancer therapy, as they can be grafted with cell-specific receptors and intracellular targeting molecules for the targeted delivery of therapeutics. Specifically, this article focuses on the current status, recent advancements, potentials and limitations of polymeric nanohybrids and functionalized carbon nanotubes as drug delivery carriers.

  8. Aptamer-functionalized PEG-PLGA nanoparticles for enhanced anti-glioma drug delivery.

    Science.gov (United States)

    Guo, Jianwei; Gao, Xiaoling; Su, Lina; Xia, Huimin; Gu, Guangzhi; Pang, Zhiqing; Jiang, Xinguo; Yao, Lei; Chen, Jun; Chen, Hongzhuan

    2011-11-01

    Targeted delivery of therapeutic nanoparticles in a disease-specific manner represents a potentially powerful technology especially when treating infiltrative brain tumors such as gliomas. We developed a nanoparticulate drug delivery system decorated with AS1411 (Ap), a DNA aptamer specifically binding to nucleolin which was highly expressed in the plasma membrane of both cancer cells and endothelial cells in angiogenic blood vessels, as the targeting ligand to facilitate anti-glioma delivery of paclitaxel (PTX). Ap was conjugated to the surface of PEG-PLGA nanoparticles (NP) via an EDC/NHS technique. With the conjugation confirmed by Urea PAGE and XPS, the resulting Ap-PTX-NP was uniformly round with particle size at 156.0 ± 54.8 nm and zeta potential at -32.93 ± 3.1 mV. Ap-nucleolin interaction significantly enhanced cellular association of nanoparticles in C6 glioma cells, and increased the cytotoxicity of its payload. Prolonged circulation and enhanced PTX accumulation at the tumor site was achieved for Ap-PTX-NP, which eventually obtained significantly higher tumor inhibition on mice bearing C6 glioma xenografts and prolonged animal survival on rats bearing intracranial C6 gliomas when compared with PTX-NP and Taxol(®). The results of this contribution demonstrated the potential utility of AS1411-functionalized nanoparticles for a therapeutic application in the treatment of gliomas.

  9. Review: Eicosanoids in preterm labor and delivery: Potential roles of exosomes in eicosanoid functions.

    Science.gov (United States)

    Peiris, H N; Vaswani, K; Almughlliq, F; Koh, Y Q; Mitchell, M D

    2016-12-09

    Preterm delivery is a major obstetric health problem contributing to poor neonatal outcome including low birth weight, respiratory distress syndrome, gastrointestinal, immunologic, central nervous system, hearing, and vision problems. Worldwide, approximately 15 million babies are born prematurely each year. The critical question which remains is how to identify women destined to deliver preterm from those who will achieve a term delivery. Prostaglandins, in all mammals are important in the parturient process. Increased intrauterine prostaglandin production is associated with labor and in fact prostaglandin E2 (PGE2) or analogs are widely used clinically for cervical ripening and labor induction. Measurements of circulating eicosanoids have been problematic because of the rapid and major clearance by the lungs and then kidneys resulting in very low concentrations in plasma. Moreover, since eicosanoids are produced by all mammalian tissues, the sources of the measured eicosanoids are unknown. Our understanding of how cells communicate has undergone a paradigm shift with the recognition of the role of exosomes in intercellular signaling. Recent publications have identified enzymes and products of arachidonic acid metabolism (eicosanoids) within exosomes. This review will explore the potential roles of exosomes in eicosanoid functions that are critical in preterm labor and delivery.

  10. Design of interior-functionalized fully acetylated dendrimers for anticancer drug delivery.

    Science.gov (United States)

    Hu, Jingjing; Su, Yunzhang; Zhang, Hongfeng; Xu, Tongwen; Cheng, Yiyun

    2011-12-01

    In this study, dendrimers was synthesized by introducing functional groups into the interior pockets of fully acetylated dendrimers. NMR techniques including COSY and 2D-NOESY revealed the molecular structures of the synthesized dendrimers and the encapsulation of guest molecule such as methotrexate within their interior pockets. The synthesized polymeric nanocarriers showed much lower cytotoxicity on two cell lines than cationic dendrimers, and exhibited better performance than fully acetylated dendrimers in the sustained release of methotrexate. The results provided a new strategy in the design of non-toxic dendrimers with high performance in the delivery of anti-cancer drugs for clinical applications.

  11. Immune response to functionalized mesoporous silica nanoparticles for targeted drug delivery.

    Science.gov (United States)

    Heidegger, Simon; Gössl, Dorothée; Schmidt, Alexandra; Niedermayer, Stefan; Argyo, Christian; Endres, Stefan; Bein, Thomas; Bourquin, Carole

    2016-01-14

    Multifunctional mesoporous silica nanoparticles (MSN) have attracted substantial attention with regard to their high potential for targeted drug delivery. For future clinical applications it is crucial to address safety concerns and understand the potential immunotoxicity of these nanoparticles. In this study, we assess the biocompatibility and functionality of multifunctional MSN in freshly isolated, primary murine immune cells. We show that the functionalized silica nanoparticles are rapidly and efficiently taken up into the endosomal compartment by specialized antigen-presenting cells such as dendritic cells. The silica nanoparticles showed a favorable toxicity profile and did not affect the viability of primary immune cells from the spleen in relevant concentrations. Cargo-free MSN induced only very low immune responses in primary cells as determined by surface expression of activation markers and release of pro-inflammatory cytokines such as Interleukin-6, -12 and -1β. In contrast, when surface-functionalized MSN with a pH-responsive polymer capping were loaded with an immune-activating drug, the synthetic Toll-like receptor 7 agonist R848, a strong immune response was provoked. We thus demonstrate that MSN represent an efficient drug delivery vehicle to primary immune cells that is both non-toxic and non-inflammagenic, which is a prerequisite for the use of these particles in biomedical applications.

  12. PEG-Functionalized Magnetic Nanoparticles for Drug Delivery and Magnetic Resonance Imaging Applications

    Science.gov (United States)

    Yallapu, Murali Mohan; Foy, Susan P; Jain, Tapan K; Labhasetwar, Vinod

    2010-01-01

    Purpose Polyethylene glycol (PEG) functionalized magnetic nanoparticles (MNPs) were tested as a drug carrier system, magnetic resonance imaging (MRI) agent, and ability to conjugate to an antibody. Methods An iron oxide core coated with oleic acid (OA) and then with OA-PEG forms a water dispersible MNP formulation. Hydrophobic doxorubicin partitions into the OA layer for sustained drug delivery. The T1 and T2 MRI contrast properties were determined in vitro and the circulation of the MNPs measured in mouse carotid arteries. An N-hydroxysuccinimide group (NHS) on the OA-PEG-80 was used to conjugate the amine functional group on antibodies for active targeting in the human MCF-7 breast cancer cell line. Results The optimized formulation had a mean hydrodynamic diameter of 184 nm with an 8 nm iron-oxide core. The MNPs enhance the T2 MRI contrast, and have a long circulation time in vivo with 30% relative concentration 50 min post-injection. Doxorubicin-loaded MNPs showed sustained drug release and dose-dependent antiproliferative effects in vitro; the drug effect was enhanced with transferrin antibody conjugated MNPs. Conclusion PEG functionalized MNPs could be developed as a targeted drug delivery system and MRI contrast agent. PMID:20845067

  13. Tailored functionalization of iron oxide nanoparticles for MRI, drug delivery, magnetic separation and immobilization of biosubstances.

    Science.gov (United States)

    Hola, Katerina; Markova, Zdenka; Zoppellaro, Giorgio; Tucek, Jiri; Zboril, Radek

    2015-11-01

    In this critical review, we outline various covalent and non-covalent approaches for the functionalization of iron oxide nanoparticles (IONPs). Tuning the surface chemistry and design of magnetic nanoparticles are described in relation to their applicability in advanced medical technologies and biotechnologies including magnetic resonance imaging (MRI) contrast agents, targeted drug delivery, magnetic separations and immobilizations of proteins, enzymes, antibodies, targeting agents and other biosubstances. We review synthetic strategies for the controlled preparation of IONPs modified with frequently used functional groups including amine, carboxyl and hydroxyl groups as well as the preparation of IONPs functionalized with other species, e.g., epoxy, thiol, alkane, azide, and alkyne groups. Three main coupling strategies for linking IONPs with active agents are presented: (i) chemical modification of amine groups on the surface of IONPs, (ii) chemical modification of bioactive substances (e.g. with fluorescent dyes), and (iii) the activation of carboxyl groups mainly for enzyme immobilization. Applications for drug delivery using click chemistry linking or biodegradable bonds are compared to non-covalent methods based on polymer modified condensed magnetic nanoclusters. Among many challenges, we highlight the specific surface engineering allowing both therapeutic and diagnostic applications (theranostics) of IONPs and magnetic/metallic hybrid nanostructures possessing a huge potential in biocatalysis, green chemistry, magnetic bioseparations and bioimaging.

  14. Prediction of spontaneous preterm delivery from maternal factors, obstetric history and placental perfusion and function at 11-13 weeks.

    Science.gov (United States)

    Beta, Jarek; Akolekar, Ranjit; Ventura, Walter; Syngelaki, Argyro; Nicolaides, Kypros H

    2011-01-01

    To develop a model for prediction of spontaneous delivery before 34 weeks based on maternal factors, placental perfusion and function at 11-13 weeks' gestation. Two groups of studies: first, screening study of maternal characteristics, serum pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotrophin (β-hCG) and uterine artery pulsatility index (PI). Second, case-control studies of maternal serum or plasma concentration of placental growth factor (PlGF), placental protein 13 (PP13), a disintegrin and metalloprotease 12 (ADAM12), inhibin-A and activin-A. Regression analysis was used to develop a model for the prediction of spontaneous early delivery. Spontaneous early delivery occurred in 365 (1.1%) of the 34 025 pregnancies. A model based on maternal factors could detect 38.2% of the preterm deliveries in women with previous pregnancies at or beyond 16 weeks and 18.4% in those without, at a false positive rate (FPR) of 10%. In the preterm delivery group, compared with unaffected pregnancies there were no significant differences in the markers of placental perfusion or function, except for PAPP-A which was reduced. Patient-specific risk of preterm delivery is provided by maternal factors and obstetric history. Placental perfusion and function at 11-13 weeks are not altered in pregnancies resulting in spontaneous early delivery. Copyright © 2011 John Wiley & Sons, Ltd.

  15. 3RD WP PROBABILISTIC CRITICALITY ANALYSIS: METHODOLOGY FOR BASKET DEGRADATION WITH APPLICANTION TO COMMERICAL SNF

    Energy Technology Data Exchange (ETDEWEB)

    P. Goulib

    1997-09-15

    This analysis is prepared by the Mined Geologic Disposal System (MGDS) Waste Package Development (WPD) department to describe the latest version of the probabilistic criticality analysis methodology and its application to the entire commercial waste stream of commercial pressurized water reactor (PWR) spent nuclear fuel (SNF) expected to be emplaced in the repository. The purpose of this particular application is to evaluate the 21 assembly PWR absorber plate waste package (WP) with respect to degraded mode criticality performance. The degradation of principal concern is the borated stainless steel absorber plates which are part of the waste package basket and which constitute a major part of the waste package criticality control. The degradation (corrosion, dissolution) of this material will result in the release of most of the boron from the waste package and increase the possibility of criticality. The results of this evaluation will be expressed in terms of the fraction of the PWR SNF which can exceed a given k{sub eff}, as a function of time and the peak value of that fraction over a time period up to several hundred thousand years. The ultimate purpose of this analysis is to support the waste package design which defines waste packages to cover a range of SNF characteristics. In particular, with respect to PWR criticality the current categories are: (1) no specific criticality control material, (2) borated stainless steel plates in the waste package basket, and (3) zirconium clad boron carbide control rods (Ref. 5.4). The results of this analysis will indicate the coverage provided by the first two categories. With these results, this study will provide the first quantitative estimate of the benefit expected from the control measure consisting of borated stainless steel plates. This document is the third waste package probabilistic criticality analysis. The first two (Ref. 5.12 for the first and Ref. 5.15 for the second) analyses were based primarily on the

  16. Structure and functionalization of mesoporous bioceramics for bone tissue regeneration and local drug delivery.

    Science.gov (United States)

    Vallet-Regí, María; Izquierdo-Barba, Isabel; Colilla, Montserrat

    2012-03-28

    This review article describes the importance of structure and functionalization in the performance of mesoporous silica bioceramics for bone tissue regeneration and local drug delivery purposes. Herein, we summarize the pivotal features of mesoporous bioactive glasses, also known as 'templated glasses' (TGs), which present chemical compositions similar to those of conventional bioactive sol-gel glasses and the added value of an ordered mesopore arrangement. An in-depth study concerning the possibility of tailoring the structural and textural characteristics of TGs at the nanometric scale and their influence on bioactive behaviour is discussed. The highly ordered mesoporous arrangement of cavities allows these materials to confine drugs to be subsequently released, acting as drug delivery devices. The functionalization of mesoporous silica walls has been revealed as the cornerstone in the performance of these materials as controlled release systems. The synergy between the improved bioactive behaviour and local sustained drug release capability of mesostructured materials makes them suitable to manufacture three-dimensional macroporous scaffolds for bone tissue engineering. Finally, this review tackles the possibility of covalently grafting different osteoinductive agents to the scaffold surface that act as attracting signals for bone cells to promote the bone regeneration process.

  17. Development and characterization of porous functionalized collagen scaffolds for delivery of FGF-2

    Directory of Open Access Journals (Sweden)

    Pokholenko Ia. O.

    2014-05-01

    Full Text Available Aim. To develop the porous functionalized collagen scaffold for the delivery of FGF-2 and studying its properties in vitro and in vivo. Methods. Porous collagen scaffolds were prepared by freeze- drying collagen I solutions containing the polymer developed on the basis of cross-linked modified heparin. The scaffolds have been analyzed by SEM, AFM and SCLM. The angiogenic activity of these scaffolds loaded with FGF-2 was tested in a CAM assay. Results. The data obtained by SEM and SCLM analysis revealed that the scaffold mainly has a layered structure with pores forming a connection between the layers. The average pore size of the scaffolds varied from 76 to 150 µm. Scaffolds containing the polymer were able to incorporate human FGF-2. Proposed compositions promoted angiogenesis in CAM assay. Conclusions. The developed porous functionalized collagen scaffold incorporating FGF-2 can be used as a vehicle for the sustained delivery of the growth factor both in vitro and in vivo.

  18. Exosome-mediated delivery of functionally active miRNA-155 inhibitor to macrophages.

    Science.gov (United States)

    Momen-Heravi, Fatemeh; Bala, Shashi; Bukong, Terence; Szabo, Gyongyi

    2014-10-01

    Exosomes, membranous nanovesicles, naturally carry bio-macromolecules and play pivotal roles in both physiological intercellular crosstalk and disease pathogenesis. Here, we showed that B cell-derived exosomes can function as vehicles to deliver exogenous miRNA-155 mimic or inhibitor into hepatocytes or macrophages, respectively. Stimulation of B cells significantly increased exosome production. Unlike in parental cells, baseline level of miRNA-155 was very low in exosomes derived from stimulated B cells. Exosomes loaded with a miRNA-155 mimic significantly increased miRNA-155 levels in primary mouse hepatocytes and the liver of miRNA-155 knockout mice. Treatment of RAW macrophages with miRNA-155 inhibitor loaded exosomes resulted in statistically significant reduction in LPS-induced TNFα production and partially prevented LPS-induced decrease in SOCS1 mRNA levels. Furthermore, exosome-mediated miRNA-155 inhibitor delivery resulted in functionally more efficient inhibition and less cellular toxicity compared to conventional transfection methods. Similar approaches could be useful in modification of target biomolecules in vitro and in vivo. From the clinical editor: In this study, exosome-based delivery of miRNA-155 mimicker or inhibitor was found to have significant biological response in hepatocytes and macrophages. Exosome-based approaches may be useful in the modification of other target biomolecules.

  19. Structure-Function Assessment of Mannosylated Poly(β-amino esters) upon Targeted Antigen Presenting Cell Gene Delivery.

    Science.gov (United States)

    Jones, Charles H; Chen, Mingfu; Gollakota, Akhila; Ravikrishnan, Anitha; Zhang, Guojian; Lin, Sharon; Tan, Myles; Cheng, Chong; Lin, Haiqing; Pfeifer, Blaine A

    2015-05-11

    Antigen presenting cell (APC) gene delivery is a promising avenue for modulating immunological outcomes toward a desired state. Recently, our group developed a delivery methodology to elicit targeted and elevated levels of APC-mediated gene delivery. During these initial studies, we observed APC-specific structure-function relationships with the vectors used during gene delivery that differ from current non-APC cell lines, thus, emphasizing a need to re-evaluate vector-associated parameters in the context of APC gene transfer. Thus, we describe the synthesis and characterization of a second-generation mannosylated poly(β-amino ester) library stratified by molecular weight. To better understand the APC-specific structure-function relationships governing polymeric gene delivery, the library was systematically characterized by (1) polymer molecular weight, (2) relative mannose content, (3) polyplex biophysical properties, and (4) gene delivery efficacy. In this library, polymers with the lowest molecular weight and highest relative mannose content possessed gene delivery transfection efficiencies as good as or better than commercial controls. Among this group, the most effective polymers formed the smallest polymer-plasmid DNA complexes (∼300 nm) with moderate charge densities (structure and polyplex biophysical properties suggests a unique mode of action and provides a framework within which future APC-targeting polymers can be designed.

  20. Triphenyl Phosphine-Functionalized Chitosan Nanoparticles Enhanced Antitumor Efficiency Through Targeted Delivery of Doxorubicin to Mitochondria

    Science.gov (United States)

    Hou, Jiahui; Yu, Xiwei; Shen, Yaping; Shi, Yijie; Su, Chang; Zhao, Liang

    2017-02-01

    Mitochondria as an important organ in eukaryotic cells produced energy through oxidative phosphorylation and also played an important role in regulating the apoptotic signal transduction process. Importantly, mitochondria like nuclei also contained the functional DNA and were very sensitive to anticancer drugs which could effectively inhibit the synthesis of nucleic acid, especially the production of DNA. In this work, we designed novel triphenyl phosphine (TPP)-conjugated chitosan (CS) nanoparticles (NPs) for efficient drug delivery to cell mitochondria. The results showed that compared with free doxorubicin (Dox), Dox-loaded TPP-NPs were specifically distributed in mitochondria of tumor cells and interfered with the function of mitochondria, thus resulted in the higher cytotoxicity and induced the significant cell apoptosis effect. Taken together, triphenyl phosphine-conjugated chitosan nanoparticles may become a promising mitochondria-targeting nanocarrier candidate for enhancing antitumor effects.

  1. Double-section curvature tunable functional actuator with micromachined buckle and grid wire for electricity delivery

    Science.gov (United States)

    Feng, Guo-Hua; Hou, Sheng-You

    2015-09-01

    This paper presents an ionic polymer metal composite (IPMC)-driven tentacle-like biocompatible flexible actuator with double-section curvature tunability. This actuator, possessing an embedded electrical transmission ability that mimics skeletal muscle nerves in the human body, affords versatile device functions. Novel micromachined copper buckles and grid wires are fabricated and their superiority in electricity delivery and driving the IPMC component with less flexural rigidity is demonstrated. In addition, soft conductive wires realized on a polydimethylsiloxane structure function as electrical signal transmitters. A light-emitting diode integrated with the developed actuator offers directional guiding light ability while the actuator performs a snake-like motion. The electrical conductivity and Young’s modulus of the key actuator components are investigated, and flexural rigidity and dynamic behavior analyses of the actuator under electrical manipulation are elaborated.

  2. Immune response to functionalized mesoporous silica nanoparticles for targeted drug delivery

    CERN Document Server

    Heidegger, S; Schmidt, A; Gößl, D; Argyo, C; Endres, S; Bein, T; Bourquin, C

    2015-01-01

    Multifunctional mesoporous silica nanoparticles (MSN) have attracted substantial attention with regard to their high potential for targeted drug delivery. For future clinical applications it is crucial to address safety concerns and understand the potential immunotoxicity of these nanoparticles. In this study, we assess the biocompatibility and functionality of multifunctional MSN in freshly isolated, primary murine immune cells. We show that the functionalized silica nanoparticles are rapidly and efficiently taken up into the endosomal compartment by specialized antigen-presenting cells such as dendritic cells. The silica nanoparticles showed a favorable toxicity profile and did not affect the viability of primary immune cells from the spleen in relevant concentrations. Cargo-free MSN induced only very low immune responses in primary cells as determined by surface expression of activation markers and release of pro-inflammatory cytokines such as Interleukin-6, -12 and -1\\beta. In contrast, when surface-funct...

  3. Aptamer-functionalized gold nanoparticles as photoresponsive nanoplatform for co-drug delivery.

    Science.gov (United States)

    Shiao, Yi-Syun; Chiu, Huai-Hsuan; Wu, Pin-Hsuan; Huang, Yu-Fen

    2014-12-24

    Various platforms have been developed as innovative nanocarriers to deliver therapeutic agents to the diseased sites. Multifunctional surface modification allows an enhanced recognition and uptake of drug carriers by targeted cells. However, the development of drug resistance in some tumor cells plays a major role in the failure of chemotherapy. Drugs given in combination, called multidrug delivery approach, was designed to improve the therapeutic efficacy and has become an increasingly used strategy that is of great importance in clinical cancer treatments. In this study, aptamer-functionalized gold nanoparticles (Au NPs) have been used as a nanoplatform to codeliver two different anticancer drugs for improving the drug effectiveness. The surface of Au NPs (13 nm in diameter) was assembled with AS1411 aptamers, which tethered with 21-base pairs of (CGATCGA)3 sequence approached to the Au NPs. Both the photosensitizer 5,10,15,20-tetrakis(1-methylpyridinium-4-yl) porphyrin (TMPyP4) and the chemotherapeutic drug doxorubicin (Dox) were then physically attached to the AS1411-conjugated Au NPs (T/D:ds-NPs) and delivered to the target tumor cells such as HeLa and Dox-resistant MCF-7R cell lines. When exposed to a 632 nm light, reactive oxygen species induced by TMPyP4 molecules were generated inside the living cells, followed by cell damage. In addition, triggered release of the complementary drugs also occurred simultaneously during the photodynamic reaction. In the presence of Dox molecules, the toxicity toward the target cells was superior to individual drug treatment. Overall, a co-drug delivery platform was successfully established to improve the therapeutic efficacy in tumor cells. The improvement of the photodynamic-stimulated triggered release was enhanced, thus highly promising precise drug release in targeted drug delivery.

  4. Mesoporous silica nanoparticles functionalized with folic acid/methionine for active targeted delivery of docetaxel

    Directory of Open Access Journals (Sweden)

    Khosravian P

    2016-12-01

    Full Text Available Pegah Khosravian,1 Mehdi Shafiee Ardestani,2 Mehdi Khoobi,3 Seyed Naser Ostad,4 Farid Abedin Dorkoosh,1 Hamid Akbari Javar,1,* Massoud Amanlou5,6,* 1Department of Pharmaceutics, 2Department of Radiopharmacy, 3Department of Pharmaceutical Biomaterials, 4Department of Pharmacology and Toxicology, 5Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, 6Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran *These authors contributed equally to this work Abstract: Mesoporous silica nanoparticles (MSNs are known as carriers with high loading capacity and large functionalizable surface area for target-directed delivery. In this study, a series of docetaxel-loaded folic acid- or methionine-functionalized mesoporous silica nanoparticles (DTX/MSN-FA or DTX/MSN-Met with large pores and amine groups at inner pore surface properties were prepared. The results showed that the MSNs were successfully synthesized, having good pay load and pH-sensitive drug release kinetics. The cellular investigation on MCF-7 cells showed better performance of cytotoxicity and cell apoptosis and an increase in cellular uptake of targeted nanoparticles. In vivo fluorescent imaging on healthy BALB/c mice proved that bare MSN-NH2 are mostly accumulated in the liver but MSN-FA or MSN-Met are more concentrated in the kidney. Importantly, ex vivo fluorescent images of tumor-induced BALB/c mice organs revealed the ability of MSN-FA to reach the tumor tissues. In conclusion, DTX/MSNs exhibited a good anticancer activity and enhanced the possibility of targeted drug delivery for breast cancer. Keywords: targeted delivery, mesoporous silica nanoparticle, folic acid, methionine, docetaxel

  5. Design of multi-functional cotton gauze with antimicrobial and drug delivery properties.

    Science.gov (United States)

    Rehan, Mohamed; Zaghloul, S; Mahmoud, F A; Montaser, A S; Hebeish, A

    2017-11-01

    The ideal biomedical fiber/fabric materials can both promote the drug delivery properties and prevent microbial infection. Herein we present an innovation-based strategy for fabrication of biomedical cotton gauze which concomitantly displays antimicrobial and drug delivery performance properties. The innovative strategy involved three distinct steps: (1) Cationization of cotton gauze by reacting it with 3-chloro-2-hydroxypropyl trimethyl ammonium chloride [Quat-188] or anionization of cotton gauze through partial carboxymethylation. (2) Thus modified samples of cotton gauze along with unmodified blank samples were submitted to in situ formation of silver nanoparticles (AgNPs) using trisodium citrate (TSC) which has three-fold functions: (a) reducing agent for conversion of Ag(+) to Ag(o) (atom), (b) stabilizing agent to prevent aggregation of AgNPs and, (c) linker for fixation of AgNPs on the surfaces of the cotton gauze. (3) All the modified and unmodified cotton gauze samples were loaded with oxytetracyline hydrochloride drug. To this end, characterization of the modified and unmodified cotton samples before and after being loaded with drug using state-of-the-art facilities was undertaken. These facilities comprised UV-vis spectroscopy, energy dispersive X-ray, scanning electron microscope and Infrared Spectroscopy by Attenuated total Reflectance (ATR/IR). Evaluation of the antimicrobial and drug release properties of the cotton gauze samples in question was conducting. Results obtained signified that the modified cotton gauze can be used in the area of biomedical textiles particularly as antimicrobial and drug delivery. Also reported were mechanisms entailed in chemical modifications of cotton gauze and interactions of this modified cotton gauze with antimicrobial as well as with drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Immune response to functionalized mesoporous silica nanoparticles for targeted drug delivery

    Science.gov (United States)

    Heidegger, Simon; Gößl, Dorothée; Schmidt, Alexandra; Niedermayer, Stefan; Argyo, Christian; Endres, Stefan; Bein, Thomas; Bourquin, Carole

    2015-12-01

    Multifunctional mesoporous silica nanoparticles (MSN) have attracted substantial attention with regard to their high potential for targeted drug delivery. For future clinical applications it is crucial to address safety concerns and understand the potential immunotoxicity of these nanoparticles. In this study, we assess the biocompatibility and functionality of multifunctional MSN in freshly isolated, primary murine immune cells. We show that the functionalized silica nanoparticles are rapidly and efficiently taken up into the endosomal compartment by specialized antigen-presenting cells such as dendritic cells. The silica nanoparticles showed a favorable toxicity profile and did not affect the viability of primary immune cells from the spleen in relevant concentrations. Cargo-free MSN induced only very low immune responses in primary cells as determined by surface expression of activation markers and release of pro-inflammatory cytokines such as Interleukin-6, -12 and -1β. In contrast, when surface-functionalized MSN with a pH-responsive polymer capping were loaded with an immune-activating drug, the synthetic Toll-like receptor 7 agonist R848, a strong immune response was provoked. We thus demonstrate that MSN represent an efficient drug delivery vehicle to primary immune cells that is both non-toxic and non-inflammagenic, which is a prerequisite for the use of these particles in biomedical applications.Multifunctional mesoporous silica nanoparticles (MSN) have attracted substantial attention with regard to their high potential for targeted drug delivery. For future clinical applications it is crucial to address safety concerns and understand the potential immunotoxicity of these nanoparticles. In this study, we assess the biocompatibility and functionality of multifunctional MSN in freshly isolated, primary murine immune cells. We show that the functionalized silica nanoparticles are rapidly and efficiently taken up into the endosomal compartment by specialized

  7. Sustained delivery of VEGF from designer self-assembling peptides improves cardiac function after myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Hai-dong [Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Cui, Guo-hong; Yang, Jia-jun [Department of Neurology, Shanghai No. 6 People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200233 (China); Wang, Cun [Institutes of Biomedical Sciences, Fudan University, Shanghai 200032 (China); Zhu, Jing; Zhang, Li-sheng; Jiang, Jun [Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Shao, Shui-jin, E-mail: shaoshuijin@163.com [Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China)

    2012-07-20

    Highlights: Black-Right-Pointing-Pointer The designer peptide LRKKLGKA could self-assemble into nanofibers. Black-Right-Pointing-Pointer Injection of LRKKLGKA peptides could promote the sustained delivery of VEGF. Black-Right-Pointing-Pointer Injection of VEGF with LRKKLGKA peptides lead to sufficient angiogenesis. Black-Right-Pointing-Pointer Injection of VEGF with LRKKLGKA peptides improves heart function. -- Abstract: Poor vascularization and insufficient oxygen supply are detrimental to the survival of residual cardiomyocytes or transplanted stem cells after myocardial infarction. To prolong and slow the release of angiogenic factors, which stimulate both angiogenesis and vasculogenesis, we constructed a novel self-assembling peptide by attaching the heparin-binding domain sequence LRKKLGKA to the self-assembling peptide RADA16. This designer self-assembling peptide self-assembled into nanofiber scaffolds under physiological conditions, as observed by atomic force microscopy. The injection of designer self-assembling peptides can efficiently provide the sustained delivery of VEGF for at least 1 month. At 4 weeks after transplantation, cardiac function was improved, and scar size and collagen deposition were markedly reduced in the group receiving VEGF with the LRKKLGKA scaffolds compared with groups receiving VEGF alone, LRKKLGKA scaffolds alone or VEGF with RADA16 scaffolds. The microvessel density in the VEGF with LRKKLGKA group was higher than that in the VEGF with RADA16 group. TUNEL and cleaved caspase-3 expression assays showed that the transplantation of VEGF with LRKKLGKA enhanced cell survival in the infarcted heart. These results present the tailor-made peptide scaffolds as a new generation of sustained-release biomimetic biomaterials and suggest that the use of angiogenic factors along with designer self-assembling peptides can lead to myocardial protection, sufficient angiogenesis, and improvement in cardiac function.

  8. Dual-functionalized graphene oxide for enhanced siRNA delivery to breast cancer cells.

    Science.gov (United States)

    Imani, Rana; Shao, Wei; Taherkhani, Samira; Emami, Shahriar Hojjati; Prakash, Satya; Faghihi, Shahab

    2016-11-01

    The aim of this study is to improve hydrocolloid stability and siRNA transfection ability of a reduced graphene oxide (rGO) based nano-carrier using a phospholipid-based amphiphilic polymer (PL-PEG) and cell penetrating peptide (CPPs). The dual functionalized nano-carrier is comprehensively characterized for its chemical structure, size, surface charge and morphology as well as thermal stability. The nano-carrier cytocompatibility, siRNA condensation ability both in the presence and absence of enzyme, endosomal buffering capacity, cellular uptake and intracellular localization are also assessed. The siRNA loaded nano-carrier is used for internalization to MCF-7 cells and its gene silencing ability is compared with AllStars Hs Cell Death siRNA as a model gene. The nano-carrier remains stable in biological solution, exhibits excellent cytocompatibility, retards the siRNA migration and protects it against enzyme degradation. The buffering capacity analysis shows that incorporation of the peptide in nano-carrier structure would increase the resistance to endo/lysosomal like acidic condition (pH 6-4) The functionalized nano-carrier which is loaded with siRNA in an optimal N:P ratio presents superior internalization efficiency (82±5.1% compared to HiPerFect(®)), endosomal escape quality and capable of inducing cell death in MCF-7 cancer cells (51±3.1% compared to non-treated cells). The success of siRNA-based therapy is largely dependent on the safe and efficient delivery system, therefore; the dual functionalized rGO introduced here could have a great potential to be used as a carrier for siRNA delivery with relevancy in therapeutics and clinical applications.

  9. Conception, preparation and properties of functional carrier particles for pulmonary drug delivery.

    Science.gov (United States)

    Odziomek, Marcin; Sosnowski, Tomasz R; Gradoń, Leon

    2012-08-20

    The effectiveness of aerosol therapy is significantly reduced by the mucus layer covering the airways of the tracheobronchial tree. According to the present concept, drug particles are delivered to the lung together with the functional carrier particle that facilitates both the drug transport into the lungs and the penetration of deposited particles through the mucus. The approach of manufacturing multi-component powders with mucoactive compounds and anti-asthmatic medicines (DSCG) bound together in a single particle is additionally considered. Powders were produced with the spray-drying technique from aqueous precursor solutions containing pure low molecular weight dextran, pure mannitol and dextran/mannitol-N-acetyl cysteine (NAC) mixtures (4:1 and 1:1). NAC has been selected for this purpose as a compound, which is known to be mucolytic. Dextran and mannitol are potentially applicable in the field of inhalation drug delivery. They have been used as stabilizers of functional carrier particles. Powders were characterized for their yield and physicochemical properties including: morphology (SEM), moisture content and thermal properties (DSC). Aerosol performance was determined with NGI impactor after standardized aerosolization of the produced powders in a commercial DPI. Particle size distributions of dextran-NAC powders were characterized by high fine particle fraction (45-62%), which assures good particle deposition in the lower airways. The thermodynamic properties of the powders based on the temperature of the glass transition T(g) (50-63 °C) suggest the required stability during storage at moderate humidity. Preliminary examination of the required properties of these particles confirms their potential as functional carriers for pulmonary drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Biodegradable polyglycerols with randomly distributed ketal groups as multi-functional drug delivery systems.

    Science.gov (United States)

    Shenoi, Rajesh A; Lai, Benjamin F L; Imran ul-haq, Muhammad; Brooks, Donald E; Kizhakkedathu, Jayachandran N

    2013-08-01

    Biodegradable multi-functional polymeric nanostructures that undergo controlled degradation in response to physiological cues are important in numerous biomedical applications including drug delivery, bio-conjugation and tissue engineering. In this paper, we report the development of a new class of water soluble multi-functional branched biodegradable polymer with high molecular weight and biocompatibility which demonstrates good correlation of in vivo biodegradation and in vitro hydrolysis. Main chain degradable hyperbranched polyglycerols (HPG) (20-100 kDa) were synthesized by the introduction of acid labile groups within the polymer structure by an anionic ring opening copolymerization of glycidol with ketal-containing epoxide monomers with different ketal structures. The water soluble biodegradable HPGs with randomly distributed ketal groups (RBHPGs) showed controlled degradation profiles in vitro depending on the pH of solution, temperature and the structure of incorporated ketal groups, and resulted in non-toxic degradation products. NMR studies demonstrated the branched nature of RBHPGs which is correlating with their smaller hydrodynamic radii. The RBHPGs and their degradation products exhibited excellent blood compatibility and tissue compatibility based on various analyses methods, independent of their molecular weight and ketal group structure. When administered intravenously in mice, tritium labeled RBHPG of molecular weight 100 kDa with dimethyl ketal group showed a circulation half life of 2.7 ± 0.3 h, correlating well with the in vitro polymer degradation half life (4.3 h) and changes in the molecular weight profile during the degradation (as measured by gel permeation chromatography) in buffer conditions at 37 °C. The RBHPG degraded into low molecular weight fragments that were cleared from circulation rapidly. The biodistribution and excretion studies demonstrated that RBHPG exhibited significantly lower tissue accumulation and enhanced urinary

  11. Functionalized nanoscale graphene oxide for high efficient drug delivery of cisplatin

    Science.gov (United States)

    Tian, Lingyang; Pei, Xibo; Zeng, Yongxiang; He, Rui; Li, Zhongjie; Wang, Jian; Wan, Qianbing; Li, Xiaoyu

    2014-11-01

    Graphene oxide has attracted particular interests in drug delivery. The sp2-aromatic structure and abundant oxygen-containing groups of nanoscale graphene oxide (NGO) were frequently utilized to load anti-cancer drugs, resulting in high loading efficiency. This research employed a polyethylene glycol (PEG, PL-PEG(2000)-NH2) functionalized NGO as a drug delivery vehicle for cis-diamminedichloroplatinum (II) (cisplatin, CDDP). The covalent reaction between platinum (II) atom and carboxylic group was utilized to attach CDDP onto NGO-PEG. The NGO, NGO-PEG, and NGO-PEG/CDDP nanohybrids were characterized by atomic force microscope imaging, transmission electron microscope imaging, Fourier transform infrared spectroscopy, and Raman spectroscopy. From the AFM images, the average thickness of the nanohybrids was ranged from 3.4 to 7.0 nm and the average sheet diameter was ranged from 21.7 to 30.5 nm. NGO-PEG demonstrated improved CDDP loading efficiency as high as 0.58 mg mg-1. The NGO-PEG/CDDP nanohybrids released CDDP in a sustained profile for 72 h and demonstrated remarkable cytotoxicity to human breast cancer MCF-7 cells and oral adenosquamous carcinoma CAL-27 cells by in vitro assays. The drug vehicle NGO-PEG was observed nontoxic. The inhibited cell proliferation and morphology deformation induced by NGO-PEG/CDDP were further illustrated by fluorescent images.

  12. Preparation and characterization of cationic Pluronic for surface modification and functionalization of polymeric drug delivery nanoparticles

    Directory of Open Access Journals (Sweden)

    G. Gyulai

    2016-03-01

    Full Text Available Biodegradable poly(lactic-co-glycolic acid copolymer, PLGA nanoparticles (NPs with a surface layer of poly (ethylene oxide-poly(propylene oxide-poly(ethylene oxide triblock copolymers, Pluronics, are promising drug carrier systems. With the aim to increase the potential of targeted drug delivery the end group derivative of Pluronics was synthesized in a straightforward way to obtain Pluronic-amines. The formation of functional amine groups was confirmed by fluorescamine method and NMR analysis of their N-(tert-Butoxycarbonyl-L-phenylalanine (Boc-Phe-OH and N-(9-Fluorenylmethoxycarbonyl-L-phenylalanine (Fmoc-Phe-OH conjugates. Pluronic and Pluronic-amine stabilized PLGA NPs prepared by nanoprecipitation were characterized by dynamic light scattering and zeta potential measurements. All of the systems showed high colloidal stability checked by electrolyte induced aggregation, although the presence of Pluronicamine on the surface decreased the zeta potential in some extent. The introduction of reactive primary amine groups into the surface layer of PLGA NPs while preserving the aggregation stability, provides a possibility for coupling of various ligands allowing targeted delivery and also contributes to the improved membrane affinity of NPs.

  13. Dendrimer-Functionalized Laponite Nanodisks as a Platform for Anticancer Drug Delivery

    Directory of Open Access Journals (Sweden)

    Rania Mustafa

    2015-10-01

    Full Text Available In this study, we synthesized dendrimer-functionalized laponite (LAP nanodisks for loading and delivery of anticancer drug doxorubicin (DOX. Firstly, LAP was modified with silane coupling agents and succinic anhydride to render abundant carboxyl groups on the surface of LAP. Then, poly(amidoamine (PAMAM dendrimer of generation 2 (G2 were conjugated to form LM-G2 nanodisks. Anticancer drug DOX was then loaded on the LM-G2 with an impressively high drug loading efficiency of 98.4% and could be released in a pH-sensitive and sustained manner. Moreover, cell viability assay results indicate that LM-G2/DOX complexes could more effectively inhibit the proliferation of KB cells (a human epithelial carcinoma cell line than free DOX at the same drug concentration. Flow cytometry analysis and confocal laser scanning microscope demonstrated that LM-G2/DOX could be uptaken by KB cells more effectively than free DOX. Considering the exceptional high drug loading efficiency and the abundant dendrimer amine groups on the surface that can be further modified, the developed LM-G2 nanodisks may hold a great promise to be used as a novel platform for anticancer drug delivery.

  14. Polyethylenimine functionalized magnetic nanoparticles as a potential non-viral vector for gene delivery.

    Science.gov (United States)

    Zhou, Yangbo; Tang, Zhaomin; Shi, Chunli; Shi, Shuai; Qian, Zhiyong; Zhou, Shaobing

    2012-11-01

    Polyethylenimine (PEI) functionalized magnetic nanoparticles were synthesized as a potential non-viral vector for gene delivery. The nanoparticles could provide the magnetic-targeting, and the cationic polymer PEI could condense DNA and avoid in vitro barriers. The magnetic nanoparticles were characterized by Fourier transform infrared spectroscopy, X-ray powder diffraction, dynamic light scattering measurements, transmission electron microscopy, vibrating sample magnetometer and atomic force microscopy. Agarose gel electrophoresis was used to asses DNA binding and perform a DNase I protection assay. The Alamar blue assay was used to evaluate negative effects on the metabolic activity of cells incubated with PEI modified magnetic nanoparticles and their complexes with DNA both in the presence or absence of an external magnetic field. Flow cytometry and fluorescent microscopy were also performed to investigate the transfection efficiency of the DNA-loaded magnetic nanoparticles in A549 and B16-F10 tumor cells with (+M) or without (-M) the magnetic field. The in vitro transfection efficiency of magnetic nanoparticles was improved obviously in a permanent magnetic field. Therefore, the magnetic nanoparticles show considerable potential as nanocarriers for gene delivery.

  15. Synthesis of New Functionalized Citric Acid-based Dendrimers as Nanocarrier Agents for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Sanaz Motamedi

    2011-06-01

    Full Text Available Introduction: Citric acid-polyethylene glycol-citric acid (CPEGC triblock dendrimers can serve as potential delivery systems. Methods: In this investigation, CPEGC triblock dendrimers were synthesized and then imidazole groups were conjugated onto the surface of the G1, G2 and G3 of the obtained dendrimers. In order to study the type of the interactions between the functionalized dendrimers and a drug molecule, Naproxen which contains acidic groups, was examined as a hydrophobic drug in which the interactions would be of the electrostatic kind between its acidic groups and the lone pair electrons of nitrogen atom in imidazole groups. The quantity of the trapped drug and also the amount of its release were measured with UV spectrometric method in pH 1, 7.4 and 10. The average diameter of the nanocarriers was measured by Dynamic Light Scattering (DLS technique Results: The size range of particles was determined to be 16-50 nm for different generations. The rate of the release increased in pH=10 in all generations due to the increase in Naproxen solubility and the hydrolysis of the esteric bonds in the mentioned pH. The results showed that the amount of the trapped drug increased with the increase in the generation of the dendrimer and pH. Conclusion: Based on our findings, we suggest CPEGC triblock dendrimers possess great potential to be used as drug/gene delivery system.

  16. A Comparative Evaluation of Hydroxycamptothecin Drug Nanorods With and Without Methotrexate Prodrug Functionalization for Drug Delivery

    Science.gov (United States)

    Guo, Fuqiang; Fan, Zhongxiong; Yang, Jinbin; Li, Yang; Wang, Yange; Zhao, Hai; Xie, Liya; Hou, Zhenqing

    2016-08-01

    We developed a novel self-targeted multi-drug co-delivery system based on rod-shaped 10-hydroxycamptothecin (CPT) nanoanticancer drug (CPT NRs) followed by a surface functionalization with self-targeting PEGylated lipid-conjugated methotrexate (MTX) pro-anticancer drug. The self-targeting effect and in vitro cell viability of the MTX-PEG-CPT NRs on HeLa cells were demonstrated by comparative cellular uptake and MTT assay of the PEG-CPT NRs. In vitro studies showed the feasibility of using this high drug-loading MTX-PEG-CPT NRs in self-targeted drug delivery, controlled-/sustained-release, and synergistic cancer therapy. More importantly, this work would stimulate interest in the use of PEGylated lipid-conjugated MTX by introducing an early-phase tumor-targeting role and then driving a late-phase anticancer role for the highly convergent design of nanomulti-drug, which may advantageously offer a new and simple strategy for simultaneously targeting and treating FA receptor-overexpressing cancer cells.

  17. Mesoporous silica nanoparticles functionalized with folic acid/methionine for active targeted delivery of docetaxel

    Science.gov (United States)

    Khosravian, Pegah; Shafiee Ardestani, Mehdi; Khoobi, Mehdi; Ostad, Seyed Naser; Dorkoosh, Farid Abedin; Akbari Javar, Hamid; Amanlou, Massoud

    2016-01-01

    Mesoporous silica nanoparticles (MSNs) are known as carriers with high loading capacity and large functionalizable surface area for target-directed delivery. In this study, a series of docetaxel-loaded folic acid- or methionine-functionalized mesoporous silica nanoparticles (DTX/MSN-FA or DTX/MSN-Met) with large pores and amine groups at inner pore surface properties were prepared. The results showed that the MSNs were successfully synthesized, having good pay load and pH-sensitive drug release kinetics. The cellular investigation on MCF-7 cells showed better performance of cytotoxicity and cell apoptosis and an increase in cellular uptake of targeted nanoparticles. In vivo fluorescent imaging on healthy BALB/c mice proved that bare MSN-NH2 are mostly accumulated in the liver but MSN-FA or MSN-Met are more concentrated in the kidney. Importantly, ex vivo fluorescent images of tumor-induced BALB/c mice organs revealed the ability of MSN-FA to reach the tumor tissues. In conclusion, DTX/MSNs exhibited a good anticancer activity and enhanced the possibility of targeted drug delivery for breast cancer. PMID:27980423

  18. Delivery of small interfering RNAs in human cervical cancer cells by polyethylenimine-functionalized carbon nanotubes

    Science.gov (United States)

    Huang, Yuan-Pin; Lin, I.-Jou; Chen, Chih-Chen; Hsu, Yi-Chiang; Chang, Chi-Chang; Lee, Mon-Juan

    2013-06-01

    Carbon nanotubes are capable of penetrating the cell membrane and are widely considered as potential carriers for gene or drug delivery. Because the C-C and C=C bonds in carbon nanotubes are nonpolar, functionalization is required for carbon nanotubes to interact with genes or drugs as well as to improve their biocompatibility. In this study, polyethylenimine (PEI)-functionalized single-wall (PEI-NH-SWNTs) and multiwall carbon nanotubes (PEI-NH-MWNTs) were produced by direct amination method. PEI functionalization increased the positive charge on the surface of SWNTs and MWNTs, allowing carbon nanotubes to interact electrostatically with the negatively charged small interfering RNAs (siRNAs) and to serve as nonviral gene delivery reagents. PEI-NH-MWNTs and PEI-NH-SWNTs had a better solubility in water than pristine carbon nanotubes, and further removal of large aggregates by centrifugation produced a stable suspension of reduced particle size and improved homogeneity and dispersity. The amount of grafted PEI estimated by thermogravimetric analysis was 5.08% ( w/ w) and 5.28% ( w/ w) for PEI-NH-SWNTs and PEI-NH-MWNTs, respectively. For the assessment of cytotoxicity, various concentrations of PEI-NH-SWNTs and PEI-NH-MWNTs were incubated with human cervical cancer cells, HeLa-S3, for 48 h. PEI-NH-SWNTs and PEI-NH-MWNTs induced cell deaths in a dose-dependent manner but were less cytotoxic compared to pure PEI. As determined by electrophoretic mobility shift assay, siRNAs directed against glyceraldehyde-3-phosphate dehydrogenase (siGAPDH) were completely associated with PEI-NH-SWNTs or PEI-NH-MWNTs at a PEI-NH-SWNT/siGAPDH or PEI-NH-MWNT/siGAPDH mass ratio of 80:1 or 160:1, respectively. Furthermore, PEI-NH-SWNTs and PEI-NH-MWNTs successfully delivered siGAPDH into HeLa-S3 cells at PEI-NH-SWNT/siGAPDH and PEI-NH-MWNT/siGAPDH mass ratios of 1:1 to 20:1, resulting in suppression of the mRNA level of GAPDH to an extent similar to that of DharmaFECT, a common transfection

  19. Linear programming to build food-based dietary guidelines: Romanian food baskets

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Robertson, Aileen; Hondru, Gabriela

    basket that incorporates only WHO food-based dietary guidelines does not meet all the recommended nutrient intake values for, for example, vitamins A, D, K, iodine and calcium. • The version of a Romanian fully nutritious, health-promoting food basket for a family (two adults, two children) costs 19.......65 lei (~€ 4.46) for a day. • Key nutrients, primarily vitamin D, calcium, potassium and iron, were found to control the overall price. • The least expensive basket (one day’s rations) is monotonous and the linear programming approach is used to select a wide range of foods that can be recommended......, potatoes and fish and considerably less meat, fats, oils and sugar. In conclusion, the linear programming methodology can facilitate the development of national dietary recommendations that meet both recommended nutrient intake values and WHO food-based dietary guidelines in a cost-efficient manner. How...

  20. Early- and late-born parvalbumin basket cell subpopulations exhibiting distinct regulation and roles in learning.

    Science.gov (United States)

    Donato, Flavio; Chowdhury, Ananya; Lahr, Maria; Caroni, Pico

    2015-02-18

    Brain networks can support learning by promoting acquisition of task-relevant information or by adhering to validated rules, but the mechanisms involved are poorly understood. Upon learning, local inhibitory parvalbumin (PV)-expressing Basket cell networks can switch to opposite configurations that either favor or interfere with further learning, but how this opposite plasticity is induced and relates to distinct learning requirements has remained unclear. Here, we show that PV Basket cells consist of hitherto unrecognized subpopulations, with distinct schedules of neurogenesis, input connectivities, output target neurons, and roles in learning. Plasticity of hippocampal early-born PV neurons was recruited in rule consolidation, whereas plasticity of late-born PV neurons was recruited in new information acquisition. This involved regulation of early-born neuron plasticity specifically through excitation, and of late-born neuron plasticity specifically through inhibition. Therefore, opposite learning requirements are implemented by distinct local networks involving PV Basket cell subpopulations specifically regulated through inhibition or excitation.

  1. DNA-carbon dots function as fluorescent vehicles for drug delivery.

    Science.gov (United States)

    Ding, Han; Du, Feiyue; Liu, Pengchang; Chen, Zhijun; Shen, Jiacong

    2015-04-01

    Carbon dots (CDs) are a new representative in the carbon-based material family, attracting tremendous interest in a large variety of fields, including biomedicine. In this report, we described a facile and green system for synthesizing DNA-CDs using genomic DNA isolated from Escherichia coli. DNA-CDs can be purified using a simple column centrifugation-based system. During DNA-CD synthesis, ribose was collapsed, accompanied by the release of nitrogen, and several new bonds (C-OH, N-O, and N-P) were formed, while the other covalent bonds of DNA were largely maintained. The presence of abundant chemical groups, such as amino or hydroxyl groups on DNA-CDs, may facilitate their future functionalization. These highly biocompatible DNA-CDs can serve as a new type of fluorescent vehicle for cell imaging and drug delivery studies. Our research may hasten the development of CDs for prominent future biomedical applications.

  2. Self-assembled lecithin/chitosan nanoparticles for oral insulin delivery: preparation and functional evaluation

    Directory of Open Access Journals (Sweden)

    Liu LY

    2016-02-01

    Full Text Available Liyao Liu, Cuiping Zhou, Xuejun Xia, Yuling Liu State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Drug Delivery Technology and Novel Formulations, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China Purpose: Here, we investigated the formation and functional properties of self-assembled lecithin/chitosan nanoparticles (L/C NPs loaded with insulin following insulin–phospholipid complex preparation, with the aim of developing a method for oral insulin delivery.Methods: Using a modified solvent-injection method, insulin-loaded L/C NPs were obtained by combining insulin–phospholipid complexes with L/C NPs. The nanoparticle size distribution was determined by dynamic light scattering, and morphologies were analyzed by cryogenic transmission electron microscopy. Fourier transform infrared spectroscopy analysis was used to disclose the molecular mechanism of prepared insulin-loaded L/C NPs. Fast ultrafiltration and a reversed-phase high-performance liquid chromatography assay were used to separate free insulin from insulin entrapped in the L/C NPs, as well as to measure the insulin-entrapment and drug-loading efficiencies. The in vitro release profile was obtained, and in vivo hypoglycemic effects were evaluated in streptozotocin-induced diabetic rats.Results: Our results indicated that insulin-containing L/C NPs had a mean size of 180 nm, an insulin-entrapment efficiency of 94%, and an insulin-loading efficiency of 4.5%. Cryogenic transmission electron microscopy observations of insulin-loaded L/C NPs revealed multilamellar structures with a hollow core, encircled by several bilayers. In vitro analysis revealed that insulin release from L/C NPs depended on the L/C ratio. Insulin-loaded L/C NPs orally administered to streptozotocin-induced diabetic rats exerted a significant

  3. Functionalized gold nanoparticles for topical delivery of methotrexate for the possible treatment of psoriasis.

    Science.gov (United States)

    Bessar, Hagar; Venditti, Iole; Benassi, Luisa; Vaschieri, Cristina; Azzoni, Paola; Pellacani, Giovanni; Magnoni, Cristina; Botti, Elisabetta; Casagrande, Viviana; Federici, Massimo; Costanzo, Antonio; Fontana, Laura; Testa, Giovanna; Mostafa, Fawzia Farag; Ibrahim, Samia Ali; Russo, Maria Vittoria; Fratoddi, Ilaria

    2016-05-01

    Gold nanoparticles (AuNPs) represent an effective choice for topical drug delivery systems thanks to their small size, general non-toxicity, ease of functionalization and high surface to volume ratio. Even if systemic, methotrexate still plays an important role in psoriasis treatment: its topical use shows insufficient percutaneus penetration owing to limited passive diffusion, high molecular weight and dissociation at physiological pH. The aim of our study was to design a new drug delivery nanocarrier for Methotrexate and to improve its solubility, stability and biodistribution. AuNPs were on purpose prepared with a hydrophilic stabilizing layer, in order to improve the colloidal stability in water. Water-soluble gold nanoparticles functionalized by sodium 3-mercapto-1-propansulfonate (Au-3MPS) were prepared and loaded with methotrexate (MTX). The loading efficiency of MTX on Au-3MPS was assessed in the range 70-80%, with a fast release (80% in one hour). The release was studied up to 24h reaching the value of 95%. The Au-3MPS@MTX conjugate was fully characterized by spectroscopic techniques (UV-vis, FTIR) and DLS. Preliminary toxicity tests in the presence of keratinocytes monolayers allowed to assess that the used Au-3MPS are not toxic. The conjugate was then topically used on C57BL/6 mouse normal skin in order to trace the absorption behavior. STEM images clearly revealed the distribution of gold nanoparticles inside the cells. In vitro studies showed that Methotrexate conjugated with Au-3MPS is much more efficient than Methotrexate alone. Moreover, DL50, based on MTT analysis, is 20 folds reduced at 48 h, by the presence of nanoparticles conjugation. UV-vis spectra for in vivo tracing of the conjugate on bare mouse skin after 24h of application, show increased delivery of Methotrexate in the epidermis and dermis using Au-3MPS@MTX conjugate, compared to MTX alone. Moreover we observed absence of the Au-3MPS in the dermis and in the epidermis, suggesting that

  4. Peptide-Decorated Gold Nanoparticles as Functional Nano-Capping Agent of Mesoporous Silica Container for Targeting Drug Delivery.

    Science.gov (United States)

    Chen, Ganchao; Xie, Yusheng; Peltier, Raoul; Lei, Haipeng; Wang, Ping; Chen, Jun; Hu, Yi; Wang, Feng; Yao, Xi; Sun, Hongyan

    2016-05-11

    A stimuli-responsive drug delivery system (DDS) with bioactive surface is constructed by end-capping mesoporous silica nanoparticles (MSNs) with functional peptide-coated gold nanoparticles (GNPs). MSNs are first functionalized with acid-labile α-amide-β-carboxyl groups to carry negative charges, and then capped with positively charged GNPs that are decorated with oligo-lysine-containing peptide. The resulting hybrid delivery system exhibits endo/lysosomal pH triggered drug release, and the incorporation of RGD peptide facilitates targeting delivery to αvβ3 integrin overexpressing cancer cells. The system can serve as a platform for preparing diversified multifunctional nanocomposites using various functional inorganic nanoparticles and bioactive peptides.

  5. PENGARUH MODEL LATIHAN DAN KOORDINASI TERHADAP KETERAMPILAN SISWI EKSTRAKURIKULER BOLA BASKET SMPN I BANTUL

    Directory of Open Access Journals (Sweden)

    Nurhidayah Nurhidayah

    2015-04-01

    Full Text Available Penelitian ini bertujuan untuk mengetahui (1 perbedaan pengaruh model latihan guided discovery style dan model latihan command style terhadap keterampilan bola basket siswi, (2 perbeda-an pengaruh siswi yang memiliki koordinasi tinggi dan koordinasi rendah terhadap keterampilan bola basket, dan (3 interaksi antara model latihan dengan koordinasi terhadap keterampilan bola basket siswi. Penelitian ini merupakan penelitian eksperimen. Populasi penelitian adalah seluruh siswi ekstrakurikuler bola basket yang berjumlah 43 orang. Sampel berjumlah 24 siswi ditentukan dengan teknik purposive sampling. Intrumen tes yang digunakan adalah tes Wall Bounce Pass untuk mengukur koordinasi mata-tangan dan tes Sekolah Tinggi Olahraga (STO untuk mengukur keterampilan bola basket siswi. Teknik analisis data yang menggunakan ANAVA. Hasil penelitian adalah sebagai berikut: (1 Tidak terdapat perbedaan pengaruh antara model latihan guided discovery style dan model latihan command style terhadap keterampilan bola basket siswi. (2 Terdapat perbedaan pengaruh siswi yang memiliki koordinasi tinggi dan rendah terhadap keterampilan bola basket. (3 Tidak terdapat interaksi yang signifikan antara model latihan dan koordinasi terhadap keterampilan bola basket siswi.   THE EFFECT OF TRAINING MODEL AND COORDINATION ON THE BASKETBALL SKILLS OF EXTRACURRICULAR STUDENTS OF JUNIOR HIGH SCHOOL 1 BANTUL   Abstract This study aims to investigate: (1 the different effects of the guided discovery style model training and command style model training on basketball skills of students, (2 the different effects on basketball skills of students who have high and low coordination, and (3 the interaction effects between training models of guided discovery style and command style with coordination (high and low on the basketball skills of students.This research was an experiment. The population comprised 43 basketball extracurricular students. A sample of 24 students was established using the

  6. Data Warehouse Designs Achieving ROI with Market Basket Analysis and Time Variance

    CERN Document Server

    Silvers, Fon

    2011-01-01

    Market Basket Analysis (MBA) provides the ability to continually monitor the affinities of a business and can help an organization achieve a key competitive advantage. Time Variant data enables data warehouses to directly associate events in the past with the participants in each individual event. In the past however, the use of these powerful tools in tandem led to performance degradation and resulted in unactionable and even damaging information. Data Warehouse Designs: Achieving ROI with Market Basket Analysis and Time Variance presents an innovative, soup-to-nuts approach that successfully

  7. Functionalized bridged silsesquioxane-based nanostructured microspheres: performance as novel drug-delivery devices in bone tissue-related applications.

    Science.gov (United States)

    Romeo, Hernán Esteban; Fanovich, María Alejandra

    2012-05-01

    Two kinds of functionalized nanostructured hybrid microspheres, based on the bridged silsesquioxane family, were synthesized by employing the sol-gel method via self-assembly of two different organic-inorganic bridged monomers. The architecture reached at molecular level allowed the incorporation of acetylsalicylic acid (ASA) as an anti-inflammatory model drug. The ASA-functionalized microspheres were characterized as delivery devices in simulated body fluid (SBF). The release behaviors of the synthesized microspheres (Fickian or anomalous diffusion mechanisms) were shown to be dependent on the chemical nature of the bridged monomers employed to synthesize the hybrid materials. The functionalized microspheres were proposed as delivery systems into calcium phosphate cements (CPCs), in order to slow down the characteristic drug-delivery kinetics of this kind of bone tissue-related materials. The incorporation of the new functionalized microparticles into the CPCs represented a viable methodology to modify the ASA-release kinetics in comparison to a conventional CPC containing the drug dispersed into the solid phase. The ASA-delivery profiles obtained from the microsphere-loaded CPCs showed that 40-60% of drug can be released after 2 weeks of testing in SBF. The inclusion of the microspheres into the CPC matrices allowed modification of the release profiles through a mechanism that involved two stages: (1) the diffusion of the drug through the organic-inorganic matrix of the microspheres (according to a Fickian or anomalous diffusion, depending on the nanostructuring) and (2) the subsequent diffusion of the drug through the ceramic matrix of the hardened cements. The release behavior of the composite cements was shown to be dependent on the nanostructuring of the hybrid microspheres, which can be selectively tailored by choosing the desired chemical structure of the bridged precursors employed in the sol-gel synthesis. The obtained results demonstrated the ability of

  8. Peptide-22 and Cyclic RGD Functionalized Liposomes for Glioma Targeting Drug Delivery Overcoming BBB and BBTB.

    Science.gov (United States)

    Chen, Cuitian; Duan, Ziqing; Yuan, Yan; Li, Ruixiang; Pang, Liang; Liang, Jianming; Xu, Xinchun; Wang, Jianxin

    2017-02-22

    Chemotherapy outcomes for the treatment of glioma remain unsatisfied due to the inefficient drug transport across BBB/BBTB and poor drug accumulation in the tumor site. Nanocarriers functionalized with different targeting ligands are considered as one of the most promising alternatives. However, few studies were reported to compare the targeting efficiency of the ligands and develop nanoparticles to realize BBB/BBTB crossing and brain tumor targeting simultaneously. In this study, six peptide-based ligands (Angiopep-2, T7, Peptide-22, c(RGDfK), D-SP5 and Pep-1), widely used for brain delivery, were selected to decorate liposomes, respectively, so as to compare their targeting ability to BBB or BBTB. Based on the in vitro cellular uptake results on BCECs and HUVECs, Peptide-22 and c(RGDfK) were picked to construct a BBB/BBTB dual-crossing, glioma-targeting liposomal drug delivery system c(RGDfK)/Pep-22-DOX-LP. In vitro cellular uptake demonstrated that the synergetic effect of c(RGDfK) and Peptide-22 could significantly increase the internalization of liposomes on U87 cells. In vivo imaging further verified that c(RGDfK)/Pep-22-LP exhibited higher brain tumor distribution than single ligand modified liposomes. The median survival time of glioma-bearing mice treated with c(RGDfK)/Pep-22-DOX-LP (39.5 days) was significantly prolonged than those treated with free doxorubicin or other controls. In conclusion, the c(RGDfK) and Peptide-22 dual-modified liposome was constructed based on the targeting ability screening of various ligands. The system could effectively overcome BBB/BBTB barriers, target to tumor cells and inhibit the growth of glioma, which proved its potential for improving the efficacy of chemotherapeutics for glioma therapy.

  9. Formulation of Functionalized PLGA-PEG Nanoparticles for In Vivo Targeted Drug Delivery

    Science.gov (United States)

    Cheng, Jianjun; Teply, Benjamin A.; Sherifi, Ines; Sung, Josephine; Luther, Gaurav; Gu, Frank X.; Levy-Nissenbaum, Etgar; Radovic-Moreno, Aleksandar F.; Langer, Robert; Farokhzad, Omid C.

    2009-01-01

    Nanoparticle (NP) size has been shown to significantly effect the biodistribution of targeted and non-targeted NPs in an organ specific manner. Herein we have developed NPs from carboxy-terminated poly (d,l-lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-b-PEG-COOH) polymer and studied the effects of altering the following formulation parameters on the size of NPs, including: 1) polymer concentration, 2) drug loading, 3) water miscibility of solvent, and 4) the ratio of water to solvent. We found that NP mean volumetric size correlates linearly with polymer concentration for NPs between 70 and 250 nm in diameter (linear coefficient = 0.99 for NPs formulated with solvents studied). NPs with desirable size, drug loading, and polydispersity were conjugated to the A10 RNA aptamer (Apt) that binds to the Prostate Specific Membrane Antigen (PSMA), and NP and NP-Apt biodistribution was evaluated in a LNCaP (PSMA+) xenograft mouse model of PCa. The surface functionalization of NPs with the A10 PSMA aptamer significantly enhanced delivery of NPs to tumors vs. equivalent NPs lacking the A10 PSMA aptamer (a 3.77-fold increase at 24 hrs; NP-Apt 0.83% ± 0.21% vs. NP 0.22% ± 0.07% of injected dose per gram of tissue; mean ± s.d., n = 4, p = 0.002). The ability to control NP size together with targeted delivery may result in favorable biodistribution and development of clinically relevant targeted therapies. PMID:17055572

  10. Deformable microparticles with multiple functions for drug delivery and device testing

    Science.gov (United States)

    Thula, Taili T.

    Since the HIV epidemic of the 1990s, researchers have attempted to develop a red blood cell analog. Even though some of these substitutes are now in Phase III of clinical trials, their use is limited by side effects and short half-life in the human body. As a result, there is still a need for an effective erythrocyte analog with minimum immunogenic and side effects, so that it can be used for multiple applications. Finding new approaches to develop more efficient blood substitutes will not only bring valuable advances in the clinical approach, but also in the area of in vitro testing of medical devices. We examined the feasibility of creating a deformable multi-functional, biodegradable, biocompatible particle for applications in drug delivery and device testing. As a preliminary evaluation, we synthesized different types of microcapsules using natural and synthetic polymers, various cross-linking agents, and diverse manufacturing techniques. After fully characterizing of each system, we determined the most promising red blood cell analog in terms of deformability, stability and toxicity. We also examined the encapsulation and release of bovine serum albumin (BSA) within these deformable particles. After removal of cross-linkers, zinc- and copper-alginate microparticles surrounded by multiple polyelectrolyte layers of chitosan oligosaccharide and alginate were deformable and remained stable under physiological pressures applied by the micropipette technique. In addition, multiple coatings decreased toxicity of heavy-metal crosslinked particles. BSA encapsulation and release from chitosan-alginate microspheres were contingent on the crosslinker and number of polyelectrolyte coatings, respectively. Further rheological studies are needed to determine how closely these particles simulate the behavior of erythrocytes. Also, studies on the encapsulation and release of different proteins, including hemoglobin, are needed to establish the desired controlled release of

  11. Recent Advances in Stimuli-Responsive Release Function Drug Delivery Systems for Tumor Treatment

    Directory of Open Access Journals (Sweden)

    Chendi Ding

    2016-12-01

    Full Text Available Benefiting from the development of nanotechnology, drug delivery systems (DDSs with stimuli-responsive controlled release function show great potential in clinical anti-tumor applications. By using a DDS, the harsh side effects of traditional anti-cancer drug treatments and damage to normal tissues and organs can be avoided to the greatest extent. An ideal DDS must firstly meet bio-safety standards and secondarily the efficiency-related demands of a large drug payload and controlled release function. This review highlights recent research progress on DDSs with stimuli-responsive characteristics. The first section briefly reviews the nanoscale scaffolds of DDSs, including mesoporous nanoparticles, polymers, metal-organic frameworks (MOFs, quantum dots (QDs and carbon nanotubes (CNTs. The second section presents the main types of stimuli-responsive mechanisms and classifies these into two categories: intrinsic (pH, redox state, biomolecules and extrinsic (temperature, light irradiation, magnetic field and ultrasound ones. Clinical applications of DDS, future challenges and perspectives are also mentioned.

  12. Intravenous delivery of hydrophobin-functionalized porous silicon nanoparticles: stability, plasma protein adsorption and biodistribution.

    Science.gov (United States)

    Sarparanta, Mirkka; Bimbo, Luis M; Rytkönen, Jussi; Mäkilä, Ermei; Laaksonen, Timo J; Laaksonen, Päivi; Nyman, Markus; Salonen, Jarno; Linder, Markus B; Hirvonen, Jouni; Santos, Hélder A; Airaksinen, Anu J

    2012-03-01

    Rapid immune recognition and subsequent elimination from the circulation hampers the use of many nanomaterials as carriers to targeted drug delivery and controlled release in the intravenous route. Here, we report the effect of a functional self-assembled protein coating on the intravenous biodistribution of (18)F-labeled thermally hydrocarbonized porous silicon (THCPSi) nanoparticles in rats. (18)F-Radiolabeling enables the sensitive and easy quantification of nanoparticles in tissues using radiometric methods and allows imaging of the nanoparticle biodistribution with positron emission tomography. Coating with Trichoderma reesei HFBII altered the hydrophobicity of (18)F-THCPSi nanoparticles and resulted in a pronounced change in the degree of plasma protein adsorption to the nanoparticle surface in vitro. The HFBII-THCPSi nanoparticles were biocompatible in RAW 264.7 macrophages and HepG2 liver cells making their intravenous administration feasible. In vivo, the distribution of the nanoparticles between the liver and spleen, the major mononuclear phagocyte system organs in the body, was altered compared to that of uncoated (18)F-THCPSi. Identification of the adsorbed proteins revealed that certain opsonins and apolipoproteins are enriched in HFBII-functionalized nanoparticles, whereas the adsorption of abundant plasma components such as serum albumin and fibrinogen is decreased.

  13. Targeting ligand-functionalized and redox-sensitive heparin-Pluronic nanogels for intracellular protein delivery

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Dai Hai; Joung, Yoon Ki; Choi, Jong Hoon; Park, Ki Dong [Department of Molecular Science and Technology, Ajou University, 5 Wonchon, Yeoungtong, Suwon 443-749 (Korea, Republic of); Moon, Hyun Tae, E-mail: kdp@ajou.ac.kr [Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul 151-742 (Korea, Republic of)

    2011-10-15

    The heparin-Pluronic (HP) conjugate was coupled via redox-sensitive disulfide bond and contains a vinyl sulfone (VS) group with high reactivity to some functional groups such as thiol group. Heparin was conjugated with cystamine and the terminal hydroxyl groups of Pluronic were activated with the VS group, followed by coupling of VS groups of Pluronic with cystamine of heparin. The chemical structure, heparin content and VS group content of the resulting product were determined by {sup 1}H NMR, FT-IR, toluidine blue assay and Ellman's method. The HP conjugate formed a type of nanogel in an aqueous medium, showing a critical micelle concentration of approximately 129.35 mg L{sup -1}, a spherical shape and the mean diameter of 115.7 nm, which were measured by AFM and DLS. The release test demonstrated that HP nanogel was rapidly degraded when treated with glutathione. Cytotoxicity results showed a higher viability of drug-free HP nanogel than that of drug-loaded one. Cyclo(Arg-Gly-Asp-D-Phe-Cys) (cRGDfC) peptide was efficiently conjugated to VS groups of HP nanogel and exhibited higher cellular uptake than unmodified nanogels. All results suggest a novel multi-functional nanocarrier delivery and effective release of proteins to the intracellular region in a redox-sensitive manner.

  14. Elastic-contractile model proteins: Physical chemistry, protein function and drug design and delivery.

    Science.gov (United States)

    Urry, Dan W; Urry, Kelley D; Szaflarski, Witold; Nowicki, Michal

    2010-12-30

    This review presents the structure and physico-chemical properties of ECMPs, elastic-contractile model proteins using sparse design modifications of elastic (GVGVP)(n); it describes the capacity of ECMP to perform the energy conversions that sustain living organisms; it arrives at the hydration thermodynamics of ECMP in terms of the change in Gibbs free energy of hydrophobic association, ΔG(HA), and the apolar-polar repulsive free energy of hydration, ΔG(ap); it applies ΔG(HA), ΔG(ap), and the nature of elasticity to describe the function of basic diverse proteins, namely - the F₁-motor of ATP synthase, Complex III of mitochondria, the KscA potassium-channel, and the molecular chaperonin, GroEL/ES; it applies ΔG(HA) and ΔG(ap) to describe the function of ABC exporter proteins that confer multi-drug resistance (MDR) on micro-organisms and human carcinomas and suggests drug modifications with which to overcome MDR. Using ECMP, means are demonstrated, for quantifying drug hydrophobicity with which to combat MDR and for preparing ECMP drug delivery nanoparticles, ECMPddnp, decorated with synthetic antigen-binding fragments, Fab1 and Fab2, with which to target specific up-regulated receptors, characteristic of human carcinoma cells, for binding and localized drug release. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. Synthesis of a drug delivery vehicle for cancer treatment utilizing DNA-functionalized gold nanoparticles

    Science.gov (United States)

    Brann, Tyler

    The treatment of cancer with chemotherapeutic agents has made great strides in the last few decades but still introduces major systemic side effects. The potent drugs needed to kill cancer cells often cause irreparable damage to otherwise healthy organs leading to further morbidity and mortality. A therapy with intrinsic selective properties and/or an inducible activation has the potential to change the way cancer can be treated. Gold nanoparticles (GNPs) are biocompatible and chemically versatile tools that can be readily functionalized to serve as molecular vehicles. The ability of these particles to strongly absorb light with wavelengths in the therapeutic window combined with the heating effect of surface plasmon resonance makes them uniquely suited for noninvasive heating in biologic applications. Specially designed DNA aptamers have shown their ability to serve as drug carriers through intercalation as well as directly acting as therapeutic agents. By combining these separate molecules a multifaceted drug delivery vehicle can be created with great potential as a selective and controllable treatment for cancer. Oligonucleotide-coated GNPs have been created using spherical GNPs but little work has been reported using gold nanoplates in this way. Using the Diasynth method gold nanoplates were produced to absorb strongly in the therapeutic near infrared (nIR) window. These particles were functionalized with two DNA oligonucleotides: one serving as an intercalation site for doxorubicin, and another, AS1411, serving directly as an anticancer targeting/therapeutic agent. These functional particles were fully synthesized and processed along with confirmation of DNA functionalization and doxorubicin intercalation. Doxorubicin is released via denaturation of the DNA structure into which doxorubicin is intercalated upon the heating of the gold nanoplate well above the DNA melting temperature. This temperature increase, due to light stimulation of surface plasmon

  16. Use of Linear Programming to Develop Cost-Efficient Minimized Nutritionally Adequate Health Promoting Food Baskets

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Tetens, Inge; Jensen, Jørgen Dejgård;

    2016-01-01

    ). The variety of food in the simplest forms of the five resulting baskets was increased through delimiting the maximum relative share of single foods. Results: The one-day version of N contained 12 foods at a minimal cost of DKK 27 (€ 3.6). The C, D, and DN were about twice as expensive and the NC cost ~DKK 81...

  17. The basket plate in the osteosynthesis of comminuted fractures of distal pole of the patella.

    Science.gov (United States)

    Matejcić, A; Smiljanić, B; Bekavac-Beslin, M; Ledinsky, M; Puljiz, Z

    2006-06-01

    The purpose of this study was to evaluate the basket plate in the treatment of comminuted fractures of the distal pole of the patella (patellar apex fracture). The basket plate was designed by Smiljanić Branimir M.D., Clinical Professor of Surgery, at the Department of Surgery, The University Hospital Sestre milosrdnice, Zagreb, Croatia. In the period from 1988 to 2003, more than 100 patients with comminuted patellar apex fractures had been treated with basket plate osteosynthesis in the Department of Surgery. Only 51 patients were subsequently available for knee examination. For evaluation of the knee, we used a modified Cincinnati knee rating system, using a manual dynamometer in the evaluation of the knee extension. The results were excellent in 30 patients, good in 16 and satisfactory in 5 patients; no poor results were observed. The stability of the osteosynthesis by basket plate allows osseous consolidation if the fracture and permits loading the leg with full body weight early in the postoperative period.

  18. Astronaut Judith Resnik in the 'basket' portion of the slidewire system

    Science.gov (United States)

    1984-01-01

    Astronaut Judith A. Resnik, 41-D mission specialist, is pictured in the 'basket' portion of the slidewire system at Pad A, as she participates in training for emergency evacuation from the fixed service structure. The Kennedy Space Center alternative photo number is 108-KSC-84PC-325.

  19. Teaching Conceptual Complexity to Adults Using an In-Basket Instructional Design.

    Science.gov (United States)

    Montuori, Lucinda A.; Kimmel, Ellen B.

    A study investigated the feasibility of teaching conceptual complexity to adults using an in-basket simulation. Training incorporated Kelly's components of differentiation and integration with Schroder's Cognitive Competencies and followed Lewin's Experiential Learning Model. Research participants in the original study were 24 women and 18 men,…

  20. Use of Linear Programming to Develop Cost-Efficient Minimized Nutritionally Adequate Health Promoting Food Baskets

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Tetens, Inge; Jensen, Jørgen Dejgård;

    2016-01-01

    using linear programming. The FBs were defined depending on the type of constraints applied: cultural acceptability (C), or dietary guidelines (D), or nutrient recommendations (N), or cultural acceptability and nutrient recommendations (CN), or dietary guidelines and nutrient recommendations (DN......: Use of linear programming facilitates the generation of low-cost food baskets that are nutritionally adequate, health promoting, and culturally acceptable....

  1. Multiple functionalization of fluorescent nanoparticles for specific biolabeling and drug delivery of dopamine

    Science.gov (United States)

    Malvindi, Maria Ada; di Corato, Riccardo; Curcio, Annalisa; Melisi, Daniela; Rimoli, Maria Grazia; Tortiglione, Claudia; Tino, Angela; George, Chandramohan; Brunetti, Virgilio; Cingolani, Roberto; Pellegrino, Teresa; Ragusa, Andrea

    2011-12-01

    The development of fluorescent biolabels for specific targeting and controlled drug release is of paramount importance in biological applications due to their potential in the generation of novel tools for simultaneous diagnosis and treatment of diseases. Dopamine is a neurotransmitter involved in several neurological diseases, such as Parkinson's disease and attention deficit hyperactivity disorder (ADHD), and the controlled delivery of its agonists already proved to have beneficial effects both in vitro and in vivo. Here, we report the synthesis and multiple functionalization of highly fluorescent CdSe/CdS quantum rods for specific biolabeling and controlled drug release. After being transferred into aqueous media, the nanocrystals were made highly biocompatible through PEG conjugation and covered by a carbohydrate shell, which allowed specific GLUT-1 recognition. Controlled attachment of dopamine through an ester bond also allowed hydrolysis by esterases, yielding a smart nanotool for specific biolabeling and controlled drug release.The development of fluorescent biolabels for specific targeting and controlled drug release is of paramount importance in biological applications due to their potential in the generation of novel tools for simultaneous diagnosis and treatment of diseases. Dopamine is a neurotransmitter involved in several neurological diseases, such as Parkinson's disease and attention deficit hyperactivity disorder (ADHD), and the controlled delivery of its agonists already proved to have beneficial effects both in vitro and in vivo. Here, we report the synthesis and multiple functionalization of highly fluorescent CdSe/CdS quantum rods for specific biolabeling and controlled drug release. After being transferred into aqueous media, the nanocrystals were made highly biocompatible through PEG conjugation and covered by a carbohydrate shell, which allowed specific GLUT-1 recognition. Controlled attachment of dopamine through an ester bond also allowed

  2. Use of Linear Programming to Develop Cost-Minimized Nutritionally Adequate Health Promoting Food Baskets

    Science.gov (United States)

    Tetens, Inge; Dejgård Jensen, Jørgen; Smed, Sinne; Gabrijelčič Blenkuš, Mojca; Rayner, Mike; Darmon, Nicole; Robertson, Aileen

    2016-01-01

    Background Food-Based Dietary Guidelines (FBDGs) are developed to promote healthier eating patterns, but increasing food prices may make healthy eating less affordable. The aim of this study was to design a range of cost-minimized nutritionally adequate health-promoting food baskets (FBs) that help prevent both micronutrient inadequacy and diet-related non-communicable diseases at lowest cost. Methods Average prices for 312 foods were collected within the Greater Copenhagen area. The cost and nutrient content of five different cost-minimized FBs for a family of four were calculated per day using linear programming. The FBs were defined using five different constraints: cultural acceptability (CA), or dietary guidelines (DG), or nutrient recommendations (N), or cultural acceptability and nutrient recommendations (CAN), or dietary guidelines and nutrient recommendations (DGN). The variety and number of foods in each of the resulting five baskets was increased through limiting the relative share of individual foods. Results The one-day version of N contained only 12 foods at the minimum cost of DKK 27 (€ 3.6). The CA, DG, and DGN were about twice of this and the CAN cost ~DKK 81 (€ 10.8). The baskets with the greater variety of foods contained from 70 (CAN) to 134 (DGN) foods and cost between DKK 60 (€ 8.1, N) and DKK 125 (€ 16.8, DGN). Ensuring that the food baskets cover both dietary guidelines and nutrient recommendations doubled the cost while cultural acceptability (CAN) tripled it. Conclusion Use of linear programming facilitates the generation of low-cost food baskets that are nutritionally adequate, health promoting, and culturally acceptable. PMID:27760131

  3. Non-Covalently Functionalized of Single-Walled Carbon Nanotubes by DSPE-PEG-PEI for SiRNA Delivery.

    Science.gov (United States)

    Siu, King Sun; Zhang, Yujuan; Zheng, Xiufen; Koropatnick, James; Min, Wei-Ping

    2016-01-01

    The expression of a gene can be specifically downregulated by small interfering RNA (SiRNA). Modified carbon nanotubes (CNT) can be used to protect SiRNA and facilitate its entry into cells. Regardless of that, simple and efficient functionalization of CNT is lacking. Effective SiRNA delivery can be carried out using non-covalently functionalized CNT, where non-covalent (versus covalent) functionalization is simpler and more expeditious. Non-covalently functionalized single walled carbon nanotubes (SWCNT) that include a lipopolymer are described here. Polyethylenimine (PEI) conjugated to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG) was generated and the products used to disperse CNT to form DSPE-PEG-PEI/CNT (DGI/C), an agent capable of facilitating SiRNA delivery to cells in vitro and organs and cells in vivo.

  4. Functionalized nanoscale oil bodies for targeted delivery of a hydrophobic drug

    Energy Technology Data Exchange (ETDEWEB)

    Chiang, Chung-Jen; Lin, Che-Chin; Lu, Tzu-Li; Wang, Hesin-Fu, E-mail: cjchiang@mail.cmu.edu.tw [Department of Medical Laboratory Science and Biotechnology, China Medical University, 91 Hsue-Shih Road, Taichung 40402, Taiwan (China)

    2011-10-14

    Effective formulations of hydrophobic drugs for cancer therapies are challenging. To address this issue, we have sought to nanoscale artificial oil bodies (NOBs) as an alternative. NOBs are lipid-based particles which consist of a central oil space surrounded by a monolayer of oleosin (Ole)-embedded phospholipids (PLs). Ole was first fused with the anti-HER2/neu affibody (Ole-ZH2), and the resulting hybrid protein was overproduced in Escherichia coli. ZH2-displayed NOBs were then assembled by sonicating the mixture containing plant oil, PLs, and isolated Ole-ZH2 in one step. To illustrate their usefulness, functionalized NOBs were employed to encapsulate a hydrophobic anticancer drug, Camptothecin (CPT). As a result, these CPT-loaded NOBs remained stable in serum and the release of CPT at the non-permissive condition exhibited a sustained and prolonged profile. Moreover, plain NOBs were biocompatible whereas CPT-loaded NOBs exerted a strong cytotoxic effect on HER2/neu-positive cells in vitro. Administration of xenograft nude mice with CPT-loaded NOBs also led to the regression of solid tumors in an effective way. Overall, the result indicates the potential of NOBs for targeted delivery of hydrophobic drugs.

  5. Targeted drug delivery to circulating tumor cells via platelet membrane-functionalized particles.

    Science.gov (United States)

    Li, Jiahe; Ai, Yiwei; Wang, Lihua; Bu, Pengcheng; Sharkey, Charles C; Wu, Qianhui; Wun, Brittany; Roy, Sweta; Shen, Xiling; King, Michael R

    2016-01-01

    Circulating tumor cells (CTCs) are responsible for metastases in distant organs via hematogenous dissemination. Fundamental studies in the past decade have suggested that neutralization of CTCs in circulation could represent an effective strategy to prevent metastasis. Current paradigms of targeted drug delivery into a solid tumor largely fall into two main categories: unique cancer markers (e.g. overexpression of surface receptors) and tumor-specific microenvironment (e.g. low pH, hypoxia, etc.). While relying on a surface receptor to target CTCs can be greatly challenged by cancer heterogeneity, targeting of tumor microenvironments has the advantage of recognizing a broader spectrum of cancer cells regardless of genetic differences or tumor types. The blood circulation, however, where CTCs transit through, lacks the same tumor microenvironment as that found in a solid tumor. In this study, a unique "microenvironment" was confirmed upon introduction of cancer cells of different types into circulation where activated platelets and fibrin were physically associated with blood-borne cancer cells. Inspired by this observation, synthetic silica particles were functionalized with activated platelet membrane along with surface conjugation of tumor-specific apoptosis-inducing ligand cytokine, TRAIL. Biomimetic synthetic particles incorporated into CTC-associated micro-thrombi in lung vasculature and dramatically decreased lung metastases in a mouse breast cancer metastasis model. Our results demonstrate a "Trojan Horse" strategy of neutralizing CTCs to attenuate metastasis.

  6. Functionalized nanoscale oil bodies for targeted delivery of a hydrophobic drug

    Science.gov (United States)

    Chiang, Chung-Jen; Lin, Che-Chin; Lu, Tzu-Li; Wang, Hesin-Fu

    2011-10-01

    Effective formulations of hydrophobic drugs for cancer therapies are challenging. To address this issue, we have sought to nanoscale artificial oil bodies (NOBs) as an alternative. NOBs are lipid-based particles which consist of a central oil space surrounded by a monolayer of oleosin (Ole)-embedded phospholipids (PLs). Ole was first fused with the anti-HER2/neu affibody (Ole-ZH2), and the resulting hybrid protein was overproduced in Escherichia coli. ZH2-displayed NOBs were then assembled by sonicating the mixture containing plant oil, PLs, and isolated Ole-ZH2 in one step. To illustrate their usefulness, functionalized NOBs were employed to encapsulate a hydrophobic anticancer drug, Camptothecin (CPT). As a result, these CPT-loaded NOBs remained stable in serum and the release of CPT at the non-permissive condition exhibited a sustained and prolonged profile. Moreover, plain NOBs were biocompatible whereas CPT-loaded NOBs exerted a strong cytotoxic effect on HER2/neu-positive cells in vitro. Administration of xenograft nude mice with CPT-loaded NOBs also led to the regression of solid tumors in an effective way. Overall, the result indicates the potential of NOBs for targeted delivery of hydrophobic drugs.

  7. Targeted drug delivery to circulating tumor cells via platelet membrane-functionalized particles

    Science.gov (United States)

    Li, Jiahe; Ai, Yiwei; Wang, Lihua; Bu, Pengcheng; Sharkey, Charles C.; Wu, Qianhui; Wun, Brittany; Roy, Sweta; Shen, Xiling; King, Michael R.

    2015-01-01

    Circulating tumor cells (CTCs) are responsible for metastases in distant organs via hematogenous dissemination. Fundamental studies in the past decade have suggested that neutralization of CTCs in circulation could represent an effective strategy to prevent metastasis. Current paradigms of targeted drug delivery into a solid tumor largely fall into two main categories: unique cancer markers (e.g. overexpression of surface receptors) and tumor-specific microenvironment (e.g. low pH, hypoxia, etc.). While relying on a surface receptor to target CTCs can be greatly challenged by cancer heterogeneity, targeting of tumor microenvironments has the advantage of recognizing a broader spectrum of cancer cells regardless of genetic differences or tumor types. The blood circulation, however, where CTCs transit through, lacks the same tumor microenvironment as that found in a solid tumor. In this study, a unique “microenvironment” was confirmed upon introduction of cancer cells of different types into circulation where activated platelets and fibrin were physically associated with blood-borne cancer cells. Inspired by this observation, synthetic silica particles were functionalized with activated platelet membrane along with surface conjugation of tumor-specific apoptosis-inducing ligand cytokine, TRAIL. Biomimetic synthetic particles incorporated into CTC-associated micro-thrombi in lung vasculature and dramatically decreased lung metastases in a mouse breast cancer metastasis model. Our results demonstrate a “Trojan Horse” strategy of neutralizing CTCs to attenuate metastasis. PMID:26519648

  8. Functional Assays for Specific Targeting and Delivery of RNA Nanoparticles to Brain Tumor

    Science.gov (United States)

    Lee, Tae Jin; Haque, Farzin; Vieweger, Mario; Yoo, Ji Young; Kaur, Balveen; Guo, Peixuan; Croce, Carlo M.

    2017-01-01

    Cumulative progress in nanoparticle development has opened a new era of targeted delivery of therapeutics to cancer cells and tissue. However, developing proper detection methods has lagged behind resulting in the lack of precise evaluation and monitoring of the systemically administered nanoparticles. RNA nanoparticles derived from the bacteriophage phi29 DNA packaging motor pRNA have emerged as a new generation of drugs for cancer therapy. Multifunctional RNA nanoparticles can be fabricated by bottom-up self-assembly of engineered RNA fragments harboring targeting (RNA aptamer or chemical ligand), therapeutic (siRNA, miRNA, ribozymes, and small molecule drugs), and imaging (fluorophore, radiolabels) modules. We have recently demonstrated that RNA nanoparticles can reach and target intracranial brain tumors in mice upon systemic injection with little or no accumulation in adjacent healthy brain tissues or in major healthy internal organs. Herein, we describe various functional imaging methods (fluorescence confocal microscopy, flow cytometry, fluorescence whole body imaging, and magnetic resonance imaging) to evaluate and monitor RNA nanoparticle targeting to intracranial brain tumors in mice. Such imaging techniques will allow in-depth evaluation of specifically delivered RNA therapeutics to brain tumors. PMID:25896001

  9. Chemically modified inulin microparticles serving dual function as a protein antigen delivery vehicle and immunostimulatory adjuvant.

    Science.gov (United States)

    Gallovic, Matthew D; Montjoy, Douglas G; Collier, Michael A; Do, Clement; Wyslouzil, Barbara E; Bachelder, Eric M; Ainslie, Kristy M

    2016-03-01

    To develop a new subunit vaccine adjuvant, we chemically modified a naturally-occurring, immunostimulatory inulin polysaccharide to produce an acid-sensitive biopolymer (acetalated inulin, Ace-IN). Various hydrophobic Ace-IN polymers were formed into microparticles (MPs) by oil-in-water emulsions followed by solvent evaporation These Ace-IN MPs possessed tunable degradation characteristics that, unlike polyesters used in FDA-approved microparticulate formulations, had only pH-neutral hydrolytic byproducts. Macrophages were passively targeted with cytocompatible Ace-IN MPs. TNF-α production by macrophages treated with Ace-IN MPs could be altered by adjusting the polymers' chemistry. Mice immunized with Ace-IN MPs encapsulating a model ovalbumin (OVA) antigen showed higher production of anti-OVA IgG antibody levels relative to soluble antigen. The antibody titers were also comparable to an alum-based formulation. This proof-of-concept establishes the potential for chemically-modified inulin MPs to simultaneously enable dual functionality as a stimuli-controlled antigen delivery vehicle and immunostimulatory adjuvant.

  10. Design, development and characterization of multi-functionalized gold nanoparticles for biodetection and targeted boron delivery in BNCT applications

    Energy Technology Data Exchange (ETDEWEB)

    Mandal, Subhra [Department of Tumor Immunology, Radboud University Nijmegen Medical Centre (Netherlands); Bakeine, Gerald J., E-mail: Jamesbakeine1@yahoo.com [Department of Internal Medicine and Therapeutics-Section of Clinical Toxicology, University of Pavia, Piazza Botta 10, 27100 Pavia (Italy); Krol, Silke [Institute of Neurology, Fondazione IRCCS Carlo Besta, Milan (Italy); Ferrari, Cinzia; Clerici, Anna M.; Zonta, Cecilia; Cansolino, Laura [Department of Surgery, Laboratory of Experimental Surgery, University of Pavia (Italy); Ballarini, Francesca [Department of Nuclear and Theoretical Physics, University of Pavia (Italy); Bortolussi, Silva [Department of Nuclear and Theoretical Physics, University of Pavia (Italy)] [National Institute of Nuclear Physics (INFN), Section of Pavia (Italy); Stella, Subrina; Protti, Nicoletta [Department of Nuclear and Theoretical Physics, University of Pavia (Italy); Bruschi, Piero [National Institute of Nuclear Physics (INFN), Section of Pavia (Italy); Altieri, Saverio [Department of Nuclear and Theoretical Physics, University of Pavia (Italy)] [National Institute of Nuclear Physics (INFN), Section of Pavia (Italy)

    2011-12-15

    The aim of this study is to optimize targeted boron delivery to cancer cells and its tracking down to the cellular level. To this end, we describe the design and synthesis of novel nanovectors that double as targeted boron delivery agents and fluorescent imaging probes. Gold nanoparticles were coated with multilayers of polyelectrolytes functionalized with the fluorescent dye (FITC), boronophenylalanine and folic acid. In vitro confocal fluorescence microscopy demonstrated significant uptake of the nanoparticles in cancer cells that are known to overexpress folate receptors. - Highlights: Black-Right-Pointing-Pointer Synthesis of multi-labeled gold nanoparticles for selective boron delivery to tumor cells. Black-Right-Pointing-Pointer Tumor selectivity is achieved through folic acid receptor targeting. Black-Right-Pointing-Pointer Optical fluorescent microscopy allows tracking of cellular uptake of the gold nanoparticle. Black-Right-Pointing-Pointer In vitro tests demonstrate selective nanoparticle up in folate receptor positive tumor cells.

  11. A rapid pathway toward a superb gene delivery system: programming structural and functional diversity into a supramolecular nanoparticle library.

    Science.gov (United States)

    Wang, Hao; Liu, Kan; Chen, Kuan-Ju; Lu, Yujie; Wang, Shutao; Lin, Wei-Yu; Guo, Feng; Kamei, Ken-ichiro; Chen, Yi-Chun; Ohashi, Minori; Wang, Mingwei; Garcia, Mitch André; Zhao, Xing-Zhong; Shen, Clifton K-F; Tseng, Hsian-Rong

    2010-10-26

    Nanoparticles are regarded as promising transfection reagents for effective and safe delivery of nucleic acids into a specific type of cells or tissues providing an alternative manipulation/therapy strategy to viral gene delivery. However, the current process of searching novel delivery materials is limited due to conventional low-throughput and time-consuming multistep synthetic approaches. Additionally, conventional approaches are frequently accompanied with unpredictability and continual optimization refinements, impeding flexible generation of material diversity creating a major obstacle to achieving high transfection performance. Here we have demonstrated a rapid developmental pathway toward highly efficient gene delivery systems by leveraging the powers of a supramolecular synthetic approach and a custom-designed digital microreactor. Using the digital microreactor, broad structural/functional diversity can be programmed into a library of DNA-encapsulated supramolecular nanoparticles (DNA⊂SNPs) by systematically altering the mixing ratios of molecular building blocks and a DNA plasmid. In vitro transfection studies with DNA⊂SNPs library identified the DNA⊂SNPs with the highest gene transfection efficiency, which can be attributed to cooperative effects of structures and surface chemistry of DNA⊂SNPs. We envision such a rapid developmental pathway can be adopted for generating nanoparticle-based vectors for delivery of a variety of loads.

  12. Biocompatible polymers coated on carboxylated nanotubes functionalized with betulinic acid for effective drug delivery.

    Science.gov (United States)

    Tan, Julia M; Karthivashan, Govindarajan; Abd Gani, Shafinaz; Fakurazi, Sharida; Hussein, Mohd Zobir

    2016-02-01

    Chemically functionalized carbon nanotubes are highly suitable and promising materials for potential biomedical applications like drug delivery due to their distinct physico-chemical characteristics and unique architecture. However, they are often associated with problems like insoluble in physiological environment and cytotoxicity issue due to impurities and catalyst residues contained in the nanotubes. On the other hand, surface coating agents play an essential role in preventing the nanoparticles from excessive agglomeration as well as providing good water dispersibility by replacing the hydrophobic surfaces of nanoparticles with hydrophilic moieties. Therefore, we have prepared four types of biopolymer-coated single walled carbon nanotubes systems functionalized with anticancer drug, betulinic acid in the presence of Tween 20, Tween 80, polyethylene glycol and chitosan as a comparative study. The Fourier transform infrared spectroscopy studies confirm the bonding of the coating molecules with the SWBA and these results were further supported by Raman spectroscopy. All chemically coated samples were found to release the drug in a slow, sustained and prolonged fashion compared to the uncoated ones, with the best fit to pseudo-second order kinetic model. The cytotoxic effects of the synthesized samples were evaluated in mouse embryonic fibroblast cells (3T3) at 24, 48 and 72 h. The in vitro results reveal that the cytotoxicity of the samples were dependent upon the drug release profiles as well as the chemical components of the surface coating agents. In general, the initial burst, drug release pattern and cytotoxicity could be well-controlled by carefully selecting the desired materials to suit different therapeutic applications.

  13. Synthesis and characterization of amino acid-functionalized calcium phosphate nanoparticles for siRNA delivery.

    Science.gov (United States)

    Bakan, Feray; Kara, Goknur; Cokol Cakmak, Melike; Cokol, Murat; Denkbas, Emir Baki

    2017-06-27

    Small interfering RNAs (siRNA) are short nucleic acid fragments of about 20-27 nucleotides, which can inhibit the expression of specific genes. siRNA based RNAi technology has emerged as a promising method for the treatment of a variety of diseases. However, a major limitation in the therapeutic use of siRNA is its rapid degradation in plasma and cellular cytoplasm, resulting in short half-life. In addition, as siRNA molecules cannot penetrate into the cell efficiently, it is required to use a carrier system for its delivery. In this work, chemically and morphologically different calcium phosphate (CaP) nanoparticles, including spherical-like hydroxyapatite (HA-s), needle-like hydroxyapatite (HA-n) and calcium deficient hydroxyapatite (CDHA) nanoparticles were synthesized by the sol-gel technique and the effects of particle characteristics on the binding capacity of siRNA were investigated. In order to enhance the gene loading efficiency, the nanoparticles were functionalized with arginine and the morphological and their structural characteristics were analyzed. The addition of arginine did not significantly change the particle sizes; however, it provided a significantly increased binding of siRNA for all types of CaP nanoparticles, as revealed by spectrophotometric measurements analysis. Arginine functionalized HA-n nanoparticles showed the best binding behavior with siRNA among the other nanoparticles due to its high, positive zeta potential (+18.8mV) and high surface area of Ca(++) rich "c" plane. MTT cytotoxicity assays demonstrated that all the nanoparticles tested herein were biocompatible. Our results suggest that high siRNA entrapment in each of the three modified non-toxic CaP nanoparticles make them promising candidates as a non-viral vector for delivering therapeutic siRNA molecules to treat cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Production of succinic acid in basket and mobile bed bioreactors-Comparative analysis of substrate mass transfer aspects☆

    Institute of Scientific and Technical Information of China (English)

    Anca-Irina Galaction; Dan Cacaval; Ramona-Mihaela Matran; Alexandra Tucaliuc

    2016-01-01

    The glucose mass transfer in the biosynthesis of succinic acid with immobilized Actinobacil us succinogenes cel s has been comparatively analyzed for a bioreactor with mobile bed vs. a stationary basket bioreactor. The process has been considered to occur under substrate and product inhibitory effects. The results indicated that the biore-actor with mobile bed is more efficient for biocatalyst particles with a diameter over 3 mm, while the basket bio-reactor is more efficient for smal er biocatalyst particles and basket bed thickness below 5 mm. The performances of both configurations of immobilized A. succinogenes cell beds were found to be superior to the column packed bed bioreactor.

  15. Selective Delivery of an Anticancer Drug with Aptamer-Functionalized Liposomes to Breast Cancer Cells in Vitro and in Vivo.

    Science.gov (United States)

    Xing, Hang; Tang, Li; Yang, Xujuan; Hwang, Kevin; Wang, Wendan; Yin, Qian; Wong, Ngo Yin; Dobrucki, Lawrence W; Yasui, Norio; Katzenellenbogen, John A; Helferich, William G; Cheng, Jianjun; Lu, Yi

    2013-10-21

    Selective targeting of cancer cells is a critical step in cancer diagnosis and therapy. To address this need, DNA aptamers have attracted significant attention as possible targeting ligands. However, while their use in targeting cancer cells in vitro has been reported, their effectiveness has rarely been established in vivo. Here we report the development of a liposomal drug delivery system for targeted anticancer chemotherapy. Liposomes were prepared containing doxorubicin as a payload, and functionalized with AS1411, a DNA aptamer with strong binding affinity for nucleolin. AS1411 aptamer-functionalized liposomes increased cellular internalization and cytotoxicity to MCF-7 breast cancer cells as compared to non-targeting liposomes. Furthermore, targeted liposomal doxorubicin improved antitumor efficacy against xenograft MCF-7 breast tumors in athymic nude mice, attributable to their enhanced tumor tissue penetration. This study suggests that AS1411 aptamer-functionalized liposomes can recognize nucleolin overexpressed on MCF-7 cell surface, and therefore enable drug delivery with high specificity and selectivity.

  16. Advanced drug and gene delivery systems based on functional biodegradable polycarbonates and copolymers

    NARCIS (Netherlands)

    Chen, Wei; Meng, F.; Cheng, R.; Deng, C.; Feijen, J.; Zhong, Z.

    2014-01-01

    Biodegradable polymeric nanocarriers are one of the most promising systems for targeted and controlled drug and gene delivery. They have shown several unique advantages such as excellent biocompatibility, prolonged circulation time, passive tumor targeting via the enhanced permeability and retention

  17. A DNA nanocapsule with aptamer-controlled open-closure function for targeted delivery

    DEFF Research Database (Denmark)

    Bentin, Thomas

    2012-01-01

    A DNA capsule fitted with aptamer controlled target sensing has been "woven" using a 7308-base single-stranded DNA "thread" and 196 staple oligonucleotides. The capsule enables logic-gated molecular cargo delivery to targeted cell surfaces.......A DNA capsule fitted with aptamer controlled target sensing has been "woven" using a 7308-base single-stranded DNA "thread" and 196 staple oligonucleotides. The capsule enables logic-gated molecular cargo delivery to targeted cell surfaces....

  18. Non-covalent functionalization of single-walled carbon nanotubes with modified polyethyleneimines for efficient gene delivery.

    Science.gov (United States)

    Behnam, Behzad; Shier, Wayne T; Nia, Azadeh Hashem; Abnous, Khalil; Ramezani, Mohammad

    2013-09-15

    Functionalized carbon nanotubes (CNTs) have been recently emerged as important class of vectors for delivery of DNA and other biomolecules into various cells. In this study, single-walled carbon nanotubes (SWNTs) were functionalized by non-covalent binding of hydrophobic moieties, which were covalently linked to polyethyleneimines (PEIs). PEIs of three molecular weights (25, 10 and 1.8kDa) were used. CNTs were functionalized with the PEI series either through phospholipid moiety (via a polyethyleneglycol linker) or through directly-attached long (18 carbons) or intermediate (10 carbons) hydrophobic alkyl moieties. All PEI-functionalized CNTs exhibited good stability and dispersibility in biological media. Visualizing of functionalized CNTs and lack of aggregation were confirmed by atomic force microscopy. The PEI derivatives bound to CNTs retained the ability to fully condense plasmid DNA at low N/P ratios and substantial buffering capacity in the endosomal pH range. PEI-functionalized CNTs exhibited increased transfection efficiency compared to underivatized PEIs up to 19-fold increase being observed in the functionalized CNT with the smallest PEI tested, the smallest hydrophobic attachment moiety tested and no linker. Also PEI-functionalized CNTs were effective gene delivery vectors in vivo following tail vein injection in mice with the largest expression occurring with the vector PEI-functionalized through a polyethyleneglycol linker.

  19. Self-assembled lecithin/chitosan nanoparticles for oral insulin delivery: preparation and functional evaluation.

    Science.gov (United States)

    Liu, Liyao; Zhou, Cuiping; Xia, Xuejun; Liu, Yuling

    2016-01-01

    Here, we investigated the formation and functional properties of self-assembled lecithin/chitosan nanoparticles (L/C NPs) loaded with insulin following insulin-phospholipid complex preparation, with the aim of developing a method for oral insulin delivery. Using a modified solvent-injection method, insulin-loaded L/C NPs were obtained by combining insulin-phospholipid complexes with L/C NPs. The nanoparticle size distribution was determined by dynamic light scattering, and morphologies were analyzed by cryogenic transmission electron microscopy. Fourier transform infrared spectroscopy analysis was used to disclose the molecular mechanism of prepared insulin-loaded L/C NPs. Fast ultrafiltration and a reversed-phase high-performance liquid chromatography assay were used to separate free insulin from insulin entrapped in the L/C NPs, as well as to measure the insulin-entrapment and drug-loading efficiencies. The in vitro release profile was obtained, and in vivo hypoglycemic effects were evaluated in streptozotocin-induced diabetic rats. Our results indicated that insulin-containing L/C NPs had a mean size of 180 nm, an insulin-entrapment efficiency of 94%, and an insulin-loading efficiency of 4.5%. Cryogenic transmission electron microscopy observations of insulin-loaded L/C NPs revealed multilamellar structures with a hollow core, encircled by several bilayers. In vitro analysis revealed that insulin release from L/C NPs depended on the L/C ratio. Insulin-loaded L/C NPs orally administered to streptozotocin-induced diabetic rats exerted a significant hypoglycemic effect. The relative pharmacological bioavailability following oral administration of L/C NPs was 6.01%. With the aid of phospholipid-complexation techniques, some hydrophilic peptides, such as insulin, can be successfully entrapped into L/C NPs, which could improve oral bioavailability, time-dependent release, and therapeutic activity.

  20. Functionalized biocompatible polyelectrolyte multilayers for drug delivery: In situ investigation of mechanical properties by dissipative quartz crystal microbalance

    Energy Technology Data Exchange (ETDEWEB)

    Habibi, Neda [Department of Informatics, Bioengineering, Robotics and Systems Engineering, University of Genova, Genova (Italy); Nanotechnology and Advanced Material Institute, Isfahan University of Technology, Isfahan (Iran, Islamic Republic of); Pastorino, Laura, E-mail: laura.pastorino@unige.it [Department of Informatics, Bioengineering, Robotics and Systems Engineering, University of Genova, Genova (Italy); Ruggiero, Carmelina [Department of Informatics, Bioengineering, Robotics and Systems Engineering, University of Genova, Genova (Italy)

    2014-02-01

    Nanostructured polymeric capsules have been applied in different fields, and specifically are regarded as promising for smart drug delivery applications. The physical–chemical and mechanical properties, and thus the permeability of the polyelectrolyte multilayer shell, play an important role in efficient delivery. Quartz crystal microbalance working in liquid has been used for the characterization of the buildup process and of the viscoelastic properties of biocompatible multilayers and of their functionalization by S-layer proteins. Optical and scanning electron microscopy have been used for the morphological characterization of nanostructured capsules obtained at physiological conditions by the assembly of the characterized multilayers onto spherical cores and by their subsequent removal. The proposed functionalized biocompatible capsules can be regarded as promising candidates for smart drug delivery applications. - Graphical abstract: SEM image of nanostructured polymeric capsules made by 4 bilayers of collagen/alginate at pH 7.4. - Highlights: • Build-up of biocompatible multilayers and functionalization by S-layer proteins • Characterization of multilayer growth and mechanical properties by QCM • Fabrication of S-layer functionalized biocompatible capsules.

  1. Utilizing food effects to overcome challenges in delivery of lipophilic bioactives: structural design of medical and functional foods.

    Science.gov (United States)

    McClements, David Julian

    2013-12-01

    The oral bioavailability of many lipophilic bioactives, such as pharmaceuticals and nutraceuticals, is relatively low due to their poor solubility, permeability and/or chemical stability within the human gastrointestinal tract (GIT). The oral bioavailability of lipophilic bioactives can be improved by designing food matrices that control their release, solubilization, transport and absorption within the GIT. This article discusses the challenges associated with delivering lipophilic bioactive components, the impact of food composition and structure on oral bioavailability and the design of functional and medical foods for improving the oral bioavailability of lipophilic bioactives. Food-based delivery systems can be used to improve the oral bioavailability of lipophilic bioactives. There are a number of potential advantages to delivering lipophilic bioactives using functional or medical foods: greater compliance than conventional delivery forms; increased bioavailability and efficacy; and reduced variability in biological effects. However, food matrices are structurally complex multicomponent materials and research is still needed to identify optimum structures and compositions for particular bioactives.

  2. Use of Linear Programming to Develop Cost-Efficient Minimized Nutritionally Adequate Health Promoting Food Baskets

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Tetens, Inge; Jensen, Jørgen Dejgård

    2016-01-01

    Background: Food-Based Dietary Guidelines (FBDGs) are developed to promote healthier eating patterns, but increasing food prices may make healthy eating less affordable. The aim of this study was to design a range of cost-minimized nutritionally adequate health-promoting food baskets (FBs......) that help prevent both micronutrient inadequacy and diet-related non-communicable diseases at lowest cost. Methods: Average prices for 312 foods were collected within the Greater Copenhagen area. The cost and nutrient content of five different cost-minimized FBs for a family of four were calculated per day......: Use of linear programming facilitates the generation of low-cost food baskets that are nutritionally adequate, health promoting, and culturally acceptable....

  3. Linear programming to build food-based dietary guidelines: Romanian food baskets

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Robertson, Aileen; Hondru, Gabriela

    As in many Member States of the WHO European Region, Romania is seeing an increase in the prevalence of overweight and obesity, particularly among children and adolescents. This is a major risk factor for the development of noncommunicable diseases (NCDs), and innovative approaches using...... approach using linear programming methodology to design national dietary recommendations which aim to prevent both NCDs and micronutrient deficiencies and still be affordable by low income groups. This new approach is applied within the context of food availability in Romania in 2014. Eating the same food...... basket that incorporates only WHO food-based dietary guidelines does not meet all the recommended nutrient intake values for, for example, vitamins A, D, K, iodine and calcium. • The version of a Romanian fully nutritious, health-promoting food basket for a family (two adults, two children) costs 19...

  4. Structure-function investigations of DNA condensing agents with application to gene delivery

    Science.gov (United States)

    Evans, Heather Marie

    Lipid-based systems are notoriously poor for gene delivery, and their use has been primarily empirical. In order to improve these systems, it is imperative to obtain a greater understanding of molecular interactions between DNA and positively charged molecules. A variety of cationic molecules have been studied with DNA, in an attempt to correlate structural properties of these assemblies (using x-ray diffraction) with their efficiency as DNA carriers for gene delivery (using a luciferase assay). Several systems have been studied, some of which use the same charged amine moieties presented in three distinct morphologies: the multivalent salts spermine and spermidine, dendrimers, and dendrimeric lipids. The dendrimers somewhat approximate the properties of histories, cylindrical proteins that condense intracellular DNA. Structural studies of histone and DNA have also been conducted in order to better understand these interactions and their possible relevance to the gene delivery pathway. In addition, empirical evidence suggests that for successful in vivo gene delivery, cholesterol should be used as a helper lipid. The delivery efficiency and structural behavior of cholesterol and other sterol molecules have been studied in ternary lipid mixtures.

  5. Chiral and achiral basket-handle porphyrins: short synthesis and stereostructures of these versatile building blocks.

    Science.gov (United States)

    Gehrold, Andreas C; Bruhn, Torsten; Schneider, Heidi; Radius, Udo; Bringmann, Gerhard

    2015-01-16

    Both, chiral and achiral basket-handle porphyrins were synthesized via a short, reliable, and efficient route in multigram quantities. Standard synthetic protocols such as metalation of the macrocycle, halogenation, and borylation of the porphyrin core or alkyl- and arylation with lithium organyls were successfully adapted. The planar-chiral representatives were resolved into their enantiomers, whose absolute configurations were determined by comparison of experimental CD spectra with TDCAM-B3LYP calculated ones.

  6. Basket and basal-duct cells in domestic animals: different cytokeratin expression and shape.

    Science.gov (United States)

    Zedda, M; Farina, V

    1996-12-01

    Cytokeratins (CKs) are a multigenic family of proteins constituting intermediate filaments in epithelia, indicated in humans by the numbers 1-20. Different cell-types can be immunocytochemically identified on the grounds of their CK expression. This investigation was designed to study CK expression of basket cells (BCs) and basal-duct cells (BDCs) in some domestic animals. Frozen sections of mammary and major salivary glands from cows, sheep, pigs and rabbits were treated using the immunofluorescent method, using as monoclonal antibodies clones CK-E3, CKB1, KS-1A3, and LDS-68, respectively, revealing the human CKs 17, 14, 13, 7. BCs surrounding acini and BDCs were stained by CK 17 antibody only in the rabbit. CK 14 was detectable in both cell types in cows, sheep and pigs, except in the case of bovine salivary BCs. CK 13 was revealed in BCs and BDCs of all mammary glands and also rabbit salivary glands. In the salivary glands of the other species, only BDCs were stained. CK 7 gave unreliable results in all the species and cell types examined. Interestingly, in the rabbit, also BDCs are basket-like in shape. The antibodies employed showed different staining depending on species and gland. On the grounds of immunoreactivity and shape, BCs and BDCs can be considered the same cell type in the rabbit. In the other species, they appear to be different, since BDCs may express additional CKs and are triangular-shaped, whereas BCs are truly basket-like. It is worth noting that clone KS-1A3 in the rabbit and CKB1 in the sheep and pig can be considered markers of the basket/ basal system.

  7. DO CHANGES IN ANAL SPHINCTER ANATOMY CORRELATE WITH ANAL FUNCTION IN WOMEN WITH A HISTORY OF VAGINAL DELIVERY?

    Directory of Open Access Journals (Sweden)

    Sthela Maria MURAD-REGADAS

    2014-09-01

    Full Text Available Objectives To evaluate anal sphincter anatomy using three-dimensional ultrasonography (3-DAUS in incontinent women with vaginal delivery, correlate anatomical findings with symptoms of fecal incontinence and determine the effect of vaginal delivery on anal canal anatomy and function. Methods Female with fecal incontinence and vaginal delivery were assessed with Wexner’s score, manometry, and 3DAUS. A control group comprising asymptomatic nulliparous was included. Anal pressure, the angle of the defect and length of the external anal sphincter (EAS, the anterior and posterior internal anal sphincter (IAS, the EAS + puborectal and the gap were measured and correlated with score. Results Of the 62, 49 had fecal incontinence and 13 were asymptomatic. Twenty five had EAS defects, 8 had combined EAS+IAS defects, 16 had intact sphincters and continence scores were similar. Subjects with sphincter defects had a shorter anterior EAS, IAS and longer gap than women without defects. Those with a vaginal delivery and intact sphincters had a shorter anterior EAS and longer gap than nulliparous. We found correlations between resting pressure and anterior EAS and IAS length in patients with defects. Conclusions Avaliar a anatomia do esfíncter anal usando ultra-sonografia tridimensional (3D-US em mulheres incontinentes com parto vaginal, correlacionar os achados anatômicos com sintomas de incontinência fecal e, determinar o efeito do parto vaginal sobre a anatomia e função do canal anal.

  8. Postnatal dendritic morphogenesis of cerebellar basket and stellate cells in vitro.

    Science.gov (United States)

    Spatkowski, Gabriele; Schilling, Karl

    2003-05-01

    Inhibitory interneurons in the molecular layer of the cerebellar cortex play an essential role in cerebellar physiology by providing feed-forward inhibition to efferent Purkinje cells. Morphologic characteristics have been utilized to classify these cells as either basket cells or stellate cells. Conflicting evidence exists as to whether these cells are of distinct lineage and develop by employing discrete genetic programs, or whether their characteristic morphologic differences result from external cues that they encounter only after they have settled in their final territory in the molecular layer. We used primary dissociated cerebellar cultures established from early postnatal mice to study dendritogenesis of basket/stellate cells, identified by immunostaining for parvalbumin, under experimentally controlled conditions. We find that the radial axonal orientation of stem dendrites is non-random, suggesting a cell-intrinsic component defining this morphologic trait. In contrast, the expanse and complexity of basket/stellate cell dendrites is modulated by the granule cell derived neurotrophin, BDNF. BDNF-induced morphogenetic effects decline with ongoing development. Overall, our data do not provide evidence for a distinct lineage or genetic makeup of cerebellar molecular layer inhibitory interneurons.

  9. The virtual shopping basket versus the shopping trolley: An ...

    African Journals Online (AJOL)

    Seugnet

    attempts to optimise virtual marketing strategies (for example Frost ... fuller understanding of the individual level of consumer functioning is ... son, thought, experience and emotion are connected. ... respondents explain their views from multiple perspec- tives that let .... Ethical considerations discounted the use of virtual.

  10. In vitro and in vivo delivery of functionalized nanoparticles via coiled-coil interactions

    NARCIS (Netherlands)

    Yang, J.

    2016-01-01

    This thesis presents another approach for direct cytosolic delivery via membrane fusion. This approach is based on a complementary pair of coiled-coil forming peptides, K (KIAALKE)4 and E (EIAALEK)4 and is mimicking the action of the SNARE-complex. The SNARE-complex is responsible for fusion between

  11. Assessment of the Ehlanzeni District health transport and logistics function: Enhancing rural healthcare delivery systems

    CSIR Research Space (South Africa)

    Mashiri, MAM

    2009-07-01

    Full Text Available This paper seeks to establish a baseline against which to assess the impacts of the ‘Ehlanzeni District Health Transport Function’ for the district’s healthcare service delivery output, and by extension, health and welfare outcomes. The main...

  12. Boron nitride nanotubes functionalized with mesoporous silica for intracellular delivery of chemotherapy drugs.

    Science.gov (United States)

    Li, Xia; Zhi, Chunyi; Hanagata, Nobutaka; Yamaguchi, Maho; Bando, Yoshio; Golberg, Dmitri

    2013-08-25

    Boron nitride nanotube (BNNT)@mesoporous silica hybrids with controllable surface zeta potential were fabricated for intracellular delivery of doxorubicin. The materials showed higher suspension ability, doxorubicin intracellular endocytosis efficiency, and LNcap prostate cancer cell killing ability compared with naked BNNTs.

  13. Moral, Legal, and Functional Dimensions of Inclusive Service Delivery in Catholic Schools

    Science.gov (United States)

    Scanlan, Martin

    2009-01-01

    Catholic school educators are morally compelled by Catholic social teaching to foster inclusive service delivery for students who have traditionally been marginalized in schools, including students in poverty, students of color, English language learners, and students with special needs. This article applies this moral context to analyze the legal…

  14. On the role of guests in enforcing the mechanism of action of gated baskets.

    Science.gov (United States)

    Ruan, Yian; Wang, Bao-Yu; Erb, Jeremy M; Chen, Shigui; Hadad, Christopher M; Badjić, Jovica D

    2013-11-28

    We designed and prepared a spacious and gated basket of type 2 (V = 318 Å(3)) in ten synthetic steps. With the assistance of (1)H NMR spectroscopy, we found that the pyridine gates at the rim of 2 form a seam of N-H∙∙∙N hydrogen bonds, thereby adopting right- (P) and left-handed (M) helical arrangements. The recognition characteristics of the smaller basket 1 (V = 226 Å(3)) and the larger 2 for various solvents as guests were quantified by (1)H NMR spectroscopy in CD2Cl2 (61 Å(3)), CDCl3 (75 Å(3)), CFCl3 (81 Å(3)) and CCl4 (89 Å(3)); the apparent guest binding equilibria Ka were found to be inversely proportional to the affinity of bulk solvents KS for populating each host. The rate of the P/M racemization (krac, s(-1)) was, for both 1 and 2, studied in all four solvents using dynamic NMR spectroscopy. From these experiments, two isokinetic relationships (ΔS++P/M vs. ΔH++P/M) were identified with each one corresponding to a different mechanism of P/M racemization. A computational study (B3LYP/6-31+G**//PM6) of 1 and 2 in the gas phase indicates two competing racemization pathways: (a) RM1-2 describes a pivoting of a single gate followed by the rotation of the remaining two gates, while (b) RM3 depicts simultaneous (geared) rotation of all three gates. The racemization of the larger basket 2, in all four solvents (packing coefficient, PC = 0.19-0.28), conformed to one isokinetic relationship, which also coincided with the operation of the smaller basket 1 in CD2Cl2 (PC = 0.27). However, in CDCl3, CFCl3 and CCl4 (PC = 0.33-0.39), the mode of action of 1 appears to correlate with a different isokinetic relationship. Thus, we propose that the population of the basket's inner space (PC) determines the mechanism of P/M racemization. When PC 0.3, enforces the geared RM3 mechanistic alternative.

  15. The application of Markov decision process with penalty function in restaurant delivery robot

    Science.gov (United States)

    Wang, Yong; Hu, Zhen; Wang, Ying

    2017-05-01

    As the restaurant delivery robot is often in a dynamic and complex environment, including the chairs inadvertently moved to the channel and customers coming and going. The traditional Markov decision process path planning algorithm is not save, the robot is very close to the table and chairs. To solve this problem, this paper proposes the Markov Decision Process with a penalty term called MDPPT path planning algorithm according to the traditional Markov decision process (MDP). For MDP, if the restaurant delivery robot bumps into an obstacle, the reward it receives is part of the current status reward. For the MDPPT, the reward it receives not only the part of the current status but also a negative constant term. Simulation results show that the MDPPT algorithm can plan a more secure path.

  16. Localized Delivery of Mechano-Growth Factor E-domain Peptide via Polymeric Microstructures Improves Cardiac Function following Myocardial Infarction

    Science.gov (United States)

    Peña, James R.; Pinney, James; Ayala, Perla; Desai, Tejal; Goldspink, Paul H.

    2015-01-01

    The Insulin like growth factor-I isoform mechano-growth factor (MGF), is expressed in the heart following myocardial infarction and encodes a unique E-domain region. To examine E-domain function, we delivered a synthetic peptide corresponding to the unique E-domain region of the human MGF (IGF-1Ec) via peptide eluting polymeric microstructures to the heart. The microstructures were made of poly (ethylene glycol) dimethacrylate hydrogel and bioengineered to be the same size as an adult cardiac myocyte (100×15×15 μm) and with a stiffness of 20 kPa. Peptide eluting microrods and empty microrods were delivered via intramuscular injection following coronary artery ligation in mice. To examine the physiologic consequences, we assessed the impact of peptide delivery on cardiac function and cardiovascular hemodynamics using pressure-volume loops and gene expression by quantitative RT-PCR. A significant decline in both systolic and diastolic function accompanied by pathologic hypertrophy occurred by 2 weeks which decompensated further by 10 weeks post-infarct in the untreated groups. Delivery of the E-domain peptide eluting microrods decreased mortality, ameliorated the decline in hemodynamics, and delayed decompensation. This was associated with the inhibition of pathologic hypertrophy despite increasing vascular impedance. Delivery of the empty microrods had limited effects on hemodynamics and while pathologic hypertrophy persisted there was a decrease in ventricular stiffness. Our data show that cardiac restricted administration of the MGF E-domain peptide using polymeric microstructures may be used to prevent adverse remodeling of the heart and improve function following myocardial infarction. PMID:25678113

  17. Development of a Prolonged-Release Drug Delivery System with Magnolol Loaded in Amino-Functionalized Mesoporous Silica

    Directory of Open Access Journals (Sweden)

    Alina Stefanache

    2017-03-01

    Full Text Available Magnolol (MG is a small-molecule neolignan polyphenolic compound isolated from the genus Magnolia. The anti-inflammatory, anti-oxidative, anti-diabetic, anti-tumorgenic, anti-neurodegenerative, anti-depressant and anti-microbial properties of MG are well documented in recent literature. These fascinating multiple biological activities of MG encourage research about the development of new delivery and administration approaches able to maximize its potential benefits. This study describes the amino-functionalization of the SBA-15 (Santa Barbara Amorphous mesoporous matrix by post-synthesis grafting using APTES (3-aminopropyltriethoxysilane and the characterization of amino-functionalized mesoporous silica SBA-15 loaded with MG in order to achieve modified drug delivery systems. The amino-functionalization of silica SBA-15 was carried out by grafting by refluxing in dry toluene. The powders obtained were characterized texturally by Brunauer-Emmett-Teller (BET surface area analysis measurements and morphologically by scanning electron microscopy. MG loading degree in the nanoporous matrix was determined by the HPLC method at λ = 290 nm. Results showed that by grafting the amino groups in the silica SBA-15, we obtained amino-functionalized silica SBA-15 with an ordered structure, with specific surfaces and pore sizes that differ from the original matrix, which was reflected in the amount of MG immobilized and release kinetics profile.

  18. Broad functional correction of molecular impairments by systemic delivery of scAAVrh74-hSGSH gene delivery in MPS IIIA mice.

    Science.gov (United States)

    Duncan, F Jason; Naughton, Bartholomew J; Zaraspe, Kimberly; Murrey, Darren A; Meadows, Aaron S; Clark, Kelly Reed; Newsom, David E; White, Peter; Fu, Haiyan; McCarty, Douglas M

    2015-04-01

    Mucopolysaccharidosis (MPS) IIIA is a neuropathic lysosomal storage disease caused by deficiency in N-sulfoglucosamine sulfohydrolase (SGSH). Genome-wide gene expression microarrays in MPS IIIA mice detected broad molecular abnormalities (greater than or equal to twofold, false discovery rate ≤10) in numerous transcripts (314) in the brain and blood (397). Importantly, 22 dysregulated blood transcripts are known to be enriched in the brain and linked to broad neuronal functions. To target the root cause, we used a self-complementary AAVrh74 vector to deliver the human SGSH gene into 4-6 weeks old MPS IIIA mice by an intravenous injection. The treatment resulted in global central nervous system (CNS) and widespread somatic restoration of SGSH activity, clearance of CNS and somatic glycosaminoglycan storage, improved behavior performance, and significantly extended survival. The scAAVrh74-hSGSH treatment also led to the correction of the majority of the transcriptional abnormalities in the brain (95.9%) and blood (97.7%), of which 182 and 290 transcripts were normalized in the brain and blood, respectively. These results demonstrate that a single systemic scAAVrh74-hSGSH delivery mediated efficient restoration of SGSH activity and resulted in a near complete correction of MPS IIIA molecular pathology. This study also demonstrates that blood transcriptional profiles reflect the biopathological status of MPS IIIA, and also respond well to effective treatments.

  19. Pengembangan Aplikasi Android Pada UKM Basket Universitas Diponegoro

    Directory of Open Access Journals (Sweden)

    Adrian Putranda Rispurwadi

    2016-04-01

    Full Text Available Until now, Diponegoro University has become one of the most favored State University for High School students to proceed their study. So far, there hasn’t been any information system for basketball student organization in Diponegoro University such as mobile device application that provides information, field location, and reminder for the basketball practice. Based on this concern, an application for the information system must be made on Android Operation System. Design of mobile information system for basketball student organization in Diponegoro University based android, a client server application created by using theJava, PHP, jQuery and MySQL for database. The intake of latitude and longitude coordinate will utilize the GPS feature on the mobile device and will be displayed on Google Maps API. JSON will collect the data of schedules into the mobile device, continued to recieve dialog alert and broadcast reciever for the alarm feature. The result of this design is realization of a application that able to search location of a basketball field based on android system, equipped with features that can help user to find the field and alarm to remind them of practice time. This design is also used to introduce android application developers using the Global Positioning System functions for user navigation.

  20. EpCAM aptamer-functionalized mesoporous silica nanoparticles for efficient colon cancer cell-targeted drug delivery.

    Science.gov (United States)

    Xie, Xiaodong; Li, Fengqiao; Zhang, Huijuan; Lu, Yusheng; Lian, Shu; Lin, Hang; Gao, Yu; Jia, Lee

    2016-02-15

    Targeted delivery of anticancer agents by functional nanoparticles is an attractive strategy to increase their therapeutic efficacy while reducing toxicity. In this work, doxorubicin (DOX)-loaded mesoporous silica nanoparticles (MSNs) were modified with aptamer (Ap) against the epithelial cell adhesion molecule (EpCAM) for targeted delivery of DOX to colon cancer cells. These nanoparticles (Ap-MSN-DOX) were characterized by particle size, zeta potential, aptamer conjugation efficiency, drug encapsulation efficiency, and drug release properties. The in vitro cell recognition, cellular uptake, EpCAM protein inhibition efficiency, and cytotoxicity of Ap-MSN-DOX were also studied. Results demonstrated that EpCAM conjugation increased binding of Ap-MSN-DOX to EpCAM over-expressing SW620 colon cancer cells but not EpCAM-negative Ramos cells, resulting in enhanced cellular uptake and increased cytotoxicity of the DOX in SW620 cells when compared to non-Ap-modified nanoparticles (MSN-DOX). Additionally, Ap-MSN-DOX exhibited significant inhibition effects on the expression of EpCAM on SW620 cells. These results suggested that Ap-MSN-DOX has the potential for the targeted delivery of therapeutic agents into EpCAM positive colon cancer cells to improve therapeutic index while reducing side effects.

  1. Functional Recovery of Human Cells Harbouring the Mitochondrial DNA Mutation MERRF A8344G via Peptide-Mediated Mitochondrial Delivery

    Directory of Open Access Journals (Sweden)

    Jui-Chih Chang

    2012-09-01

    Full Text Available We explored the feasibility of mitochondrial therapy using the cell-penetrating peptide Pep-1 to transfer mitochondrial DNA (mtDNA between cells and rescue a cybrid cell model of the mitochondrial disease myoclonic epilepsy with ragged-red fibres (MERRF syndrome. Pep-1-conjugated wild-type mitochondria isolated from parent cybrid cells incorporating a mitochondria-specific tag were used as donors for mitochondrial delivery into MERRF cybrid cells (MitoB2 and mtDNA-depleted Rho-zero cells (Mitoρ°. Forty-eight hours later, translocation of Pep-1-labelled mitochondria into the mitochondrial regions of MitoB2 and Mitoρ° host cells was observed (delivery efficiencies of 77.48 and 82.96%, respectively. These internalized mitochondria were maintained for at least 15 days in both cell types and were accompanied by mitochondrial function recovery and cell survival by preventing mitochondria-dependent cell death. Mitochondrial homeostasis analyses showed that peptide-mediated mitochondrial delivery (PMD also increased mitochondrial biogenesis in both cell types, but through distinct regulatory pathways involving mitochondrial dynamics. Dramatic decreases in mitofusin-2 (MFN2 and dynamin-related protein 1/fission 1 were observed in MitoB2 cells, while Mitoρ° cells showed a significant increase in optic atrophy 1 and MFN2. These findings suggest that PMD can be used as a potential therapeutic intervention for mitochondrial disorders.

  2. Transactivator of transcription (TAT) peptide- chitosan functionalized multiwalled carbon nanotubes as a potential drug delivery vehicle for cancer therapy.

    Science.gov (United States)

    Dong, Xia; Liu, Lanxia; Zhu, Dunwan; Zhang, Hailing; Leng, Xigang

    2015-01-01

    Carbon nanotube (CNT)-based drug delivery vehicles might find great potential in cancer therapy via the combination of chemotherapy with photothermal therapy due to the strong optical absorbance of CNTs in the near-infrared region. However, the application of CNTs in cancer therapy was considerably constrained by their lack of solubility in aqueous medium, as well as the cytotoxicity caused by their hydrophobic surface. Intracellular delivery efficiency is another factor determining the application potential of CNTs in cancer therapy. In the present study, low-molecular-weight chitosan conjugated with transactivator of transcription (TAT) peptide was used for noncovalent functionalization of multiwalled carbon nanotubes (MWCNTs), aiming at providing a more efficient drug delivery vehicle for cancer therapy. The TAT-chitosan-conjugated MWCNTs (MWCNTs-TC) were further investigated for their water solubility, cytotoxicity, cell-penetrating capability, and accumulation in tumor. It was found that MWCNTs-TC were essentially nontoxic with satisfying water solubility, and they were more efficient in terms of cancer-targeted intracellular transport both in vitro and in vivo as compared with chitosan-modified MWCNTs (MWCNTs-CS), suggesting the great application potential of MWCNTs-TC in cancer therapy.

  3. Controlled delivery of SDF-1α and IGF-1: CXCR4(+) cell recruitment and functional skeletal muscle recovery.

    Science.gov (United States)

    Rybalko, Viktoriya Y; Pham, Chantal B; Hsieh, Pei-Ling; Hammers, David W; Merscham-Banda, Melissa; Suggs, Laura J; Farrar, Roger P

    2015-11-01

    Therapeutic delivery of regeneration-promoting biological factors directly to the site of injury has demonstrated its efficacy in various injury models. Several reports describe improved tissue regeneration following local injection of tissue specific growth factors, cytokines and chemokines. Evidence exists that combined cytokine/growth factor treatment is superior for optimizing tissue repair by targeting different aspects of the regeneration response. The purpose of this study was to evaluate the therapeutic potential of the controlled delivery of stromal cell-derived factor-1alpha (SDF-1α) alone or in combination with insulin-like growth factor-I (SDF-1α/IGF-I) for the treatment of tourniquet-induced ischemia/reperfusion injury (TK-I/R) of skeletal muscle. We hypothesized that SDF-1α will promote sustained stem cell recruitment to the site of muscle injury, while IGF-I will induce progenitor cell differentiation to effectively restore muscle contractile function after TK-I/R injury while concurrently reducing apoptosis. Utilizing a novel poly-ethylene glycol PEGylated fibrin gel matrix (PEG-Fib), we incorporated SDF-1α alone (PEG-Fib/SDF-1α) or in combination with IGF-I (PEG-Fib/SDF-1α/IGF-I) for controlled release at the site of acute muscle injury. Despite enhanced cell recruitment and revascularization of the regenerating muscle after SDF-1α treatment, functional analysis showed no benefit from PEG-Fib/SDF-1α therapy, while dual delivery of PEG-Fib/SDF-1α/IGF-I resulted in IGF-I-mediated improvement of maximal force recovery and SDF-1α-driven in vivo neovasculogenesis. Histological data supported functional data, as well as highlighted the important differences in the regeneration process among treatment groups. This study provides evidence that while revascularization may be necessary for maximizing muscle force recovery, without modulation of other effects of inflammation it is insufficient.

  4. Rapid Synthesis of a Lipocationic Polyester Library via Ring-Opening Polymerization of Functional Valerolactones for Efficacious siRNA Delivery.

    Science.gov (United States)

    Hao, Jing; Kos, Petra; Zhou, Kejin; Miller, Jason B; Xue, Lian; Yan, Yunfeng; Xiong, Hu; Elkassih, Sussana; Siegwart, Daniel J

    2015-07-29

    The ability to control chemical functionality is an exciting feature of modern polymer science that enables precise design of drug delivery systems. Ring-opening polymerization of functional monomers has emerged as a versatile method to prepare clinically translatable degradable polyesters.1 A variety of functional groups have been introduced into lactones; however, the direct polymerization of tertiary amine functionalized cyclic esters has remained elusive. We report a strategy that enabled the rapid synthesis of >130 lipocationic polyesters directly from functional monomers without protecting groups. These polymers are highly effective for siRNA delivery at low doses in vitro and in vivo.

  5. Delivery of Functionality in Complex Food Systems: Physically Inspired Approaches from Nanoscale to Microscale, Wageningen 18-21 October 2009.

    Science.gov (United States)

    van der Linden, Erik; Ubbink, Job; Duchateau, Guus

    2010-12-01

    The Wageningen Delivery of Functionality symposium covered all aspects involved with food structural design to arrive at high-quality foods which meet demanding customer expectations and regulatory requirements. The symposium integrated aspects from the structural organization of foods at molecular and supramolecular scales to dedicated techniques required to describe and visualize such structures, the gastro-intestinal events and how to model these in a laboratory setting, and finally the impact those food structures and ingredients have on the consumer's physiology and on the human perception. As an interdisciplinary platform, bringing together more than 160 researchers from academia and industry, the symposium meanwhile fulfills an important role in the food science community.

  6. From Neuron Biophysics to Orientation Selectivity in Electrically Coupled Networks of Neocortical L2/3 Large Basket Cells.

    Science.gov (United States)

    Amsalem, Oren; Van Geit, Werner; Muller, Eilif; Markram, Henry; Segev, Idan

    2016-08-01

    In the neocortex, inhibitory interneurons of the same subtype are electrically coupled with each other via dendritic gap junctions (GJs). The impact of multiple GJs on the biophysical properties of interneurons and thus on their input processing is unclear. The present experimentally based theoretical study examined GJs in L2/3 large basket cells (L2/3 LBCs) with 3 goals in mind: (1) To evaluate the errors due to GJs in estimating the cable properties of individual L2/3 LBCs and suggest ways to correct these errors when modeling these cells and the networks they form; (2) to bracket the GJ conductance value (0.05-0.25 nS) and membrane resistivity (10 000-40 000 Ω cm(2)) of L2/3 LBCs; these estimates are tightly constrained by in vitro input resistance (131 ± 18.5 MΩ) and the coupling coefficient (1-3.5%) of these cells; and (3) to explore the functional implications of GJs, and show that GJs: (i) dynamically modulate the effective time window for synaptic integration; (ii) improve the axon's capability to encode rapid changes in synaptic inputs; and (iii) reduce the orientation selectivity, linearity index, and phase difference of L2/3 LBCs. Our study provides new insights into the role of GJs and calls for caution when using in vitro measurements for modeling electrically coupled neuronal networks.

  7. Non-operative residual biliary stone extraction by using steerable catheter and basket

    Energy Technology Data Exchange (ETDEWEB)

    Kim, K. W.; Chang, J. C.; Park, C. Y. [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1983-06-15

    Nonoperative residual biliary stone removal through the T-tube sinus tract was performed in 9 patients by using steerable catheter and basket under fluoroscopic guidance and the result was satisfactory. There is no significant complication or morbidity. We concluded that this method is 1. easy of performance, highly successful and of no demonstrable risk. 2. can be performed without any medication and in our patient department. 3. the method of choice of treatment in post-op residual biliary stone with T-tube.

  8. Use of Linear Programming to Develop Cost-Minimized Nutritionally Adequate Health Promoting Food Baskets

    DEFF Research Database (Denmark)

    Parlesak, A.; Tetens, Inge; Dejgård Jensen, Jørgen

    2016-01-01

    programming. The FBs were defined using five different constraints: cultural acceptability (CA), or dietary guidelines (DG), or nutrient recommendations (N), or cultural acceptability and nutrient recommendations (CAN), or dietary guidelines and nutrient recommendations (DGN). The variety and number of foods...... variety of foods contained from 70 (CAN) to 134 (DGN) foods and cost between DKK 60 (€ 8.1, N) and DKK 125 (€ 16.8, DGN). Ensuring that the food baskets cover both dietary guidelines and nutrient recommendations doubled the cost while cultural acceptability (CAN) tripled it. Use of linear programming...

  9. Spices as a source of lead exposure: a market-basket survey in Sri Lanka.

    Science.gov (United States)

    Senanayake, M P; Perera, R; Liyanaarachchi, L A; Dassanayake, M P

    2013-12-01

    We performed a laboratory analysis of spices sold in Sri Lanka for lead content. Samples of curry powder, chili powder and turmeric powder from seven provinces, collected using the market basket survey method, underwent atomic absorption spectrometry. Blanks and standards were utilised for instrument calibration and measurement accuracy. The results were validated in two different laboratories. All samples were found to have lead levels below the US Food and Drug Administration's action level of 0.5 μg/g. Spices sold in Sri Lanka contain lead concentrations that are low and within the stipulated safety standards.

  10. Magnetic nanoparticles with dual functional properties: drug delivery and magnetic resonance imaging.

    Science.gov (United States)

    Jain, Tapan K; Richey, John; Strand, Michelle; Leslie-Pelecky, Diandra L; Flask, Chris A; Labhasetwar, Vinod

    2008-10-01

    There is significant interest in recent years in developing magnetic nanoparticles (MNPs) having multifunctional characteristics with complimentary roles. In this study, we investigated the drug delivery and magnetic resonance imaging (MRI) properties of our novel oleic acid-coated iron-oxide and pluronic-stabilized MNPs. The drug incorporation efficiency of doxorubicin and paclitaxel (alone or in combination) in MNPs was 74-95%; the drug release was sustained and the incorporated drugs had marginal effects on physical (size and zeta potential) and magnetization properties of the MNPs. The drugs in combination incorporated in MNPs demonstrated highly synergistic antiproliferative activity in MCF-7 breast cancer cells. The T2 relaxivity (r(2)) was higher for our MNPs than Feridex IV, whereas the T1 relaxivity (r(1)) was better for Feridex IV than for our MNPs, suggesting greater sensitivity of our MNPs than Feridex IV in T2 weighted imaging. The circulation half-life (t(1/2)), determined from the changes in the MRI signal intensity in carotid arteries in mice, was longer for our MNPs than Feridex IV (t(1/2)=31.2 vs. 6.4 min). MNPs with combined characteristics of MRI and drug delivery could be of high clinical significance in the treatment of various disease conditions.

  11. Bleomycin Loaded Magnetite Nanoparticles Functionalized by Polyacrylic Acid as a New Antitumoral Drug Delivery System

    Directory of Open Access Journals (Sweden)

    Yue Xu

    2013-01-01

    Full Text Available Objective. To prepare, characterize, and analyze the release behavior of bleomycin-loaded magnetite nanoparticles (BLM-MNPs coated with polyacrylic acid (PAA as a new drug delivery system that can be specifically distributed in the tumor site. Methods. BLM-MNPs coated with PAA were prepared using a solvothermal approach. The particles were characterized using scanning electron microscope (SEM, vibrating sample magnetometer (VSM, and Fourier transform infrared spectroscopy (FTIR. The loading and release behaviors of BLM-MNPs were examined by a mathematical formula and in vitro release profile at pH 7.5. Results. The sphere Fe3O4 nanoparticles with the size of approximately 30 nm exhibit a saturation magnetization of 87 emu/g. The noncoordinated carboxylate groups of PAA confer on the good dispersibility in the aqueous solution and lead to a good loading efficiency of BLM reaching 50% or higher. Approximately 98% of immobilized BLM could be released within 24 h, of which 22.4% was released in the first hour and then the remaining was released slowly and quantitatively in the next 23 hours. Conclusion. BLM-MNPs were prepared and characterized successfully. The particles show high saturation magnetization, high drug loading capacity, and favorable release property, which could contribute to the specific delivery and controllable release of BLM, and the BLM-MNPs could be a potential candidate for the development of treating solid tumors.

  12. Covalent functionalization of graphene oxide with biocompatible poly(ethylene glycol) for delivery of paclitaxel.

    Science.gov (United States)

    Xu, Zhiyuan; Wang, Song; Li, Yongjun; Wang, Mingwei; Shi, Ping; Huang, Xiaoyu

    2014-10-08

    Graphene oxide (GO), a novel 2D nanomaterial prepared by the oxidation of natural graphite, has been paid much attention in the area of drug delivery due to good biocompatibility and low toxicity. In the present work, 6-armed poly(ethylene glycol) was covalently introduced into the surface of GO sheets via a facile amidation process under mild conditions, making the modified GO, GO-PEG (PEG: 65 wt %, size: 50-200 nm), stable and biocompatible in physiological solution. This nanosized GO-PEG was found to be nontoxic to human lung cancer A549 and human breast cancer MCF-7 cells via cell viability assay. Furthermore, paclitaxel (PTX), a widely used cancer chemotherapy drug, was conjugated onto GO-PEG via π-π stacking and hydrophobic interactions to afford a nanocomplex of GO-PEG/PTX with a relatively high loading capacity for PTX (11.2 wt %). This complex could quickly enter into A549 and MCF-7 cells evidenced by inverted fluorescence microscopy using Fluorescein isothiocyanate as a probe, and it also showed remarkably high cytotoxicity to A549 and MCF-7 cells in a broad range of concentration of PTX and time compared to free PTX. This kind of nanoscale drug delivery system on the basis of PEGylated GO may find potential application in biomedicine.

  13. Cysteine-Functionalized Nanostructured Lipid Carriers for Oral Delivery of Docetaxel: A Permeability and Pharmacokinetic Study.

    Science.gov (United States)

    Fang, Guihua; Tang, Bo; Chao, Yanhui; Xu, Helin; Gou, Jingxin; Zhang, Yu; Xu, Hui; Tang, Xing

    2015-07-06

    Here we report the development and evaluation of cysteine-modified nanostructured lipid carriers (NLCs) for oral delivery of docetaxel (DTX). The NLCs ensure high encapsulation efficiency of docetaxel, while the cysteine bound the NLCs with PEG2000-monostearate (PEG2000-MSA) as a linker, and allowed a specific interaction with mucin of the intestinal mucus layer and facilitated the intestinal transport of docetaxel. The cysteine-modified NLCs (cNLCs) had a small particle size (cysteine group on the surface of the NLCs obtained by X-ray photoelectron spectroscopy (XPS). The cNLCs significantly improved the mucoadhesion properties compared with uNLCs. The intestinal absorption of cNLCs in total intestinal segments was greatly improved in comparison with uNLCs and docetaxel solution (DTX-Sol), and the in vivo imaging system captured pictures also showed not only increased intestinal absorption but also improved accumulation in blood. The cNLCs could be absorbed into the enterocytes via both endocytosis and passive transport. The results of the in vivo pharmacokinetic study indicated that the AUC0-t of cNLCs (1533.00 ng/mL·h) was markedly increased 12.3-fold, and 1.64-fold compared with docetaxel solution and uNLCs, respectively. Overall, the cysteine modification makes nanostructured lipid carriers more suitable as nanocarriers for oral delivery of docetaxel.

  14. Microencapsulated foods as a functional delivery vehicle for omega-3 fatty acids: a pilot study

    Directory of Open Access Journals (Sweden)

    David Robert M

    2009-05-01

    Full Text Available Abstract It is well established that the ingestion of the omega-3 (N3 fatty acids docosahexaenoic acid (DHA and eicosapentaenoic acid (EPA positively benefit a variety of health indices. Despite these benefits the actual intake of fish derived N3 is relatively small in the United States. The primary aim of our study was to examine a technology capable of delivering omega-3 fatty acids in common foods via microencapsulation (MicroN3 in young, healthy, active participants who are at low risk for cardiovascular disease. Accordingly, we randomized 20 participants (25.4 ± 6.2 y; 73.4 ± 5.1 kg to receive the double blind delivery of a placebo-matched breakfast meal (~2093 kJ containing MicroN3 (450–550 mg EPA/DHA during a 2-week pilot trial. Overall, we observed no differences in overall dietary macronutrient intake other than the N3 delivery during our treatment regimen. Post-test ANOVA analysis showed a significant elevation in mean (SE plasma DHA (91.18 ± 9.3 vs. 125.58 ± 11.3 umol/L; P

  15. Functional study of p38 mitogen-activated protein kinase based on cell-penetrating peptide delivery system

    Institute of Scientific and Technical Information of China (English)

    Liping Yang; Yongming Yao; Zhiyong Sheng; Xiaomei Zhu; Yong Jiang

    2009-01-01

    Objective p38 Mitogen-activated protein kinase (MAPK) is a crossing center of various pathways. In this study, protein transduction system based on human immunodeficiency virus (HIV)-1 transactivator of transcription (TAT), which is an efficient delivery peptide of the foreign proteins into cells, was employed to study p38 MAPK functions in eukaryotic cells. Methods p38 And its dominant negative form, p38AF, were constructed into pET-His-TAT vector correctly to verify that the recombinant plasmids were well-founded through restriction enzyme digestion and DNA sequencing. The two proteins, His-TAT-p38 and His-TAT-p38AF, were expressed and purified in Escherichia coli by SDS-PAGE. Then they were incubated with ECV304 cells respectively and readily transduced into cells in a time-dependent and dose-dependent manner. The cells were stimulated by sorbitol. Activating transcription factor (ATF) 2 phosphorylation level was checked using Western blot to assess the activity of endogenous p38. Results Compared with controls, it was found that His-TAT-p38 increased the level ofATF2 phosphorylation in sorbitol-stimulated ECV304 cells, while His-TAT-p38AF inhibited it, indicating p38 MAPK protein delivery system based on TAT was constructed successfully. TAT-p38 and its dominant negative form possessed high biological activity after transduction into ECV304 cells by TAT protein delivery system. The results showed that p38AF fused with TAT could inhibit the transduction of endogenous p38 signal pathway in part, and other pathway might regulate p38 phosphorylation. Conclusions Our study provides a novel pathway to inhibit p38 signal pathway and establish a new method to study p38 function.

  16. Dendritic cells control CD4+CD25+ Treg cell suppressor function in vitro through juxtacrine delivery of IL-2.

    Directory of Open Access Journals (Sweden)

    Katarina Kulhankova

    Full Text Available CD4(+CD25(+Foxp3(+ regulatory T cells (Tregs restrict inflammatory responses to self and nonself. Aberrant Treg activity is pathologic: Insufficient Treg activity is implicated in autoimmunity, allergy, and graft-versus-host-disease; overabundant activity is implicated in chronic infection and cancer. Tregs require IL-2 for their expansion and acquisition/execution of suppressor function; however, because Tregs cannot produce IL-2, they depend on IL-2 from an exogenous source. Until now, that IL-2 source had not been established. We asked whether dendritic cells (DCs could supply IL-2 to Tregs and, if so, what was required for that delivery. We used flow cytometry, IL-2 ELISPOT, RT-qPCR, and IL-2 promoter-driven reporter assays to measure intracytoplasmic IL-2, secreted protein, IL-2 message and IL-2 promoter activity in bone marrow-derived (BMDC and splenic DCs. We examined conjugate formation between Tregs, conventional CD4(+ cells, and IL-2-expressing DCs. We measured Treg levels of CD25, Foxp3, and suppressor function after co-culture with IL-2 sufficient and IL-2(-/- DCs. We generated IL-2-mCherry-expressing DCs and used epifluorescence microscopy and flow cytometry to track IL-2 transfer to Tregs and test requirements for transfer. Between 0.7 to 2.4% of DCs constitutively produced IL-2 and diverted IL-2 secretion to Tregs by preferentially forming conjugates with them. Uptake of DC IL-2 by Tregs required cell-cell contact and CD25. Tregs increased levels of CD25 and Foxp3 from baseline and showed greater suppressor function when co-cultured with IL-2-sufficient DCs, but not when co-cultured with IL-2(-/- DCs. Exogenous IL-2, added in excess of 500 U/ml to co-cultures with IL-2(-/- DCs, restored Treg suppressor function. These data support a model of juxtacrine delivery of IL-2 from DCs to Tregs and suggest that a subset of DCs modulates Treg function through controlled, spatial delivery of IL-2. Knowledge of how DCs regulate Tregs should

  17. Localized and Sustained Delivery of Erythropoietin from PLGA Microspheres Promotes Functional Recovery and Nerve Regeneration in Peripheral Nerve Injury

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2015-01-01

    Full Text Available Erythropoietin (EPO has been demonstrated to exert neuroprotective effects on peripheral nerve injury recovery. Though daily intraperitoneal injection of EPO during a long period of time was effective, it was a tedious procedure. In addition, only limited amount of EPO could reach the injury sites by general administration, and free EPO is easily degraded in vivo. In this study, we encapsulated EPO in poly(lactide-co-glycolide (PLGA microspheres. Both in vitro and in vivo release assays showed that the EPO-PLGA microspheres allowed sustained release of EPO within a period of two weeks. After administration of such EPO-PLGA microspheres, the peripheral nerve injured rats had significantly better recovery compared with those which received daily intraperitoneal injection of EPO, empty PLGA microspheres, or saline treatments. This was supported by the functional, electrophysiological, and histological evaluations of the recovery done at week 8 postoperatively. We conclude that sustained delivery of EPO could be achieved by using EPO-PLGA microspheres, and such delivery method could further enhance the recovery function of EPO in nerve injury recovery.

  18. Localized and sustained delivery of erythropoietin from PLGA microspheres promotes functional recovery and nerve regeneration in peripheral nerve injury.

    Science.gov (United States)

    Zhang, Wei; Gao, Yuan; Zhou, Yan; Liu, Jianheng; Zhang, Licheng; Long, Anhua; Zhang, Lihai; Tang, Peifu

    2015-01-01

    Erythropoietin (EPO) has been demonstrated to exert neuroprotective effects on peripheral nerve injury recovery. Though daily intraperitoneal injection of EPO during a long period of time was effective, it was a tedious procedure. In addition, only limited amount of EPO could reach the injury sites by general administration, and free EPO is easily degraded in vivo. In this study, we encapsulated EPO in poly(lactide-co-glycolide) (PLGA) microspheres. Both in vitro and in vivo release assays showed that the EPO-PLGA microspheres allowed sustained release of EPO within a period of two weeks. After administration of such EPO-PLGA microspheres, the peripheral nerve injured rats had significantly better recovery compared with those which received daily intraperitoneal injection of EPO, empty PLGA microspheres, or saline treatments. This was supported by the functional, electrophysiological, and histological evaluations of the recovery done at week 8 postoperatively. We conclude that sustained delivery of EPO could be achieved by using EPO-PLGA microspheres, and such delivery method could further enhance the recovery function of EPO in nerve injury recovery.

  19. Mucoadhesive Amphiphilic Methacrylic Copolymer-Functionalized Poly(ε-caprolactone) Nanocapsules for Nose-to-Brain Delivery of Olanzapine.

    Science.gov (United States)

    Fonseca, Francisco N; Betti, Andresa H; Carvalho, Flávia C; Gremião, Maria P D; Dimer, Frantiescoli A; Guterres, Sílvia S; Tebaldi, Marli L; Rates, Stela M K; Pohlmann, Adriana R

    2015-08-01

    Nose-to-brain drug delivery has been proposed to overcome the low absorption of drugs in central nervous system due to the absence of brain-blood barrier in the olfactory nerve pathway. However, the presence of a mucus layer and quick clearance limit the use of this route. Herein, amphiphilic methacrylic copolymer-functionalized poly(ε-caprolactone) nanocapsules were proposed as a mucoadhesive system to deliver olanzapine after intranasal administration. In vitro evaluations showed that these nanocapsules were able to interact with mucin (up to 17% of increment in particle size and 30% of reduction of particle concentration) and nasal mucosa (2-fold higher force for detaching), as well as to increase the retention of olanzapine (about 40%) on the nasal mucosa after continuous wash. The olanzapine-loaded amphiphilic methacrylic copolymer-functionalized PCL nanocapsules enhanced the amount of drug in the brain of rats (1.5-fold higher compared to the drug solution). In accordance with this finding, this formulation improved the prepulse inhibition impairment induced by apomorphine, which is considered as an operational measure of pre-attentive sensorimotor gating impairment present in schizophrenia. Besides, nanoencapsulated olanzapine did not affect the nasal mucosa integrity after repeated doses. These data evidenced that the designed nanocapsules are a promising mucoadhesive system for nose-to-brain delivery of drugs.

  20. Monitoring the Affordability of Healthy Eating: A Case Study of 10 Years of the Illawarra Healthy Food Basket

    Directory of Open Access Journals (Sweden)

    Peter Williams

    2010-11-01

    Full Text Available Healthy food baskets have been used around the world for a variety of purposes, including: examining the difference in cost between healthy and unhealthy food; mapping the availability of healthy foods in different locations; calculating the minimum cost of an adequate diet for social policy planning; developing educational material on low cost eating and examining trends on food costs over time. In Australia, the Illawarra Healthy Food Basket was developed in 2000 to monitor trends in the affordability of healthy food compared to average weekly wages and social welfare benefits for the unemployed. It consists of 57 items selected to meet the nutritional requirements of a reference family of five. Bi-annual costing from 2000–2009 has shown that the basket costs have increased by 38.4% in the 10-year period, but that affordability has remained relatively constant at around 30% of average household incomes.

  1. Engineered red blood cells as carriers for systemic delivery of a wide array of functional probes.

    Science.gov (United States)

    Shi, Jiahai; Kundrat, Lenka; Pishesha, Novalia; Bilate, Angelina; Theile, Chris; Maruyama, Takeshi; Dougan, Stephanie K; Ploegh, Hidde L; Lodish, Harvey F

    2014-07-15

    We developed modified RBCs to serve as carriers for systemic delivery of a wide array of payloads. These RBCs contain modified proteins on their plasma membrane, which can be labeled in a sortase-catalyzed reaction under native conditions without inflicting damage to the target membrane or cell. Sortase accommodates a wide range of natural and synthetic payloads that allow modification of RBCs with substituents that cannot be encoded genetically. As proof of principle, we demonstrate site-specific conjugation of biotin to in vitro-differentiated mouse erythroblasts as well as to mature mouse RBCs. Thus modified, RBCs remain in the bloodstream for up to 28 d. A single domain antibody attached enzymatically to RBCs enables them to bind specifically to target cells that express the antibody target. We extend these experiments to human RBCs and demonstrate efficient sortase-mediated labeling of in vitro-differentiated human reticulocytes.

  2. Oral colon delivery of insulin with the aid of functional adjuvants.

    Science.gov (United States)

    Maroni, Alessandra; Zema, Lucia; Del Curto, Maria Dorly; Foppoli, Anastasia; Gazzaniga, Andrea

    2012-05-01

    Oral colon delivery is currently considered of importance not only for the treatment of local pathologies, such as primarily inflammatory bowel disease (IBD), but also as a means of accomplishing systemic therapeutic goals. Although the large bowel fails to be ideally suited for absorption processes, it may indeed offer a number of advantages over the small intestine, including a long transit time, lower levels of peptidases and higher responsiveness to permeation enhancers. Accordingly, it has been under extensive investigation as a possible strategy to improve the oral bioavailability of peptide and protein drugs. Because of a strong underlying rationale, most of these studies have focused on insulin. In the present review, the impact of key anatomical and physiological characteristics of the colon on its viability as a protein release site is discussed. Moreover, the main formulation approaches to oral colon targeting are outlined along with the design features and performance of insulin-based devices.

  3. Supramolecular assemblies of alkane functionalized poly ethylene glycol copolymer for drug delivery

    Science.gov (United States)

    Zhu, Lida

    The therapeutic effects of many modern drugs were limited owing to their physical properties and half-life in the blood stream. The purpose of this research is to study the relationship between drug delivery performances and chemical properties of the polymer micelle drug carriers. Polyethylene glycol (PEG) based alternating copolymer poly[(polyoxyethylene)-oxy-5-hydroxyisophthalic] (Ppeg) with PEG molecular weights of 600 and 1000 were synthesized and modified with different alkanes to study the effects of altering the hydrophobic and hydrophilic chain lengths. The nuclear magnetic resonance (NMR) spectrum, critical micelle concentration (CMC), micelle size, and micelle zeta potential of the synthesized polymers were measured. The resulting polymer particles were able to form micelles in aqueous solution with CMCs lower than 0.04 wt%. Drug delivery studies were performed with a model hydrophobic drug, pyrene. Drug loading data showed the polymer particles were able to encapsulate pyrene and has a loading capacity up to 8 wt%. The sustain release ability was measured and the pyrene release was extended over 5 days. Both loading capacity and sustain release ability were found to be highly dependent on CMC. Cell culture study was implemented with RAW 264.7 cells in order to determine the polymer micelle's cytocompatibility, Most Ppeg polymer micelles showed more than 85% cell viability with and without pyrene loading. Cell internalization of the micelles encapsulated drug was measured both quantitatively and qualitatively and was enhanced comparing to unencapsulated drug. The results indicated that the internalization enhancement effect of polymer micelle was mainly affected by hydrophilic chain length; neither hydrophobic chain length nor loading capacity has significant influence on internalization.

  4. Anisotropic noble metal nanoparticles: Synthesis, surface functionalization and applications in biosensing, bioimaging, drug delivery and theranostics.

    Science.gov (United States)

    Paramasivam, Gokul; Kayambu, Namitharan; Rabel, Arul Maximus; Sundramoorthy, Ashok K; Sundaramurthy, Anandhakumar

    2017-02-01

    Anisotropic nanoparticles have fascinated scientists and engineering communities for over a century because of their unique physical and chemical properties. In recent years, continuous advances in design and fabrication of anisotropic nanoparticles have opened new avenues for application in various areas of biology, chemistry and physics. Anisotropic nanoparticles have the plasmon absorption in the visible as well as near-infrared (NIR) region, which enables them to be used for crucial applications such as biological imaging, medical diagnostics and therapy ("theranostics"). Here, we describe the progress in anisotropic nanoparticles achieved since the millennium in the area of preparation including various shapes and modification of the particle surface, and in areas of application by providing examples of applications in biosensing, bio-imaging, drug delivery and theranostics. Furthermore, we also explain various mechanisms involved in cellular uptake of anisotropic nanoparticles, and conclude with our opinion on various obstacles that limit their applications in biomedical field. Anisotropy at the molecular level has always fascinated scientists and engineering communities for over a century, however, the research on novel methods through which shape and size of nanoparticles can be precisely controlled has opened new avenues for anisotropic nanoparticles in various areas of biology, chemistry and physics. In this manuscript, we describe progress achieved since the millennium in the areas of preparation of various shapes of anisotropic nanoparticles, investigate various methods involved in modifying the surface of these NPs, and provide examples of applications in biosensing and bio-imaging, drug delivery and theranostics. We also present mechanisms involved in cellular uptake of nanoparticles, describe different methods of preparation of anisotropic nanoparticles including biomimetic and photochemical synthesis, and conclude with our opinion on various

  5. The NIFS protein can function as a selenide delivery protein in the biosynthesis of selenophosphate.

    Science.gov (United States)

    Lacourciere, G M; Stadtman, T C

    1998-11-20

    The NIFS protein from Azobacter vinelandii is a pyridoxal phosphate-containing homodimer that catalyzes the formation of equimolar amounts of elemental sulfur and L-alanine from the substrate L-cysteine (Zheng, L., White, R. H., Cash, V. L., Jack, R. F., and Dean, D. R. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 2754-2758). A sulfur transfer role of NIFS in which the enzyme donates sulfur for iron sulfur center formation in nitrogenase was suggested. The fact that NIFS also can catalyze the decomposition of L-selenocysteine to elemental selenium and L-alanine suggested the possibility that this enzyme might serve as a selenide delivery protein for the in vitro biosynthesis of selenophosphate. In agreement with this hypothesis, we have shown that replacement of selenide with NIFS and L-selenocysteine in the in vitro selenophosphate synthetase assay results in an increased rate of formation of selenophosphate. These results thus support the view that a selenocysteine-specific enzyme similar to NIFS may be involved as an in vivo selenide delivery protein for selenophosphate biosynthesis. A kinetic characterization of the two NIFS catalyzed reactions carried out in the present study indicates that the enzyme favors L-cysteine as a substrate compared with its selenium analog. A specific activity for L-cysteine of 142 nmol/min/mg compared with 55 nmol/min/mg for L-selenocysteine was determined. This level of enzyme activity on the selenoamino acid substrate is adequate to deliver selenium to selenophosphate synthetase in the in vitro assay system described.

  6. Basket-Type Catheters: Diagnostic Pitfalls Caused by Deformation and Limited Coverage

    Directory of Open Access Journals (Sweden)

    Tobias Oesterlein

    2016-01-01

    Full Text Available Whole-chamber mapping using a 64-pole basket catheter (BC has become a featured approach for the analysis of excitation patterns during atrial fibrillation. A flexible catheter design avoids perforation but may lead to spline bunching and influence coverage. We aim to quantify the catheter deformation and endocardial coverage in clinical situations and study the effect of catheter size and electrode arrangement using an in silico basket model. Atrial coverage and spline separation were evaluated quantitatively in an ensemble of clinical measurements. A computational model of the BC was implemented including an algorithm to adapt its shape to the atrial anatomy. Two clinically relevant mapping positions in each atrium were assessed in both clinical and simulated data. The simulation environment allowed varying both BC size and electrode arrangement. Results showed that interspline distances of more than 20 mm are common, leading to a coverage of less than 50% of the left atrial (LA surface. In an ideal in silico scenario with variable catheter designs, a maximum coverage of 65% could be reached. As spline bunching and insufficient coverage can hardly be avoided, this has to be taken into account for interpretation of excitation patterns and development of new panoramic mapping techniques.

  7. Nucleoporins as components of the nuclear pore complex core structure and Tpr as the architectural element of the nuclear basket.

    Science.gov (United States)

    Krull, Sandra; Thyberg, Johan; Björkroth, Birgitta; Rackwitz, Hans-Richard; Cordes, Volker C

    2004-09-01

    The vertebrate nuclear pore complex (NPC) is a macromolecular assembly of protein subcomplexes forming a structure of eightfold radial symmetry. The NPC core consists of globular subunits sandwiched between two coaxial ring-like structures of which the ring facing the nuclear interior is capped by a fibrous structure called the nuclear basket. By postembedding immunoelectron microscopy, we have mapped the positions of several human NPC proteins relative to the NPC core and its associated basket, including Nup93, Nup96, Nup98, Nup107, Nup153, Nup205, and the coiled coil-dominated 267-kDa protein Tpr. To further assess their contributions to NPC and basket architecture, the genes encoding Nup93, Nup96, Nup107, and Nup205 were posttranscriptionally silenced by RNA interference (RNAi) in HeLa cells, complementing recent RNAi experiments on Nup153 and Tpr. We show that Nup96 and Nup107 are core elements of the NPC proper that are essential for NPC assembly and docking of Nup153 and Tpr to the NPC. Nup93 and Nup205 are other NPC core elements that are important for long-term maintenance of NPCs but initially dispensable for the anchoring of Nup153 and Tpr. Immunogold-labeling for Nup98 also results in preferential labeling of NPC core regions, whereas Nup153 is shown to bind via its amino-terminal domain to the nuclear coaxial ring linking the NPC core structures and Tpr. The position of Tpr in turn is shown to coincide with that of the nuclear basket, with different Tpr protein domains corresponding to distinct basket segments. We propose a model in which Tpr constitutes the central architectural element that forms the scaffold of the nuclear basket.

  8. Pulmonary vein isolation using the Rhythmia mapping system: Verification of intracardiac signals using the Orion mini-basket catheter.

    Science.gov (United States)

    Anter, Elad; Tschabrunn, Cory M; Contreras-Valdes, Fernando M; Li, Jianqing; Josephson, Mark E

    2015-09-01

    During pulmonary vein isolation (PVI), a circular lasso catheter is positioned at the junction between the left atrium (LA) and the pulmonary vein (PV) to confirm PVI. The Rhythmia mapping system uses the Orion mini-basket catheter with 64 electrodes instead of the lasso catheter. However, its feasibility to determine PVI has not been studied. The purpose of this study was to compare signals between the mini-basket and lasso catheters at the LA-PV junction. In 12 patients undergoing PVI using Rhythmia, the mini-basket and lasso catheters were placed simultaneously at the LA-PV junction for baseline and post-PVI signal assessment. Pacing from both catheters was performed to examine the presence of exit block. At baseline, recordings of LA and PV potentials were concordant in all PVs. However, after PVI, concordance between the catheters was only 68%. Discordance in all cases resulted from loss of PV potentials on the lasso catheter with persistence of PV potentials on the mini-basket catheter. In 9 of 13 PVs (69%), these potentials represented true PV potentials that were exclusively recorded with the smaller and closely spaced mini-basket electrodes. In the other 4 PVs (31%), these potentials originated from neighboring structures and resulted in underestimation of PVI. The use of the mini-basket catheter alone is sufficient to determine PVI. While it improves recording of PV potentials after incomplete ablation, it is also associated with frequent recording of "PV-like" potentials originating from neighboring structures. In these cases, pacing maneuvers are helpful to determine PVI and avoid excessive ablation. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  9. α, ω-Cholesterol-functionalized low molecular weight polyethylene glycol as a novel modifier of cationic liposomes for gene delivery.

    Science.gov (United States)

    Ma, Cui-Cui; He, Zhi-Yao; Xia, Shan; Ren, Ke; Hui, Li-Wei; Qin, Han-Xiao; Tang, Ming-Hai; Zeng, Jun; Song, Xiang-Rong

    2014-11-06

    Here, three novel cholesterol (Ch)/low molecular weight polyethylene glycol (PEG) conjugates, termed α, ω-cholesterol-functionalized PEG (Ch2-PEGn), were successfully synthesized using three kinds of PEG with different average molecular weight (PEG600, PEG1000 and PEG2000). The purpose of the study was to investigate the potential application of novel cationic liposomes (Ch2-PEGn-CLs) containing Ch2-PEGn in gene delivery. The introduction of Ch2-PEGn affected both the particle size and zeta potential of cationic liposomes. Ch2-PEG2000 effectively compressed liposomal particles and Ch2-PEG2000-CLs were of the smallest size. Ch2-PEG1000 and Ch2-PEG2000 significantly decreased zeta potentials of Ch2-PEGn-CLs, while Ch2-PEG600 did not alter the zeta potential due to the short PEG chain. Moreover, the in vitro gene transfection efficiencies mediated by different Ch2-PEGn-CLs also differed, in which Ch2-PEG600-CLs achieved the strongest GFP expression than Ch2-PEG1000-CLs and Ch2-PEG2000-CLs in SKOV-3 cells. The gene delivery efficacy of Ch2-PEGn-CLs was further examined by addition of a targeting moiety (folate ligand) in both folate-receptor (FR) overexpressing SKOV-3 cells and A549 cells with low expression of FR. For Ch2-PEG1000-CLs and Ch2-PEG2000-CLs, higher molar ratios of folate ligand resulted in enhanced transfection efficacies, but Ch2-PEG600-CLs had no similar in contrast. Additionally, MTT assay proved the reduced cytotoxicities of cationic liposomes after modification by Ch2-PEGn. These findings provide important insights into the effects of Ch2-PEGn on cationic liposomes for delivering genes, which would be beneficial for the development of Ch2-PEGn-CLs-based gene delivery system.

  10. Cationic poly(ɛ-caprolactone) surface functionalized mesoporous silica nanoparticles and their application in drug delivery

    Science.gov (United States)

    Zhang, Yan; Wang, Zhaojun; Zhou, Weimin; Min, Guoquan; Lang, Meidong

    2013-07-01

    Cationic poly(ɛ-caprolactone) modified hollow mesoporous silica (HMSNs) was achieved by a post graft method via covalent linkage between the silanols on the surface of silica and the trimethoxysilane groups at the end of the poly(γ-(carbamic acid benzyl ester)-ɛ-caprolactone). The trimethoxysilane groups were introduced to poly(γ-(carbamic acid benzyl ester)-ɛ-caprolactone) by ring opening polymerization of γ-(carbamic acid benzyl ester)-ɛ-caprolactone (γCABɛCL) with 3-aminopropyl trimethoxysilane as initiator. Subsequently, the polymer was grafted to the HMSNs and the protected groups of Cbz were removed, thus the amino groups were obtained accordingly. The structure of the polymer was confirmed by 1H NMR. In addition, the TEM and SEM demonstrated that the HMSNs were spherical and the polymer was well coated on the spheres. FTIR, TGA and N2 adsorption results proved that the modified processes were effective and the structure of the HMSNs was well reserved. The cationic surface was further confirmed by zeta potential. Moreover, the potential application of the HMSNs in drug delivery was studied with ammonium glycyrrhizinate (AMG) as model drug. Results showed that the cationic HMSNs could be an efficient AMG carrier.

  11. Expression, Delivery and Function of Insecticidal Proteins Expressed by Recombinant Baculoviruses

    Directory of Open Access Journals (Sweden)

    Jeremy A. Kroemer

    2015-01-01

    Full Text Available Since the development of methods for inserting and expressing genes in baculoviruses, a line of research has focused on developing recombinant baculoviruses that express insecticidal peptides and proteins. These recombinant viruses have been engineered with the goal of improving their pesticidal potential by shortening the time required for infection to kill or incapacitate insect pests and reducing the quantity of crop damage as a consequence. A wide variety of neurotoxic peptides, proteins that regulate insect physiology, degradative enzymes, and other potentially insecticidal proteins have been evaluated for their capacity to reduce the survival time of baculovirus-infected lepidopteran host larvae. Researchers have investigated the factors involved in the efficient expression and delivery of baculovirus-encoded insecticidal peptides and proteins, with much effort dedicated to identifying ideal promoters for driving transcription and signal peptides that mediate secretion of the expressed target protein. Other factors, particularly translational efficiency of transcripts derived from recombinant insecticidal genes and post-translational folding and processing of insecticidal proteins, remain relatively unexplored. The discovery of RNA interference as a gene-specific regulation mechanism offers a new approach for improvement of baculovirus biopesticidal efficacy through genetic modification.

  12. A new targeted delivery approach by functionalizing drug nanocrystals through polydopamine coating.

    Science.gov (United States)

    Zhan, Honglei; Jagtiani, Tina; Liang, Jun F

    2017-05-01

    Tumor target specificity via chemotherapy is widely considered to be very effective on tumor treatment. For an ideal chemotherapeutic agent like Camptothecin (CPT) (CPT is the abbreviation for Camptothecin), improved therapeutic efficacy and high selectivity are equally important. Inspired by adhesive proteins in mussels, here we developed a novel tumor targeting peptide XQ1 grafted CPT nanocrystals with polydopamine coating as a spacer. In this study, CPT nanocrystals were coated by polymerization of dopamine that was induced by plasma-activated water under an acidic environment, and then the tumor targeting peptide was grafted onto polydopamine (PDA) (PDA is the abbreviation for polydopamine) coated CPT nanocrystals through catechol chemistry. The PDA layer had negligible effects on drug crystallinity and structure but resulted in drug nanocrystals with excellent dispersion properties, improved dissolution rate and drug stability by preventing water hydrolysis. More importantly, tumor targeting peptide XQ1 facilitated a rapid cross-membrane translocation of drug nanocrystals via receptor-mediated endocytosis, leading to efficient intracellular drug delivery. Moreover, this novel drug formulation demonstrated more potent anti-cancer activity against tumor cells in comparison with free CPT and naked CPT nanocrystals and exhibited high selectivity, all of which are attributed to the tumor target specificity property and inherent pH-dependent drug release behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Structural characterization of functionalized gold nanoparticles for drug delivery in cancer therapy: a NMR based approach.

    Science.gov (United States)

    Coelho, Sílvia C; Rangel, Maria; Pereira, Maria C; Coelho, Manuel A N; Ivanova, Galya

    2015-07-15

    In the present paper, we report results from a study of the structure and physicochemical properties of gold nanoparticles modified with poly(ethylene glycol) (PEG) designed for the drug delivery of the proteasome inhibitor Bortezomib (BTZ) in cancer therapy. A number of advanced analytical techniques were used to define important physicochemical characteristics such as composition, structure, surface properties, particle size and morphology. A new approach based on detailed NMR studies was employed to define specific intermolecular interactions and mechanisms of drug immobilization and location into surface modified gold nanoparticles (AuNPs). Particularly important information was gained from analysis of NMR spectroscopic parameters such as the spectral line shape, translation diffusion, the nuclear Overhauser effect (NOE) and spin-lattice relaxation (T1). The results confirmed the coexistence of two different types of BTZ inclusion into polyethylene glycol coated gold nanoparticles: (i) association with the polymer chains by weak H-bonds and/or dipole-charge interactions and (ii) adsorption on the surface of the gold nanoparticles. The results allowed for determination of the overall structure of Bortezomib loaded PEG coated AuNPs, which is related to the therapeutic drug efficacy and activity in the treatment of cancer.

  14. Differential surface density and modulatory effects of presynaptic GABAB receptors in hippocampal cholecystokinin and parvalbumin basket cells.

    Science.gov (United States)

    Booker, Sam A; Althof, Daniel; Degro, Claudius E; Watanabe, Masahiko; Kulik, Ákos; Vida, Imre

    2017-05-02

    The perisomatic domain of cortical neurons is under the control of two major GABAergic inhibitory interneuron types: regular-spiking cholecystokinin (CCK) basket cells (BCs) and fast-spiking parvalbumin (PV) BCs. CCK and PV BCs are different not only in their intrinsic physiological, anatomical and molecular characteristics, but also in their presynaptic modulation of their synaptic output. Most GABAergic terminals are known to contain GABAB receptors (GABABR), but their role in presynaptic inhibition and surface expression have not been comparatively characterized in the two BC types. To address this, we performed whole-cell recordings from CCK and PV BCs and postsynaptic pyramidal cells (PCs), as well as freeze-fracture replica-based quantitative immunogold electron microscopy of their synapses in the rat hippocampal CA1 area. Our results demonstrate that while both CCK and PV BCs contain functional presynaptic GABABRs, their modulatory effects and relative abundance are markedly different at these two synapses: GABA release is dramatically inhibited by the agonist baclofen at CCK BC synapses, whereas a moderate reduction in inhibitory transmission is observed at PV BC synapses. Furthermore, GABABR activation has divergent effects on synaptic dynamics: paired-pulse depression (PPD) is enhanced at CCK BC synapses, but abolished at PV BC synapses. Consistent with the quantitative differences in presynaptic inhibition, virtually all CCK BC terminals were found to contain GABABRs at high densities, but only 40% of PV BC axon terminals contain GABABRs at detectable levels. These findings add to an increasing list of differences between these two interneuron types, with implications for their network functions.

  15. Robust aptamer–polydopamine-functionalized M-PLGA–TPGS nanoparticles for targeted delivery of docetaxel and enhanced cervical cancer therapy

    Science.gov (United States)

    Xu, Guojun; Yu, Xinghua; Zhang, Jinxie; Sheng, Yingchao; Liu, Gan; Tao, Wei; Mei, Lin

    2016-01-01

    One limitation of current biodegradable polymeric nanoparticles (NPs) is the contradiction between functional modification and maintaining formerly excellent bioproperties with simple procedures. Here, we reported a robust aptamer–polydopamine-functionalized mannitol-functionalized poly(lactide-co-glycolide) (M-PLGA)–D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoformulation (Apt-pD-NPs) for the delivery of docetaxel (DTX) with enhanced cervical cancer therapy effects. The novel DTX-loaded Apt-pD-NPs possess satisfactory advantages: 1) increased drug loading content and encapsulation efficiency induced by star-shaped copolymer M-PLGA–TPGS; 2) significant active targeting effect caused by conjugated AS1411 aptamers; and 3) excellent long-term compatibility by incorporation of TPGS. Therefore, with simple preparation procedures and excellent bioproperties, the new functionalized Apt-pD-NPs could maximally increase the local effective drug concentration on tumor sites, achieving enhanced treatment effectiveness and minimizing side effects. In a word, the robust DTX-loaded Apt-pD-NPs could be used as potential nanotherapeutics for cervical cancer treatment, and the aptamer–polydopamine modification strategy could be a promising method for active targeting of cancer therapy with simple procedures. PMID:27382282

  16. Robust aptamer-polydopamine-functionalized M-PLGA-TPGS nanoparticles for targeted delivery of docetaxel and enhanced cervical cancer therapy.

    Science.gov (United States)

    Xu, Guojun; Yu, Xinghua; Zhang, Jinxie; Sheng, Yingchao; Liu, Gan; Tao, Wei; Mei, Lin

    2016-01-01

    One limitation of current biodegradable polymeric nanoparticles (NPs) is the contradiction between functional modification and maintaining formerly excellent bioproperties with simple procedures. Here, we reported a robust aptamer-polydopamine-functionalized mannitol-functionalized poly(lactide-co-glycolide) (M-PLGA)-D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoformulation (Apt-pD-NPs) for the delivery of docetaxel (DTX) with enhanced cervical cancer therapy effects. The novel DTX-loaded Apt-pD-NPs possess satisfactory advantages: 1) increased drug loading content and encapsulation efficiency induced by star-shaped copolymer M-PLGA-TPGS; 2) significant active targeting effect caused by conjugated AS1411 aptamers; and 3) excellent long-term compatibility by incorporation of TPGS. Therefore, with simple preparation procedures and excellent bioproperties, the new functionalized Apt-pD-NPs could maximally increase the local effective drug concentration on tumor sites, achieving enhanced treatment effectiveness and minimizing side effects. In a word, the robust DTX-loaded Apt-pD-NPs could be used as potential nanotherapeutics for cervical cancer treatment, and the aptamer-polydopamine modification strategy could be a promising method for active targeting of cancer therapy with simple procedures.

  17. Amine functionalized cubic mesoporous silica nanoparticles as an oral delivery system for curcumin bioavailability enhancement

    Science.gov (United States)

    Budi Hartono, Sandy; Hadisoewignyo, Lannie; Yang, Yanan; Meka, Anand Kumar; Antaresti; Yu, Chengzhong

    2016-12-01

    In the present work, a simple method was used to develop composite curcumin-amine functionalized mesoporous silica nanoparticles (MSN). The nanoparticles were used to improve the bioavailability of curcumin in mice through oral administration. We investigated the effect of particle size on the release profile, solubility and oral bioavailability of curcumin in mice, including amine functionalized mesoporous silica micron-sized-particles (MSM) and MSN (100-200 nm). Curcumin loaded within amine functionalized MSN (MSN-A-Cur) had a better release profile and a higher solubility compared to amine MSM (MSM-A-Cur). The bioavailability of MSN-A-Cur and MSM-A-Cur was considerably higher than that of ‘free curcumin’. These results indicate promising features of amine functionalized MSN as a carrier to deliver low solubility drugs with improved bioavailability via the oral route.

  18. The RMB and "A Basket of Currencies" Exchange Rates Fluctuation——Nonlinear Fourier Function Analysis%人民币对“一篮子货币”汇率的波动——非线性Fourier函数分析

    Institute of Scientific and Technical Information of China (English)

    安烨; 张国兵

    2012-01-01

    This paper analyzed the relationship of RMB and USA dollar and non-usa dollars(Euro、Japan yen)exchange rates use nonlinear Fourier function method since July,2005.Co-integration test analysis indicated RMB and Usa dollar、Euro、Japan yen exchange rates have cointegration relationship and nonlinear characters;VECM indicated the size of short term RMB and Euro、Japan yen exchange rate adjust to the long equilibrium exchange rates is bigger than RMB and Usa dollar exchange rate,and the processes of adjustment between RMB and Usa dollar、Euro have nonlinear fluctuation characters;IRF indicated the inflation in China promoted RMB appreciation toward Usa dollar and Japan yen,and slow down RMB appreciation toward Euro.%本文采用非线性Fourier函数方法分析了2005年7月份以来,人民币对美元及非美元货币(欧元、日元)汇率之间的关系。协整检验分析结果显示,人民币对美元、欧元、日元汇率与物价水平之间存在协整关系,且具有非线性特征;向量误差修正模型分析结果显示,短期内人民币对欧元、日元汇率向长期均衡汇率调整值大于人民币对美元汇率的调整值,且人民币对美元、欧元汇率的短期调整具有非线性波动特征;脉冲响应函数分析结果显示,中国物价水平升高,推动了人民币对美元、日元升值,但减缓了人民币对欧元升值。

  19. Development of biocompatible and functional polymeric nanoparticles for site-specific delivery of radionuclides

    Directory of Open Access Journals (Sweden)

    Nicolas eLepareur

    2015-09-01

    Full Text Available Introduction: Encapsulation of biologically active molecules into nanoparticles (NPs, for sitespecific delivery, is a fast growing area. These NPs must be biocompatible, non-toxic, and ableto release their load in a controlled way. We have developed a series of NPs based on (biodegradable and biocompatible poly(malic acid derivatives, poly(benzyl malate (PMLABe, with its PEG-grafted stealth analogue and target-specific biotin-PEG-b-PMLABe one. A lipophilic radiotracer has then been encapsulated into these NPs.Methods: Monomers were synthesized from DL-aspartic acid. PEG42-b-PMLABe73 and Biot-PEG66-b-PMLABe73 block copolymers were obtained by anionic ring-opening polymerization of benzyl malolactonate in presence of -methoxy--carboxy-PEG42 and -biotin--carboxy-PEG66 as initiators. NPs were prepared by nanoprecipitation. Size, polydispersity and zeta potential were measured by DLS and zetametry. 99mTc-SSS was prepared as previously described. Encapsulation efficacy was assessed varying different parameters, such as encapsulation with preformed NPs or during their formation, influence of the solvent, and of the method to prepare the NPs. After decay, 99mTc-loaded NPs were also analyzed by DLS and zetametry. NPs’ morphology was assessed by TEM.Results: 99mTc-SSS was added during nanoprecipitation, using two different methods, to ensure good encapsulation. Radiolabeled NPs present increased diameters, with identical low polydispersity indexes and negative zeta potentials in comparison to non-radiolabeled NPs. Conclusion: A radiotracer was successfully encapsulated, but some further optimization are still needed. Next step will be to modify these radiolabeled NPs with an hepatotrope peptide, and to replace 99mTc with 188Re for therapy. Our team is also working on drugs’ encapsulation and grafting of a fluorescent probe. Combining these modalities is of interest for combined chemo-/radiotherapy, bimodal imaging and/or theranostic

  20. Parvalbumin-expressing basket-cell network plasticity induced by experience regulates adult learning.

    Science.gov (United States)

    Donato, Flavio; Rompani, Santiago Belluco; Caroni, Pico

    2013-12-12

    Learning and memory processes can be influenced by recent experience, but the mechanisms involved are poorly understood. Enhanced plasticity during critical periods of early life is linked to differentiating parvalbumin (PV)-interneuron networks, suggesting that recent experience may modulate learning by targeting the differentiation state of PV neurons in the adult. Here we show that environmental enrichment and Pavlovian contextual fear conditioning induce opposite, sustained and reversible hippocampal PV-network configurations in adult mice. Specifically, enrichment promotes the emergence of large fractions of low-differentiation (low PV and GAD67 expression) basket cells with low excitatory-to-inhibitory synaptic-density ratios, whereas fear conditioning leads to large fractions of high-differentiation (high PV and GAD67 expression) basket cells with high excitatory-to-inhibitory synaptic-density ratios. Pharmacogenetic inhibition or activation of PV neurons was sufficient to induce such opposite low-PV-network or high-PV-network configurations, respectively. The low-PV-network configuration enhanced structural synaptic plasticity, and memory consolidation and retrieval, whereas these were reduced by the high-PV-network configuration. We then show that maze navigation learning induces a hippocampal low-PV-network configuration paralleled by enhanced memory and structural synaptic plasticity throughout training, followed by a shift to a high-PV-network configuration after learning completion. The shift to a low-PV-network configuration specifically involved increased vasoactive intestinal polypeptide (VIP)-positive GABAergic boutons and synaptic transmission onto PV neurons. Closely comparable low- and high-PV-network configurations involving VIP boutons were specifically induced in primary motor cortex upon rotarod motor learning. These results uncover a network plasticity mechanism induced after learning through VIP-PV microcircuit modulation, and involving

  1. pH-responsive drug delivery system based on AIE luminogen functionalized layered zirconium phosphate nano-platelets

    Science.gov (United States)

    Li, Dongdong; Zhang, Yuping; Zhou, Bingbing

    2015-05-01

    Aggregation-induced emission (AIE) luminogen, quaternary tetraphenylethene cation (TPEN), was successfully incorporated into layered α-zirconium phosphate (α-ZrP) by using co-precipitation method to form inorganic-organic hybrid materials. The obtained materials show the characteristic hexagonal platelet shape with the interlayer distance did not reveal significant difference compared with pure α-ZrP. In addition, the obtained hybrid materials emit strong blue emission centered at 476 nm in aqueous media due to the electrostatic interactions of TPEN with the anionic framework of α-ZrP, which largely restrict their intramolecular rotation. More importantly, the materials provide a pH dependent release of doxorubicin (DOX), suggesting that AIE luminogen functionalized α-ZrP may be used as an imaging guided and pH-responsive delivery system for targeting therapy.

  2. Aptamer-Functionalized and Backbone Redox-Responsive Hyperbranched Polymer for Targeted Drug Delivery in Cancer Therapy.

    Science.gov (United States)

    Zhuang, Yuanyuan; Deng, Hongping; Su, Yue; He, Lin; Wang, Ruibin; Tong, Gangsheng; He, Dannong; Zhu, Xinyuan

    2016-06-13

    A novel type of backbone redox-responsive hyperbranched poly(2-((2-(acryloyloxy)ethyl)disulfanyl)ethyl 4-cyano-4-(((propylthio)carbonothioyl)-thio)-pentanoate-co-poly(ethylene glycol) methacrylate) (HPAEG) has been designed and prepared successfully via the combination of reversible addition-fragmentation chain-transfer (RAFT) polymerization and self-condensing vinyl polymerization (SCVP). Owing to the existence of surface vinyl groups, HPAEG could be efficiently functionalized by DNA aptamer AS1411 via Michael addition reaction to obtain an active tumor targeting drug delivery carrier (HPAEG-AS1411). The amphiphilic HPAEG-AS1411 could form nanoparticles by macromolecular self-assembly strategy. Cell Counting Kit-8 (CCK-8) assay illustrated that HPAEG-AS1411 nanoparticles had low cytotoxicity to normal cell line. Flow cytometry and confocal laser scanning microscopy (CLSM) results demonstrated that HPAEG-AS1411 nanoparticles could be internalized into tumor cells via aptamer-mediated endocytosis. Compared with pure HPAEG nanoparticles, HPAEG-AS1411 nanoparticles displayed enhanced tumor cell uptake. When the HPAEG-AS1411 nanoparticles loaded with anticancer drug doxorubicin (DOX) were internalized into tumor cells, the disulfide bonds in the backbone of HPAEG-AS1411 were cleaved by glutathione (GSH) in the cytoplasm, so that DOX was released rapidly. Therefore, DOX-loaded HPAEG-AS1411 nanoparticles exhibited a high tumor cellular proliferation inhibition rate and low cytotoxicity to normal cells. This aptamer-functionalized and backbone redox-responsive hyperbranched polymer provides a promising platform for targeted drug delivery in cancer therapy.

  3. Modulation by K+ channels of action potential-evoked intracellular Ca2+ concentration rises in rat cerebellar basket cell axons.

    Science.gov (United States)

    Tan, Y P; Llano, I

    1999-10-01

    1. Action potential-evoked [Ca2+]i rises in basket cell axons of rat cerebellar slices were studied using two-photon laser scanning microscopy and whole-cell recording, to identify the K+ channels controlling the shape of the axonal action potential. 2. Whole-cell recordings of Purkinje cell IPSCs were used to screen K+ channel subtypes which could contribute to axonal repolarization. alpha-Dendrotoxin, 4-aminopyridine, charybdotoxin and tetraethylammonium chloride increased IPSC rate and/or amplitude, whereas iberiotoxin and apamin failed to affect the IPSCs. 3. The effects of those K+ channel blockers that enhanced transmitter release on the [Ca2+]i rises elicited in basket cell axons by action potentials fell into three groups: 4-aminopyridine strongly increased action potential-evoked [Ca2+]i; tetraethylammonium and charybdotoxin were ineffective alone but augmented the effects of 4-aminopyridine; alpha-dendrotoxin had no effect. 4. We conclude that cerebellar basket cells contain at least three pharmacologically distinct K+ channels, which regulate transmitter release through different mechanisms. 4-Aminopyridine-sensitive, alpha-dendrotoxin-insensitive K+ channels are mainly responsible for repolarization in basket cell presynaptic terminals. K+ channels blocked by charybdotoxin and tetraethylammonium have a minor role in repolarization. alpha-Dendrotoxin-sensitive channels are not involved in shaping the axonal action potential waveform. The two last types of channels must therefore exert control of synaptic activity through a pathway unrelated to axonal action potential broadening.

  4. Novel method to achieve price-optimized, fully nutritious, health-promoting and acceptable national food baskets

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Robertson, Aileen

    2015-01-01

    Purpose: The purpose of this study was to generate a framework for the development of health-promoting, fully nutritious, socially acceptable, and affordable national food baskets to be used as an advocacy tool by governments. In addition to containing all (micro-)nutrient requirements, food bask....... Fully nutritious and health-promoting food baskets can be achieved at a relatively low price. However if these are not socially acceptable to the target population, the use of a framework using linear programming based solely on nutritional values seems limited.......Purpose: The purpose of this study was to generate a framework for the development of health-promoting, fully nutritious, socially acceptable, and affordable national food baskets to be used as an advocacy tool by governments. In addition to containing all (micro-)nutrient requirements, food...... baskets should also reflect dietary guidelines to prevent non-communicable diseases and be optimized to achieve the highest possible social acceptance. So far, integrative approaches that include all these aspects are lacking. Methods: Food composition, local availability, food prices, national...

  5. Collocherides astroboae n. gen., n. sp., a siphonostome cyclopoid copepod living in the stomach of basket stars

    NARCIS (Netherlands)

    Stock, Jan H.

    1971-01-01

    The new genus Collocherides, which is created for the reception of C. astroboae n. sp., is closely related to Collocheres. Whereas the species of Collocheres all are, as far as we know, ectoparasites of echinoderms, Collocherides was found endoparasitic in basket stars (Astroboa nuda, A. albatrossi)

  6. AVIS DES ARBITRES DE BASKET-BALL DE SEPT PAYS EUROPÉENS SUR LEUR ÉVALUATION PHYSIQUE

    OpenAIRE

    Van Hoye, Martin; Cloes, Marc

    2014-01-01

    Le test Léger est-il adapté aux efforts fournis par les arbitres de basket-ball au cours d'une rencontre ? Quels sont les avis des arbitres à ce niveau ? Quels tests plus adaptés pourraient être réalisés ?

  7. What Was in That Basket: The Choices Authors Make. (Part One of a Three-Part Series).

    Science.gov (United States)

    Ohanian, Susan

    1997-01-01

    Discusses the many different versions of "Little Red Riding Hood" and the extended classroom discussions they provoked, especially about what foodstuffs were in her basket. States that teachers should encourage their students to read in different ways at different times in their lives. Includes questions for stimulating student response.…

  8. Improving transport service delivery in the Capricorn district municipality by strengthening ITS transport function

    CSIR Research Space (South Africa)

    Mashiri, M

    2010-08-01

    Full Text Available society’s socio-economic needs with a view to permanently transforming the quality of life of all citizens (Cameron, 2005). Transportation is one such critical socio-economic need – crucial because it is integral to society’s functioning... consist only of councillors of the participating municipalities and which acts on behalf of the TA. • Options for the performance of the technical and administrative functions of the TA, and • Financial arrangements. 227 For Cameron (2005), it also...

  9. OH-functionalization strategy in Metal-Organic Frameworks for drug delivery

    Science.gov (United States)

    Kotzabasaki, Marianna; Tylianakis, Emmanuel; Klontzas, Emmanuel; Froudakis, George E.

    2017-10-01

    With the goal in mind of developing new and much-improved drug anchoring regimes, we strategically modified the organic linker of IRMOF-16 by introducing hydroxyl groups. In this way, we improved the interaction energy of the anticancer drug gemcitabine with the nano-carrier by 40% compared to the unmodified one. Moreover, our simulations revealed high drug loading capacity in the OH-functionalized-IRMOF-16 (4343 mg/g), outperforming other drug storage materials. Drug release profiles, obtained via Grand Canonical Monte Carlo simulations, confirmed slower drug release in the case of the OH-functionalized IRMOF.

  10. Solid lipid nanoparticles as a vehicle for brain-targeted drug delivery: two new strategies of functionalization with apolipoprotein E

    Science.gov (United States)

    Rute Neves, Ana; Fontes Queiroz, Joana; Weksler, Babette; Romero, Ignacio A.; Couraud, Pierre-Olivier; Reis, Salette

    2015-12-01

    Nanotechnology can be an important tool to improve the permeability of some drugs for the blood-brain barrier. In this work we created a new system to enter the brain by functionalizing solid lipid nanoparticles with apolipoprotein E, aiming to enhance their binding to low-density lipoprotein receptors on the blood-brain barrier endothelial cells. Solid lipid nanoparticles were successfully functionalized with apolipoprotein E using two distinct strategies that took advantage of the strong interaction between biotin and avidin. Transmission electron microscopy images revealed spherical nanoparticles, and dynamic light scattering gave a Z-average under 200 nm, a polydispersity index below 0.2, and a zeta potential between -10 mV and -15 mV. The functionalization of solid lipid nanoparticles with apolipoprotein E was demonstrated by infrared spectroscopy and fluorimetric assays. In vitro cytotoxic effects were evaluated by MTT and LDH assays in the human cerebral microvascular endothelial cells (hCMEC/D3) cell line, a human blood-brain barrier model, and revealed no toxicity up to 1.5 mg ml-1 over 4 h of incubation. The brain permeability was evaluated in transwell devices with hCMEC/D3 monolayers, and a 1.5-fold increment in barrier transit was verified for functionalized nanoparticles when compared with non-functionalized ones. The results suggested that these novel apolipoprotein E-functionalized nanoparticles resulted in dynamic stable systems capable of being used for an improved and specialized brain delivery of drugs through the blood-brain barrier.

  11. PENGGUNAAN METODE FUZZY c-COVERING UNTUK ANALISA MARKET BASKET PADA SUPERMARKET

    Directory of Open Access Journals (Sweden)

    Gregorius Satia Budhi

    2005-01-01

    Full Text Available Data mining application with fuzzy c-covering method for market basket analysis on supermarket. As one of data mining applications, market basket analysis is generally performed using apriori method. However this method tends to searh the association degree of items by only counting how many times the items appears on the overall transaction without considering the items quantity on each transaction. Therefore, we propose a new method which is based on perception that the more items bought in a transaction, the weaker the relation between items on that transaction. For the experimental purpose of the realization the concept, we collect a month sales transaction data from a supermarket. The data are transformed to another form that can be used by the software. Then, an algorithm is created to process the data in order to generate association rule of items in transaction. The rules can be previewed in a table or graphic. Borland Ceplhi 7 and MS Access 2003 is used to build this experiment software. By using the output of this software, which are the association rules, association degree of items, can be obtained which is useful to help the decision maker to make market policies. Based on the testing result, it can concluded that the smaller minimum support and confidence, the more rule to be generated and the more processing time needed. Also, the higher the combination count to be searched, the less processing time needed. Abstract in Bahasa Indonesia : Sebagai salah satu aplikasi data mining, market basket analysis umumnya dilakukan dengan memakai metode Apriori. Metode ini mencari asosiasi antar item dengan hanya menghitung berapa kali item-item tersebut muncul dalam keseluruhan transaksi tanpa memperhatikan quantitas item dalam transaksi. Oleh karena itu, peneliti mengusulkan metode Fuzzy c-Covering. Metode ini didasarkan pada persepsi bahwa semakin banyak item yang dibeli dalam suatu transaksi, maka hubungan antar item dalam transaksi

  12. The basket trainer: A homemade laparoscopic trainer attainable to every resident

    Directory of Open Access Journals (Sweden)

    Jaber Nidal

    2010-01-01

    Full Text Available Laparoscopic trainers have been proved to be effective to improve skills of laparoscopic surgery; they are usually installed at hospital in the surgical department with limited access hours, usually inconvenient to the schedule of the resident. Simple trainer boxes are necessary for residents who desire developing their skills at home independently to the venue and hours of surgical departments. Our goal is to bring the laparoscopic trainer to the desktop of the surgical resident by making it very cheap, small, light, secure and easy to construct. We describe a model of laparoscopic trainer using steel basket which, we believe, meets all of the above-mentioned requirements. It is accessible to any personal budget and can be constructed with a minimum of hand skill. It is small and light enough to permit its daily use on the desktop of the resident for a couple of hours, then after it can be stocked in any locker.

  13. CLUSTER ANALYSIS UNTUK MEMPREDIKSI TALENTA PEMAIN BASKET MENGGUNAKAN JARINGAN SARAF TIRUAN SELF ORGANIZING MAPS (SOM

    Directory of Open Access Journals (Sweden)

    Gregorius Satia Budhi

    2008-01-01

    Full Text Available Basketball World has grown rapidly as the time goes on. This is signed by many competition and game all over the world. With the result there are many basketball players with their different playing characteristics. Demand for a coach or scout to look for or search great players to make a solid team as a coach requirement. With this application, a coach or scout will be helped in analyzing in decision making. This application uses Self Organizing Maps algorithm (SOM for Cluster Analysis. The real NBA player data is used for competitive learning or training process and real player data from Indonesian or Petra Christian University Basketball Players is used for testing process. The NBA Player data is prepared through cleaning process and then is transformed into a form that can be processed by SOM Algorithm. After that, the data is clustered with the SOM algorithm. The result of that clusters is displayed into a form that is easy to view and analyze. This result can be saved into a text file. By using the output / result of this application, that are the clusters of NBA player, the user can see the statistics of each cluster. With these cluster statistics coach or scout can predict the statistic and the position of a testing player who is in the same cluster. This information can give a support for the coach or scout to make a decision. Abstract in Bahasa Indonesia : Dunia bola basket telah berkembang dengan pesat seiring dengan berjalannya waktu. Hal ini ditandai dengan munculnya berbagai macam dan jenis kompetisi dan pertandingan baik dunia maupun dalam negeri. Sehingga makin banyak dilahirkannya pemain berbakat dengan berbagai karakteristik permainan yang berbeda. Tuntutan bagi seorang pelatih/pemandu bakat, untuk dapat melihat secara jeli dalam memenuhi kebutuhan tim untuk membentuk tim yang solid. Dengan dibuatnya aplikasi ini, maka akan membantu proses analisis dan pengambilan keputusan bagi pelatih maupun pemandu bakat Aplikasi ini

  14. Solar drying of West Indian ginger (Zingiber officinale Roscoe) rhizome using a wire basket dryer

    Energy Technology Data Exchange (ETDEWEB)

    Balladin, D.A.; Headley, O. [University of the West Indies (Barbados). Dept. of Chemistry; Chang Yen, I. [University of the West Indies, St. Augustine (Trinidad and Tobago). Dept. of Chemistry; McGaw, D.R. [University of the West Indies, St. Augustine (Trinidad and Tobago). Dept. of Chemical Engineering

    1996-09-01

    A wire basket dryer (1.8 m x 0.9 m x 0.2 m) was used to dry sliced (0.15 cm) West Indian ginger (Zingiber officinale Roscoe) rhizome to an acceptable moisture content of 10.2% (dry weight basis) over a 3 day period. The optimum charge size was 14.97 kg, with a packing density of 462.04 kg m{sup -3} and a specific drying rate of 0.446 h{sup -1}. The quantities (determined by high-pressure liquid chromatography) of the main pungent principles (ginerol and shogaol) extracted from fresh, non-steam-distilled solar-dried and steam-distilled solar-dried ginger rhizomes showed increases of 0.068, 0.46 and 0.67 g [per 100 g (dry weight basis)], respectively, with a decrease in the oleoresin quality (reflected in pungency profile) of the same order. (author)

  15. Perforinopathy: a spectrum of human immune disease caused by defective perforin delivery or function.

    Science.gov (United States)

    Voskoboinik, Ilia; Trapani, Joseph A

    2013-12-12

    Congenital perforin deficiency is considered a rare cause of human immunopathology and immune dysregulation, and classically presents as a fatal illness early in infancy. However, we propose that a group of related disorders in which killer lymphocytes deliver only partially active perforin or a reduced quantum of wild-type perforin to the immune synapse should be considered part of an extended syndrome with overlapping but more variable clinical features. Apart from the many rare mutations scattered over the coding sequences, up to 10% of Caucasians carry the severely hypomorphic PRF1 allele C272 > T (leading to A91V mutation) and the overall prevalence of the homozygous state for A91V is around 1 in 600 individuals. We therefore postulate that the partial loss of perforin function and its clinical consequences may be more common then currently suspected. An acute clinical presentation is infrequent in A91V heterozygous individuals, but we postulate that the partial loss of perforin function may potentially be manifested in childhood or early adulthood as "idiopathic" inflammatory disease, or through increased cancer susceptibility - either hematological malignancy or multiple, independent primary cancers. We suggest the new term "perforinopathy" to signify the common functional endpoints of all the known consequences of perforin deficiency and failure to deliver fully functional perforin.

  16. Perforinopathy: a spectrum of human immune disease caused by defective perforin delivery or function

    Directory of Open Access Journals (Sweden)

    Joseph A. Trapani

    2013-12-01

    Full Text Available Congenital perforin deficiency is considered a rare cause of human immunopathology and immune dysregulation, and classically presents as a fatal illness early in infancy. However, we propose that a group of related disorders in which killer lymphocytes deliver only partially active perforin or a reduced quantum of wild-type perforin to the immune synapse should be considered part of an extended syndrome with overlapping but more variable clinical features. Apart from the many rare mutations scattered over the coding sequences, up to 10% of Caucasians carry the severely hypomorphic PRF1 allele C272>T (leading to A91V mutation and the overall prevalence of the homozygous state for A91V is around 1 in 600 individuals. We therefore postulate that the partial loss of perforin function and its clinical consequences may be more common then currently suspected. An acute clinical presentation is infrequent in A91V heterozygous individuals, but we postulate that the partial loss of perforin function may potentially be manifested in childhood or early adulthood as ‘idiopathic’ inflammatory disease, or through increased cancer susceptibility – either hematological malignancy or multiple, independent primary cancers. We suggest the new term ‘perforinopathy’ to signify the common functional endpoints of all the known consequences of perforin-deficiency and failure to deliver fully functional perforin.

  17. Functionalization of acrylic hydrogels with alpha-, beta- or gamma-cyclodextrin modulates protein adsorption and antifungal delivery.

    Science.gov (United States)

    dos Santos, Jose-Fernando Rosa; Torres-Labandeira, Juan-Jose; Matthijs, Nele; Coenye, Tom; Concheiro, Angel; Alvarez-Lorenzo, Carmen

    2010-10-01

    Poly(hydroxyethyl methacrylate) (pHEMA) hydrogels were functionalized with pendant alpha-, beta- and gamma-cyclodextrins (CD) with the aim of improving the biocompatibility and increasing the ability to host drug molecules. Pendant alpha-, beta- and gamma-CDs did not affect swelling of the hydrogels but slightly decreased the water contact angle. Protein deposition was notably dependent on the nature of the CD, due to their different affinities for hydrophobic moieties of proteins. Lysozyme and albumin sorption was hindered by gamma-CD. Functionalization with beta-CD also reduced protein sorption, although less so, while alpha-CD decreased lysozyme deposition but enhanced albumin sorption compared with control pHEMA hydrogels. Loading of the hydrogels with miconazole was carried out by immersion in drug suspension followed by autoclaving. Functionalization with gamma-CD doubled the affinity of the network for the drug and resulted in the highest amount loaded (up to 170 mgg(-1)). Sustained delivery was observed for several days. Some miconazole-loaded hydrogels completely prevented Candida albicans biofilm formation as assayed in an in vitro microbiological test. 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  18. Food group contribution of essential elements of the Sao Paulo State market basket

    Energy Technology Data Exchange (ETDEWEB)

    Avegliano, Roseane P.; Maihara, Vera A., E-mail: pagliaro@usp.b, E-mail: vmaihara@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Silva, Fabio F. da, E-mail: ffsusp@uol.com.b [Universidade de Sao Paulo (USP), SP (Brazil). Inst. de Matematica e Estatistica. Empresa Junior de Informatica, Matematica e Estatistica

    2009-07-01

    To establish a Market Basket of Sao Paulo state seventy-one foods, with a mean consumption of more than 2 g day{sup -1} per person, were grouped into 30 food categories. The food groups were: cereals, leguminous, leafy vegetables, fruity vegetables, tuberous vegetables, tropical fruits, other fruits, flours, pastas, breads, biscuits, prime grade beef, standard grade beef, pork meats, other meats, poultry, milk/cream, other dairy products, sugars, sweets, salts, sauces, oils, fats, alcoholic beverages, non-alcoholic beverages, coffee, ready-made dishes, saltwater and freshwater fishes. Information about individual food consumption was obtained from a recent national household food budget survey 'POF 2002-2003' conducted by the Brazilian Institute for Geography and Statistics from July 2002 to June 2003. Sampling and kitchen preparation of foods were carried out in restaurants of the University of Sao Paulo. Each food item was individually prepared table-ready. Foods of the same group were mixed, homogenized, pulverized and analyzed for the determination of Ca, Cr, Fe, K, Na and Zn concentrations by Instrumental Neutron Activation Analysis. Average daily intake of each element was calculated by multiplying the element concentration in the food by the corresponding weight of the ready-to-consume food group. The contribution of each food group to the total daily intake of elements by the ready-to-consume food groups of the Market Basket was evaluated. The food groups representing the highest contributions were salts: 79% Na; breads: 37% Fe and 46% Cr; cereals: 19% Zn and milk/cream: 58% Ca and 24% K. (author)

  19. EpiBasket: how e-commerce tools can improve epidemiological preparedness.

    Science.gov (United States)

    Xing, Weijia; Hejblum, Gilles; Valleron, Alain-Jacques

    2013-10-31

    Should an emerging infectious disease outbreak or an environmental disaster occur, the collection of epidemiological data must start as soon as possible after the event's onset. Questionnaires are usually built de novo for each event, resulting in substantially delayed epidemiological responses that are detrimental to the understanding and control of the event considered. Moreover, the public health and/or academic institution databases constructed with responses to different questionnaires are usually difficult to merge, impairing necessary collaborations. We aimed to show that e-commerce concepts and software tools can be readily adapted to enable rapid collection of data after an infectious disease outbreak or environmental disaster. Here, the 'customers' are the epidemiologists, who fill their shopping 'baskets' with standardised questions. For each epidemiological field, a catalogue of questions is constituted by identifying the relevant variables based on a review of the published literature on similar circumstances. Each question is tagged with information on its source papers. Epidemiologists can then tailor their own questionnaires by choosing appropriate questions from this catalogue. The software immediately provides them with ready-to-use forms and online questionnaires. All databases constituted by the different EpiBasket users are interoperable, because the corresponding questionnaires are derived from the same corpus of questions. A proof-of-concept prototype was developed for Knowledge, Attitudes and Practice (KAP) surveys, which is one of the fields of the epidemiological investigation frequently explored during, or after, an outbreak or environmental disaster. The catalogue of questions was initiated from a review of the KAP studies conducted during or after the 2003 severe acute respiratory syndrome epidemic. Rapid collection of standardised data after an outbreak or environmental disaster can be facilitated by transposing the e-commerce paradigm

  20. Evaluation of maximum allowable temperature inside basket of dry storage module for CANDU spent fuel

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyung Ho; Yoon, Jeong Hyoun; Chae, Kyoung Myoung; Choi, Byung Il; Lee, Heung Young; Song, Myung Jae [Nuclear Environment Technology Institute, Taejon (Korea, Republic of); Cho, Gyu Seong [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of)

    2002-10-01

    This study provides a maximum allowable fuel temperature through a preliminary evaluation of the UO{sub 2} weight gain that may occur on a failed (breached sheathing) element of a fuel bundle. Intact bundles would not be affected as the UO{sub 2} would not be in contact with the air for the fuel storage basket. The analysis is made for the MACSTOR/KN-400 to be operated in Wolsong ambient air temperature conditions. The design basis fuel is a 6-year cooled fuel bundle that, on average has reached a burnup of 7,800 MWd/MTU. The fuel bundle considered for analysis is assumed to have a high burnup of 12,000 MWd/MTU and be located in a hot basket. The MACSTOR/KN-400 has the same air circuit as the MACSTOR and the air circuit will require a slightly higher temperature difference to exit the increased heat load. The maximum temperature of a high burnup bundle stored in the new MACSTOR/KN-400 is expected to be about 9 .deg. C higher than the fuel temperature of the MACSTOR at an equivalent constant ambient temperature. This temperature increase will in turn increase the UO{sub 2} weight gain from 0.06% (MACSTOR for Wolsong conditions) to an estimated 0.13% weight gain for the MACSTOR/KN-400. Compared to an acceptable UO{sub 2} weight gain of 0.6%, we are thus expecting to maintain a very acceptable safety factor of 4 to 5 for the new module against unacceptable stresses in the fuel sheathing. For the UO{sub 2} weight gain, the maximum allowable fuel temperature was shown by 164 .deg. C.

  1. STS-103 MS Clervoy and Pilot Kelly inspect slideware basket at Pad 39B

    Science.gov (United States)

    1999-01-01

    At Launch Pad 39B. STS-103 Mission Specialist Jean-Frangois Clervoy of France, who is with the European Space Agency (ESA), and Pilot Steven J. Kelly inspect the slidewire basket, part of the emergency egress system for persons in the Shuttle vehicle or on the Rotating Service Structure. Seven slidewires extend from the orbiter access arm, with a netted, flatbottom basket suspended from each wire. The STS-103 crew have been participating in Terminal Countdown Demonstration Test (TCDT) activities at KSC. Other crew members are Commander Curtis L. Brown Jr. and Mission Specialists Steven L. Smith, C. Michael Foale (Ph.D.), John M. Grunsfeld (Ph.D.), and Claude Nicollier of Switzerland, also with ESA. The TCDT provides the crew with the emergency egress training, opportunities to inspect their mission payloads in the orbiter's payload bay, and simulated countdown exercises. STS-103 is a 'call-up' mission due to the need to replace and repair portions of the Hubble Space Telescope, including the gyroscopes that allow the telescope to point at stars, galaxies and planets. The STS-103 crew will be replacing a Fine Guidance Sensor, an older computer with a new enhanced model, an older data tape recorder with a solid-state digital recorder, a failed spare transmitter with a new one, and degraded insulation on the telescope with new thermal insulation. The crew will also install a Battery Voltage/Temperature Improvement Kit to protect the spacecraft batteries from overcharging and overheating when the telescope goes into a safe mode. Four EVA's are planned to make the necessary repairs and replacements on the telescope. The mission is targeted for launch Dec. 6 at 2:37 a.m. EST.

  2. River channel morphology and hydraulics properties due to introduction of plant basket hydraulic structures for river channel management

    Science.gov (United States)

    Kałuża, Tomasz; Radecki-Pawlik, Artur; Plesiński, Karol; Walczak, Natalia; Szoszkiewicz, Krzysztof; Radecki-Pawlik, Bartosz

    2016-04-01

    In the present time integrated water management is directly connected with management and direct works in river channels themselves which are taking into account morphological processes in rivers and improve flow conditions. Our work focused on the hydraulic and hydrodynamic consequences upon the introduction of the concept of the improvement of the hydromorphological conditions of the Flinta River in a given reach following river channel management concept. Based on a comprehensive study of the hydromorphological state of the river, four sections were selected where restoration measures can efficiently improve river habitat conditions in the river. For each section a set of technical and biological measures were proposed and implemented in practice. One of the proposed solutions was to construct plant basket hydraulic structures (PBHS) within the river channel, which are essentially plant barriers working as sediment traps, changing river channel morphology and are in line with concepts of Water Framework Directive. These relatively small structures work as crested weirs and unquestionably change the channel morphology. Along our work we show the results of three-year long (2013-2015) systematic measurements that provided information on the morphological consequences of introducing such structures into a river channel. Our main conclusions are as follows: 1. Plant basket hydraulic structures cause changes in hydrodynamic conditions and result in sediment accumulation and the formation of river backwaters upstream and downstream the obstacle; 2. The introduced plant basket hydraulic structures cause plant debris accumulation which influences the hydrodynamic flow conditions; 3. The installation of plant basket hydraulic structures on the river bed changes flow pattern as well as flow hydrodynamic conditions causing river braiding process; 4. The erosion rate below the plant basket hydraulic structures is due to the hydraulic work conditions of the PBHS and its

  3. Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells

    Science.gov (United States)

    Li, Lei; Xiang, Dongxi; Shigdar, Sarah; Yang, Wenrong; Li, Qiong; Lin, Jia; Liu, Kexin; Duan, Wei

    2014-01-01

    To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (P<0.01). Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells. PMID:24591829

  4. Systemic delivery of siRNA by hyaluronan-functionalized calcium phosphate nanoparticles for tumor-targeted therapy

    Science.gov (United States)

    Qiu, Chong; Wei, Wei; Sun, Jing; Zhang, Hai-Tao; Ding, Jing-Song; Wang, Jian-Cheng; Zhang, Qiang

    2016-06-01

    In this study, hyaluronan (HA)-functionalized calcium phosphate nanoparticles (CaP-AHA/siRNA NPs) were developed for an injectable and targetable delivery of siRNA, which were prepared by coating the alendronate-hyaluronan graft polymer (AHA) around the surface of calcium phosphate-siRNA co-precipitates. The prepared CaP-AHA/siRNA NPs had a uniform spherical core-shell morphology with an approximate size of 170 nm and zeta potential of -12 mV. The coating of hydrophilic HA improved the physical stability of nanoparticles over one month due to the strong interactions between phosphonate and calcium. In vitro experiments demonstrated that the negatively charged CaP-AHA/siRNA NPs could effectively deliver EGFR-targeted siRNA into A549 cells through CD44-mediated endocytosis and significantly down-regulate the level of EGFR expression. Also, the internalized CaP-AHA/siRNA NPs exhibited a pH-responsive release of siRNA, indicating that the acidification of lysosomes probably facilitated the disassembling of nanoparticles and the resultant ions sharply increased the inner osmotic pressure and thus expedited the release of siRNA from late lysosomes into the cytoplasm. Furthermore, in vivo tumor therapy demonstrated that high accumulation of CaP-AHA/siEGFR NPs in tumor led to a significant tumor growth inhibition with a specific EGFR gene silencing effect after intravenous administration in nude mice xenografted with A549 tumor, along with a negligible body weight loss. These results suggested that the CaP-AHA/siRNA NPs could be an effective and safe systemic siRNA delivery system for a RNAi-based tumor targeted therapy strategy.In this study, hyaluronan (HA)-functionalized calcium phosphate nanoparticles (CaP-AHA/siRNA NPs) were developed for an injectable and targetable delivery of siRNA, which were prepared by coating the alendronate-hyaluronan graft polymer (AHA) around the surface of calcium phosphate-siRNA co-precipitates. The prepared CaP-AHA/siRNA NPs had a uniform

  5. Enhanced mucosal immune responses against tetanus toxoid using novel delivery system comprised of chitosan-functionalized gold nanoparticles and botanical adjuvant: characterization, immunogenicity, and stability assessment.

    Science.gov (United States)

    Barhate, Ganesh; Gautam, Manish; Gairola, Sunil; Jadhav, Suresh; Pokharkar, Varsha

    2014-11-01

    Approaches based on combined use of delivery systems and adjuvants are being favored to maximize efficient mucosal delivery of antigens. Here, we describe a novel delivery system comprised of chitosan-functionalized gold nanoparticles (CsAuNPs) and saponin-containing botanical adjuvant; Asparagus racemosus extract (ARE) for oral delivery of tetanus toxoid (TT). A significant increase in TT-specific IgG (34.53-fold) and IgA (43.75-fold) was observed when TT-CsAuNPs were formulated with ARE (TT-ARE-CsAuNPs). The local IgA immune responses for TT also showed a significant increase (106.5-fold in intestine washes and 99.74-fold in feces) with ARE-based formulations as compared with plain TT group. No effect of ARE was observed on size, charge, and loading properties of CsAuNPs. Additionally, no effect of ARE and CsAuNPs was observed on antigenicity and secondary structure of TT as determined by fluorescence, circular dichroism, and Fourier transform infrared spectroscopy. The stability studies demonstrated excellent stability profile of formulation at recommended storage conditions. The study establishes the possible role of immunomodulatory adjuvants in particulate delivery systems for mucosal delivery of vaccines.

  6. Comparison of drug delivery potentials of surface functionalized cobalt and zinc ferrite nanohybrids for curcumin in to MCF-7 breast cancer cells

    Science.gov (United States)

    Sawant, V. J.; Bamane, S. R.; Shejwal, R. V.; Patil, S. B.

    2016-11-01

    The functionalization and surface engineering of CoFe2O4 and ZnFe2O4 nanoparticles were performed by coating with PEG and Chitosan respectively using simple wet co-precipitation. Then multiactive therapeutic drug curcumin was loaded to form drug delivery nanohybrids by precipitation. These nanohybrids were characterized separately using UV-vis, FTIR, PL spectroscopy, XRD, VSM, SEM and TEM analysis. The moderate antibacterial activities of the nanohybrids were elaborated by in vitro antibacterial screening on Escherichia coli and Staphylococcus aureus. The anticancer potentials, apoptotic effects and enhanced drug delivery properties of these nanohybrids were confirmed and compared on MCF-7 cells by in vitro MTT assay. The drug delivery activities for hydrophobic drug and anticancer effects of chitosan coated zinc ferrite functionalized nanoparticles were higher than PEG coated cobalt ferrite nanohybrids.

  7. Aptamer-functionalized hydrogel as effective anti-cancer drugs delivery agents.

    Science.gov (United States)

    Wang, Zonghua; Xia, Jianfei; Cai, Feng; Zhang, Feifei; Yang, Min; Bi, Sai; Gui, Rijun; Li, Yanhui; Xia, Yanzhi

    2015-10-01

    An aptamer-functionalized hydrogel has been developed, which can be regulated by the AS1411 aptamer with the sol-gel conversion. Also the hydrogel can be further utilized for the controlled encapsulation and release of the cancer drugs. Specially, the AS1411 initiates the hybridization of acrydite-modified oligonucleotides to form the hydrogels and the presence of the target protein nucleolin leads the gel to dissolve as a result of reducing the cross-linking density by competitive target-aptamer binding. Based on the rheology of hydrogels, it is possible to utilize this material for storing and releasing molecules. In this research, the cancer drug doxorubicin is encapsulated inside the gel during the formation of the hydrogel and then released in the presence of nucleolin. Further experiments are carried out to prove the specific recognition of target matter. In vitro researches confirm that the aptamer-functionalized hydrogels can be used as drug carriers in targeted therapy and other biotechnological applications.

  8. Intranasal Delivery of A Novel Amnion Cell Secretome Prevents Neuronal Damage and Preserves Function In A Mouse Multiple Sclerosis Model

    Science.gov (United States)

    Khan, Reas S.; Dine, Kimberly; Bauman, Bailey; Lorentsen, Michael; Lin, Lisa; Brown, Helayna; Hanson, Leah R.; Svitak, Aleta L.; Wessel, Howard; Brown, Larry; Shindler, Kenneth S.

    2017-01-01

    The ability of a novel intranasally delivered amnion cell derived biologic to suppress inflammation, prevent neuronal damage and preserve neurologic function in the experimental autoimmune encephalomyelitis animal model of multiple sclerosis was assessed. Currently, there are no existing optic nerve treatment methods for disease or trauma that result in permanent vision loss. Demyelinating optic nerve inflammation, termed optic neuritis, induces permanent visual dysfunction due to retinal ganglion cell damage in multiple sclerosis and experimental autoimmune encephalomyelitis. ST266, the biological secretome of Amnion-derived Multipotent Progenitor cells, contains multiple anti-inflammatory cytokines and growth factors. Intranasally administered ST266 accumulated in rodent eyes and optic nerves, attenuated visual dysfunction, and prevented retinal ganglion cell loss in experimental optic neuritis, with reduced inflammation and demyelination. Additionally, ST266 reduced retinal ganglion cell death in vitro. Neuroprotective effects involved oxidative stress reduction, SIRT1-mediated mitochondrial function promotion, and pAKT signaling. Intranasal delivery of neuroprotective ST266 is a potential novel, noninvasive therapeutic modality for the eyes, optic nerves and brain. The unique combination of biologic molecules in ST266 provides an innovative approach with broad implications for suppressing inflammation in autoimmune diseases, and for preventing neuronal damage in acute neuronal injury and chronic neurodegenerative diseases such as multiple sclerosis. PMID:28139754

  9. Surface-mediated functional gene delivery: an effective strategy for enhancing competitiveness of endothelial cells over smooth muscle cells.

    Science.gov (United States)

    Chang, Hao; Ren, Ke-feng; Wang, Jin-Lei; Zhang, He; Wang, Bai-liang; Zheng, Shan-mei; Zhou, Yuan-yuan; Ji, Jian

    2013-04-01

    The non-biorecognition of general biomaterials and inherent biospecificity of biological systems pose key challenges to the optimal functions of medical devices. In this study, we constructed the surface-mediated functional gene delivery through layer-by-layer self-assembly of protamine sulfate (PrS) and plasmid DNA encoding hepatocyte growth factor (HGF), aiming at specific enhancing endothelial cells (EC) compeititiveness over smooth muscle cells (SMC). Characterizations of the (PrS/HGF-pDNA) multilayered films present the linear buildup with homogeneous and flat topographical feature. The amount of DNA can be easily controlled. By using these multilayered films, both human umbilical vein endothelial cells (HUVEC) and human umbilical artery smooth muscle cells (HUASMC) can be directly transfected when they contact with the multilayered films. On transfection, increasing secretion of HGF has been detected in both HUVEC and HUASMC culture, which leads to selective promotion of HUVEC proliferation. In the co-culture experiment, we also exhibit the promoted and hindered growth of HUVEC and HUASMC, respectively, which could be attributed to the inverse influence of HUVEC on HUASMC. These results collectively demonstrate that our system can be served as a powerful tool for enhancing competitiveness of EC over SMC, which opens perspectives for the regulation of intercellular competitiveness in the field of interventional therapy.

  10. pH-responsive drug delivery system based on AIE luminogen functionalized layered zirconium phosphate nano-platelets

    Energy Technology Data Exchange (ETDEWEB)

    Li, Dongdong, E-mail: lidongdong@jlu.edu.cn; Zhang, Yuping; Zhou, Bingbing

    2015-05-15

    Aggregation-induced emission (AIE) luminogen, quaternary tetraphenylethene cation (TPEN), was successfully incorporated into layered α-zirconium phosphate (α-ZrP) by using co-precipitation method to form inorganic–organic hybrid materials. The obtained materials show the characteristic hexagonal platelet shape with the interlayer distance did not reveal significant difference compared with pure α-ZrP. In addition, the obtained hybrid materials emit strong blue emission centered at 476 nm in aqueous media due to the electrostatic interactions of TPEN with the anionic framework of α-ZrP, which largely restrict their intramolecular rotation. More importantly, the materials provide a pH dependent release of doxorubicin (DOX), suggesting that AIE luminogen functionalized α-ZrP may be used as an imaging guided and pH-responsive delivery system for targeting therapy. - Graphical abstract: AIE luminogen was successfully incorporated into layered α-zirconium phosphate by a co-precipitation method to form inorganic–organic hybrid materials, showing a pH dependent release of DOX. - Highlights: • AIE luminogen cation was incorporated into layered α-ZrP by co-precipitation method. • The obtained material emits strong blue emission upon UV irradiation. • The material exhibits pH dependent release of DOX. • The AIE functionalized α-ZrP has potential applications in imaging guided therapy.

  11. Robust aptamer–polydopamine-functionalized M-PLGA–TPGS nanoparticles for targeted delivery of docetaxel and enhanced cervical cancer therapy

    Directory of Open Access Journals (Sweden)

    Xu GJ

    2016-06-01

    Full Text Available Guojun Xu,1–3,* Xinghua Yu,2,* Jinxie Zhang,1,2,* Yingchao Sheng,4 Gan Liu,2 Wei Tao,1,2 Lin Mei1,2 1School of Life Sciences, Tsinghua University, Beijing, 2Graduate School at Shenzhen, Tsinghua University, Shenzhen, 3School of Materials Science and Engineering, Tsinghua University, Beijing, 4Department of Orthopedic Surgery, Changshu Hospital of TCM, Changshu, People’s Republic of China *These authors contributed equally to this work Abstract: One limitation of current biodegradable polymeric nanoparticles (NPs is the contradiction between functional modification and maintaining formerly excellent bioproperties with simple procedures. Here, we reported a robust aptamer–polydopamine-functionalized mannitol-functionalized poly(lactide-co-glycolide (M-PLGA–D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS nanoformulation (Apt-pD-NPs for the delivery of docetaxel (DTX with enhanced cervical cancer therapy effects. The novel DTX-loaded Apt-pD-NPs possess satisfactory advantages: 1 increased drug loading content and encapsulation efficiency induced by star-shaped copolymer M-PLGA–TPGS; 2 significant active targeting effect caused by conjugated AS1411 aptamers; and 3 excellent long-term compatibility by incorporation of TPGS. Therefore, with simple preparation procedures and excellent bioproperties, the new functionalized Apt-pD-NPs could maximally increase the local effective drug concentration on tumor sites, achieving enhanced treatment effectiveness and minimizing side effects. In a word, the robust DTX-loaded Apt-pD-NPs could be used as potential nanotherapeutics for cervical cancer treatment, and the aptamer–polydopamine modification strategy could be a promising method for active targeting of cancer therapy with simple procedures. Keywords: dopamine, AS1411 aptamer, active targeting, polymeric NPs, enhanced cervical chemotherapy

  12. Functional Polymeric Systems as Delivery Vehicles for Methylene Blue in Photodynamic Therapy.

    Science.gov (United States)

    Junqueira, Mariana V; Borghi-Pangoni, Fernanda B; Ferreira, Sabrina B S; Rabello, Bruno R; Hioka, Noboru; Bruschi, Marcos L

    2016-01-12

    Antibiotic-resistant microorganisms have become a global concern, and the search for alternative therapies is very important. Photodynamic therapy (PDT) consists of the use of a nontoxic photosensitizer (PS), light, and oxygen. This combination produces reactive oxygen species and singlet oxygen, which can alter cellular structures. Methylene blue (MB) is a substance from the phenothiazine class often used as a PS. In this work, to facilitate the PS contact within the wounds, we have used Design of Experiments 2(3) plus central point to develop functional polymeric systems. The formulations were composed by poloxamer 407 [15.0, 17.5, or 20.0% (w/w)], Carbopol 934P [0.15, 0.20, or 0.25% (w/w)], and MB [0.25, 0.50, or 0.75% (w/w)]. The sol-gel transition temperature, flow rheometry, in vitro MB release, and ex vivo study of MB cutaneous permeation and retention were investigated. Moreover, the evaluation of photodynamic activity was also analyzed by in vitro degradation of tryptophan by singlet oxygen and using Artemia salina. The determination of the gelation temperature displayed values within the range of 25-37 °C, and the systems with better characteristics were subjected to rheological analysis and in vitro release profiling. The 20/0.15/0.25 formulation showed the best release profile (42.57% at 24 h). This system displayed no significant skin permeation (0.38% at 24 h), and the photooxidation of tryptophan test showed the production of reactive species of oxygen. The toxicity test using A. salina revealed that the MB associated with the light increased the mortality rate by 61.29%. Therefore, investigating the PDT efficacy of the functional polymeric system containing MB will be necessary in the future.

  13. Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells.

    Science.gov (United States)

    Li, Lei; Xiang, Dongxi; Shigdar, Sarah; Yang, Wenrong; Li, Qiong; Lin, Jia; Liu, Kexin; Duan, Wei

    2014-01-01

    To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (Pdrug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells.

  14. Training simulator for teaching a technique to the long transmission of ball in basket-ball by a method by an arcuated hand from above with threaten

    Directory of Open Access Journals (Sweden)

    Charikova K.M.

    2012-03-01

    Full Text Available Technical devices which used in basket-ball are considered. The features of constructing of trainers and method of their application are selected in a training process. A trainer is offered for teaching a technique to the long transmission of ball in basket-ball. A trainer is a moving on a rope imitator of basket-ball ball. This construction allows to design initial position, замах for implementation of transmission and line of acceleration of ball in the final phase of motion. The method of the use of trainer is developed in an educational process.

  15. Design, development and characterization of multi-functionalized gold nanoparticles for biodetection and targeted boron delivery in BNCT applications.

    NARCIS (Netherlands)

    Mandal, S.; Bakeine, G.J.; Krol, S.; Ferrari, C.; Clerici, A.M.; Zonta, C.; Cansolino, L.; Ballarini, F.; Bortolussi, S.; Stella, S.; Protti, N.; Bruschi, P.; Altieri, S.

    2011-01-01

    The aim of this study is to optimize targeted boron delivery to cancer cells and its tracking down to the cellular level. To this end, we describe the design and synthesis of novel nanovectors that double as targeted boron delivery agents and fluorescent imaging probes. Gold nanoparticles were coate

  16. Fast-track applications: The potential for direct delivery of proteins and nucleic acids to plant cells for the discovery of gene function

    Directory of Open Access Journals (Sweden)

    Roberts Michael R

    2005-12-01

    Full Text Available Abstract In animal systems, several methods exist for the direct delivery of nucleic acids and proteins into cells for functional analysis. Until recently, these methods have not been applied to plant systems. Now, however, several preliminary reports suggest that both nucleic acids and proteins can also be delivered into plant cells by very simple, direct application. This promises to open the way for high-throughput screening for gene function in a range of plant species.

  17. Dual-functional transdermal drug delivery system with controllable drug loading based on thermosensitive poloxamer hydrogel for atopic dermatitis treatment

    Science.gov (United States)

    Wang, Wenyi; Wat, Elaine; Hui, Patrick C. L.; Chan, Ben; Ng, Frency S. F.; Kan, Chi-Wai; Wang, Xiaowen; Hu, Huawen; Wong, Eric C. W.; Lau, Clara B. S.; Leung, Ping-Chung

    2016-04-01

    The treatment of atopic dermatitis (AD) has long been viewed as a problematic issue by the medical profession. Although a wide variety of complementary therapies have been introduced, they fail to combine the skin moisturizing and drug supply for AD patients. This study reports the development of a thermo-sensitive Poloxamer 407/Carboxymethyl cellulose sodium (P407/CMCs) composite hydrogel formulation with twin functions of moisture and drug supply for AD treatment. It was found that the presence of CMCs can appreciably improve the physical properties of P407 hydrogel, which makes it more suitable for tailored drug loading. The fabricated P407/CMCs composite hydrogel was also characterized in terms of surface morphology by field emission scanning electron microscopy (FE-SEM), rheological properties by a rheometer, release profile in vitro by dialysis method and cytotoxicity test. More importantly, the findings from transdermal drug delivery behavior revealed that P407/CMCs showed desirable percutaneous performance. Additionally, analysis of cytotoxicity test suggested that P407/CMCs composite hydrogel is a high-security therapy for clinical trials and thus exhibits a promising way to treat AD with skin moisturizing and medication.

  18. Intravitreal delivery of AAV-NDI1 provides functional benefit in a murine model of Leber hereditary optic neuropathy.

    Science.gov (United States)

    Chadderton, Naomi; Palfi, Arpad; Millington-Ward, Sophia; Gobbo, Oliverio; Overlack, Nora; Carrigan, Matthew; O'Reilly, Mary; Campbell, Matthew; Ehrhardt, Carsten; Wolfrum, Uwe; Humphries, Peter; Kenna, Paul F; Farrar, G Jane

    2013-01-01

    Leber hereditary optic neuropathy (LHON) is a mitochondrially inherited form of visual dysfunction caused by mutations in several genes encoding subunits of the mitochondrial respiratory NADH-ubiquinone oxidoreductase complex (complex I). Development of gene therapies for LHON has been impeded by genetic heterogeneity and the need to deliver therapies to the mitochondria of retinal ganglion cells (RGCs), the cells primarily affected in LHON. The therapy under development entails intraocular injection of a nuclear yeast gene NADH-quinone oxidoreductase (NDI1) that encodes a single subunit complex I equivalent and as such is mutation independent. NDI1 is imported into mitochondria due to an endogenous mitochondrial localisation signal. Intravitreal injection represents a clinically relevant route of delivery to RGCs not previously used for NDI1. In this study, recombinant adenoassociated virus (AAV) serotype 2 expressing NDI1 (AAV-NDI1) was shown to protect RGCs in a rotenone-induced murine model of LHON. AAV-NDI1 significantly reduced RGC death by 1.5-fold and optic nerve atrophy by 1.4-fold. This led to a significant preservation of retinal function as assessed by manganese enhanced magnetic resonance imaging and optokinetic responses. Intraocular injection of AAV-NDI1 overcomes many barriers previously associated with developing therapies for LHON and holds great therapeutic promise for a mitochondrial disorder for which there are no effective therapies.

  19. Enteric polymer based on pH-responsive aliphatic polycarbonate functionalized with vitamin E to facilitate oral delivery of tacrolimus.

    Science.gov (United States)

    Wang, Menglin; Sun, Jin; Zhai, Yinglei; Lian, He; Luo, Cong; Li, Lin; Du, Yuqian; Zhang, Dong; Ding, Wenya; Qiu, Shuhong; Liu, Yuhai; Kou, Longfa; Han, Xiangfei; Xiang, Rongwu; Wang, Yongjun; He, Zhonggui

    2015-04-13

    To improve the bioavailability of orally administered drugs, we synthesized a pH-sensitive polymer (poly(ethylene glycol)-poly(2-methyl-2-carboxyl-propylene carbonate)-vitamin E, mPEG-PCC-VE) attempting to integrate the advantages of enteric coating and P-glycoprotein (P-gp) inhibition. The aliphatic polycarbonate chain was functionalized with carboxyl groups and vitamin E via postpolymerization modification. Optimized by comparison and central composite design, mPEG113-PCC32-VE4 exhibited low critical micelle concentration of 1.7 × 10(-6) mg/mL and high drug loading ability for tacrolimus (21.2% ± 2.7%, w/w). The pH-responsive profile was demonstrated by pH-dependent swelling and in vitro drug release. Less than 4.0% tacrolimus was released under simulated gastric fluid after 2.5 h, whereas an immediate release was observed under simulated intestinal fluid. The mPEG113-PCC32-VE4 micelles significantly increased the absorption of P-gp substrate tacrolimus in the whole intestine. The oral bioavailability of tacrolimus micelles was 6-fold higher than that of tacrolimus solution in rats. This enteric polymer therefore has the potential to become a useful nanoscale carrier for oral delivery of drugs.

  20. Comparison of drug delivery potentials of surface functionalized cobalt and zinc ferrite nanohybrids for curcumin in to MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Sawant, V.J., E-mail: v11131@rediffmail.com [Department of Chemistry, Smt.K.W.College, Sangli, MS 416416 (India); Bamane, S.R. [Department of Chemistry, Raja Shripatrao Bhagwantrao College, Aundh, Satara, MS (India); Shejwal, R.V. [L.B.S. College, Satara, MS (India); Patil, S.B. [A.Birnale College of Pharmacy, Sangli, MS (India)

    2016-11-01

    The functionalization and surface engineering of CoFe{sub 2}O{sub 4} and ZnFe{sub 2}O{sub 4} nanoparticles were performed by coating with PEG and Chitosan respectively using simple wet co-precipitation. Then multiactive therapeutic drug curcumin was loaded to form drug delivery nanohybrids by precipitation. These nanohybrids were characterized separately using UV–vis, FTIR, PL spectroscopy, XRD, VSM, SEM and TEM analysis. The moderate antibacterial activities of the nanohybrids were elaborated by in vitro antibacterial screening on Escherichia coli and Staphylococcus aureus. The anticancer potentials, apoptotic effects and enhanced drug delivery properties of these nanohybrids were confirmed and compared on MCF-7 cells by in vitro MTT assay. The drug delivery activities for hydrophobic drug and anticancer effects of chitosan coated zinc ferrite functionalized nanoparticles were higher than PEG coated cobalt ferrite nanohybrids. - Highlights: • CoFe{sub 2}O{sub 4} and ZnFe{sub 2}O{sub 4} nanoparticles were surface functionalized with PEG and Chitosan respectively. • Hydrophobic multi therapeutic anticancer drug curcumin was loaded into these nanohybrids and their structure, morphologies were confirmed. • The effects of PEG and Chitosan coating over ferrites for curcumin release have been elaborated, and the Chitosan coated curcumin loaded Zinc ferrite nanohybrid exhibited higher drug delivery and anticancer effects.

  1. Vitreal delivery of AAV vectored Cnga3 restores cone function in CNGA3-/-/Nrl-/- mice, an all-cone model of CNGA3 achromatopsia.

    Science.gov (United States)

    Du, Wei; Tao, Ye; Deng, Wen-Tao; Zhu, Ping; Li, Jie; Dai, Xufeng; Zhang, Yuxin; Shi, Wei; Liu, Xuan; Chiodo, Vince A; Ding, Xi-Qin; Zhao, Chen; Michalakis, Stylianos; Biel, Martin; Zhang, Zuoming; Qu, Jia; Hauswirth, William W; Pang, Ji-Jing

    2015-07-01

    The CNGA3(-/-)/Nrl(-/-) mouse is a cone-dominant model with Cnga3 channel deficiency, which partially mimics the all cone foveal structure of human achromatopsia 2 with CNGA3 mutations. Although subretinal (SR) AAV vector administration can transfect retinal cells efficiently, the injection-induced retinal detachment can cause retinal damage, particularly when SR vector bleb includes the fovea. We therefore explored whether cone function-structure could be rescued in CNGA3(-/-)/Nrl(-/-) mice by intravitreal (IVit) delivery of tyrosine to phenylalanine (Y-F) capsid mutant AAV8. We find that AAV-mediated CNGA3 expression can restore cone function and rescue structure following IVit delivery of AAV8 (Y447, 733F) vector. Rescue was assessed by restoration of the cone-mediated electroretinogram (ERG), optomotor responses, and cone opsin immunohistochemistry. Demonstration of gene therapy in a cone-dominant mouse model by IVit delivery provides a potential alternative vector delivery mode for safely transducing foveal cones in achromatopsia patients and in other human retinal diseases affecting foveal function. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. User centric approach to itemset utility mining in Market Basket Analysis

    Directory of Open Access Journals (Sweden)

    Jyothi Pillai

    2011-01-01

    Full Text Available Business intelligence is information about a company's past performance that is used to help predict the company's future performance. It can reveal emerging trends from which the company might profit [31]. Data mining allows users to sift through the enormous amount of information available in data warehouses; it is from this sifting process that business intelligence gems may be found [31]. Within the area of data mining, the problem of deriving associations from data has received a great deal of attention. This problem is referred as “market-basket problem”. Association Rule Mining (ARM, a well-studied technique in the data mining field, identifies frequent itemsets from databases and generates association rules by assuming that all items have the same significance andfrequency of occurrence in a record. However, items are actually different in many aspects in a number of real applications such as retail marketing, nutritional pattern mining, etc [26]. Rare items are less frequent items [32]. For many real world applications, however, utility of rare itemsets based on cost, profit or revenue is of importance. For extracting rare itemsets, the equal frequency based approaches like Apriori approach suffer from “rare item problem dilemma”. Utility mining aims at identifying rare itemsets with high utility. The main objective of Utility Mining is to identify the itemsets with highest utilities, by considering profit, quantity, costor other user preferences [40]. Also valuable patterns cannot be discovered by traditional non-temporal data mining approaches that treat all the data as one large segment, with no attention paid to utilizing the time information of transactions. Now, as increasingly complex real-world problems are addressed, temporal rare itemset utility problem, are taking center stage. In many real-life applications, high-utility itemsets consist of rare items. Rare itemsets provide useful information in different decision

  3. Synthesis of multi-functional nanocapsules via interfacial AGET ATRP in miniemulsion for tumor micro-environment responsive drug delivery.

    Science.gov (United States)

    Tian, Kun; Zeng, Jin; Zhao, Xubo; Liu, Lei; Jia, Xu; Liu, Peng

    2015-10-01

    Novel multi-functional polymeric hollow nanocapsules (PHN) based on the crosslinked poly(tert-butyl acrylate) (PtBA) shells were synthesized in a miniemulsion interfacial polymerization via activator generated electron transfer atom transfer radical polymerization (AGET ATRP) technique with N,N'-bis(acryloyl) cystamine (BACy) as cross-linking agent, CuBr₂ as catalyst, ascorbic acid (VC) as reducing agent and hexadecane as inert solvent. In the AGET ATRP, a folate-conjugated block copolymer, folate-poly(ethylene glycol)-b-poly(tert-butyl acrylate) (FA-PEG-tBA-Br), was used as macroinitiator/stabilizer, and the specific amphiphilic nature of the copolymer led the extending inward of polymer chains. The DLS analysis directly showed the PHN with an average diameter of 150 nm was obtained. After the PtBA shells were transformed into poly(acrylic acid) (PAA) by hydrolysis, doxorubicin (DOX), as a model drug, was loaded efficiently into the hydrolyzed polymeric hollow nanocapsules (HPHN), then the in vitro release of drug was carried out in phosphate buffer solution (PBS, pH 7.4 or 5.0, with or without DTT or GSH of different concentrations). It showed that the existence of folate group significantly improved pH stimuli-responsive and DOX-loading capacity of the polymeric nanocapsules. An acidic pH (5.0) and presence of GSH would accelerate the DOX release behavior. Thus, these multi-functional polymeric nanocapsules have excellent available properties in the field of targeted and controlled drug delivery for cancer therapy.

  4. Application of Market Basket Analysis for the Visualization of Transaction Data Based on Human Lifestyle and Spectroscopic Measurements.

    Science.gov (United States)

    Shiokawa, Yuka; Misawa, Takuma; Date, Yasuhiro; Kikuchi, Jun

    2016-03-01

    With the innovation of high-throughput metabolic profiling methods such as nuclear magnetic resonance (NMR), data mining techniques that can reveal valuable information from substantial data sets are constantly desired in this field. In particular, for the analytical assessment of various human lifestyles, advanced computational methods are ultimately needed. In this study, we applied market basket analysis, which is generally applied in social sciences such as marketing, and used transaction data derived from dietary intake information and urinary chemical data generated using NMR and inductively coupled plasma optical emission spectrometry measurements. The analysis revealed several relationships, such as fish diets with high trimethylamine N-oxide excretion and N-methylnicotinamide excreted at higher levels in the morning and produced from a protein that was consumed one day prior. Therefore, market basket analysis can be applied to metabolic profiling to effectively understand the relationships between metabolites and lifestyle.

  5. Analysis of Corrosion Residues Collected from the Aluminum Basket Rails of the High-Burnup Demonstration Cask.

    Energy Technology Data Exchange (ETDEWEB)

    Bryan, Charles R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-03-01

    On September, 2015, an inspection was performed on the TN-32B cask that will be used for the high-burnup demonstration project. During the survey, wooden cribbing that had been placed within the cask eleven years earlier to prevent shifting of the basket during transport was removed, revealing two areas of residue on the aluminum basket rails, where they had contacted the cribbing. The residue appeared to be a corrosion product, and concerns were raised that similar attack could exist at more difficult-to-inspect locations in the canister. Accordingly, when the canister was reopened, samples of the residue were collected for analysis. This report presents the results of that assessment, which determined that the corrosion was due to the presence of the cribbing. The corrosion was associated with fungal material, and fungal activity likely contributed to an aggressive chemical environment. Once the cask has been cleaned, there will be no risk of further corrosion.

  6. Lingo-1 expression is increased in essential tremor cerebellum and is present in the basket cell pinceau.

    Science.gov (United States)

    Kuo, Sheng-Han; Tang, Guomei; Louis, Elan D; Ma, Karen; Babji, Rachel; Balatbat, Matthew; Cortes, Etty; Vonsattel, Jean-Paul G; Yamamoto, Ai; Sulzer, David; Faust, Phyllis L

    2013-06-01

    The Lingo-1 sequence variant has been associated with essential tremor (ET) in several genome-wide association studies. However, the role that Lingo-1 might play in pathogenesis of ET is not understood. Since Lingo-1 protein is a negative regulator of axonal regeneration and neurite outgrowth, it could contribute to Purkinje cell (PC) or basket cell axonal pathology observed in postmortem studies of ET brains. In this study, we used Western blotting and immunohistochemistry to examine Lingo-1 protein in ET vs. control brains. In Western blots, Lingo-1 protein expression level was significantly increased in cerebellar cortex (1.56 ± 0.46 in ET cases vs. 0.99 ± 0.20 in controls, p = 0.002), but was similar in the occipital cortex (p = 1.00) of ET cases vs. controls. Lingo-1 immunohistochemistry in cerebellum revealed that Lingo-1 was enriched in the distal axonal processes of basket cells, which formed a "pinceau" structure around the PC axon initial segment (AIS). We found that some Lingo-1-positive pinceau had abnormally elongated processes, targeting PC axon segments distal to the AIS. In ET cases, the percentage of Lingo-1-positive pinceau that were ≥30 or ≥40 μm in length was increased 2.4- to 4.1-fold, respectively, vs. pinceau seen in control brains (p Lingo-1-positive pinceau strongly correlated with number of PC axonal torpedoes and a rating of basket cell axonal pathology. The increased cerebellar Lingo-1 expression and elongated Lingo-1-positive pinceau processes could contribute to the abnormal PC and basket cell axonal pathology and cerebellar dysfunction observed in ET.

  7. Lingo-1 Expression is Increased in Essential Tremor Cerebellum and is Present in the Basket Cell Pinceau

    OpenAIRE

    Kuo, Sheng-Han; Tang, Guomei; Louis, Elan D.; Ma, Karen; Babij, Rachel; Balatbat, Matthew; Cortes, Etty; Vonsattel, Jean-Paul G.; Yamamoto, Ai; Sulzer, David; Faust, Phyllis L.

    2013-01-01

    The Lingo-1 sequence variant has been associated with essential tremor (ET) in several genome wide association studies. However, the role that Lingo-1 might play in pathogenesis of ET is not understood. Since Lingo-1 protein is a negative regulator of axonal regeneration and neurite outgrowth, it could contribute to Purkinje cell (PC) or basket cell axonal pathology observed in postmortem studies of ET brains. In this study, we used Western blotting and immunohistochemistry to examine Lingo-1...

  8. Multiple and substitute addictions involving prescription drugs misuse among 12th graders: gateway theory revisited with Market Basket Analysis.

    Science.gov (United States)

    Jayawardene, Wasantha Parakrama; YoussefAgha, Ahmed Hassan

    2014-01-01

    This study aimed to identify the sequential patterns of drug use initiation, which included prescription drugs misuse (PDM), among 12th-grade students in Indiana. The study also tested the suitability of the data mining method Market Basket Analysis (MBA) to detect common drug use initiation sequences in large-scale surveys. Data from 2007 to 2009 Annual Surveys of Alcohol, Tobacco, and Other Drug Use by Indiana Children and Adolescents were used for this study. A close-ended, self-administered questionnaire was used to ask adolescents about the use of 21 substance categories and the age of first use. "Support%" and "confidence%" statistics of Market Basket Analysis detected multiple and substitute addictions, respectively. The lifetime prevalence of using any addictive substance was 73.3%, and it has been decreasing during past few years. Although the lifetime prevalence of PDM was 19.2%, it has been increasing. Males and whites were more likely to use drugs and engage in multiple addictions. Market Basket Analysis identified common drug use initiation sequences that involved 11 drugs. High levels of support existed for associations among alcohol, cigarettes, and marijuana, whereas associations that included prescription drugs had medium levels of support. Market Basket Analysis is useful for the detection of common substance use initiation sequences in large-scale surveys. Before initiation of prescription drugs, physicians should consider the adolescents' risk of addiction. Prevention programs should address multiple addictions, substitute addictions, common sequences in drug use initiation, sex and racial differences in PDM, and normative beliefs of parents and adolescents in relation to PDM.

  9. Percutaneous treatment of thrombosed native arteriovenous dialysis fistula insufficiency: efficacy of mechanical thrombectomy with using the stone basket

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Hwan; Ko, Sung Min; Kim, Mi Jung; Kwon, Jung Hyeok; Sohn, Cheol Ho; Choi, Jin Soo; Park, Kyung Sik [Dongsan Medical Center, Keimyung University College of Medicine, Daegu (Korea, Republic of); Kim, Yong Joo [Andong General Hospital, Andon (Korea, Republic of)

    2006-06-15

    We wanted to evaluate the procedural success after percutaneous treatment of thrombosed native arteriovenous dialysis fistula insufficiency and the efficacy of performing mechanical thrombectomy with using the stone basket. From March 2004 to June 2005, 36 thrombosed native hemodialysis access shunts in the upper limbs (brachiocephalic fistulas: 16 and radiocephalic fistulas: 20) were percutaneously treated in 30 patients. Declotting procedures were performed with using urokinase (100,00-200,000 unit) and manual catheter-directed thrombo-aspiration in all the patients. Angioplasty (6 mm in diameter and 4 cm in length) was performed at the identified area of the stenosis and /or with maceration of the thrombus. In 14 cases with massive thrombosis that was refractory to the above mentioned declotting procedures, mechanical thrombectomy with using a Wittich nitinol stone basket (Cook, Bloomington, IN) was performed. Data regarding the procedural success rate and the patency rate were analyzed by means of Fischer's exact test, and the Kaplan-Meier method with the Log-rank test was used for statistical inter-group comparisons between the brachiocephalic and radiocephalic fistulas. Successful declotting and restoration of thrill were achieved in 30 of 36 procedures (83%). Reestablishment of normal dialysis for at least one session was achieved in 29 of 36 procedures (81%). The procedural success rate for the brachiocephalic fistulas was 94% compared with 70% for the radiocephalic fistulas, but the difference was not statistically significant ({rho} = 0.104). In the cases with performing mechanical thrombectomy and using the stone basket, procedural success was achieved in 93% (13/14). The expected patency rates at 3, 6 and 12 months were 78%, 61% and 51%, respectively. The patency rates after declotting procedures were not significantly different between the brachiocephalic and radiocephlaic fistulas ({rho} = 0.871). Percutaneous treatment of thrombosed native

  10. Effect of a dual-purpose cask payload increment of spent fuel assemblies from VVER 1000 Bushehr Nuclear Power Plant on basket criticality.

    Science.gov (United States)

    Rezaeian, M; Kamali, J

    2017-01-01

    Dual-purpose casks can be utilized for dry interim storage and transportation of the highly radioactive spent fuel assemblies (SFAs) of Bushehr Nuclear Power Plant (NPP). Criticality safety analysis was carried out using the MCNP code for the cask containing 12, 18, or 19 SFAs. The basket materials of borated stainless steel and Boral (Al-B4C) were investigated, and the minimum required receptacle pitch of the basket was determined. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Determination of Dioxins in Blood Using Nano-baskets Doped in Emulsion Liquid Membranes

    Institute of Scientific and Technical Information of China (English)

    MOKHTARI Bahram; POURABDOLLAH Kobra

    2013-01-01

    Extraction of dioxins from blood samples was carried out by inclusion-facilitated emulsion liquid membrane process.The novelty of this work is the application of nano-baskets of calixarene and emulsion liquid membranes in the selective and efficient preconcentration of dioxin.For this aim,four derivatives ofp-tert-calix[4]arene bearing different sulfonamide moieties were synthesized and their inclusion-extraction parameters were optimized including the calixarene's scaffold and concentration(as the carrier/demulsifier),the diluent type in membrane,the phase and the treat ratio,mixing speed,and initial solute concentration.Determinations were followed by a gas chromatograph and the results reveal that under the optimized operating conditions,the preconcentration of dioxins was improved and the method achieved lower limit of detections(LODs).Under optimal conditions,the figures of merits were determined to be LOD 1.0 pg/L,dynamic range 0.6-112.0 pg/L,RSD 5.5%(n=5),and the maximum enrichment factor and recovery were determined to be 3.3 and 99%,respectively.

  12. Thermodynamics and Kinetics of Guest-Induced Switching between “Basket Handle” Porphyrin Isomers

    Directory of Open Access Journals (Sweden)

    Alexander B. C. Deutman

    2014-04-01

    Full Text Available The synthesis and switching properties of two “basket handle” porphyrin isomers is described. The cis-oriented meso-phenyl groups of these porphyrins are linked at their ortho-positons via benzocrown-ether-based spacers, which as a result of slow atropisomerization are located either on the same side of the porphyrin plane (cis, or on opposite sides (trans. In solution, the cis-linked isomer slowly isomerizes in the direction of the thermodynamically more stable trans-isomer. In the presence of viologen (N,N'-dialkyl-4,4'-bipyridinium derivatives, which have different affinities for the two isomers, the isomerization equilibrium could be significantly influenced. In addition, the presence of these guests was found to enhance the rate of the switching process, which was suggested to be caused by favorable interactions between the positively charged guest and the crown ethers of the receptor, stabilizing the transition state energies of the isomerization reaction between the two isomers.

  13. A food basket investigation during the autumn of 1994; Matkorgsundersoekning hoesten 1994

    Energy Technology Data Exchange (ETDEWEB)

    Moere, H.; Falk, R.; Svedjemark, G.A. [Swedish Radiation Protection Inst., Stockholm (Sweden); Becker, W.; Brugaard Konde, Aa. [National Food Administration, Uppsala (Sweden)

    1995-10-01

    During the autumn of 1994 an investigation of foodstuffs has been accomplished to assess the average intake of {sup 137}Cs by the Swedish population due to the Chernobyl accident. A standardized food basket has been collected from two grocers in 10 localities, of which the majority came from areas with the highest fallout. The estimated maximum intake of {sup 137}Cs was 815 Bq/year in the inland of the county of Vaesterbotten. The population weighted average intake for the fallout affected counties was 435 Bq/year. The rest of the county received an intake of 235 Bq/year. The population weighted average of the intake for the whole county was estimated to 274 Bq/year. From this intake the calculated body burden would be 1.3 Bq/kg for the average citizen. Whole-body measurements of a sample of the population gave 2.0 Bq/kg. A plausible explanation would be that 40% of the intake of {sup 137}Cs can have its origin from the 10% of the consumption of foodstuffs that are home produced or collected for the average individual in Sweden. The average intake of 274 Bq/year gives a committed effective dose equivalent of 3.6 {mu}Sv. 6 refs, 10 tabs.

  14. A Market-Basket Approach to Predict the Acute Aquatic Toxicity of Munitions and Energetic Materials.

    Science.gov (United States)

    Burgoon, Lyle D

    2016-06-01

    An ongoing challenge in chemical production, including the production of insensitive munitions and energetics, is the ability to make predictions about potential environmental hazards early in the process. To address this challenge, a quantitative structure activity relationship model was developed to predict acute fathead minnow toxicity of insensitive munitions and energetic materials. Computational predictive toxicology models like this one may be used to identify and prioritize environmentally safer materials early in their development. The developed model is based on the Apriori market-basket/frequent itemset mining approach to identify probabilistic prediction rules using chemical atom-pairs and the lethality data for 57 compounds from a fathead minnow acute toxicity assay. Lethality data were discretized into four categories based on the Globally Harmonized System of Classification and Labelling of Chemicals. Apriori identified toxicophores for categories two and three. The model classified 32 of the 57 compounds correctly, with a fivefold cross-validation classification rate of 74 %. A structure-based surrogate approach classified the remaining 25 chemicals correctly at 48 %. This result is unsurprising as these 25 chemicals were fairly unique within the larger set.

  15. Pharmacia and biological functionalities of nutrient broth dispersed multi-walled carbon nanotubes:A novel drug delivery system

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A new drug delivery system was developed using the interaction of nutrient broth treated multi-walled carbon nanotubes(NBT-MWCNTs) and cefotaxime sodium(CTX) as a model.Investigated factors of the drug delivery system include dispersion effect,biocompatibility of NBT-MWCNTs,pharmacodynamic effect and delivery efficiency in vitro.It was found that MWCNTs can be well dispersed in the nutrient broth and stable at least for one week at 4 °C.The formed NBT-MWCNTs suspension scarcely exhibits toxicity to E.coli at concentrations lower than 10.24 μg/mL,but displays enhanced pharmacodynamic effect of CTX via its bridge effect and targeted transport.Compared with general acid treated MWCNTs(AT-MWCNTs),our present NBT-MWCNTs show good biocompatibility,enhanced pharmacodynamic effect,and high delivery efficiency.

  16. Cell Type-Specific Delivery of RNAi by Ligand-Functionalized Curdlan Nanoparticles: Balancing the Receptor Mediation and the Charge Motivation.

    Science.gov (United States)

    Wu, Yinga; Cai, Jia; Han, Jingfen; Baigude, Huricha

    2015-09-30

    Tissue-specific delivery of therapeutic RNAi has great potential for clinical applications. Receptor-mediated endocytosis plays a crucial role in targeted delivery of biotherapeutics including short interfering RNA (siRNA). Previously we reported a novel Curdlan-based nanoparticle for intracellular delivery of siRNA. Here we designed a nanoparticle based on ligand-functionalized Curdlan. Disaccharides were site-specifically conjugated to 6-deoxy-6-amino Curdlan, and the cell line specificity, cellular uptake, cytotoxicity, and siRNA delivery efficiency of the corresponding disaccharide-modified 6-deoxy-6-amino-Curdlan were investigated. Observation by fluorescence microscopy as well as flow cytometry showed that galactose-containing Curdlan derivatives delivered fluorescently labeled short nucleic acid to HepG2 cells expressing ASGPR receptor but not in other cells lacking surface ASGPR protein. Moreover, highly galactose-substituted Curdlan derivatives delivered siRNA specifically to ASGPR-expressing cells and induced RNAi activities, silencing endogenous GAPDH gene expression. Our data demonstrated that galactose-functionalized 6-deoxy-6-amino-Curdlan is a promising carrier for short therapeutic nucleic acids for clinical applications.

  17. Vitreal delivery of AAV vectored Cnga3 restores cone function in CNGA3−/−/Nrl−/− mice, an all-cone model of CNGA3 achromatopsia†

    Science.gov (United States)

    Du, Wei; Tao, Ye; Deng, Wen-Tao; Zhu, Ping; Li, Jie; Dai, Xufeng; Zhang, Yuxin; Shi, Wei; Liu, Xuan; Chiodo, Vince A.; Ding, Xi-Qin; Zhao, Chen; Michalakis, Stylianos; Biel, Martin; Zhang, Zuoming; Qu, Jia; Hauswirth, William W.; Pang, Ji-jing

    2015-01-01

    The CNGA3−/−/Nrl−/− mouse is a cone-dominant model with Cnga3 channel deficiency, which partially mimics the all cone foveal structure of human achromatopsia 2 with CNGA3 mutations. Although subretinal (SR) AAV vector administration can transfect retinal cells efficiently, the injection-induced retinal detachment can cause retinal damage, particularly when SR vector bleb includes the fovea. We therefore explored whether cone function–structure could be rescued in CNGA3−/−/Nrl−/− mice by intravitreal (IVit) delivery of tyrosine to phenylalanine (Y-F) capsid mutant AAV8. We find that AAV-mediated CNGA3 expression can restore cone function and rescue structure following IVit delivery of AAV8 (Y447, 733F) vector. Rescue was assessed by restoration of the cone-mediated electroretinogram (ERG), optomotor responses, and cone opsin immunohistochemistry. Demonstration of gene therapy in a cone-dominant mouse model by IVit delivery provides a potential alternative vector delivery mode for safely transducing foveal cones in achromatopsia patients and in other human retinal diseases affecting foveal function. PMID:25855802

  18. Fractional thermolysis by bipolar radiofrequency facilitates cutaneous delivery of peptide and siRNA with minor loss of barrier function.

    Science.gov (United States)

    Lee, Woan-Ruoh; Shen, Shing-Chuan; Sun, Chi-Kuang; Aljuffali, Ibrahim A; Suen, Shih-Yun; Lin, Yin-Ku; Wang, Jhi-Joung; Fang, Jia-You

    2015-05-01

    In this study, we aimed to illustrate the utility of fractional radiofrequency (RF) that generated microchannels in the skin, allowing delivery of peptide and siRNA via the skin. The mechanisms involved in the correlation between macromolecule permeation and skin structure were also elucidated. The morphology of the skin was examined by transmission electron microscopy (TEM), higher harmonic generation microscopy (HGM), and physiological factors. In vivo skin distribution of macromolecules was assessed by fluorescence and confocal microscopies. RF thermolysis selectively created an array of micropores deep into the epidermis without significant removal of the stratum corneum (SC). With energy of 30 mJ, a pore depth of 35 μm was achieved. The bipolar RF resulted in a 3-fold increase of transepidermal water loss (TEWL) compared with intact skin. The respective skin accumulation and flux of the peptide with a molecular weight (MW) of 2335 Da was 3- and 23-fold greater for the RF-treated group than for the non-treatment group. RF enhanced skin accumulation of siRNAs with MW of 10 and 15 kDa by 6.2- and 2.6-fold, respectively. Cutaneous penetration of the macromolecules with an MW of at least 40 kDa could be accomplished by RF. Confocal microscopy imaging revealed that RF could effectively deliver the peptide up to at least a 74-μm depth. The penetration depth of siRNA by RF irradiation was about 50 μm. The novel RF device efficiently delivered macromolecules into the skin while reserving SC layers to support some barrier functions. In this work, for the first time the assistance of fractional RF on peptide and siRNA transport was demonstrated.

  19. Development of a Multi-functional Nano-device for Safe and Effective Gene Delivery to Target Organs.

    Science.gov (United States)

    Kodama, Yukinobu

    2016-01-01

     Nucleic acids are expected as novel effective medicines, although they require a drug delivery system (DDS). Complexes of nucleic acids with cationic liposomes and cationic polymers have been mainly used as DDS for clinical use. However, most cationic complexes have disadvantages such as strong cytotoxicity and low biocompatibility. We previously found that a plasmid DNA (pDNA) complex coated with biodegradable γ-polyglutamic acid (γ-PGA) provided adequate gene expression without cytotoxicity. Based on these results, we developed a new DDS (multi-functional Nano-device) of pDNA using biodegradable polyamino acids. A typical cationic polyamino acid, poly-L-lysine (PLL), was complexed with pDNA. The binary complexes, however, showed low gene expression and high cytotoxicity. Gene expression was enhanced by addition of poly-L-histidine (PLH) to the binary complexes. PLH can increase endosome escape of the complexes by inducing pH-buffering effects. The quaternary complexes (pDNA-PLL-PLH-γ-PGA complexes) exhibited high gene expression and low cytotoxicity. Furthermore, we used dendrigraft poly-L-lysine (DGL) instead of PLL and PLH to enhance gene expression. DGL had sterically congested cations and was biodegradable. The ternary complexes (pDNA-DGL-γ-PGA complexes) exhibited markedly high gene expression and low cytotoxicity. The pDNA-DGL-γ-PGA complexes also had high gene expression in the marginal zone (rich dendritic cells) of the spleen after intravenous injection into mice. These results indicate that pDNA-DGL-γ-PGA complexes may be useful as vaccine vectors. Therefore we prepared a novel malaria DNA vaccine using Plasmodium yoelii GPI8p-transamidase-related protein pDNA (PyTAM). The PyTAM-DGL-γ-PGA complexes markedly improved survival time of model mice infected with malaria.

  20. 功能材料在药物传递系统中的应用%Application of functional materials in drug delivery systems

    Institute of Scientific and Technical Information of China (English)

    许志刚; 彭蕊; 王东东; 徐双; 张海霞

    2014-01-01

    将功能材料引入到药物传递系统当中,极大地推动了药物传递系统研究方向的发展。重点介绍功能材料在药物传递系统中的应用现状,并总结了药物传递系统的发展趋势。%In recent years, studies in functional materials have obtained compelling achievements which are underpinned by the latest advancement in physical, chemical, biomedical and engineering sciences through the efforts of multidisciplinary research teams. Functional materials play a very important role in the field of biomedical application. Researchers have also brought functional materials into the field of drug delivery systems, which has greatly promoted the development of drug delivery systems. In this paper the current developments in the application of functional materials in drug delivery systems and the development trends were comprehensively reviewed.

  1. Single-walled carbon nanotubes noncovalently functionalized with lipid modified polyethylenimine for siRNA delivery in vitro and in vivo.

    Science.gov (United States)

    Siu, King S; Zheng, Xiufen; Liu, Yanling; Zhang, Yujuan; Zhang, Xusheng; Chen, Di; Yuan, Ken; Gillies, Elizabeth R; Koropatnick, James; Min, Wei-Ping

    2014-10-15

    siRNA can downregulate the expression of specific genes. However, delivery to specific cells and tissues in vivo presents significant challenges. Modified carbon nanotubes (CNTs) have been shown to protect siRNA and facilitate its entry into cells. However, simple and efficient methods to functionalize CNTs are needed. Here, noncovalent functionalization of CNTs is performed and shown to effectively deliver siRNA to target cells. Specifically, single-walled CNTs were functionalized by noncovalent association with a lipopolymer. The lipopolymer (DSPE-PEG) was composed of a phospholipid 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) and poly(ethylene glycol) (PEG). Three different ratios of polyethylenimine (PEI) to DSPE-PEG were synthesized and characterized and the products were used to disperse CNTs. The resulting materials were used for siRNA delivery in vitro and in vivo. The structural, biophysical, and biological properties of DGI/C and their complexes formed with siRNA were investigated. Cytotoxicity of the materials was low, and effective gene silencing in B16-F10 cells was demonstrated in vitro. In addition, significant uptake of siRNA as well as gene silencing in the liver was found following intravenous injection. This approach provides a new strategy for siRNA delivery and could provide insight for the development of noncovalently functionalized CNTs for siRNA therapy.

  2. Phosphate functionalized (4,4)-armchair CNTs as novel drug delivery systems for alendronate and etidronate anti-osteoporosis drugs.

    Science.gov (United States)

    Nikfar, Zahra; Shariatinia, Zahra

    2017-09-01

    The ability of (4,4)-armchair CNT and its three phosphate functionalized forms (CNT-nH2PO4, n=1-3) were evaluated as novel drug delivery systems (DDSs) for the two commercially well-known anti-osteoporosis drugs namely alendronate (AL) and etidronate (ET). For this purpose, the DFT calculations were accomplished at both B3LYP and B3PW91 levels using 6-31g(d) basis set. The binding energy was increased by increasing number of H2PO4 moieties attached on the CNT with the most negative binding energy was measured for the carrier containing three phosphate groups. The dipole moments of all phosphate containing CNTs were much greater (∼2.2-4.4D) than that of pristine CNT (∼0D). The contour maps proved that when the CNT was functionalized by H2PO4 groups, the symmetric distribution of electric charge was vanished with the charge distribution was the highest asymmetric for the CNT-2H2PO4 while it was the lowest asymmetric for CNT-3H2PO4 leading to the greatest dipole moment for the CNT-2H2PO4 (4.177D) while the smallest dipole moment for the CNT-3H2PO4 (1.614D). Among all compounds, those containing the CNT-3H2PO4 exhibited the smallest band gap energy, chemical potential and hardness but the greatest electronegativity and electrophilicity index which were all suitable and effective for the attachment of drugs onto the bone surface (having partial positive charge due to the presence of Ca(2+) as CaCO3) and therefore inhibiting the osteoporosis. Consequently, it was established that the drug-CNT-3H2PO4 was the most appropriate drug-carrier compound for both of the AL and ET drugs and it could be used as the most effective drug vehicle. The attachment of AL, ET drugs as well as the AL-CNT-3H2PO4 and ET-CNT-3H2PO4 drug-carrier systems to the bone tissue was modelled by optimization of the structures of these compounds bonded to the hydroxyapatite (HA)-17water (w). It was found that among these four systems, the AL-CNT-3H2PO4 could be suggested as the most suitable DDS for

  3. Transactivator of transcription (TAT peptide–chitosan functionalized multiwalled carbon nanotubes as a potential drug delivery vehicle for cancer therapy

    Directory of Open Access Journals (Sweden)

    Dong X

    2015-06-01

    Full Text Available Xia Dong, Lanxia Liu, Dunwan Zhu, Hailing Zhang, Xigang Leng Laboratory of Bioengineering, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Tianjin, People’s Republic of China Abstract: Carbon nanotube (CNT-based drug delivery vehicles might find great potential in cancer therapy via the combination of chemotherapy with photothermal therapy due to the strong optical absorbance of CNTs in the near-infrared region. However, the application of CNTs in cancer therapy was considerably constrained by their lack of solubility in aqueous medium, as well as the cytotoxicity caused by their hydrophobic surface. Intracellular delivery efficiency is another factor determining the application potential of CNTs in cancer therapy. In the present study, low-molecular-weight chitosan conjugated with transactivator of transcription (TAT peptide was used for noncovalent functionalization of multiwalled carbon nanotubes (MWCNTs, aiming at providing a more efficient drug delivery vehicle for cancer therapy. The TAT–chitosan-conjugated MWCNTs (MWCNTs-TC were further investigated for their water solubility, cytotoxicity, cell-penetrating capability, and accumulation in tumor. It was found that MWCNTs-TC were essentially nontoxic with satisfying water solubility, and they were more efficient in terms of cancer-targeted intracellular transport both in vitro and in vivo as compared with chitosan-modified MWCNTs (MWCNTs-CS, suggesting the great application potential of MWCNTs-TC in cancer therapy. Keywords: carbon nanotube, TAT, chitosan, drug delivery

  4. Delivery presentations

    Science.gov (United States)

    ... passage will take place depends on how your baby is positioned during delivery. The best position for the baby to be ... possible, but labor will generally take longer. After delivery, the baby's face or brow will be swollen and may ...

  5. Contribution of tap water to chlorate and perchlorate intake: a market basket study.

    Science.gov (United States)

    Asami, Mari; Yoshida, Nobue; Kosaka, Koji; Ohno, Koichi; Matsui, Yoshihiko

    2013-10-01

    The contributions of water to total levels of chlorate and perchlorate intake were determined using food and water samples from a market basket study from 10 locations in Japan between 2008 and 2009. Foods were categorized into 13 groups and analyzed along with tap water. The average total chlorate intake was 333 (min. 193-max. 486) μg/day for samples cooked with tap water. The contribution of tap water to total chlorate intake was as high as 47%-58%, although total chlorate intake was less than 32% of the tolerable daily intake, 1500 μg/day for body weight of 50 kg. For perchlorate, daily intake from water was 0.7 (0.1-4.4) μg/day, which is not high compared to the average total intake of 14 (2.5-84) μg/day, while the reference dose (RfD) is 35 μg/day and the provisional maximum tolerable daily intake (PMTDI) is 500 μg/day for body weight of 50 kg. The highest intake of perchlorate was 84 μg/day, where concentrations in foods were high, but not in water. The contribution of water to total perchlorate intake ranged from 0.5% to 22%, while the ratio of highest daily intake to RfD was 240% and that to PMTDI was 17%. Eight baby formulas were also tested--total chlorate and perchlorate intakes were 147 (42-332) μg/day and 1.11 (0.05-4.5) μg/day, respectively, for an ingestion volume of 1 L/day if prepared with tap water.

  6. EpiBasket: how e-commerce tools can improve epidemiological preparedness

    Directory of Open Access Journals (Sweden)

    Weijia Xing

    2013-10-01

    Full Text Available Background: Should an emerging infectious disease outbreak or an environmental disaster occur, the collection of epidemiological data must start as soon as possible after the event's onset. Questionnaires are usually built de novo for each event, resulting in substantially delayed epidemiological responses that are detrimental to the understanding and control of the event considered. Moreover, the public health and/or academic institution databases constructed with responses to different questionnaires are usually difficult to merge, impairing necessary collaborations. We aimed to show that e-commerce concepts and software tools can be readily adapted to enable rapid collection of data after an infectious disease outbreak or environmental disaster. Here, the ‘customers’ are the epidemiologists, who fill their shopping ‘baskets’ with standardised questions. Methods: For each epidemiological field, a catalogue of questions is constituted by identifying the relevant variables based on a review of the published literature on similar circumstances. Each question is tagged with information on its source papers. Epidemiologists can then tailor their own questionnaires by choosing appropriate questions from this catalogue. The software immediately provides them with ready-to-use forms and online questionnaires. All databases constituted by the different EpiBasket users are interoperable, because the corresponding questionnaires are derived from the same corpus of questions. Results: A proof-of-concept prototype was developed for Knowledge, Attitudes and Practice (KAP surveys, which is one of the fields of the epidemiological investigation frequently explored during, or after, an outbreak or environmental disaster. The catalogue of questions was initiated from a review of the KAP studies conducted during or after the 2003 severe acute respiratory syndrome epidemic. Conclusion: Rapid collection of standardised data after an outbreak or

  7. CO{sub 2} Capture from Flue Gas Using Solid Molecular Basket Sorbents

    Energy Technology Data Exchange (ETDEWEB)

    Fillerup, Eric; Zhang, Zhonghua; Peduzzi, Emanuela; Wang, Dongxiang; Guo, Jiahua; Ma, Xiaoliang; Wang, Xiaoxing; Song, Chunshan

    2012-08-31

    The objective of this project is to develop a new generation of solid, regenerable polymeric molecular basket sorbent (MBS) for more cost-efficient capture and separation of CO{sub 2} from flue gas of coal-fired power plants. The primary goal is to develop a cost-effective MBS sorbent with better thermal stability. To improve the cost-effectiveness of MBS, we have explored commercially available and inexpensive support to replace the more expensive mesoporous molecular sieves like MCM-41 and SBA- 15. In addition, we have developed some advanced sorbent materials with 3D pore structure such as hexagonal mesoporous silica (HMS) to improve the CO{sub 2} working capacity of MBS, which can also reduce the cost for the whole CO{sub 2} capture process. During the project duration, the concern regarding the desorption rate of MBS sorbents has been raised, because lower desorption rate increases the desorption time for complete regeneration of the sorbent which in turn leads to a lower working capacity if the regeneration time is limited. Thus, the improvement in the thermal stability of MBS became a vital task for later part of this project. The improvement in the thermal stability was performed via increasing the polymer density either using higher molecular weight PEI or PEI cross-linking with an organic compound. Moreover, we have used the computational approach to estimate the interaction of CO{sub 2} with different MBSs for the fundamental understanding of CO{sub 2} sorption, which may benefit the development, design and modification of the sorbents and the process.

  8. Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Li L

    2014-02-01

    Full Text Available Lei Li,1,* Dongxi Xiang,2,* Sarah Shigdar,2 Wenrong Yang,3 Qiong Li,2 Jia Lin,4 Kexin Liu,1 Wei Duan2 1College of Pharmacy, Dalian Medical University, Dalian, People's Republic of China; 2School of Medicine, Faculty of Health, Deakin University, Waurn Ponds, VIC, Australia; 3School of Life and Environmental Sciences, Faculty of Science, Engineering and Built Environment, Deakin University, Waurn Ponds, VIC, Australia; 4Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, People's Republic of China *These authors contributed equally to this work Abstract: To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles were synthesized and functionalized with ribonucleic acid (RNA Aptamers (Apts against epithelial cell adhesion molecule (EpCAM for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (P<0.01. Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug

  9. Enhanced Oral Delivery of Protein Drugs Using Zwitterion-Functionalized Nanoparticles to Overcome both the Diffusion and Absorption Barriers.

    Science.gov (United States)

    Shan, Wei; Zhu, Xi; Tao, Wei; Cui, Yi; Liu, Min; Wu, Lei; Li, Lian; Zheng, Yaxian; Huang, Yuan

    2016-09-28

    Oral delivery of protein drugs based on nanoparticulate delivery system requires permeation of the nanoparticles through the mucus layer and subsequent absorption via epithelial cells. However, overcoming these two barriers requires very different or even contradictory surface properties of the nanocarriers, which greatly limits the oral bioavailability of macromolecular drugs. Here we report a simple zwitterions-based nanoparticle (NP) delivery platform, which showed a great potency in simultaneously overcoming both the mucus and epithelium barriers. The dense and hydrophilic coating of zwitterions endows the NPs with excellent mucus penetrating ability. Moreover, the zwitterions-based NPs also possessed excellent affinity with epithelial cells, which significantly improved (4.5-fold) the cellular uptake of DLPC NPs, compared to PEGylated NPs. Our results also indicated that this affinity was due to the interaction between zwitterions and the cell surface transporter PEPT1. Moreover, the developed NPs loaded with insulin could induce a prominent hypoglycemic response in diabetic rats following oral administration. These results suggest that zwitterions-based NPs might provide a new perspective for oral delivery of protein therapeutics.

  10. Mussel inspired protein-mediated surface functionalization of electrospun nanofibers for pH-responsive drug delivery

    Science.gov (United States)

    Jiang, Jiang; Xie, Jingwei; Ma, Bing; Bartlett, David E.; Xu, An; Wang, Chi-Hwa

    2014-01-01

    pH-responsive drug delivery systems could mediate drug releasing rate by changing pH values at specific time as per the pathophysiological need of the disease. Herein, we demonstrated a mussel inspired protein polydopamine coating can tune the loading and releasing rate of charged molecules from electrospun poly (ε-caprolactone) (PCL) nanofibers in solutions with different pH values. In vitro release profiles showed that the positive charged molecules released significantly faster in acidic than those in neutral and basic environments within the same incubation time. The results of fluorescein diacetate staining and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays showed the viability of cancer cells after treatment with doxorubicin released media at different pH values qualitatively and quantitatively, indicating the media contained doxorubicin which was released in solutions at low pH values could kill significantly higher number of cells than that released in solutions at high pH values. Together, the pH-responsive drug delivery systems based on polydopamine-coated PCL nanofibers could have potential applications in oral delivery of anticancer drugs for treating gastric cancer and vaginal delivery of anti-viral drugs or anti-inflammatory drugs, which could raise their efficacy, deliver them to the specific target, and minimize their toxic side effects. PMID:24287161

  11. Usefulness of chewing gum for recovering intestinal function after cesarean delivery: A systematic review and meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Hua-Ping Huang

    2015-04-01

    Full Text Available Chewing gum has been reported to enhance bowel function. However, the efficacy remains unclear for women undergoing cesarean delivery. The aim of this meta-analysis is to evaluate the efficacy of chewing gum for recovering intestinal function following cesarean delivery in the early postoperative period. Electronic databases including MEDLINE, EMBASE, Cochrane Library were searched to identify English language randomized controlled trials comparing chewing gum with other procedures for promoting the recovery of intestinal function after cesarean delivery. Two of the authors independently extracted data from the eligibility studies, and Review Manager Version 5.2 was used to pool the data. Finally, five randomized controlled trials involving 882 patients were included and all the trials were considered as at high risk of bias. The pooled findings showed that chewing gum after cesarean delivery can significantly shorten the time to first flatus [standardized mean difference (SMD = −0.73; 95% confidence interval (CI = −1.01 to −0.14; p < 0.001]; time to first hearing of normal intestinal sounds (SMD = −0.69; 95% CI = −1.20 to −0.17; p = 0.009; I² = 92%. Time to the first defecation (SMD = −0.53; 95% CI = −1.61 to −0.07; p = 0.07; I² = 92% and length of hospital stay (SMD = −0.59; 95% CI = −1.18 to 0.00; p = 0.05; I² = 93% were also reduced in the chewing gum group; however, these results were not statistically significant. The current evidence suggests that chewing gum has a positive effect on intestinal function recovery following cesarean delivery in the early postoperative period. However, more large-scale and high-quality randomized controlled trials are needed to confirm these results.

  12. Do the equity-efficiency preferences of the Israeli Basket Committee match those of Israeli health policy makers?

    Science.gov (United States)

    Shmueli, Amir

    2017-01-01

    Prioritization of medical technologies requires a multi-dimensional view. Often, conflicting equity and efficiency criteria should be reconciled. The most dramatic manifestation of such conflict is in the prioritization of new medical technologies asking for public finance performed yearly by the Israeli Basket Committee. The aim of this paper is to compare the revealed preferences of the 2006/7 Basket Committee's members with the declared preferences of health policy-makers in Israel. We compared the ranking of a sample of 18 accepted and 16 rejected technologies evaluated by the 2006/7 Basket Committee with the ranking of these technologies as predicted based on the preferences of Israeli health policy-makers. These preferences were elicited by a recent Discrete Choice Experiment (DCE) which estimated the relative weights of four equity and three efficiency criteria. The candidate technologies were characterized by these seven criteria, and their ranking was determined. A third comparative ranking of these technologies was the efficiency ranking, which is based on international data on cost per QALY gained. The Committee's ranking of all technologies show no correspondence with the policy-makers' ranking. The correlation between the two is negative when only accepted technologies are ranked. The Committee's ranking is positively correlated with the efficiency ranking, while the health policy-makers' ranking is not. The Committee appeared to assign to efficiency considerations a higher weight than assigned by health policy-makers. The main explanation is that while policy-makers' ranking is based on stated preferences, that of the Committee reflects revealed preferences. Real life prioritization, made under a budget constraint, enhances the importance of efficiency considerations at the expense of equity ones. In order for Israeli health policy to be consistent and well coordinated across policy-makers, some discussions and exchanges are needed, to arrive at a

  13. Dual-peptide-functionalized albumin-based nanoparticles with ph-dependent self-assembly behavior for drug delivery.

    Science.gov (United States)

    Chen, Bin; He, Xiao-Yan; Yi, Xiao-Qing; Zhuo, Ren-Xi; Cheng, Si-Xue

    2015-07-22

    Drug delivery has become an important strategy for improving the chemotherapy efficiency. Here we developed a multifunctionalized nanosized albumin-based drug-delivery system with tumor-targeting, cell-penetrating, and endolysosomal pH-responsive properties. cRGD-BSA/KALA/DOX nanoparticles were fabricated by self-assembly through electrostatic interaction between cell-penetrating peptide KALA and cRGD-BSA, with cRGD as a tumor-targeting ligand. Under endosomal/lysosomal acidic conditions, the changes in the electric charges of cRGD-BSA and KALA led to the disassembly of the nanoparticles to accelerate intracellular drug release. cRGD-BSA/KALA/DOX nanoparticles showed an enhanced inhibitory effect in the growth of αvβ3-integrin-overexpressed tumor cells, indicating promising application in cancer treatments.

  14. All-optical control of neuronal function via optical delivery of light-sensitive proteins and optogenetic stimulation

    Science.gov (United States)

    Villalobos, Alex; Gu, Ling; Mohanty, Samarendra

    2012-02-01

    While pulsed laser beams have been used for stimulation of neurons, cellular specificity during optical stimulation is achieved by photo-sensitization of genetically-targeted cells by optogenetic means. However, till date, the process of optogenetic-sensitization primarily involves use of viral vectors. In rare occasions, electroporation has been used. Here, we report an all-optical method in which pulsed laser beam is used for delivery of genes, encoding optogenetic probes, to spatially-targeted cells, followed by optogenetic stimulation and optical detection of the activation process. Use of laser microbeam enabled highly precise spatially-patterned delivery of optogenes, as confirmed by expression of conjugated fluorescent protein. Light-activation of opsin-expressing cells was confirmed by calcium-imaging. The laser-assisted expression of optogenetic probes in spatially-targeted regions in combination with light-assisted activation and optical detection of neural activity will help in better understanding of the neuronal circuitry.

  15. Colloidal drug delivery systems in vaccine delivery.

    Science.gov (United States)

    Beg, Sarwar; Samad, Abdus; Nazish, Iram; Sultana, Ruksar; Rahman, Mahfoozur; Ahmad, Md Zaki; Akbar, Md

    2013-01-01

    Vaccines play a vital role in the field of community medicine to combat against several diseases of human existence. Vaccines primarily trigger the acquired immune system to develop long-lasting immunity against pathogens. Conventional approaches for vaccine delivery lacks potential to target a particular antigen to develop acquired immunity by specific antibodies. Recent advancements in vaccine delivery showed that inclusion of adjuvants in vaccine formulations or delivery of them in a carrier helps in achieving desired targeting ability, reducing the immunogenicity and significant augmentation in the immune response. Colloidal carriers (liposomes, niosomes, microspheres, proteosomes, virosomes and virus like particles (VLPs), antigen cochleates, dendrimers and carbon nanotubes) have been widely explored for vaccine delivery. Further, surface engineering of these carriers with ligands, functional moieties and monoclonal antibodies tend to enhance the immune recognition potential of vaccines by differentiation of antigen specific memory T-cells. The current review, therefore, provides an updated account on the recent advancements in various colloidal delivery systems in vaccine delivery, outlining the mechanism of immune response initiated by them along with potential applications and marketed instances in an explicit manner.

  16. Fabrication of functional hollow microspheres constructed from MOF shells: Promising drug delivery systems with high loading capacity and targeted transport

    Science.gov (United States)

    Gao, Xuechuan; Hai, Xiao; Baigude, Huricha; Guan, Weihua; Liu, Zhiliang

    2016-11-01

    An advanced multifunctional, hollow metal-organic framework (MOF) drug delivery system with a high drug loading level and targeted delivery was designed and fabricated for the first time and applied to inhibit tumour cell growth. This hollow MOF targeting drug delivery system was prepared via a simple post-synthetic surface modification procedure, starting from hollow ZIF-8 successfully obtained for the first time via a mild phase transformation under solvothermal conditions. As a result, the hollow ZIF-8 exhibits a higher loading capacity for the model anticancer drug 5-fluorouracil (5-FU). Subsequently, 5-FU-loaded ZIF-8 was encapsulated into polymer layers (FA-CHI-5-FAM) with three components: a chitosan (CHI) backbone, the imaging agent 5-carboxyfluorescein (5-FAM), and the targeting reagent folic acid (FA). Thus, an advanced drug delivery system, ZIF-8/5-FU@FA-CHI-5-FAM, was fabricated. A cell imaging assay demonstrated that ZIF-8/5-FU@FA-CHI-5-FAM could target and be taken up by MGC-803 cells. Furthermore, the as-prepared ZIF-8/5-FU@FA-CHI-5-FAM exhibited stronger cell growth inhibitory effects on MGC-803 cells because of the release of 5-FU, as confirmed by a cell viability assay. In addition, a drug release experiment in vitro indicated that ZIF-8/5-FU@FA-CHI-5-FAM exhibited high loading capacity (51%) and a sustained drug release behaviour. Therefore, ZIF-8/5-FU@FA-CHI-5-FAM could provide targeted drug transportation, imaging tracking and localized sustained release.

  17. Functional study of dextran-graft-poly((2-dimethyl amino)ethyl methacrylate) gene delivery vector for tumor therapy.

    Science.gov (United States)

    Li, Wen-Bin; Yuan, Wei; Xu, Fu-Jian; Zhao, Chen; Ma, Jie; Zhan, Qi-Min

    2013-07-01

    The obstacle of gene therapy is the shortage of efficient delivery system. The development of the gene delivery system with high transfection efficiency and low toxicity appears to be crucial. Recently, we reported that the dextran-graft-poly((2-dimethyl amino)ethyl methacrylate) (DPD) can be potentially used as efficient gene vector. Herein, DPD was systematically studied for its potential in tumor gene therapy. DPD was synthesized and characterized by agarose gel electrophoresis, particle size and zeta potential. The particle size and zeta potential of the DPD/enhanced green fluorescent protein (pEGFP-C1) plasmid complexes at various N/P ratios were 130-150 nm and about 40 mV, respectively. The results showed that DPD exhibit a higher transfection effect compared with Lipofectamine 2K (Lipo 2K), a commercialized vector. The possibility of DPD in gene therapy was evaluated using p53, a gene that has been wildly applied in the research of cancer gene therapy. DPD/pEGFP-C1-p53 complex was found to be able to inhibit tumor cell proliferation through cell cycle arrest and apoptosis. Moreover, the tumor growth was found to be restrained when DPD/pEGFP-C1-p53 complex was used in a xenograft MCF7 tumor model in vivo. These observations indicated that DPD/pEGFP-C1-p53 complex may be considered to be an efficient delivery system for tumor gene therapy.

  18. A VEGF delivery system targeting MI improves angiogenesis and cardiac function based on the tropism of MSCs and layer-by-layer self-assembly.

    Science.gov (United States)

    Liu, Ge; Li, Li; Huo, Da; Li, Yanzhao; Wu, Yangxiao; Zeng, Lingqing; Cheng, Panke; Xing, Malcolm; Zeng, Wen; Zhu, Chuhong

    2017-05-01

    Myocardial infarction (MI) is a serious ischemic condition affecting many individuals around the world. Vascular endothelial growth factor (VEGF) is considered a promising factor for enhancing cardiac function by promoting angiogenesis. However, the lack of a suitable method of VEGF delivery to the MI area is a serious challenge. In this study, we screened a suitable delivery carrier with favorable biocompatibility that targeted the MI area using the strategy of an inherent structure derived from the body and that was based on characteristics of the MI. Mesenchymal stem cells (MSCs) are important infiltrating cells that are derived from blood and have an inherent tropism for the MI zone. We hypothesized that VEGF-encapsulated MSCs targeting MI tissue could improve cardiac function by angiogenesis based on the tropism of the MSCs to the MI area. We first developed VEGF-encapsulated MSCs using self-assembled gelatin and alginate polyelectrolytes to improve angiogenesis and cardiac function. In vitro, the results showed that VEGF-encapsulated MSCs had a sustained release of VEGF and tropism to SDF-1. In vivo, VEGF-encapsulated MSCs migrated to the MI area, enhanced cardiac function, perfused the infarcted area and promoted angiogenesis. These preclinical findings suggest that VEGF-loaded layer-by-layer self-assembled encapsulated MSCs may be a promising and minimally invasive therapy for treating MI. Furthermore, other drugs loaded to layer-by-layer self-assembled encapsulated MSCs may be promising therapies for treating other diseases.

  19. Nanotopography applications in drug delivery

    Science.gov (United States)

    Walsh, Laura A; Allen, Jessica L; Desai, Tejal A

    2016-01-01

    Refinement of micro- and nanofabrication in the semiconductor field has led to innovations in biomedical technologies. Nanotopography, in particular, shows great potential in facilitating drug delivery. The flexibility of fabrication techniques has created a diverse array of topographies that have been developed for drug delivery applications. Nanowires and nanostraws deliver drug cytosolically for in vitro and ex vivo applications. In vivo drug delivery is limited by the barrier function of the epithelium. Nanowires on microspheres increase adhesion and residence time for oral drug delivery, while also increasing permeability of the epithelium. Low aspect ratio nanocolumns increase paracellular permeability, and in conjunction with microneedles increase transdermal drug delivery of biologics in vivo. In summary, nanotopography is a versatile tool for drug delivery. It can deliver directly to cells or be used for in vivo delivery across epithelial barriers. This editorial highlights the application of nanotopography in the field of drug delivery. PMID:26512871

  20. Kajian Algoritma Sequential Pattern Mining Dan Market Basket Analysis Dalam Pengenalan Pola Belanja Customer Untuk Layout Toko

    Directory of Open Access Journals (Sweden)

    Rusito Rusito

    2016-01-01

    Full Text Available Penelitian ini membahas tentang keterkaitan antar item yang dibeli oleh customer dalam toko ritel. Pengetahuan keterkaitan item yang dibeli dapat digunakan untuk  menentukan tata letak barang dagangan toko ritel. Hal ini penting agar konsumen dapat mudah mendapatkan barang yang dibutuhkan. Sehingga dapat meningkatkan omzet penjualan toko ritel sehingga akhirnya menambah keuntungan bagi pemilik toko ritel. Teknik yang digunakan untuk menyelesaikan penggalian data dan keterkaitan pembelian tersebut menggunakan pendekatan Association rule dan Market Basket Analysis. Sedangkan untuk mencari keterkaitan item tersebut digunakan algoritma Sequential Pattern Mining. Digunakan karena mampu menangani jumlah database yang besar dan sangat baik disisi kecepatan pemrosesan. Berbagai aplikasi telah diidentifikasi, termasuk misalnya, cross-selling, analisis situs Web, pendukung keputusan, evaluasi kredit, acara prediksi kriminal, analisis perilaku pelanggan  dan deteksi penipuan. Dari penelitian yang telah dilakukan diperoleh  pola-pola belanja customer untuk membentuk suatu layout display dalam toko ritel. Penelitian ini juga menyajikan suatu kerja algoritma yang lebih efektif dari algoritma asli karena terdapat pembatasan perulangan. Untuk kombinasi maksimal 5 item dengan waktu eksekusi 421.06 detik untuk 200 nota.   Kata kunci : Data Mining, Algoritma Sequential Pattern Mining, Market Basket Analysis, Apriori, Layout, Toko Ritel

  1. MUCOSAL DRUG DELIVERY SYSTEM

    OpenAIRE

    Madan Jyotsana; Banode Sagar; Dangi Mahesh

    2010-01-01

    The process of mucoadhesion involving a polymeric drug delivery system is a complex one that includes processes such as wetting, adsorption and interpenetration of polymer chains. The success and degree of mucoadhesion bonding is influenced by various polymer-based properties such as the degree of cross-linking, chain length and the presence of various functional groupings. The attractiveness of mucosal-targeted controlled drug delivery of active pharmaceutical ingredients, has led formulatio...

  2. Forceps Delivery

    Science.gov (United States)

    ... in place to control the advance of your baby's head. Forceps deliveries aren't always successful. If your health care ... com. Accessed June 12, 2015. You and your baby: Prenatal care, labor and delivery, and postpartum care. Washington, D.C.: The American ...

  3. Commissioning and early experience with a new-generation low-energy linear accelerator with advanced delivery and imaging functionalities

    Directory of Open Access Journals (Sweden)

    Fogliata Antonella

    2011-09-01

    Full Text Available Abstract Background A new-generation low-energy linear accelerator (UNIQUE was introduced in the clinical arena during 2009 by Varian Medical Systems. The world's first UNIQUE was installed at Oncology Institute of Southern Switzerland and put into clinical operation in June 2010. The aim of the present contribution was to report experience about its commissioning and first year results from clinical operation. Methods Commissioning data, beam characteristics and the modeling into the treatment planning system were summarized. Imaging system of UNIQUE included a 2D-2D matching capability and tests were performed to identify system repositioning capability. Finally, since the system is capable of delivering volumetric modulated arc therapy with RapidArc, a summary of the tests performed for such modality to assess its performance in preclinical settings and during clinical usage was included. Results Isocenter virtual diameter was measured as less than 0.2 mm. Observed accuracy of isocenter determination and repositioning for 2D-2D matching procedures in image guidance was Conclusions The results of the commissioning tests and of the first period of clinical operation, resulted meeting specifications and having good margins respect to tolerances. UNIQUE was put into operation for all delivery techniques; in particular, as shown by the pre-treatment quality assurance results, it enabled accurate and safe delivery of RapidArc plans.

  4. Smart bomb AS1411 aptamer-functionalized/PAMAM dendrimer nanocarriers for targeted drug delivery in the treatment of gastric cancer.

    Science.gov (United States)

    Barzegar Behrooz, Amir; Nabavizadeh, Fatemeh; Adiban, Jamal; Shafiee Ardestani, Mehdi; Vahabpour, Rouhollah; Aghasadeghi, Mohammad Reza; Sohanaki, Hamid

    2017-01-01

    Chemotherapy, a conventional method assessed in recent oncology studies, poses numerous problems in the clinical environment. To overcome the problems inherent in chemotherapy, an intelligent drug delivery system has come to the forefront of cancer therapeutics. In this study, we designed a dendrimer-based pharmaceutical system together with a single-stranded AS1411 aptamer (APT(AS)(1411) ) as a therapeutic strategy. The polyamidoamine (PAMAM)-polyethylene glycol (PEG) complex was then conjugated with the AS1411 aptamer and confirmed by atomic-force microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR) .In this study, we show that the conjugated PAMAM-PEG-APT(AS)(1411) complex dramatically increased PAMAM-PEG-5-FU uptake by MKN45 gastric cancer cells. We also demonstrated both the stability of the nanoparticle-5-FU-APT(AS)(1411) complex, by thin layer chromatography (TLC), and an increase in 5-fluorouracil (5-FU) accumulation in the vicinity of cancerous tumors. This smart drug delivery system is capable of effectively transferring 5-FU to MKN45 gastric cancer cells in consistent and without toxic effects.

  5. Ethylenediamine functionalized-single-walled nanotube (f-SWNT-assisted in vitro delivery of the oncogene suppressor p53 gene to breast cancer MCF-7 cells

    Directory of Open Access Journals (Sweden)

    Karmakar A

    2011-05-01

    Full Text Available Alokita Karmakar2, Stacie M Bratton1, Enkeleda Dervishi2, Anindya Ghosh3, Meena Mahmood2, Yang Xu2, Lamya Mohammed Saeed2, Thikra Mustafa2, Dan Casciano2, Anna Radominska-Pandya1, Alexandru S Biris21Biochemistry Department, University of Arkansas for Medical Sciences; 2Nanotechnology Center, Applied Science Department; 3Department of Chemistry, University of Arkansas, Little Rock, AR, USAAbstract: A gene delivery concept based on ethylenediamine-functionalized single-walled carbon nanotubes (f-SWCNTs using the oncogene suppressor p53 gene as a model gene was successfully tested in vitro in MCF-7 breast cancer cells. The f-SWCNTs-p53 complexes were introduced into the cell medium at a concentration of 20 µg mL-1 and cells were exposed for 24, 48, and 72 hours. Standard ethidium bromide and acridine orange assays were used to detect apoptotic cells and indicated that a significantly larger percentage of the cells (approx 40% were dead after 72 hours of exposure to f-SWCNTs-p53 as compared to the control cells, which were exposed to only p53 or f-SWCNTs, respectively. To further support the uptake and expression of the genes within the cells, green fluorescent protein-tagged p53, attached to the f-SWCNTs was added to the medium and the complex was observed to be strongly expressed in the cells. Moreover, caspase 3 activity was found to be highly enhanced in cells incubated with the f-SWCNTs-p53 complex, indicating strongly induced apoptosis. This system could be the foundation for novel gene delivery platforms based on the unique structural and morphological properties of multi-functional nanomaterials.Keywords: carbon nanotubes, gene delivery, cancer cells, p53 oncogene suppressor

  6. Preemptive heme oxygenase-1 gene delivery reveals reduced mortality and preservation of left ventricular function 1 yr after acute myocardial infarction.

    Science.gov (United States)

    Liu, Xiaoli; Simpson, Jeremy A; Brunt, Keith R; Ward, Christopher A; Hall, Sean R R; Kinobe, Robert T; Barrette, Valerie; Tse, M Yat; Pang, Stephen C; Pachori, Alok S; Dzau, Victor J; Ogunyankin, Kofo O; Melo, Luis G

    2007-07-01

    We reported previously that predelivery of heme oxygenase-1 (HO-1) gene to the heart by adeno-associated virus-2 (AAV-2) markedly reduces ischemia and reperfusion (I/R)-induced myocardial injury. However, the effect of preemptive HO-1 gene delivery on long-term survival and prevention of postinfarction heart failure has not been determined. We assessed the effect of HO-1 gene delivery on long-term survival, myocardial function, and left ventricular (LV) remodeling 1 yr after myocardial infarction (MI) using echocardiographic imaging, pressure-volume (PV) analysis, and histomorphometric approaches. Two groups of Lewis rats were injected with 2 x 10(11) particles of AAV-LacZ (control) or AAV-human HO-1 (hHO-1) in the anterior-posterior apical region of the LV wall. Six weeks after gene transfer, animals were subjected to 30 min of ischemia by ligation of the left anterior descending artery followed by reperfusion. Echocardiographic measurements and PV analysis of LV function were obtained at 2 wk and 12 mo after I/R. One year after acute MI, mortality was markedly reduced in the HO-1-treated animals compared with the LacZ-treated animals. PV analysis demonstrated significantly enhanced LV developed pressure, elevated maximal dP/dt, and lower end-diastolic volume in the HO-1 animals compared with the LacZ animals. Echocardiography showed a larger apical anterior-to-posterior wall ratio in HO-1 animals compared with LacZ animals. Morphometric analysis revealed extensive myocardial scarring and fibrosis in the infarcted LV area of LacZ animals, which was reduced by 62% in HO-1 animals. These results suggest that preemptive HO-1 gene delivery may be useful as a therapeutic strategy to reduce post-MI LV remodeling and heart failure.

  7. Development of an Innovative Intradermal siRNA Delivery System Using a Combination of a Functional Stearylated Cytoplasm-Responsive Peptide and a Tight Junction-Opening Peptide

    Directory of Open Access Journals (Sweden)

    Hisako Ibaraki

    2016-09-01

    Full Text Available As a new category of therapeutics for skin diseases including atopic dermatitis (AD, nucleic acids are gaining importance in the clinical setting. Intradermal administration is noninvasive and improves patients′ quality of life. However, intradermal small interfering RNA (siRNA delivery is difficult because of two barriers encountered in the skin: intercellular lipids in the stratum corneum and tight junctions in the stratum granulosum. Tight junctions are the major barrier in AD; therefore, we focused on functional peptides to devise an intradermal siRNA delivery system for topical skin application. In this study, we examined intradermal siRNA permeability in the tape-stripped (20 times back skin of mice or AD-like skin of auricles treated with 6-carboxyfluorescein-aminohexyl phosphoramidite (FAM-labeled siRNA, the tight junction modulator AT1002, and the functional cytoplasm-responsive stearylated peptide STR-CH2R4H2C by using confocal laser microscopy. We found that strong fluorescence was observed deep and wide in the epidermis and dermis of back skin and AD-like ears after siRNA with STR-CH2R4H2C and AT1002 treatment. After 10 h from administration, brightness of FAM-siRNA was significantly higher for STR-CH2R4H2C + AT1002, compared to other groups. In addition, we confirmed the nontoxicity of STR-CH2R4H2C as a siRNA carrier using PAM212 cells. Thus, our results demonstrate the applicability of the combination of STR-CH2R4H2C and AT1002 for effective intradermal siRNA delivery.

  8. Surface functionalization of inorganic nano-crystals with fibronectin and E-cadherin chimera synergistically accelerates trans-gene delivery into embryonic stem cells.

    Science.gov (United States)

    Kutsuzawa, K; Chowdhury, E H; Nagaoka, M; Maruyama, K; Akiyama, Y; Akaike, T

    2006-11-24

    Stem cells holding great promises in regenerative medicine have the potential to be differentiated to a specific cell type through genetic manipulation. However, conventional ways of gene transfer to such progenitor cells suffer from a number of disadvantages particularly involving safety and efficacy issues. Here, we report on the development of a bio-functionalized inorganic nano-carrier of DNA by embedding fibronectin and E-cadherin chimera on the carrier, leading to its high affinity interactions with embryonic stem cell surface and accelerated trans-gene delivery for subsequent expression. While only apatite nano-particles were very inefficient in transfecting embryonic stem cells, fibronectin-anchored particles and to a more significant extent, fibronectin and E-cadherin-Fc-associated particles dramatically enhanced trans-gene delivery with a value notably higher than that of commercially available lipofection system. The involvement of both cell surface integrin and E-cadherin in mediating intracellular localization of the hybrid carrier was verified by blocking integrin binding site with excess free fibronectin and up-regulating both integrin and E-cadherin through PKC activation. Thus, the new establishment of a bio-functional hybrid gene-carrier would promote and facilitate development of stem cell-based therapy in regenerative medicine.

  9. A facile one-pot synthesis of starch functionalized graphene as nano-carrier for pH sensitive and starch-mediated drug delivery.

    Science.gov (United States)

    Liu, Kunping; Wang, Yimin; Li, Huiming; Duan, Yixiang

    2015-04-01

    A fast, green and facile method was developed to prepare starch functionalized graphene nanosheets (starch-GNS) via the reduction of exfoliated graphene oxides by soluble starch, which acted both as a reductant and as a functionalization reagent for capping graphene nanosheets to prevent aggregation. The as-prepared starch-GNS exhibited good biocompatibility, which was deemed crucial for the biomedical application of graphene. Cellular toxicity tests suggested that the starch-GNS was nontoxic to SW-620 cells even at the relatively concentration of 200 μg mL(-1). After the loading of the commonly used anticancer drug hydroxycamptothecin (HCPT) via physisorption on starch-GNS, the HCPT@starch-GNS composite exhibited a high drug loading capacity and was therefore used for cellular imaging and drug delivery studies. Through the nonspecific endocytosis effect, the HCPT@starch-GNS composite was encapsulated into cytoplasm by SW-620 cancer cells. With the double action of an acid microenvironment and the diastase in SW-620 cells, the HCPT@starch-GNS composite showed high toxicity to the SW-620 cells and experienced a pH sensitive as well as a starch-mediated in vitro sustained release process, which had the potential advantage of improving therapeutic efficacy. Therefore, the starch-GNS composite could be used as an ideal nano-carrier for drug delivery and offered a new avenue for broadening the application of graphene in biomedicine. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Ethylenediamine functionalized-single-walled nanotube (f-SWNT)-assisted in vitro delivery of the oncogene suppressor p53 gene to breast cancer MCF-7 cells.

    Science.gov (United States)

    Karmakar, Alokita; Bratton, Stacie M; Dervishi, Enkeleda; Ghosh, Anindya; Mahmood, Meena; Xu, Yang; Saeed, Lamya Mohammed; Mustafa, Thikra; Casciano, Dan; Radominska-Pandya, Anna; Biris, Alexandru S

    2011-01-01

    A gene delivery concept based on ethylenediamine-functionalized single-walled carbon nanotubes (f-SWCNTs) using the oncogene suppressor p53 gene as a model gene was successfully tested in vitro in MCF-7 breast cancer cells. The f-SWCNTs-p53 complexes were introduced into the cell medium at a concentration of 20 μg mL(-1) and cells were exposed for 24, 48, and 72 hours. Standard ethidium bromide and acridine orange assays were used to detect apoptotic cells and indicated that a significantly larger percentage of the cells (approx 40%) were dead after 72 hours of exposure to f-SWCNTs-p53 as compared to the control cells, which were exposed to only p53 or f-SWCNTs, respectively. To further support the uptake and expression of the genes within the cells, green fluorescent protein-tagged p53, attached to the f-SWCNTs was added to the medium and the complex was observed to be strongly expressed in the cells. Moreover, caspase 3 activity was found to be highly enhanced in cells incubated with the f-SWCNTs-p53 complex, indicating strongly induced apoptosis. This system could be the foundation for novel gene delivery platforms based on the unique structural and morphological properties of multi-functional nanomaterials.

  11. Photomechanical wave-driven delivery of siRNAs targeting intermediate filament proteins promotes functional recovery after spinal cord injury in rats.

    Directory of Open Access Journals (Sweden)

    Takahiro Ando

    Full Text Available The formation of glial scars after spinal cord injury (SCI is one of the factors inhibiting axonal regeneration. Glial scars are mainly composed of reactive astrocytes overexpressing intermediate filament (IF proteins such as glial fibrillary acidic protein (GFAP and vimentin. In the current study, we delivered small interfering RNAs (siRNAs targeting these IF proteins to SCI model rats using photomechanical waves (PMWs, and examined the restoration of motor function in the rats. PMWs are generated by irradiating a light-absorbing material with 532-nm nanosecond laser pulses from a Q-switched Nd:YAG laser. PMWs can site-selectively increase the permeability of the cell membrane for molecular delivery. Rat spinal cord was injured using a weight-drop device and the siRNA(s solutions were intrathecally injected into the vicinity of the exposed SCI, to which PMWs were applied. We first confirmed the substantial uptake of fluorescence-labeled siRNA by deep glial cells; then we delivered siRNAs targeting GFAP and vimentin into the lesion. The treatment led to a significant improvement in locomotive function from five days post-injury in rats that underwent PMW-mediated siRNA delivery. This was attributable to the moderate silencing of the IF proteins and the subsequent decrease in the cavity area in the injured spinal tissue.

  12. Poly-functional and long-lasting anticancer immune response elicited by a safe attenuated Pseudomonas aeruginosa vector for antigens delivery

    Directory of Open Access Journals (Sweden)

    Xavier Chauchet

    2016-01-01

    Full Text Available Live-attenuated bacterial vectors for antigens delivery have aroused growing interest in the field of cancer immunotherapy. Their potency to stimulate innate immunity and to promote intracellular antigen delivery into antigen-presenting cells could be exploited to elicit a strong and specific cellular immune response against tumor cells. We previously described genetically-modified and attenuated Pseudomonas aeruginosa vectors able to deliver in vivo protein antigens into antigen-presenting cells, through Type 3 secretion system of the bacteria. Using this approach, we managed to protect immunized mice against aggressive B16 melanoma development in both a prophylactic and therapeutic setting. In this study, we further investigated the antigen-specific CD8+ T cell response, in terms of phenotypic and functional aspects, obtained after immunizations with a killed but metabolically active P. aeruginosa attenuated vector. We demonstrated that P. aeruginosa vaccine induces a highly functional pool of antigen-specific CD8+ T cell able to infiltrate the tumor. Furthermore, multiple immunizations allowed the development of a long-lasting immune response, represented by a pool of predominantly effector memory cells which protected mice against late tumor challenge. Overall, killed but metabolically active P. aeruginosa vector is a safe and promising approach for active and specific antitumor immunotherapy.

  13. Organic-Inorganic Hybrid Materials Based on Basket-like {Ca⊂P6Mo18O73} Cages.

    Science.gov (United States)

    Zhang, He; Yu, Kai; Lv, Jing-hua; Gong, Li-hong; Wang, Chun-mei; Wang, Chun-xiao; Sun, Di; Zhou, Bai-Bin

    2015-07-20

    Four basket-like organic-inorganic hybrids, formulated as [{Cu(II)(H2O)2}{Ca4(H2O)4(HO0.5)3(en)2}{Ca⊂P6Mo4(V)Mo14(VI)O73}]·7H2O (1), (H4bth)[{Fe(II)(H2O)}{Ca⊂P6Mo18(VI)O73}]·4H2O (2), (H2bih)3[{Cu(II)(H2O)2}{Ca⊂P6Mo2(V)Mo16(VI)O73}]·2H2O (3), (H2bib)3[{Fe(II)(H2O)2}{Ca⊂P6Mo2(V) Mo16(VI)O73}]·4H2O (4), (bth = 1,6-bis(triazole)hexane; bih = 1,6-bis(imidazol)hexane; bib = 1,4-bis(imidazole)butane) have been hydrothermally synthesized and fully characterized. Compounds 1-4 contain polyoxoanion [Ca⊂P6Mon(V)Mo18-n(VI)O73]((6+n)-) (n = 0, 2, or 4) (abbreviated as {P6Mo18O73}) as a basic building block, which is composed of a "basket body" {P2Mo14} unit and a "handle"-liked {P4Mo4} fragment encasing an alkaline-earth metal Ca(2+) cation in the cage. Compound 1 exhibits an infrequent 2D layer structure linked by the Cu(H2O)2 linker and an uncommon tetranuclear calcium complex, while compound 2 is 8-connected 2-D layers connected by binuclear {Fe2(H2O)3} segaments, which are observed for the first time as 2-D basket-like assemblies. Compounds 3 and 4 are similar 1D Z-typed chains bonded by M(H2O)2 units (M = Cu for 3 and Fe for 4). The optical band gaps of 1-4 reveal their semiconductive natures. They exhibit universal highly efficient degradation ability for typical dyes such as methylene blue, methyl orange, and rhodamine B under UV light. The lifetime and catalysis mechanism of the catalysts have been investigated. The compounds also show good bifunctional electrocatalytic behavior for oxidation of amino acids and reduction of NO2(-).

  14. Photoclick Hydrogels Prepared from Functionalized Cyclodextrin and Poly(ethylene glycol) for Drug Delivery and in Situ Cell Encapsulation.

    Science.gov (United States)

    Shih, Han; Lin, Chien-Chi

    2015-07-13

    Polymers or hydrogels containing modified cyclodextrin (CD) are highly useful in drug delivery applications, as CD is a cytocompatible amphiphilic molecule that can complex with a variety of hydrophobic drugs. Here, we designed modular photoclick thiol-ene hydrogels from derivatives of βCD and poly(ethylene glycol) (PEG), including βCD-allylether (βCD-AE), βCD-thiol (βCD-SH), PEG-thiol (PEGSH), and PEG-norbornene (PEGNB). Two types of CD-PEG hybrid hydrogels were prepared using radical-mediated thiol-ene photoclick reactions. Specifically, thiol-allylether hydrogels were formed by reacting multiarm PEGSH and βCD-AE, and thiol-norbornene hydrogels were formed by cross-linking βCD-SH and multiarm PEGNB. We characterized the properties of these two types of thiol-ene hydrogels, including gelation kinetics, gel fractions, hydrolytic stability, and cytocompatibility. Compared with thiol-allylether hydrogels, thiol-norbornene photoclick reaction formed hydrogels with faster gelation kinetics at equivalent macromer contents. Using curcumin, an anti-inflammatory and anticancer hydrophobic molecule, we demonstrated that CD-cross-linked PEG-based hydrogels, when compared with pure PEG-based hydrogels, afforded higher drug loading efficiency and prolonged delivery in vitro. Cytocompatibility of these CD-cross-linked hydrogels were evaluated by in situ encapsulation of radical sensitive pancreatic MIN6 β-cells. All formulations and cross-linking conditions tested were cytocompatible for cell encapsulation. Furthermore, hydrogels cross-linked by βCD-SH showed enhanced cell proliferation and insulin secretion as compared to gels cross-linked by either dithiothreitol (DTT) or βCD-AE, suggesting the profound impact of both macromer compositions and gelation chemistry on cell fate in chemically cross-linked hydrogels.

  15. Serum-resistant complex nanoparticles functionalized with imidazole-rich polypeptide for gene delivery to pulmonary metastatic melanoma.

    Science.gov (United States)

    Gu, Jijin; Chen, Xinyi; Xin, Hongliang; Fang, Xiaoling; Sha, Xianyi

    2014-01-30

    To enhance serum-resistance and overcome the lysosomal barrier are effective and feasible strategies to increase the transfection efficiency of non-viral gene delivery system. For the systemic delivery of therapeutic gene, we previously developed self-assemble carboxymethyl poly(l-histidine) (CM-PLH)/poly(β-amino ester) (PbAE)/pDNA ternary complex nanoparticles based on electrostatic coating as an effective pDNA carrier. Recharging cationic PbAE/pDNA polyplexes with CM-PLH was a promising method to reduce the cytotoxicity and enhance the stability in vivo of positive charged polyplexes. In the present study, the transfection activities of ternary complex nanoparticles were further evaluated in vitro and in vivo. The transfection efficiency of ternary complex nanoparticles showed significant serum-resistance (CM-PLH-containing (51.9±4.35)% in 50% FBS>CM-PLH-free (14.7±5.66)% in 50% FBS), cell line dependent (HEK293>MCF-7>COS7>B16F10>A549>Hela>SPC-A1>CHO>SKOV3) and incubation period dependent (24 h, 20 h, 16 h>12 h>8 h>4 h>2 h>1 h>0.5 h). After transfected with ternary complex nanoparticles loading pGV240-MDA-7/IL-24, the B16F10 cells exhibited significant apoptosis and proliferation inhibition due to the expression of IL-24. Moreover, in the pulmonary metastatic melanoma model, ternary complex nanoparticles loading pGV240-MDA-7/IL-24 showed significant antitumor therapeutic efficacy in vivo. These results suggested that CM-PLH/PbAE/pDNA ternary complex nanoparticles were promising and challenging gene vector for practical application.

  16. Synthesis and Characterization of Curcumin-Functionalized HP-β-CD-Modified GoldMag Nanoparticles as Drug Delivery Agents.

    Science.gov (United States)

    Lian, Ting; Peng, Mingli; Vermorken, Alphons J M; Jin, Yanyan; Luo, Zhiyi; Van de Ven, Wim J M; Wan, Yinsheng; Hou, Peng; Cui, Yali

    2016-06-01

    Curcumin, a polyphenol extracted from turmeric (Curcuma longa), has emerged as a potent multimodal cancer-preventing agent. It may attenuate the spread of cancer and render chemotherapy more effective. However, curcumin is neither well absorbed nor well retained in the blood, resulting in low efficacy. In an attempt to enhance the potency and to improve the bioavailability of curcumin, new delivery agents, hydroxypropyl-beta-cyclodextrin (HP-β-CD)-modified GoldMag nanoparticles (CD-GMNs) were designed and synthesized to incorporate curcumin. The CD-GMNs were characterized by Fourier Transform Infrared Spectroscopy (FT-IR), Thermo-gravimetric Analysis (TGA), X-ray Diffraction (XRD), Dynamic Light Scattering measurements (DLS), Transmission Electron Microscopy (TEM) and Vibrating Sample Magnetometer (VSM) analyses. For the magnetic carrier of CD-GMNs, the content of HP-β-CD was 26.9 wt%. CD-GMNs have a saturation magnetization of 22.7 emu/g with an average hydrodynamic diameter of 80 nm. The curcumin loading, encapsulation efficiency and releasing properties in vitro were also investigated. The results showed that the drug encapsulation ratio was 88% and the maximum curcumin loading capacity of CD-GMNs was 660 μg/5 mg. In vitro drug release studies showed a controlled and pH-sensitive curcumin release over a period of one week. Collectively, our data suggest that HP-β-CD-modified GoldMag nanoparticles can be considered to form a promising delivery system for curcumin to tumor sites. Targeting can be achieved by the combined effects of the application of an external magnetic field and the effect on drug release of lower pH values often found in the tumor microenvironment.

  17. Dual Functional Nanocarrier for Cellular Imaging and Drug Delivery in Cancer Cells Based on π-Conjugated Core and Biodegradable Polymer Arms.

    Science.gov (United States)

    Kulkarni, Bhagyashree; Surnar, Bapurao; Jayakannan, Manickam

    2016-03-14

    Multipurpose polymer nanoscaffolds for cellular imaging and delivery of anticancer drug are urgently required for the cancer therapy. The present investigation reports a new polymer drug delivery concept based on biodegradable polycaprolactone (PCL) and highly luminescent π-conjugated fluorophore as dual functional nanocarrier for cellular imaging and delivery vehicles for anticancer drug to cancer cells. To accomplish this goal, a new substituted caprolactone monomer was designed, and it was subjected to ring opening polymerization using a blue luminescent bishydroxyloligo-phenylenevinylene (OPV) fluorophore as an initiator. A series of A-B-A triblock copolymer building blocks with a fixed OPV π-core and variable chain biodegradable PCL arm length were tailor-made. These triblocks self-assembled in organic solvents to produce well-defined helical nanofibers, whereas in water they produced spherical nanoparticles (size ∼150 nm) with blue luminescence. The hydrophobic pocket of the polymer nanoparticle was found to be an efficient host for loading water insoluble anticancer drug such as doxorubicin (DOX). The photophysical studies revealed that there was no cross-talking between the OPV and DOX chromophores, and their optical purity was retained in the nanoparticle assembly for cellular imaging. In vitro studies revealed that the biodegradable PCL arm was susceptible to enzymatic cleavage at the intracellular lysosomal esterase under physiological conditions to release the loaded drugs. The nascent nanoparticles were found to be nontoxic to cancer cells, whereas the DOX-loaded nanoparticles accomplished more than 80% killing in HeLa cells. Confocal microscopic analysis confirmed the cell penetrating ability of the blue luminescent polymer nanoparticles and their accumulation preferably in the cytoplasm. The DOX loaded red luminescent polymer nanoparticles were also taken up by the cells, and the drug was found to be accumulated at the perinuclear environment

  18. 分娩方式对产后盆底肌肉功能的影响%Effect of delivery methods on postpartum pelvic floor muscle function

    Institute of Scientific and Technical Information of China (English)

    李卓

    2012-01-01

    目的 探讨分娩方式对产妇产后盆底肌肉功能的影响.方法 正常初产妇150例,按分娩方式均分为选择性剖宫产(A)组和阴道分娩(B)组.均于分娩后12周用盆底肌力检测法及盆底肌电图测定评价盆底肌力,观察女性盆底功能障碍性疾病发生情况.结果 A组肌电图活力值和功值均高于B组(76±8 vs.25±6和112±15 vs.32±7)(P<0.05);A组盆底功能障碍性疾病发生率低于B组(8.0%vs.28.0%)(P<0.05).结论 两种分娩方式对产妇产后盆底肌力均有影响,但剖宫产对盆底肌力的影响相对较轻.%Objective To investigate the effect of delivery methods on the postpartum pelvic floor muscle function. Methods A total of 150 pregnant women was equally allocated into two groups of A(underwent selective Caesarean section) and B(normal vaginal delivery). On the 12th week after childbirth,the pelvic floor muscle strength testing and electromyography(EMG) were performed to evaluate the pelvic floor muscle strength. The pelvic floor dysfunction was recorded as well. Results The activity values and power values of the pelvic floor muscles on EMG were higher in group A than those in group B(76±8 vs. 25 ± 6 and 112±15 vs. 32 ± 7)(P<0. 05). The incidence of pelvic floor muscle dysfunction was lower in group A than that in group B(8. 0% vs. 28. 0%) (P<0. 05). Conclusion The pelvic floor muscle function is impacted by both Caesarean section and vaginal delivery,which is relatively less after Caesarean section than that after vaginal delivery.

  19. Percutaneous Retrieval of a Dislodged Guide Wire by Dormia Basket in a 98-year-old Patient, Still a Safe and Feasible Approach

    Directory of Open Access Journals (Sweden)

    Gh Soltani

    2010-06-01

    Full Text Available Since the first report of percutaneous retrieval of intravascular foreign body in 1964, it has been accepted as a favorite approach for intravascular foreign body removal. Various instruments such as snares, biopsy forceps, dormia basket or tip deflecting wires are available for this approach. Herein, we report percutaneous retrieval of a dislodged guide-wire by dormia basket. The Patient was a 98-year-old female who was admitted in the Intensive care unit due to confusional state. The physian incharge left the guide-wire in her subclavian vein during central venous catheter insertion. He realized his fault immediately, so he started anti-coagulation therapy and requested surgical consult. Because of the patient’s high risk of surgery, the surgeon referred the patient to cardiologist for non-invasive guide wire removal. The guide wire was apprpached through femoral vein by a dormia basket (4/6 F and it was removed without any difficulties or complications. Utilization of baskets for intravascular foreign body removal is frequently reported and has been successful with low complication rates; In addition, the low cost of the device makes it less of a burden to the patient and the hospital.

  20. Provisional Analysis as a Means to Improve the Use of Program Evaluation Data: An Investigation of Its Effectiveness Using an In-basket Simulation.

    Science.gov (United States)

    Craig, James R.; And Others

    This investigation employed an in-basket simulation to assess the effect of provisional analysis on the use of evaluation data by program administrators in making program decisions. Sixty-five volunteers from graduate education courses and 52 volunteers from undergraduate educational psychology classes at Western Kentucky University were randomly…

  1. Algorithmic complexity. A new approach of non-linear algorithms for the analysis of atrial signals from multipolar basket catheter.

    Science.gov (United States)

    Pitschner, H F; Berkowitsch, A

    2001-01-01

    Symbolic dynamics as a non linear method and computation of the normalized algorithmic complexity (C alpha) was applied to basket-catheter mapping of atrial fibrillation (AF) in the right human atrium. The resulting different degrees of organisation of AF have been compared to conventional classification of Wells. Short time temporal and spatial distribution of the C alpha during AF and effects of propafenone on this distribution have been investigated in 30 patients. C alpha was calculated for a moving window. Generated C alpha was analyzed within 10 minutes before and after administration of propafenone. The inter-regional C alpha distribution was statistically analyzed. Inter-regional C alpha differences were found in all patients (p complexity areas according to individual patterns. A significant C alpha increase in cranio-caudal direction was confirmed inter-individually (p complexity.

  2. Design and preparation of market baskets of European Union commercial baby foods for the assessment of infant exposure to food chemicals and to their effects.

    Science.gov (United States)

    Piccinelli, R; Pandelova, M; Le Donne, C; Ferrari, M; Schramm, K-W; Leclercq, C

    2010-10-01

    The assessment of acute and chronic dietary exposure to contaminants in baby foods is needed to ensure healthy infant growth. Monthly European Union market baskets of commercial baby foods were designed for the first 9 months of life by the 'babyfood' study group of the CASCADE Network of Excellence for the specific purpose of assessing exposure to potentially toxic substances in infants fed with such foods. The present paper reports the different steps that led to the preparation of monthly pooled samples of commercial baby foods ('Infant formulae and follow-on formulae' and 'Other baby foods') that may constitute the extreme case of the diet for an infant who would not be breast fed at all. Several market baskets were generated for an 'average European Union infant' and for infants of four selected countries (Italy, Sweden, Spain, and the Slovakia), fed with either milk infant formulae, soy infant formulae or hypoallergenic infant formulae and weaned (at the fifth month) with commercial baby foods and beverages available on the European Union market. Market share data for 2007 for baby foods were used to design the baskets. Holding companies and the name of all their products were identified. Monthly diets for European Union infants were elaborated in terms of food categories (e.g. infant cereals) of typologies of products (e.g. infant cereals without gluten) and of a specific product. The number of baskets generated was 30 for 'Infant formulae and follow-on formulae' (including 62 products) and 13 for 'Other baby foods' (including 35 products). These market baskets were designed to be used for the determination of certain contaminants and nutrients in the diet of European Union infants and for the assessment of their effects on infant health.

  3. 营销中购物篮理念的技术探索%Technological Exploration of Market Basket Idea in Marketing

    Institute of Scientific and Technical Information of China (English)

    吕继东

    2014-01-01

    院随着营销创新手段的不断升华与应用,购物篮理念的技术运用成为了一种重要的营销手段,尤其是在通过对顾客、商品、订单等多方面的把握,深入分析购物篮理念的全新应用,将有着重要的实践意义。本文将围绕营销中购物篮理念的整体概念出发,分析数据技术在购物篮技术中的综合应用手段,突出营销中购物篮技术应用的综合手段,更好的实现整体购物品牌与技术的全面提升。%With the continuous distillation and application of innovative marketing means, technological application of market basket idea has become an important means of marketing especially for the grasping the overall aspects of customer, product, order and so on. It is of great practical significance to analyze the new application of market basket idea. Starting will the overall concept of market basket idea in marketing, the comprehensive application means of data technology in market basket means is analyzed. The comprehensive means of market basket application in marketing is emphasized so as to improve the overall shopping brand and technology.

  4. Surface-functionalized, pH-responsive poly(lactic-co-glycolic acid)-based microparticles for intranasal vaccine delivery: Effect of surface modification with chitosan and mannan.

    Science.gov (United States)

    Li, Ze; Xiong, Fangfang; He, Jintian; Dai, Xiaojing; Wang, Gaizhen

    2016-12-01

    In the present study, surface-functionalized, pH-responsive poly(lactic-co-glycolic acid) (PLGA) microparticles were investigated for nasal delivery of hepatitis B surface Antigen (HBsAg). pH-responsive PLGA, chitosan modified PLGA (CS-PLGA), mannan modified PLGA (MN-PLGA), mannan and chitosan co-modified PLGA (MN-CS-PLGA) microparticles were prepared utilizing a double-emulsion method. Antigen was released rapidly from four types of microparticles at pH5.0 and pH 6.0, but slowly released at pH 7.4. Mannan and chitosan surface modification enhanced intracellular microparticle uptake by macrophages. Following intracellular macrophage antigen uptake, antigen release occurred in three different patterns: fast release from PLGA and MN-PLGA microparticles in endosomes/lysosomes, slow release from CS-PLGA microparticles in cytoplasm and a combination of fast release and slow release patterns from MN-CS-PLGA microparticles. Furthermore, chitosan coating modification increased the residence time of CS-PLGA and MN-CS-PLGA microparticles in the nasal cavity. In vivo immunogenicity studies indicated that MN-CS-PLGA microparticles induced stronger humoral and cell-mediated immune responses compared with PLGA, MN-PLGA and CS-PLGA microparticles. These results suggest that surface modification of pH-responsive PLGA microparticles with mannan and chitosan is a promising tool for nasal delivery of HBsAg. Copyright © 2016. Published by Elsevier B.V.

  5. Synergistic effect of pH-responsive folate-functionalized poloxamer 407-TPGS-mixed micelles on targeted delivery of anticancer drugs

    Directory of Open Access Journals (Sweden)

    Butt AM

    2015-02-01

    Full Text Available Adeel Masood Butt, Mohd Cairul Iqbal Mohd Amin, Haliza Katas Centre for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia Background: Doxorubicin (DOX, an anthracycline anticancer antibiotic, is used for treating various types of cancers. However, its use is associated with toxicity to normal cells and development of resistance due to overexpression of drug efflux pumps. Poloxamer 407 (P407 and vitamin E TPGS (d-α-tocopheryl polyethylene glycol succinate, TPGS are widely used polymers as drug delivery carriers and excipients for enhancing the drug retention times and stability. TPGS reduces multidrug resistance, induces apoptosis, and shows selective anticancer activity against tumor cells. Keeping in view the problems, we designed a mixed micelle system encapsulating DOX comprising TPGS for its selective anticancer activity and P407 conjugated with folic acid (FA for folate-mediated receptor targeting to cancer cells. Methods: FA-functionalized P407 was prepared by carbodiimide crosslinker chemistry. P407-TPGS/FA-P407-TPGS-mixed micelles were prepared by thin-film hydration method. Cytotoxicity of blank micelles, DOX, and DOX-loaded micelles was determined by alamarBlue® assay. Results: The size of micelles was less than 200 nm with encapsulation efficiency of 85% and 73% for P407-TPGS and FA-P407-TPGS micelles, respectively. Intracellular trafficking study using nile red-loaded micelles indicated improved drug uptake and perinuclear drug localization. The micelles show minimal toxicity to normal human cell line WRL-68, enhanced cellular uptake of DOX, reduced drug efflux, increased DOX–DNA binding in SKOV3 and DOX-resistant SKOV3 human ovarian carcinoma cell lines, and enhanced in vitro cytotoxicity as compared to free DOX. Conclusion: FA-P407-TPGS-DOX micelles show potential as a targeted nano-drug delivery system for DOX due to their multiple synergistic factors of selective anticancer

  6. Functionalized gold nanoparticles for the binding, stabilization, and delivery of therapeutic DNA, RNA, and other biological macromolecules

    Directory of Open Access Journals (Sweden)

    Robert K DeLong

    2010-09-01

    Full Text Available Robert K DeLong1, Christopher M Reynolds1, Yaneika Malcolm1, Ashley Schaeffer1, Tiffany Severs2, Adam Wanekaya21Department of Biomedical Science (Cell and Molecular Biology Program, 2Department of Chemistry, Missouri State University, Springfield, MO, USAAbstract: Nanotechnology has virtually exploded in the last few years with seemingly limitless opportunity across all segments of our society. If gene and RNA therapy are to ever realize their full potential, there is a great need for nanomaterials that can bind, stabilize, and deliver these macromolecular nucleic acids into human cells and tissues. Many researchers have turned to gold nanomaterials, as gold is thought to be relatively well tolerated in humans and provides an inert material upon which nucleic acids can attach. Here, we review the various strategies for associating macromolecular nucleic acids to the surface of gold nanoparticles (GNPs, the characterization chemistries involved, and the potential advantages of GNPs in terms of stabilization and delivery.Keywords: gold, nanoparticles, nanomaterials, RNA, nucleic acid

  7. Modeling short-range delivery and collection of light: incorporating the influence of the phase function (Conference Presentation)

    Science.gov (United States)

    Post, Anouk L.; Ruis, Roosje M.; Bloemen, Paul R.; van Leeuwen, Ton G.; Sterenborg, Henricus J. C. M.; Faber, Dirk J.

    2017-02-01

    The scattering phase function (the probability distribution of the scattering angle) is intimately associated with the cellular organization and ultrastructure of tissue. Since these physical parameters change during e.g. carcinogenesis; quantification of the phase function and related parameters may allow for improved non-invasive, in vivo discrimination between healthy and diseased tissue. Furthermore, for the derivation of models to interpret measured optical signals, assumptions about the phase function of tissue are often made - regularly assuming a Modified Henyey Greenstein. However, in contrast to other optical properties, the phase function has not yet been extensively measured for different tissue types. With conventional goniometers, the exact backscatter direction of 180 degrees cannot be measured. Especially for techniques that detect backscattered light - such as Optical Coherence Tomography and Elastic Scattering spectroscopy - the details of the backward part of the phase function will have a considerable impact on the measured signal. We have therefore developed a setup that can measure the backward part of the phase function: 134 to 180 degrees. Our design is based on full field Optical Coherence Tomography. We detect all angles simultaneously with a camera, while scanning the reference mirror. The phase function scales with the amplitude of the OCT signal for each angle. We will show our results for validation measurements on two silica bead samples of 200 nm and 400 nm beads.

  8. Functional MRI of the pelvic floor: postpartum changes of primiparous women after spontaneous vaginal delivery; Funktionelle Magnetresonanztomographie (MRT) des Beckenbodens: Postpartale Veraenderungen bei Erstgebaerenden nach vaginaler Spontangeburt

    Energy Technology Data Exchange (ETDEWEB)

    Lienemann, A.; Fischer, T.; Reiser, M. [Inst. fuer Klinische Radiologie, Klinikum der Univ. Muenchen (Germany); Anthuber, C. [Klinik und Poliklinik fuer Geburtshilfe und Frauenheilkunde, Klinikum der Univ. Muenchen/Grosshadern (Germany)

    2003-08-01

    Purpose: Detection of morphological and functional changes of the pelvic floor with functional MRI in primiparous women after spontaneous vaginal delivery. Methods and Materials: The study comprises 26 primiparous women after vaginal delivery and a control group of 41 healthy asymptomatic nulliparous volunteers. MRI was performed on a 1.5 T system in supine position with vagina and rectum opacified with Sonogel. The static images consisted of sagittal and axial T{sub 2}-weighted SE sequences and functional images of true FISP sequences in midsagittal and axial planes acquired with the patient at rest, straining and during defecation. Evaluation of morphometric parameters included pelvimetry, thickness of the puborectal muscle and width of the urogenital hiatus as well as position and movement of the pelvic organs relative to the pubococcygeal reference line. Results: The configuration of the bony pelvis did not differ for both groups. The puborectal muscle was significantly thinner in the study group (0.8 cm vs 0.6 cm). The functional images showed no significant differences between both groups at rest but a significantly increased incidence in the descent of the bladder neck, vaginal fornix and anorectal junction in the study group during straining. In addition, the primiparous women had more prominent rectoceles (0.6 cm vs 1.5 cm). Conclusion: Static imaging alone fails to demonstrate relevant pelvic floor changes and a functional method is necessary to evaluate the interactions of the pelvic organs regarding organ descent. Functional MRI of the pelvic floor is an excellent method to reveal the significant changes of the pelvic floor after vaginal birth without exposing the uterus to radiation. (orig.) [German] Ziel: Darstellung von morphologischen und funktionellen Veraenderungen am Beckenboden bei Erstgebaerenden nach spontanvaginaler Entbindung mittels funktioneller MRT. Methodik: Funktionelle MRT des Beckenbodens von 26 Erstgebaerenden nach vaginaler

  9. Application-Network Cross Layer Multi-variable Cost Function for Application Layer Multicast of Multimedia Delivery over Convergent Networks

    OpenAIRE

    Le, Tien Anh; Nguyen, Hang; Nguyen, Manh Cuong

    2015-01-01

    International audience; Application layer multicast (ALM) algorithms are either similar or conceptually based on network layer multicast's cost functions. In this research work, a new application-network cross layer multi-variable cost function is proposed. It optimizes the variable requirements and available resources from both the application and the network layers. It can dynamically update the available resources required for reaching a particular node on the ALM's media distribution tree...

  10. Oil components modulate physical characteristics and function of the natural oil emulsions as drug or gene delivery system.

    Science.gov (United States)

    Chung, H; Kim, T W; Kwon, M; Kwon, I C; Jeong, S Y

    2001-04-28

    Oil-in-water (o/w) type lipid emulsions were formulated by using 18 different natural oils and egg phosphatidylcholine (egg PC) to investigate how emulsion particle size and stability change with different oils. Cottonseed, linseed and evening primrose oils formed emulsions with very large and unstable particles. Squalene, light mineral oil and jojoba bean oil formed stable emulsions with small particles. The remaining natural oils formed moderately stable emulsions. Emulsions with smaller initial particle size were more stable than those with larger particles. The correlation between emulsion size made with different oils and two physical properties of the oils was also investigated. The o/w interfacial tension and particle size of the emulsion were inversely proportional. The effect of viscosity was less pronounced. To study how the oil component in the emulsion modulates the in vitro release characteristics of lipophilic drugs, three different emulsions loaded with two different drugs were prepared. Squalene, soybean oil and linseed oil emulsions represented the most, medium and the least stable systems, respectively. For the lipophilic drugs, release was the slowest from the most stable squalene emulsion, followed by soybean oil and then by linseed oil emulsions. Cationic emulsions were also prepared with the above three different oils as gene carriers. In vitro transfection activity was the highest for the most stable squalene emulsion followed by soybean oil and then by linseed oil emulsions. Even though the in vitro transfection activity of emulsions were lower than the liposome in the absence of serum, the activity of squalene emulsion, for instance, was ca. 30 times higher than that of liposome in the presence of 80% (v/v) serum. In conclusion, the choice of oil component in o/w emulsion is important in formulating emulsion-based drug or gene delivery systems.

  11. Hybrid polymeric hydrogels for ocular drug delivery: nanoparticulate systems from copolymers of acrylic acid-functionalized chitosan and N-isopropylacrylamide or 2-hydroxyethyl methacrylate

    Energy Technology Data Exchange (ETDEWEB)

    Barbu, Eugen; Tsibouklis, John [School of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael' s Building, White Swan Road, Portsmouth PO1 2DT (United Kingdom); Verestiuc, Liliana [Faculty of Medical Bioengineering, University of Medicine and Pharmacy ' Gr T Popa' , 9-13 Kogalniceanu Street, Iasi, 700454 (Romania); Iancu, Mihaela; Jatariu, Anca [Faculty of Chemical Engineering and Environmental Protection, Technical University' Gh Asachi' , Boulevard Mangeron, 71A, 700100, Iasi (Romania); Lungu, Adriana [Faculty of Applied Chemistry and Materials Science, Polytechnic University of Bucharest, Polizu Street 1-7, 011061, Bucharest (Romania)], E-mail: eugen@barbu@port.ac.uk

    2009-06-03

    Nanoparticulate hybrid polymeric hydrogels (10-70 nm) have been obtained via the radical-induced co-polymerization of acrylic acid-functionalized chitosan with either N-isopropylacrylamide or 2-hydroxyethyl methacrylate, and the materials have been investigated for their ability to act as controlled release vehicles in ophthalmic drug delivery. Studies on the effects of network structure upon swelling properties, adhesiveness to substrates that mimic mucosal surfaces and biodegradability, coupled with in vitro drug release investigations employing ophthalmic drugs with differing aqueous solubilities, have identified nanoparticle compositions for each of the candidate drug molecules. The hybrid nanoparticles combine the temperature sensitivity of N-isopropylacrylamide or the good swelling characteristics of 2-hydroxyethyl methacrylate with the susceptibility of chitosan to lysozyme-induced biodegradation.

  12. Investigation of Functionalized Poly(N,N-dimethylacrylamide)-block-polystyrene Nanoparticles As Novel Drug Delivery System to Overcome the Blood-Brain Barrier In Vitro.

    Science.gov (United States)

    Gregori, Maria; Bertani, Daniela; Cazzaniga, Emanuela; Orlando, Antonina; Mauri, Michele; Bianchi, Alberto; Re, Francesca; Sesana, Silvia; Minniti, Stefania; Francolini, Maura; Cagnotto, Alfredo; Salmona, Mario; Nardo, Luca; Salerno, Domenico; Mantegazza, Francesco; Masserini, Massimo; Simonutti, Roberto

    2015-12-01

    In the search of new drug delivery carriers for the brain, self-assembled nanoparticles (NP) were prepared from poly(N,N-dimethylacrylamide)-block-polystyrene polymer. NP displayed biocompatibility on cultured endothelial cells, macrophages and differentiated SH-SY5Y neuronal-like cells. The surface-functionalization of NP with a modified fragment of human Apolipoprotein E (mApoE) enhanced the uptake of NP by cultured human brain capillary endothelial cells, as assessed by confocal microscopy, and their permeability through a Transwell Blood Brain Barrier model made with the same cells, as assessed by fluorescence. Finally, mApoE-NP embedding doxorubicin displayed an enhanced release of drug at low pH, suggesting the potential use of these NP for the treatment of brain tumors.

  13. A Chimeric Cetuximab-Functionalized Corona as a Potent Delivery System for Microtubule-Destabilizing Nanocomplexes to Hepatocellular Carcinoma Cells: A Focus on EGFR and Tubulin Intracellular Dynamics.

    Science.gov (United States)

    Poojari, Radhika; Kini, Sudarshan; Srivastava, Rohit; Panda, Dulal

    2015-11-01

    In this study, we have developed microtubule destabilizing agents combretastatin A4 (CA4) or 2-methoxyestradiol (2ME) encapsulated poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-b-PEG) nanocomplexes for targeted delivery to human hepatocellular carcinoma (HCC) cells. An epidermal growth factor receptor (EGFR) is known to be overexpressed in HCC cells. Therefore, the targeting moiety cetuximab (Cet), an anti-EGFR chimeric monoclonal antibody, is functionalized on the surface of these diblock copolymeric coronas. Cetuximab is associated with the extracellular domain of the EGFR; therefore, the uptake of the cetuximab conjugated nanocomplexes occurred efficiently in EGFR overexpressing HCC cells indicating potent internalization of the complex. The cetuximab targeted-PLGA-b-PEG nanocomplexes encapsulating CA4 or 2ME strongly inhibited phospho-EGFR expression, depolymerized microtubules, produced spindle abnormalities, stalled mitosis, and induced apoptosis in Huh7 cells compared to the free drugs, CA4 or 2ME. Further, the combinatorial strategy of targeted nanocomplexes, Cet-PLGA-b-PEG-CA4 NP and Cet-PLGA-b-PEG-2ME NP, significantly reduced the migration of Huh7 cells, and markedly enhanced the anticancer effects of the microtubule-targeted drugs in Huh7 cells compared to the free drugs, CA4 or 2ME. The results indicated that EGFR receptor-mediated internalization via cetuximab facilitated enhanced uptake of the nanocomplexes leading to potent anticancer efficacy in Huh7 cells. Cetuximab-functionalized PLGA-b-PEG nanocomplexes possess a strong potential for the targeted delivery of CA4 or 2ME in EGFR overexpressed HCC cells, and the strategy may be useful for selectively targeting microtubules in these cells.

  14. Validity and Test-Retest Reliability of the TIVRE-Basket Test for the Determination of Aerobic Power in Elite Male Basketball Players.

    Science.gov (United States)

    Vaquera, Alejandro; Villa, Jose G; Morante, Juan C; Thomas, Gavin; Renfree, Andrew J; Peters, Derek M

    2016-02-01

    The aims of this study were to (a) determine the relationship between performance on the court-based TIVRE-Basket test and peak aerobic power determined from a criterion laboratory-based incremental treadmill test and (b) to examine the test-retest reliability of the TIVRE-Basket test in elite male basketball players. To address aim 1, 36 elite male basketball players (age: 25.2 ± 4.7 years, weight: 94.1 ± 11.4 kg, height: 195.83 ± 9.6 cm) completed a graded treadmill exercise test and the TIVRE-Basket within 72 hours. The mean distance recorded during the TIVRE-Basket test was 4001.8 ± 176.4 m, and mean VO2 peak was 54.7 ± 2.8 ml · kg(-1) · min(-1), and the correlation between the 2 parameters was r = 0.824 (p ≤ 0.001). Linear regression analysis identified TIVRE-Basket distance (in meters) as the only unique predictor of VO2 peak in a single variable plus constant model: VO2 peak = 2.595 + (0.13 × TIVRE-Basket distance [in meters]). Performance on the TIVRE-Basket test accounted for 67.8% of the variance in VO2 peak (t = 8.466, p ≤ 0.001, 95% confidence interval: 0.01-0.016, SEE: 1.61). To address aim 2, 20 male basketball players (age: 26.7 ± 4.2 years, height: 1.94 ± 0.92 cm, weight: 94.0 ± 9.1 kg) performed the TIVRE-Basket test on 2 occasions. There was no significant difference in total distance covered between trial 1 (4138.8 ± 677.3 m) and trial 2 (4188.0 ± 648.8 m; t = 0.5798, p = 0.5688). Mean difference between trials was 49.2 ± 399.5 m, with an intraclass correlation coefficient of 0.85 suggesting a moderate level of reliability. Standardized typical error of measurement was 0.88%, representing a moderate degree of trial-to-trial error, and the Coefficient of Variation (CV) was 6.3%. The TIVRE-Basket test therefore represents a valid and moderately reliable court-based sport-specific test of aerobic power for use with individuals and teams of elite-level male basketball players. Future research is required to ascertain its validity

  15. Targeted delivery of doxorubicin-utilizing chitosan nanoparticles surface-functionalized with anti-Her2 trastuzumab

    Directory of Open Access Journals (Sweden)

    Yousefpour P

    2011-09-01

    selective uptake of CS-DOX-mAb by Her2+ cancer cells compared with nontargeted CS-DOX nanoparticles and free drug.Conclusion: Antibody-conjugated nanoparticles were shown to discriminate between Her2+ and Her2- cells, and thus have the potential to be used in active targeted drug delivery, with reduction of drug side effects in Her2+ breast and ovarian cancers.Keywords: chitosan, doxorubicin, self-assembled nanoparticles, active targeting, trastuzumab

  16. Noninvasive Assessment of Losartan-Induced Increase in Functional Microvasculature and Drug Delivery in Pancreatic Ductal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Vidhya Kumar

    2016-10-01

    Full Text Available PURPOSE: Losartan, an angiotensin II receptor blocker, can reduce desmoplasia and enhance drug delivery and efficacy through improving interstitial transport and vascular perfusion in pancreatic ductal adenocarcinoma (PDAC models in mice. The purpose of this study was to determine whether magnetic resonance imaging (MRI of magnetic iron oxide nanoparticles (MNPs and micro–positron emission tomography (PET measurements could respectively detect improvements in tumor vascular parameters and drug uptake in orthotopic PDAC in mice treated with losartan. METHOD AND MATERIALS: All experiments were approved by the local Institutional Animal Care and Use Committee. FVB mice with orthotopic PDAC were treated daily with an i.p. injection of losartan (70 mg/kg or saline (control vehicle for 5 days. In order to calculate the fractional blood volume, vessel size index, and vessel density index, MRI was performed at 4.7 T following the injection of 3 mg/kg iron ferumoxytol (i.v.. Dynamic PET images were also acquired for 60 minutes using an 18F-5FU tracer dose of 200 μCi and analyzed for time activity curves normalized to muscle. Statistical analyses compared both cohorts using an unpaired two-tailed t test. RESULTS: In comparison to the control treatment, the losartan administration significantly increased the fractional blood volume (mean ± SEM [12.1 ± 1.7 (n = 19 vs 6.7 ± 1.1 (n = 20; P < .02] and vessel size index (128.2 ± 35.6 vs 57.5 ± 18; P < .05. Losartan also induced a significant increase in the intratumoral uptake of 18F-5FU by 53% (P < .0001. CONCLUSION: MRI using FDA-approved MNPs provides a noninvasive, translatable means of assaying microvascular parameters induced by losartan in pancreatic cancer. PET measurements demonstrated that losartan significantly increased the uptake of 18F-5FU.

  17. Fabrication of Functional Nano-objects through RAFT Dispersion Polymerization and Influences of Morphology on Drug Delivery.

    Science.gov (United States)

    Qiu, Liang; Xu, Chao-Ran; Zhong, Feng; Hong, Chun-Yan; Pan, Cai-Yuan

    2016-07-20

    To study the influence of self-assembled morphologies on drug delivery, four different nano-objects, spheres, nanorods, nanowires, and vesicles having aldehdye-based polymer as core, were successfully prepared via alcoholic RAFT dispersion polymerization of p-(methacryloxyethoxy)benzaldehyde (MAEBA) using poly((N,N'-dimethylamino)ethyl methacrylate) (PDMAEMA) as a macro chain transfer agent (macro-CTA) for the first time. The morphologies and sizes of the four nano-objects were characterized by TEM and DLS, and the spheres with average diameter (D) of 70 nm, the nanorods with D of 19 nm and length of 140 nm, and the vesicles with D of 137 nm were used in the subsequent cellular internalization, in vitro release, and intracellular release of the drug. The anticancer drug doxorubicin (DOX) was conjugated onto the core polymers of nano-objects through condensation reaction between aldehyde groups of the PMAEBA with primary amine groups in the DOX. Because the aromatic imine is stable under neutral conditions, but is decomposed in a weakly acidic solution, in vitro release of the DOX from the DOX-loaded nano-objects was investigated in the different acidic solutions. All of the block copolymer nano-objects show very low cytotoxicity to HeLa cells up to the concentration of 1.2 mg/mL, but the DOX-loaded nano-objects reveal different cell viability and their IC50s increase as the following order: nanorods-DOX nano-objects owing to their too large size to be internalized. Endocytosis tests demonstrate that the internalization of vesicles-DOX by the HeLa cells is faster than that of the nanorods-DOX, and the spheres-DOX are the slowest to internalize among the studied nano-objects. Relatively more nanorods localized in the acidic organelles of the HeLa cells lead to faster intracellular release of the DOX, so the IC50 of nanorods is lower than that of the vesicles-DOX.

  18. Intramyocardial delivery of mesenchymal stem cell-seeded hydrogel preserves cardiac function and attenuates ventricular remodeling after myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Eva Mathieu

    Full Text Available BACKGROUND: To improve the efficacy of bone marrow-derived mesenchymal stem cell (MSC therapy targeted to infarcted myocardium, we investigated whether a self-setting silanized hydroxypropyl methylcellulose (Si-HPMC hydrogel seeded with MSC (MSC+hydrogel could preserve cardiac function and attenuate left ventricular (LV remodeling during an 8-week follow-up study in a rat model of myocardial infarction (MI. METHODOLOGY/PRINCIPAL FINDING: Si-HPMC hydrogel alone, MSC alone or MSC+hydrogel were injected into the myocardium immediately after coronary artery ligation in female Lewis rats. Animals in the MSC+hydrogel group showed an increase in cardiac function up to 28 days after MI and a mid-term prevention of cardiac function alteration at day 56. Histological analyses indicated that the injection of MSC+hydrogel induced a decrease in MI size and an increase in scar thickness and ultimately limited the transmural extent of MI. These findings show that intramyocardial injection of MSC+hydrogel induced short-term recovery of ventricular function and mid-term attenuation of remodeling after MI. CONCLUSION/SIGNIFICANCE: These beneficial effects may be related to the specific scaffolding properties of the Si-HPMC hydrogel that may provide the ability to support MSC injection and engraftment within myocardium.

  19. Intramyocardial Delivery of Mesenchymal Stem Cell-Seeded Hydrogel Preserves Cardiac Function and Attenuates Ventricular Remodeling after Myocardial Infarction

    Science.gov (United States)

    Mathieu, Eva; Lamirault, Guillaume; Toquet, Claire; Lhommet, Pierre; Rederstorff, Emilie; Sourice, Sophie; Biteau, Kevin; Hulin, Philippe; Forest, Virginie; Weiss, Pierre

    2012-01-01

    Background To improve the efficacy of bone marrow-derived mesenchymal stem cell (MSC) therapy targeted to infarcted myocardium, we investigated whether a self-setting silanized hydroxypropyl methylcellulose (Si-HPMC) hydrogel seeded with MSC (MSC+hydrogel) could preserve cardiac function and attenuate left ventricular (LV) remodeling during an 8-week follow-up study in a rat model of myocardial infarction (MI). Methodology/Principal Finding Si-HPMC hydrogel alone, MSC alone or MSC+hydrogel were injected into the myocardium immediately after coronary artery ligation in female Lewis rats. Animals in the MSC+hydrogel group showed an increase in cardiac function up to 28 days after MI and a mid-term prevention of cardiac function alteration at day 56. Histological analyses indicated that the injection of MSC+hydrogel induced a decrease in MI size and an increase in scar thickness and ultimately limited the transmural extent of MI. These findings show that intramyocardial injection of MSC+hydrogel induced short-term recovery of ventricular function and mid-term attenuation of remodeling after MI. Conclusion/Significance These beneficial effects may be related to the specific scaffolding properties of the Si-HPMC hydrogel that may provide the ability to support MSC injection and engraftment within myocardium. PMID:23284842

  20. Optimization of self-microemulsifying drug delivery systems (SMEDDS) using a D-optimal design and the desirability function

    DEFF Research Database (Denmark)

    Holm, R.; Jensen, I.H.M.; Sonnergaard, Jørn

    2006-01-01

    with the hard gelatin capsule. Three formulation variables, PEG200, a surfactant mixture, and an oil mixture, were included in the experimental design. The results of the mathematical analysis of the data demonstrated significant interactions among the formulation variables, and the desirability function...

  1. Photo-Crosslinked Biodegradable Hydrogels Prepared From Fumaric Acid Monoethyl Ester-Functionalized Oligomers for Protein Delivery

    NARCIS (Netherlands)

    Jansen, Janine; Mihov, George; Feijen, Jan; Grijpma, Dirk W.

    2012-01-01

    Photo-crosslinkable, fumaric acid monoethyl ester-functionalized triblock oligomers are synthesized and copolymerized with N-vinyl-2-pyrrolidone to form biodegradable photo-crosslinked hydrogels. Poly(ethylene glycol) is used as the middle hydrophilic segment and the hydrophobic segments are based o

  2. Amphiphilic chitosan-grafted-functionalized polylactic acid based nanoparticles as a delivery system for doxorubicin and temozolomide co-therapy.

    Science.gov (United States)

    Di Martino, Antonio; Sedlarik, Vladimir

    2014-10-20

    The aim of this work was to investigate the potential of an amphiphilic system comprising chitosan-grafted polylactide and carboxyl-functionalized polylactide acid as a carrier for the controlled release and co-release of two DNA alkylating drugs: doxorubicin and temozolomide. Polylactide and carboxyl-functionalized polylactide acid were obtained through direct melt polycondensation reaction, using methanesulfonic acid as a non-toxic initiator, and subsequently these were grafted to the chitosan backbone through a coupling reaction, utilizing 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide as a condensing agent. ATR-FTIR analysis and conductometric titration confirmed that a reaction between CS and PLA, PLACA2% and PLACA5% occurred. Chitosan-grafted-polylactide and polylactide-citric acid nanoparticles were prepared via the polyelectrolyte complex technique, applying dextran sulphate as a polyanion, and loaded with doxorubicin and temozolomide. The diameter of particles, ζ-potential and their relationship to temperature and pH were analysed in all formulations. Encapsulation, co-encapsulation efficiency and release studies were conducted in different physiological simulated environments and human serum. Results showed the continuous release of drugs without an initial burst in different physiological media.

  3. Development of a bread delivery vehicle for dietary prebiotics to enhance food functionality targeted at those with metabolic syndrome.

    Science.gov (United States)

    Costabile, Adele; Walton, Gemma E; Tzortzis, George; Vulevic, Jelena; Charalampopoulos, Dimitris; Gibson, Glenn R

    2015-01-01

    Prebiotics are dietary carbohydrates that favourably modulate the gut microbiota. The aims of the present study were to develop a functional prebiotic bread using Bimuno®, (galactooligosaccharide (B-GOS) mixture), for modulation of the gut microbiota in vitro in individuals at risk of metabolic syndrome. A control bread, (no added prebiotic) and positive control bread (containing equivalent carbohydrate to B-GOS bread) were also developed. A 3-stage continuous in vitro colonic model was used to assess prebiotic functionality of the breads. Bacteria were quantified by fluorescence in situ hybridization and short chain fatty acids by gas chromatography. Ion-exchange chromatography was used to determine GOS concentration after bread production. Following B-GOS bread fermentation numbers of bifidobacteria and lactobacilli were significantly higher compared to controls. There was no significant degradation of B-GOS during bread manufacture, indicating GOS withstood the manufacturing process. Furthermore, based on previous research, increased bifidobacteria and butyrate levels could be of benefit to those with obesity related conditions. Our findings support utilization of prebiotic enriched bread for improving gastrointestinal health.

  4. Extracellular vesicles for drug delivery

    NARCIS (Netherlands)

    Vader, Pieter; Mol, Emma A; Pasterkamp, Gerard; Schiffelers, Raymond M

    Extracellular vesicles (EVs) are cell-derived membrane vesicles, and represent an endogenous mechanism for intercellular communication. Since the discovery that EVs are capable of functionally transferring biological information, the potential use of EVs as drug delivery vehicles has gained

  5. Self-assembly of pH-sensitive fluorinated peptide dendron functionalized dextran nanoparticles for on-demand intracellular drug delivery.

    Science.gov (United States)

    Ma, Shengnan; Zhou, Jie; Wali, Aisha Roshan Mohamed; He, Yiyan; Xu, Xianghui; Tang, James Zhenggui; Gu, Zhongwei

    2015-08-01

    In this study, the amphiphilic fluorinated peptide dendrons functionalized dextran (FPD-HZN-Dex) via an acid-sensitive hydrazone linkage was successfully designed and prepared for the first time. We demonstrated a spontaneous self-assembly of amphiphilic FPD-HZN-Dex into the well-defined nanoparticles with the core-shell architecture in aqueous media, which is attributed to the efficient amphiphilic functionalization of dextran by the hydrophobic fluorinated peptide dendrons. The spherical morphology, uniform particle size and good storage stability of the prepared FPD-HZN-Dex nanoparticles were characterized by dynamic light scattering and transmission electron microscopy, respectively. In vitro drug release studies showed a controlled and pH dependent hydrophobic drug release profile. The cell viability assays show excellent biocompatibility of the FPD-HZN-Dex nanoparticles for both normal cells and tumor cells. Moreover, the FPD-HZN-Dex self-assembled systems based on pH-sensitive hydrazone linkage also can serve as stimulus bioresponsive carriers for on-demand intracellular drug delivery. These self-assembled nanoparticles exhibit a stimulus-induced response to endo/lysosome pH (pH 5.0) that causes their disassembly over time, enabling controlled release of encapsulated DOX. This work has unveiled a unique non-covalent interaction useful for engineering amphiphilic dendrons or dendrimers self-assembled systems.

  6. Peptide-mediated delivery of donor mitochondria improves mitochondrial function and cell viability in human cybrid cells with the MELAS A3243G mutation.

    Science.gov (United States)

    Chang, Jui-Chih; Hoel, Fredrik; Liu, Ko-Hung; Wei, Yau-Huei; Cheng, Fu-Chou; Kuo, Shou-Jen; Tronstad, Karl Johan; Liu, Chin-San

    2017-09-06

    The cell penetrating peptide, Pep-1, has been shown to facilitate cellular uptake of foreign mitochondria but further research is required to evaluate the use of Pep-1-mediated mitochondrial delivery (PMD) in treating mitochondrial defects. Presently, we sought to determine whether mitochondrial transplantation rescue mitochondrial function in a cybrid cell model of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) disease. Following PMD, recipient cells had internalized donor mitochondria after 1 h, and expressed higher levels of normal mitochondrial DNA, particularly at the end of the treatment and 11 days later. After 4 days, mitochondrial respiratory function had recovered and biogenesis was evident in the Pep-1 and PMD groups, compared to the untreated MELAS group. However, only PMD was able to reverse the fusion-to-fission ratio of mitochondrial morphology, and mitochondria shaping proteins resembled the normal pattern seen in the control group. Cell survival following hydrogen peroxide-induced oxidative stress was also improved in the PMD group. Finally, we observed that PMD partially normalized cytokine expression, including that of interleukin (IL)-7, granulocyte macrophage-colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF), in the MELAS cells. Presently, our data further confirm the protective effects of PMD as well in MELAS disease.

  7. Research of level of formed knowledge, abilities and skills on basket-ball for the students of faculty of physical education.

    Directory of Open Access Journals (Sweden)

    Kovalenko J.A.

    2011-06-01

    Full Text Available The results of a zero control of students of faculty of physical education are presented. The estimation of theoretical knowledge's is conducted, abilities and skills on basket-ball for the students of a 1 course of directions of preparation «Physical education», «Health of man» and «Sport». It is set that the level of their formed at most students of different directions of preparation is insufficient. It is certain that by reason of such position, foremost, there is insufficient preparation and playing practice of students during teaching at general school. A diary is developed on basket-ball for student general schools.

  8. Effects of physical therapy delivery via home video telerehabilitation on functional and health–related quality of life outcomes

    Directory of Open Access Journals (Sweden)

    Charles E. Levy, MD

    2015-06-01

    Full Text Available This study examined functional outcomes, health-related quality of life (HRQoL, and satisfaction in a group of Veterans who received physical therapy via an in-home video telerehabilitation program, the Rural Veterans TeleRehabilitation Initiative (RVTRI. A retrospective, pre–post study design was used. Measures obtained from 26 Veterans who received physical therapy in the RVTRI program between February 22, 2010, and April 1, 2011, were analyzed. Outcomes were the Functional Independence Measure (FIM; Quick Disabilities of the Arm, Shoulder, and Hand measure; Montreal Cognitive Assessment (MoCA; and the 2-minute walk test (2MWT. HRQoL was assessed using the Veterans RAND 12-Item Health Survey (VR-12, and program satisfaction was evaluated using a telehealth satisfaction scale. Average length of participation was 99.2 +/– 43.3 d and Veterans, on average, received 15.2 +/– 6.0 therapeutic sessions. Significant improvement was shown in the participants' FIM (p < 0.001, r = 0.63, MoCA (p = 0.01, r = 0.44, 2MWT (p = 0.006, r = 0.73, and VR-12 (p = 0.02, r = 0.42. All Veterans reported satisfaction with their telerehabilitation experiences. Those enrolled in the RVTRI program avoided an average of 2,774.7 +/– 3,197.4 travel miles, 46.3 +/– 53.3 hr of driving time, and $1,151.50 +/– $1,326.90 in travel reimbursement. RVTRI provided an effective real-time, home-based, physical therapy.

  9. Comparative release studies on suppositories using the basket, paddle, dialysis tubing and flow-through cell methods I. Acetaminophen in a lipophilic base suppository.

    Science.gov (United States)

    Hori, Seiichi; Kawada, Tsubasa; Kogure, Sanae; Yabu, Shinako; Mori, Kenji; Akimoto, Masayuki

    2017-02-01

    The release characteristics of lipophilic suppositories containing acetaminophen (AAP) were examined using four types of dissolution methods: the basket, paddle, dialysis tubing (DT) and flow-through cell (FTC) methods. The suitability of each apparatus for quality control in AAP compounded suppositories was evaluated using statistical procedures. More than 80% of the drug was released over 60 min in all the release methods studied, with the exception of the basket method. Reproducible and faster release was achieved using the paddle method at 100 and 200 rpm, whereas poor release occurred with the basket method. The mean dissolution time (MDT), maximum dissolved quantity of AAP at the end of the sampling time (Q) and dissolution efficiency (DE) were calculated by model-independent methods. The FTC method with a single chamber used in this study was also appreciable for AAP suppositories (Q of 100%, MDT of 71-91 min and DE of 75-80%). The DT apparatus is considered similar to the FTC apparatus from a quality control perspective for judging the release properties of lipophilic base suppositories containing AAP. However, even the single chamber FTC used in this study has potential as an in vitro drug release test for suppositories. The comparative dissolution method is expected to become one of the valuable tools for selecting an adequate dissolution test.

  10. Hyaluronic acid concentration-mediated changes in structure and function of porous carriers for corneal endothelial cell sheet delivery.

    Science.gov (United States)

    Lai, Jui-Yang

    2016-02-01

    In this study, the effects of hyaluronic acid (HA) concentrations (0.05-1.25wt.%) on the properties of porous carriers for corneal endothelial tissue engineering were investigated. The pore size and porosity gradually increased with decreasing solid content. However, at relatively low HA concentration (i.e., 0.05wt.%), the material samples contained small interior pores and a dense surface skin layer, probably due to no gas bubble effect on the stirring processing of porous microstructures of freeze-dried polysaccharide hydrogels. The carriers prepared from 0.25wt.% HA solution had the highest freezable water content and oxygen and glucose permeability among the samples evaluated. Results of cell viability assays and quantitative real-time reverse transcription polymerase chain reaction analyses showed that the HA concentration-related alteration of porous microstructure dictates the compatibility of biopolymer carriers with corneal endothelial cell (CEC) cultures. In vivo studies demonstrated that the CEC sheet/HA carrier construct implants are therapeutically efficacious in the reconstruction of endothelial scrape-wounded corneas. It is concluded that the polysaccharide concentration is the major factor for affecting the processing of carriers and their structure and function. Porous hydrogels prepared from 0.25wt.% HA solution are capable of delivering bioengineered CEC sheets to the posterior surface of cornea.

  11. Criticality Analysis for Proposed Maximum Fuel Loading in a Standardized SNF Canister with Type 1a Baskets

    Energy Technology Data Exchange (ETDEWEB)

    Chad Pope; Larry L. Taylor; Soon Sam Kim

    2007-02-01

    This document represents a summary version of the criticality analysis done to support loading SNF in a Type 1a basket/standard canister combination. Specifically, this engineering design file (EDF) captures the information pertinent to the intact condition of four fuel types with different fissile loads and their calculated reactivities. These fuels are then degraded into various configurations inside a canister without the presence of significant moderation. The important aspect of this study is the portrayal of the fuel degradation and its effect on the reactivity of a single canister given the supposition there will be continued moderation exclusion from the canister. Subsequent analyses also investigate the most reactive ‘dry’ canister in a nine canister array inside a hypothetical transport cask, both dry and partial to complete flooding inside the transport cask. The analyses also includes a comparison of the most reactive configuration to other benchmarked fuels using a software package called TSUNAMI, which is part of the SCALE 5.0 suite of software.

  12. Entorhinal cortical innervation of parvalbumin-containing neurons (Basket and Chandelier cells) in the rat Ammon's horn.

    Science.gov (United States)

    Kiss, J; Buzsaki, G; Morrow, J S; Glantz, S B; Leranth, C

    1996-01-01

    Physiological data suggest that in the CA1-CA3 hippocampal areas of rats, entorhinal cortical efferents directly influence the activity of interneurons, in addition to pyramidal cells. To verify this hypothesis, the following experiments were performed: 1) light microscopic double-immunostaining for parvalbumin and the anterograde tracer Phaseolus vulgaris-leucoagglutinin injected into the entorhinal cortex; 2) light and electron microscopic analysis of cleaved spectrin-immunostained (i.e., degenerating axons and boutons) hippocampal sections following entorhinal cortex lesion; and 3) an electron microscopic study of parvalbumin-immunostained hippocampal sections after entorhinal cortex lesion. The results demonstrate that in the stratum lacunosum-moleculare of the CA1 and CA3 regions, entorhinal cortical axons form asymmetric synaptic contacts on parvalbumin-containing dendritic shafts. In the stratum lacunosum-moleculare, parvalbumin-immunoreactive dendrites represent processes of GABAergic, inhibitory basket and chandelier cells; these interneurons innervate the perisomatic area and axon initial segments of pyramidal cells, respectively. A feed-forward activation of these neurons by the entorhinal input may explain the strong, short-latency inhibition of pyramidal cells.

  13. Fast gamma oscillations are generated intrinsically in CA1 without the involvement of fast-spiking basket cells.

    Science.gov (United States)

    Craig, Michael T; McBain, Chris J

    2015-02-25

    Information processing in neuronal networks relies on the precise synchronization of ensembles of neurons, coordinated by the diverse family of inhibitory interneurons. Cortical interneurons can be usefully parsed by embryonic origin, with the vast majority arising from either the caudal or medial ganglionic eminences (CGE and MGE). Here, we examine the activity of hippocampal interneurons during gamma oscillations in mouse CA1, using an in vitro model where brief epochs of rhythmic activity were evoked by local application of kainate. We found that this CA1 KA-evoked gamma oscillation was faster than that in CA3 and, crucially, did not appear to require the involvement of fast-spiking basket cells. In contrast to CA3, we also found that optogenetic inhibition of pyramidal cells in CA1 did not significantly affect the power of the oscillation, suggesting that excitation may not be essential for gamma genesis in this region. We found that MGE-derived interneurons were generally more active than CGE interneurons during CA1 gamma, although a group of CGE-derived interneurons, putative trilaminar cells, were strongly phase-locked with gamma oscillations and, together with MGE-derived axo-axonic and bistratified cells, provide attractive candidates for being the driver of this locally generated, predominantly interneuron-driven model of gamma oscillations.

  14. Noninvasive targeting delivery and in vivo magnetic resonance tracking method for live apoptotic cells in cerebral ischemia with functional Fe2O3 magnetic nanoparticles.

    Science.gov (United States)

    Saito, Atsushi; Mekawy, Moataz M; Sumiyoshi, Akira; Riera, Jorge J; Shimizu, Hiroaki; Kawashima, Ryuta; Tominaga, Teiji

    2016-03-11

    Apoptotic neuronal death is known as programmed cell death. Inhibition of this progression might contribute to a new treatment strategy. However, methods for in vivo detection of live apoptotic cells are in need to be developed and established. The purpose of this study is to develop a new method for in vivo brain imaging for live apoptotic lesions using magnetic resonance imaging (MRI). We focused on the specific accumulation of our recently developed functional magnetic nanoparticles (FMNPs) into apoptotic cells using a rat cerebral ischemia model. Sulphorhodamine B, fluorescent dye was linked to valylalanylaspartic acid fluoromethyl ketone as a pan-caspase inhibitor to form SR-FLIVO. SR-FLIVO was bound with FMNPs to develop SR-FLIVO-FMNP probe. Ischemic rat brains were scanned by 7T MRI before and after intravenous injection of SR-FLIVO-FMNP and the distribution was evaluated by subtraction images of T2* colored mapping. SR-FLIVO, intracellular FMNPs, and T2* reduction area were histologically analyzed. The distribution of SR-FLIVO-FMNP was evaluated by subtracting the T2* signal images and was significantly correlated with the histological findings by TUNEL staining. Our experimental results revealed several findings where our newly developed probe SR-FLIVO-FMNP was intravenously administered into ischemic rats and FLIVO expression was tracked and found in apoptotic cells in rat brains after cerebral ischemia. A remarkable T2* reduction within the ischemic lesion was recorded using MRI based SR-FLIVO-FMNP probe as a contrasting agent due to the specific probe accumulation in apoptotic cells whereas, no observation of T2* reduction within the non-ischemic lesion due to no probe accumulation in non-apoptotic cells. Histological analysis based on the correlation between FLIVO and TUNEL staining showed that almost all FLIVO-positive cells were positive for TUNEL staining. These findings suggest the possibility for establishment of in vivo targeting delivery

  15. DFT computational study on the phosphate functionalized SWCNTs as efficient drug delivery systems for anti-osteoporosis zolendronate and risedronate drugs

    Science.gov (United States)

    Nikfar, Zahra; Shariatinia, Zahra

    2017-07-01

    The pristine (4,4)-armchair SWCNT as well as its three phosphate functionalized (CNT-nH2PO4, n=1-3) forms were studied as novel drug delivery systems for the two commercially famous anti-osteoporosis drugs including risedronate (RIS) and zolendronate (ZOL) using the density functional theory (DFT) computations at both B3LYP and B3PW91 levels. Results revealed that the binding energy was increased by increasing number of H2PO4 moieties attached on the CNT with the most negative binding energy was measured for the CNT-3H2PO4 carrier. The dipole moments of all phosphate containing CNTs were much greater ( 1.5-4.5 D) than that of pristine CNT ( 0 D). The contour maps verified that when the CNT was functionalized by H2PO4 groups, the symmetric distribution of electric charge was vanished so that the highest and the lowest asymmetric charge distributions were achieved for the CNT-2H2PO4 and CNT-3H2PO4, respectively, leading to the greatest and the smallest dipole moments for the CNT-2H2PO4 (4.177 D) and the CNT-3H2PO4 (1.614 D). The compounds RIS-CNT-3H2PO4 and ZOL-CNT-3H2PO4 displayed the greatest electronegativity and electrophilicity index which were appropriate for the binding of drugs onto the bone surface (having partial positive charge due to the presence of Ca2+) and therefore effectively inhibiting the osteoporosis. Consequently, it was proposed that the drug-CNT-3H2PO4 was the most appropriate drug-carrier system for both of the RIS and ZOL drugs which could be employed as the most efficient vehicle.

  16. Distribution of assimilated carbon in plants and rhizosphere soil of basket willow (Salix viminalis L.)

    NARCIS (Netherlands)

    Neergaard, de A.; Porter, J.R.; Gorissen, A.

    2002-01-01

    Willow is often used in bio-energy plantations for its potential to function as a renewable energy source, but knowledge about its effect on soil carbon dynamics is limited. Therefore, we investigated the temporal variation in carbon dynamics in willow, focusing on below-ground allocation and seques

  17. APLIKASI DATA MINING MARKET BASKET ANALYSIS PADA TABEL DATA ABSENSI ELEKTRONIK UNTUK MENDETEKSI KECURANGAN ABSENSI (CHECK-LOCK KARYAWAN DI PERUSAHAAN

    Directory of Open Access Journals (Sweden)

    Gregorius Satia Budhi

    2007-01-01

    Full Text Available Taking attendance from employees always becomes a problem for Human Resource Department (HRD in many companies lately. Although there is an automatic check-lock machine, it still has a weakness. This machine can't detect some frauds like the employee swipes double identity card, his card and the others card. Reseachers want to solve this problem by using data mining method, especially market basket analysis.This software will transform the attendance data to compact transaction format by using MaxDiff Histogram method. And it will be processed into frequent itemset with Pincer Search Algoritm. At the final process the employee's association rule will got from frequent itemset. This output will be served to user that is the HRD of a firm.Testing result shows that Data Mining Market Basket Analysis can be used to get pattern of employee's check-lock from a company. And this pattern can help user to detect fraud that is done by employee. Abstract in Bahasa Indonesia : Absensi pegawai selama ini selalu menjadi permasalahan yang pelik bagi bagian HRD di perusahaan - perusahaan yang ada. Walaupun telah ada peralatan absensi otomatis, alat ini masih memiliki kelemahan yaitu, tidak dapat mendeteksi kecurangan pegawai untuk menitipkan kartu absensinya pada karyawan lain untuk diabsenkan. Peneliti berkeinginan untuk mengatasi permasalahan absensi tersebut dengan memanfaatkan metode data mining, khususnya metode market basket analysis, untuk mendeteksi kecurangan ini.Perangkat lunak yang dibuat ini akan mentranformasikan data absensi pegawai menggunakan metode MaxDiff Histogram menjadi format compact transaction yang selanjutnya akan diproses menggunakan Algoritma Pincer Search menjadi frequent itemset. Pada akhirnya dari data frequent itemset ini didapat association rule pegawai untuk disajikan kepada pengguna, yaitu bagian HRD perusahaan.Dari hasil pengujian dapat diketahui bahwa metode Data Mining Market Basket Analysis dapat dimanfaatkan untuk menggali

  18. Preparation of collagen peptide functionalized chitosan nanoparticles by ionic gelation method: An effective carrier system for encapsulation and release of doxorubicin for cancer drug delivery.

    Science.gov (United States)

    Anandhakumar, S; Krishnamoorthy, G; Ramkumar, K M; Raichur, A M

    2017-01-01

    In recent years, nanoparticles (NPs) based on biopolymers or peptides are gaining popularity for the encapsulation and release of drug molecules, especially for cancer therapy, due to their ability for targeted and controlled release. The use of collagen peptide (CP) for the preparation of chitosan (CN) NPs is especially interesting as it results in NPs that are stable under physiological conditions. In this work, mono-dispersed pH responsive CPCN NPs of about 100nm were prepared via ionic gelation method by simple and mild co-precipitation of CN and CP. Investigation of NPs with Fourier transform infra-red (FTIR) spectroscopy and dynamic light scattering (DLS) measurements reveals that hydrogen bonding and electrostatic interactions are believed to be major driving forces for NP formation and drug encapsulation, respectively. Scanning electron microscopic (SEM) investigations show that hard and fine CPCN NPs transform to soft and bigger gel like particles as a function of collagen concentration. The unique "polymeric gel" structure of NPs showed high encapsulation efficiency towards doxorubicin hydrochloride (DOX) as well as pH controlled release. Anti-proliferative and cell viability analysis revealed that DOX loaded NPs showed excellent anti-proliferative characteristics against HeLa cells with favorable biocompatibility against normal cells. Such NPs have high potential for use as smart drug delivery carriers in advanced cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Functional peptide nanocarriers for delivery of novel anti-RelA RNA interference agents as a topical treatment of atopic dermatitis.

    Science.gov (United States)

    Kanazawa, Takanori; Hamasaki, Tomohiro; Endo, Takahiro; Tamano, Kuniko; Sogabe, Kana; Seta, Yasuo; Ohgi, Tadaaki; Okada, Hiroaki

    2015-07-15

    Small interfering RNAs (siRNAs) are a potential treatment of atopic dermatitis (AD) because they can specifically silence the gene expression of AD-related factors. However, siRNA alone cannot exert a sufficiently strong therapeutic effect due to low delivery efficiency to the target tissues and cells; simply increasing the amount used is not possible due to the possibility of off-target effects. We previously reported a novel class of therapeutic RNA interference (RNAi) agents called nkRNA(®) and PnkRNA(®), which have been shown to be effective in several disease models, have greater resistance to nuclease degradation than canonical siRNAs, and do not induce any immunotoxicity. In the present study, we describe a non-invasive and effective transdermal RNAi therapeutic system for atopic dermatitis that uses the functional cell-penetrating stearoyl-oligopeptide OK-102 as a cytoplasm-responsive nanocarrier for nkRNA(®) and PnkRNA(®). The two RNAi agents were targeted against RelA, a subclass of NF-κB (nuclear factor kappa B), and, as part of OK-102 complexes, they strongly silenced RelA mRNA in macrophage cells and demonstrated a significant therapeutic effect in a mouse model of AD. It was shown that OK-102-complexed RNAi agents were an efficient therapeutic system for AD and caused no adverse reactions.

  20. Effectiveness of intracavernous delivery of adenovirus encoding Smad7 gene on erectile function in a mouse model of cavernous nerve injury.

    Science.gov (United States)

    Song, Kang Moon; Chung, Jae-Seung; Choi, Min Ji; Jin, Hai-Rong; Yin, Guo Nan; Kwon, Mi-Hye; Park, Jin-Mi; Kim, Woo Jean; Lee, Sang-Jin; Kim, Seong-Jin; Ryu, Ji-Kan; Suh, Jun-Kyu

    2014-01-01

    Men with erectile dysfunction (ED) respond poorly to oral phosphodiesterase-5 inhibitors following radical prostatectomy. Recent studies have reported that up-regulation of transforming growth factor-β1 (TGF-β1) and activation of the Smad signaling pathway play important roles in cavernous fibrosis and in the deterioration of erectile function in a mouse model of cavernous nerve injury (CNI) and in patients with spinal cord injury. The mothers against decapentaplegic homolog 7 (Smad7) is known to inhibit the phosphorylation of Smad2 and Smad3. To investigate the effectiveness of adenoviruses encoding Smad7 gene (Ad-Smad7) on erectile function in a mouse model of CNI. Twelve-week-old C57BL/6J mice were used and distributed into 7 groups: sham operation group, untreated CNI group, and CNI groups receiving a single intracavernous injection of adenovirus encoding LacZ (1 × 10(8) virus particles [vp]/20 μL) or adenovirus encoding Smad7 (Ad-Smad7; 1 × 10(7), 1 × 10(8), 2 × 10(8), or 1 × 10(9) vp/20 μL). Two weeks after bilateral cavernous nerve crushing and treatment, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was harvested for histologic examinations and Western blot analysis. The highest erectile response was noted in CNI mice treated with Ad-Smad7 at a dose of 1 × 10(8)  vp, which reached up to 82-85% of sham control values. Local delivery of Ad-Smad7 significantly decreased endothelial cell apoptosis and the production of extracellular matrix proteins, including plasminogen activator inhibitor-1, fibronectin, collagen I, and collagen IV, and induced endothelial nitric oxide synthase phosphorylation in the corpus cavernosum tissue of CNI mice. The adenovirus-mediated gene transfer of Smad7 successfully restored erectile function by enhancing endothelial cell function and through antifibrotic effects. These findings suggest that inhibition of the TGF-β signaling pathway by use of

  1. Premature delivery

    Directory of Open Access Journals (Sweden)

    Bernardita Donoso Bernales

    2012-09-01

    Full Text Available Preterm delivery is the single most important cause of perinatal morbidity and mortality. In Chile, preterm births have increased in the past decade, although neonatal morbidity and mortality attributable to it shows a downward trend, thanks to improvements in neonatal care of premature babies, rather than the success of obstetric preventive and therapeutic strategies. This article describes clinical entities, disease processes and conditions that constitute predisposing factors of preterm birth, as well as an outline for the prevention and clinical management of women at risk of preterm birth.

  2. Half-Antibody Functionalized Lipid-Polymer Hybrid Nanoparticles for Targeted Drug Delivery to Carcinoembryonic Antigen (CEA) Presenting Pancreatic Cancer Cells

    Science.gov (United States)

    Hu, Che-Ming Jack; Kaushal, Sharmeela; Tran Cao, Hop S.; Aryal, Santosh; Sartor, Marta; Esener, Sadik; Bouvet, Michael; Zhang, Liangfang

    2010-01-01

    Current chemotherapy regimens against pancreatic cancer are met with little success as poor tumor vascularization significantly limits the delivery of oncological drugs. High-dose targeted drug delivery, through which a drug delivery vehicle releases a large payload upon tumor localization, is thus a promising alternative strategy against this lethal disease. Herein, we synthesize anti-CEA half-antibody conjugated lipid-polymer hybrid nanoparticles and characterize their ligand conjugation yields, physicochemical properties, and targeting ability against pancreatic cancer cells. Under the same drug loading, the half-antibody targeted nanoparticles show enhanced cancer killing effect compared to the corresponding non-targeted nanoparticles. PMID:20394436

  3. Pharmaceuticals and personal care products in chicken meat and other food animal products: a market-basket pilot study.

    Science.gov (United States)

    Baron, Patrick A; Love, David C; Nachman, Keeve E

    2014-08-15

    Pharmaceutical drugs are extensively used in industrial food animal production. We examined whether residues of veterinary antibiotics and other pharmaceuticals and personal care products (PPCPs) were detectable in a small market-basket sample of retail chicken (n=39), ground beef (n=3) and milk (n=3) samples. High-performance liquid chromatography and tandem mass spectrometry were used to assess the concentration of 59 PPCPs and their residues in animal products. All samples of ground beef, milk, and 14 chickens were analyzed individually, while an additional 25 chicken samples were pooled and analyzed in groups of five. The majority of PPCPs were not detected in meat and milk samples. Caffeine was detected in two of three milk samples (0.4 ng/mL, 2.0 ng/mL) and in 10 of 19 individual and pooled chicken samples (median: 18.6 ng/g, range: 6.1-28.8 ng/g). Acetaminophen was detected in three of three milk samples (median: 1.5 ng/mL, range: 1.4-2.1 ng/mL). Antibiotics in the tetracycline class were detected in two of three milk samples (median: 1.0 ng/mL, range: 0.1-2.0 ng/mL) and did not exceed regulatory residue tolerances of 300 ng/mL. There are no regulatory residue tolerances for caffeine or acetaminophen in animal products. The acetaminophen detections in milk, however, raise questions about extra-label and unapproved use of pharmaceutical drugs in food animal production, as this drug is not approved for use in lactating dairy cattle or any other type of food animal production. Additional studies are needed to confirm our finding of PPCPs in meat and dairy products.

  4. Delivery technologies for genome editing.

    Science.gov (United States)

    Yin, Hao; Kauffman, Kevin J; Anderson, Daniel G

    2017-03-24

    With the recent development of CRISPR technology, it is becoming increasingly easy to engineer the genome. Genome-editing systems based on CRISPR, as well as transcription activator-like effector nucleases (TALENs) and zinc-finger nucleases (ZFNs), are becoming valuable tools for biomedical research, drug discovery and development, and even gene therapy. However, for each of these systems to effectively enter cells of interest and perform their function, efficient and safe delivery technologies are needed. This Review discusses the principles of biomacromolecule delivery and gene editing, examines recent advances and challenges in non-viral and viral delivery methods, and highlights the status of related clinical trials.

  5. The Near Future Impaction on Primiparas’Pelvic Floor Function After the Unprotected Vaginal Delivery%初产妇无保护阴道分娩对盆底功能的近期影响

    Institute of Scientific and Technical Information of China (English)

    范承玲; 周宏霞; 张荣善

    2015-01-01

    目的:探讨初产妇无保护阴道分娩对盆底功能的近期影响。方法选择经阴道分娩的初产妇208例为研究对象,无保护阴道分娩无侧切138例为观察组,常规阴道分娩行会阴侧切70例为对照组,于产后42 d返院专人对产妇临床症状及盆底功能进行检测,对比两组分娩方式对盆底功能的近期影响。结果观察组切口疼痛发生率、性生活障碍发生率低于对照组(P0.05)。结论无保护阴道分娩可减少产后盆底功能障碍疾病的发生。%Objective To discuss the near future impaction on primiparas’pelvic floor function after unprotected vaginal delivery. Methods Selected 208 cases of primiparas after vaginal delivery as the research objects,138 cases of unprotected vaginal delivery with no side cut were taken as observation group, 70 cases of normal vaginal delivery with line episiotomy were taken as control group. The puerperas came back to hospital after postpartum 42 day,and were tested the clinical symptoms and pelvic floor function by personnels. Compared the two groups recent impaction on pelvic floor function. Results The incidences of incision pain and sexual dysfunction in observation group was obviously lower than these in control group(P0.05). Conclusion Unprotected vaginal delivery can reduce the incidence of postpartum pelvic floor dysfunction diseases.

  6. New energy efficiency technologies associated with increased natural gas demand in delivery and consumption sectors of Iran

    Energy Technology Data Exchange (ETDEWEB)

    Alghalandis, Saeid Mansouri

    2010-09-15

    Increasing population and economic growth in developing countries has changed their energy consumption patterns. So, the conventional systems of energy supply have become inadequate to deal with rising energy demand. Iran has great reservoirs of natural gas and its natural gas usage is far more than average international standard. Dominance of natural gas share in energy basket in Iran, make it necessary to consider energy efficient technologies and solutions for this domain. In this study new technologies for increasing energy efficiency (EE) in natural gas delivery and consumption sub sectors are discussed and evaluated according to available infrastructures in Iran.

  7. Software tool for analysing the family shopping basket without candidate generation

    Directory of Open Access Journals (Sweden)

    Roberto Carlos Naranjo Cuervo

    2010-05-01

    Full Text Available Tools leading to useful knowledge being obtained for supporting marketing decisions being taken are currently needed in the e-commerce environment. A process is needed for this which uses a series of techniques for data-processing; data-mining is one such technique enabling automatic information discovery. This work presents the association rules as a suitable technique for dis-covering how customers buy from a company offering business to consumer (B2C e-business, aimed at supporting decision-ma-king in supplying its customers or capturing new ones. Many algorithms such as A priori, DHP, Partition, FP-Growth and Eclat are available for implementing association rules; the following criteria were defined for selecting the appropriate algorithm: database insert, computational cost, performance and execution time. The development of a software tool is also presented which involved the CRISP-DM approach; this software tool was formed by the following four sub-modules: data pre-processing, data-mining, re-sults analysis and results application. The application design used three-layer architecture: presentation logic, business logic and service logic. Data warehouse design and algorithm design were included in developing this data-mining software tool. It was tested by using a FoodMart company database; the tests included performance, functionality and results’ validity, thereby allo-wing association rules to be found. The results led to concluding that using association rules as a data mining technique facilita-tes analysing volumes of information for B2C e-business services which represents a competitive advantage for those companies using Internet as their sales’ media.

  8. Near-Complete Correction of Profound Metabolomic Impairments Corresponding to Functional Benefit in MPS IIIB Mice after IV rAAV9-hNAGLU Gene Delivery.

    Science.gov (United States)

    Fu, Haiyan; Meadows, Aaron S; Ware, Tierra; Mohney, Robert P; McCarty, Douglas M

    2017-03-01

    Mucopolysaccharidosis (MPS) IIIB is a lysosomal storage disease with complex CNS and somatic pathology due to a deficiency in α-N-acetylglucosaminidase (NAGLU). Using global metabolic profiling by mass spectrometry targeting 361 metabolites, this study detected significant decreases in 225 and increases in six metabolites in serum samples from 7-month-old MPS IIIB mice, compared to wild-type (WT) mice. The metabolic disturbances involve virtually all major pathways of amino acid, peptide (58/102), carbohydrate (18/28), lipid (111/139), nucleotide (12/24), energy (2/9), vitamin and cofactor (11/16), and xenobiotic (11/28) metabolism. Notably, the reduced metabolites included eight essential amino acids, vitamins (C, E, B2, and B6), and neurotransmitters (serotonin, glutamate, aspartate, tryptophan, and N-acetyltyrosine). The metabolic impairments appear to emerge early during disease progression before the age of 2 months. Importantly, the restoration of NAGLU activity with an intravenous (i.v.) injection of rAAV9-hNAGLU vector led to near-complete correction of all serum metabolite abnormalities, with 201 (87%) metabolites normalized and 30 (13%) over-corrected. While the mechanisms are unclear, our data demonstrate that the lack of NAGLU activity triggers profound functional metabolic disturbances in MPS IIIB. These metabolic impairments respond well to a systemic rAAV9-hNAGLU gene delivery, supporting the surrogate biomarker potential of serum metabolomic profiles for MPS IIIB therapies. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  9. AS1411 aptamer and folic acid functionalized pH-responsive ATRP fabricated pPEGMA-PCL-pPEGMA polymeric nanoparticles for targeted drug delivery in cancer therapy.

    Science.gov (United States)

    Lale, Shantanu V; R G, Aswathy; Aravind, Athulya; Kumar, D Sakthi; Koul, Veena

    2014-05-12

    Nonspecificity and cardiotoxicity are the primary limitations of current doxorubicin chemotherapy. To minimize side effects and to enhance bioavailability of doxorubicin to cancer cells, a dual-targeted pH-sensitive biocompatible polymeric nanosystem was designed and developed. An ATRP-based biodegradable triblock copolymer, poly(poly(ethylene glycol) methacrylate)-poly(caprolactone)-poly(poly(ethylene glycol) methacrylate) (pPEGMA-PCL-pPEGMA), conjugated with doxorubicin via an acid-labile hydrazone bond was synthesized and characterized. Dual targeting was achieved by attaching folic acid and the AS1411 aptamer through EDC-NHS coupling. Nanoparticles of the functionalized triblock copolymer were prepared using the nanoprecipitation method, resulting in an average particle size of ∼140 nm. The biocompatibility of the nanoparticles was evaluated using MTT cytotoxicity assays, blood compatibility studies, and protein adsorption studies. In vitro drug release studies showed a higher cumulative doxorubicin release at pH 5.0 (∼70%) compared to pH 7.4 (∼25%) owing to the presence of the acid-sensitive hydrazone linkage. Dual targeting with folate and the AS1411 aptamer increased the cancer-targeting efficiency of the nanoparticles, resulting in enhanced cellular uptake (10- and 100-fold increase in uptake compared to single-targeted NPs and non-targeted NPs, respectively) and a higher payload of doxorubicin in epithelial cancer cell lines (MCF-7 and PANC-1), with subsequent higher apoptosis, whereas a normal (noncancerous) cell line (L929) was spared from the adverse effects of doxorubicin. The results indicate that the dual-targeted pH-sensitive biocompatible polymeric nanosystem can act as a potential drug delivery vehicle against various epithelial cancers such as those of the breast, ovary, pancreas, lung, and others.

  10. Delivery strategies for antiparasitics.

    Science.gov (United States)

    Kayser, Oliver; Kiderlen, Albrecht F

    2003-02-01

    Optimisation of drug carrier systems and drug delivery strategies that take into account the peculiarities of individual infectious agents and diseases are key elements of modern drug development. In the following, different aspects of a rational design for antiparasitic drug formulation will be reviewed, covering delivery systems such as nano- and microparticles, liposomes, emulsions and microemulsions, cochleates and bioadhesive macromolecules. Functional properties for each carrier system will be discussed as well as their therapeutic efficacy for parasitic diseases, including leishmaniasis, human African trypanosomiasis, human cryptosporidiosis, malaria and schistosomiasis. Critical issues for the application of drug carrier systems will be discussed, focusing on biopharmaceutical and pathophysiological parameters such as routes of application, improvement of body distribution and targeting intracellularly persisting pathogens.

  11. Transcutaneous antigen delivery system

    Directory of Open Access Journals (Sweden)

    Mi-Young Lee

    2013-01-01

    Full Text Available Transcutaneous immunization refers to the topical applicationof antigens onto the epidermis. Transcutaneous immunizationtargeting the Langerhans cells of the skin has received muchattention due to its safe, needle-free, and noninvasive antigendelivery. The skin has important immunological functions withunique roles for antigen-presenting cells such as epidermalLangerhans cells and dermal dendritic cells. In recent years,novel vaccine delivery strategies have continually beendeveloped; however, transcutaneous immunization has not yetbeen fully exploited due to the penetration barrier representedby the stratum corneum, which inhibits the transport ofantigens and adjuvants. Herein we review recent achievementsin transcutaneous immunization, focusing on the variousstrategies for the enhancement of antigen delivery andvaccination efficacy. [BMB Reports 2013; 46(1: 17-24

  12. Drug-eluting or bare-metal stents for large coronary vessel stenting? The BASKET-PROVE (PROspective Validation Examination) trial: Study protocol and design

    DEFF Research Database (Denmark)

    Pfisterer, M.; Bertel, O.; Bonetti, P.O.;

    2008-01-01

    Background Based on a subgroup analysis of 18-month BAsel Stent Kosten Effektivitats Trial (BASKET) outcome data, we hypothesized that very late (>12 months) stent thrombosis occurs predominantly after drug-eluting stent implantation in large native coronary vessel stenting. Methods To prove...... stent use in patients with large native vessel stenting. The 2-year death/myocardial infarction-as well as target vessel revascularization-and bleeding rates in these patients with a first-versus second-generation drug-eluting stent should demonstrate the benefit or harm of these stents compared...

  13. Research of level of formed knowledge, abilities and skills on basket-ball for the students of faculty of physical education.

    OpenAIRE

    Kovalenko J.A.

    2011-01-01

    The results of a zero control of students of faculty of physical education are presented. The estimation of theoretical knowledge's is conducted, abilities and skills on basket-ball for the students of a 1 course of directions of preparation «Physical education», «Health of man» and «Sport». It is set that the level of their formed at most students of different directions of preparation is insufficient. It is certain that by reason of such position, foremost, there is insufficient preparation...

  14. Oral delivery of anticancer drugs

    DEFF Research Database (Denmark)

    Thanki, Kaushik; Gangwal, Rahul P; Sangamwar, Abhay T

    2013-01-01

    The present report focuses on the various aspects of oral delivery of anticancer drugs. The significance of oral delivery in cancer therapeutics has been highlighted which principally includes improvement in quality of life of patients and reduced health care costs. Subsequently, the challenges...... incurred in the oral delivery of anticancer agents have been especially emphasized. Sincere efforts have been made to compile the various physicochemical properties of anticancer drugs from either literature or predicted in silico via GastroPlus™. The later section of the paper reviews various emerging...... trends to tackle the challenges associated with oral delivery of anticancer drugs. These invariably include efflux transporter based-, functional excipient- and nanocarrier based-approaches. The role of drug nanocrystals and various others such as polymer based- and lipid based...

  15. Metadata and API Based Environment Aware Content Delivery Architecture

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    One of the limitations of current content delivery networks is lack of support for environment aware content delivery. This paper first discusses the requirements of such support, and proposes a new metadata gateway based environment aware content delivery architecture. The paper discusses in some details key functions and technologies of environment aware content delivery architecture, including its APIs and control policies. Finally the paper presents an application to illustrate advantages of environment aware content delivery architecture in the context of next generation network.

  16. Amino-functionalized poly(L-lactide lamellar single crystals as a valuable substrate for delivery of HPV16-E7 tumor antigen in vaccine development

    Directory of Open Access Journals (Sweden)

    Di Bonito P

    2015-05-01

    Full Text Available Paola Di Bonito,1 Linda Petrone,1 Gabriele Casini,2 Iolanda Francolini,2 Maria Grazia Ammendolia,3 Luisa Accardi,1 Antonella Piozzi,2 Lucio D’Ilario,2 Andrea Martinelli2 1Department of Infectious, Parasitic and Immune-mediated Diseases, Italian National Institute of Health, 2Department of Chemistry, Sapienza University of Rome, Rome, Italy; 3Department of Technology and Health, Italian National Institute of Health, Rome, Italy Background: Poly(L-lactide (PLLA is a biodegradable polymer currently used in many biomedical applications, including the production of resorbable surgical devices, porous scaffolds for tissue engineering, nanoparticles and microparticles for the controlled release of drugs or antigens. The surfaces of lamellar PLLA single crystals (PLLAsc were provided with amino groups by reaction with a multifunctional amine and used to adsorb an Escherichia coli-produced human papillomavirus (HPV16-E7 protein to evaluate its possible use in antigen delivery for vaccine development.Methods: PLLA single crystals were made to react with tetraethylenepentamine to obtain amino-functionalized PLLA single crystals (APLLAsc. Pristine and amino-functionalized PLLAsc showed a two-dimensional microsized and one-dimensional nanosized lamellar morphology, with a lateral dimension of about 15–20 µm, a thickness of about 12 nm, and a surface specific area of about 130 m2/g. Both particles were characterized and loaded with HPV16-E7 before being administered to C57BL/6 mice for immunogenicity studies. The E7-specific humoral-mediated and cell-mediated immune response as well as tumor protective immunity were analyzed in mice challenged with TC-1 cancer cells.Results: Pristine and amino-functionalized PLLAsc adsorbed similar amounts of E7 protein, but in protein-release experiments E7-PLLAsc released a higher amount of protein than E7-APLLAsc. When the complexes were dried for observation by scanning electron microscopy, both samples showed a

  17. Polyethylenimine-functionalized carbon nanotubes tagged with AS1411 aptamer for combination gene and drug delivery into human gastric cancer cells.

    Science.gov (United States)

    Taghavi, Sahar; Nia, Azadeh Hashem; Abnous, Khalil; Ramezani, Mohammad

    2017-01-10

    In this project, synergistic cancer cell death was achieved by a targeted delivery system comprising Bcl-xL-specific shRNA and a very low DOX content, which simultaneously activated an intrinsic apoptotic pathway. A modified branched polyethylenimine (PEI 10kDa) was grafted through polyethylene glycol (PEG) linker to carboxylated single-walled carbon nanotubes (SWCNT) to serve as a vehicle for shRNA delivery. The SWNT-PEG-PEI conjugate was covalently attached to AS1411 aptamer as the nucleolin ligand to target the co-delivery system to the tumor cells overexpressing nucleolin receptors on their surface. The final vehicle was eventually obtained after intercalation of DOX with pBcl-xL shRNA-SWCNT-PEG-10-10%PEI-Apt. Cell viability assay, GFP expression and transfection experiment against L929 (-nucleolin) and AGS (+nucleolin) cells illustrated that the tested targeted delivery system inhibited the growth of nucleolin-abundant gastric cancer cells with strong cell selectivity. Subsequently, we illustrated that the combination treatment of the selected shRNAs and DOX had excellent tumoricidal efficacy as verified by MTT assay. Furthermore, very low concentration of DOX, approximately 58-fold lower than its IC50 concentration, was used which could mitigate toxic side effects of DOX. Overall, our work revealed that combination of shRNA-mediated gene-silencing strategy with chemotherapeutic agents constitutes a valuable and safe approach for antitumor activity.

  18. Adsorption separation of carbon dioxide from flue gas of natural gas-fired boiler by a novel nanoporous 'molecular basket' adsorbent

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Xiaochun; Song, Chunshan; Miller, Bruce G.; Scaroni, Alan W. [Clean Fuels and Catalysis Program, The Energy Institute, and Department of Energy and Geo-Environmental Engineering, Pennsylvania State University, 209 Academic Projects Building, University Park, PA 16802 (United States)

    2005-10-15

    A novel nanoporous CO{sub 2} 'molecular basket' adsorbent has been developed and applied in the separation of CO{sub 2} from the flue gas of a natural gas fired boiler. The nanoporous CO{sub 2} 'molecular basket' adsorbent was prepared by uniformly dispersing polyethylenimine (PEI) into the pores of mesoporous molecular sieve MCM-41. The use of MCM-41 and PEI had a synergetic effect on the CO{sub 2} adsorption. The rates of CO{sub 2} adsorption/desorption of PEI were also greatly improved. Adsorption separation results showed that CO{sub 2} was selectively separated from simulated flue gas and flue gas of a natural gas-fired boiler by using this novel adsorbent. The adsorbent adsorbed very little N{sub 2}, O{sub 2} and CO in the flue gas. Moisture had a promoting effect on the adsorption separation of CO{sub 2} from flue gas. The adsorbent simultaneously adsorbed CO{sub 2} and NO{sub x} from flue gas. The adsorbed amount of CO{sub 2} was around 3000 times larger than that of NO{sub x}. The adsorbent was stable in several cyclic adsorption/desorption operations. However, very little NO{sub x} desorbed after adsorption indicating the need for pre-removal of NO{sub x} from flue gas before capture of CO{sub 2} by this novel adsorbent. (author)

  19. Density functional and molecular docking studies towards investigating the role of single-wall carbon nanotubes as nanocarrier for loading and delivery of pyrazinamide antitubercular drug onto pncA protein

    Science.gov (United States)

    Saikia, Nabanita; Rajkhowa, Sanchaita; Deka, Ramesh C.

    2013-03-01

    The potential biomedical application of carbon nanotubes (CNTs) pertinent to drug delivery is highly manifested considering the remarkable electronic and structural properties exhibited by CNT. To simulate the interaction of nanomaterials with biomolecular systems, we have performed density functional calculations on the interaction of pyrazinamide (PZA) drug with functionalized single-wall CNT ( fSWCNT) as a function of nanotube chirality and length using two different approaches of covalent functionalization, followed by docking simulation of fSWCNT with pncA protein. The functionalization of pristine SWCNT facilitates in enhancing the reactivity of the nanotubes and formation of such type of nanotube-drug conjugate is thermodynamically feasible. Docking studies predict the plausible binding mechanism and suggests that PZA loaded fSWCNT facilitates in the target specific binding of PZA within the protein following a lock and key mechanism. Interestingly, no major structural deformation in the protein was observed after binding with CNT and the interaction between ligand and receptor is mainly hydrophobic in nature. We anticipate that these findings may provide new routes towards the drug delivery mechanism by CNTs with long term practical implications in tuberculosis chemotherapy.

  20. Functional

    Directory of Open Access Journals (Sweden)

    Fedoua Gandia

    2014-07-01

    Full Text Available The study was carried out to investigate the effects of inhaled Mg alone and associated with F in the treatment of bronchial hyperresponsiveness. 43 male Wistar rats were randomly divided into four groups and exposed to inhaled NaCl 0.9%, MeCh, MgSO4 and MgF2. Pulmonary changes were assessed by means of functional tests and quantitative histological examination of lungs and trachea. Results revealed that delivery of inhaled Mg associated with F led to a significant decrease of total lung resistance better than inhaled Mg alone (p < 0.05. Histological examinations illustrated that inhaled Mg associated with F markedly suppressed muscular hypertrophy (p = 0.034 and bronchoconstriction (p = 0.006 in MeCh treated rats better than inhaled Mg alone. No histological changes were found in the trachea. This study showed that inhaled Mg associated with F attenuated the main principle of the central components of changes in MeCh provoked experimental asthma better than inhaled Mg alone, potentially providing a new therapeutic approach against asthma.

  1. 选择性剖宫产和阴道分娩对产后盆底功能的影响%Effects of selective cesarean section and vaginal delivery on postpartum pelvic floor function

    Institute of Scientific and Technical Information of China (English)

    张慧敏

    2012-01-01

    目的:探讨不同分娩方式对产后早期盆底功能的影响.方法:随机抽取2011年1~5月在荣成市妇幼保健院分娩的产妇65例,根据不同分娩方式分为选择性剖宫产组(32例)和阴道顺产组(33例).分别于产后6周及12周行POP -Q评分、尿垫试验、超声检测残余尿以及会阴超声检查,比较两组产妇压力性尿失禁(SUI)、盆腔器官脱垂(POP)的发生率及膀胱颈移动度情况.结果:产后6周和产后12周随访时,SUI发生率选择性剖宫产组3.13% (1/32)和0(0/19),顺产组24.24% (8/33)和27.78% (5/18),两组比较差异无统计学意义(P >0.05);POP发生率选择性剖宫产组37.50% (12/32)和36.84% (7/19),顺产组72.73%(24/33)和77.78% (14/18),差异有统计学意义(P<0.05).产后6周和产后12周会阴超声显示选择性剖宫产组与顺产组膀胱颈角度及膀胱颈旋转角度比较差异有统计学意义(P<0.05).结论:选择性剖宫产可降低产后早期POP的发生率,并可减少发生SUI的风险.%Objective: To explore the effects of different delivery modes on early postpartum pelvic floor function. Methods; Sixty -five pregnant women who deliveried in the hospital from January to May in 2011 were selected randomly, then they were divided into selective cesarean section group (32 cases) and vaginal delivery group (33 cases) according to different delivery modes. POP - Q score, pad test, residual urine detection by ultrasonography and perineal ultrasonography were carried out at six and twelve weeks after delivery; the incidences of stress urinary incontinence (SUI) and pelvic organ prolapse ( POP) , and the degree of bladder neck mobility were compared between the two groups. Results: During follow - up at six and twelve weeks after delivery, the incidences of SUI in selective cesarean section group were 3. 13% (1/32) and 0 (0/19), respectively, while the incidences of SUI in vaginal delivery group were 24. 24% (8/33) and 27. 78% (5

  2. Transdermal drug delivery

    OpenAIRE

    Prausnitz, Mark R.; Langer, Robert

    2008-01-01

    Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability ...

  3. 剖宫产与经阴道分娩对产妇盆底功能的影响%Cesarean Section and Vaginal Delivery Impact on Maternal Pelvic Floor Function

    Institute of Scientific and Technical Information of China (English)

    刘芳华

    2014-01-01

    ObjectiveTo study the effect of cesarean section and vaginal delivery on maternal pelvic floor function.Methods Select 120 cases of lying in women in our hospital received, with different modes of delivery wil be divided into the observation group and the control group, the control group using vaginal delivery, cesarean section was used in the observation group, two groups were compared with POP and pelvic floor muscle condition.Results The patients in the observation group the vaginal and uterine prolapse, pelvic floor muscle tension score were significantly better than the control group (P<0.05).Conclusion Compared with vaginal delivery, cesarean section can effectively reduce the effect of postpartum pelvic floor function on postpartum rehabilitation, but to promote the recovery of pelvic floor function has better effect, so there is no need to be selected as the main part according to mode of delivery.%目的:探讨剖宫产与经阴道分娩对产妇盆底功能的影响。方法选取我院接收的120例产妇,以分娩方式的不同将其分为观察组和对照组,对照组采用经阴道分娩,观察组采用剖宫产,比较两组产妇的POP及盆底肌力情况。结果观察组患者阴道及子宫脱垂情况、产后盆底肌张力评分均明显优于对照组(P<0.05)。结论相较于阴道分娩,剖宫产可有效的减少产后对盆底功能的影响,但产后康复对促进盆底功能恢复有较好的效果,因而无需将其作为选择分娩方式的主要依据。

  4. Sustained (S)-roscovitine delivery promotes neuroprotection associated with functional recovery and decrease in brain edema in a randomized blind focal cerebral ischemia study.

    Science.gov (United States)

    Rousselet, Estelle; Létondor, Anne; Menn, Bénédicte; Courbebaisse, Yann; Quillé, Marie-Lise; Timsit, Serge

    2017-01-01

    Stroke is a devastating disorder that significantly contributes to death, disability and healthcare costs. In ischemic stroke, the only current acute therapy is recanalization, but the narrow therapeutic window less than 6 h limits its application. The current challenge is to prevent late cell death, with concomitant therapy targeting the ischemic cascade to widen the therapeutic window. Among potential neuroprotective drugs, cyclin-dependent kinase inhibitors such as (S)-roscovitine are of particular relevance. We previously showed that (S)-roscovitine crossed the blood-brain barrier and was neuroprotective in a dose-dependent manner in two models of middle cerebral artery occlusion (MCAo). According to the Stroke Therapy Academic Industry Roundtable guidelines, the pharmacokinetics of (S)-roscovitine and the optimal mode of delivery and therapeutic dose in rats were investigated. Combination of intravenous (IV) and continuous sub-cutaneous (SC) infusion led to early and sustained delivery of (S)-roscovitine. Furthermore, in a randomized blind study on a transient MCAo rat model, we showed that this mode of delivery reduced both infarct and edema volume and was beneficial to neurological outcome. Within the framework of preclinical studies for stroke therapy development, we here provide data to improve translation of pre-clinical studies into successful clinical human trials.

  5. Highly efficient in vitro and in vivo delivery of functional RNAs using new versatile MS2-chimeric retrovirus-like particles

    Directory of Open Access Journals (Sweden)

    Anne Prel

    2015-01-01

    Full Text Available RNA delivery is an attractive strategy to achieve transient gene expression in research projects and in cell- or gene-based therapies. Despite significant efforts investigating vector-directed RNA transfer, there is still a requirement for better efficiency of delivery to primary cells and in vivo. Retroviral platforms drive RNA delivery, yet retrovirus RNA-packaging constraints limit gene transfer to two genome-molecules per viral particle. To improve retroviral transfer, we designed a dimerization-independent MS2-driven RNA packaging system using MS2-Coat-retrovirus chimeras. The engineered chimeric particles promoted effective packaging of several types of RNAs and enabled efficient transfer of biologically active RNAs in various cell types, including human CD34+ and iPS cells. Systemic injection of high-titer particles led to gene expression in mouse liver and transferring Cre-recombinase mRNA in muscle permitted widespread editing at the ROSA26 locus. We could further show that the VLPs were able to activate an osteoblast differentiation pathway by delivering RUNX2- or DLX5-mRNA into primary human bone-marrow mesenchymal-stem cells. Thus, the novel chimeric MS2-lentiviral particles are a versatile tool for a wide range of applications including cellular-programming or genome-editing.

  6. Part II: Functional delivery of a neurotherapeutic gene to neural stem cells using minicircle DNA and nanoparticles: Translational advantages for regenerative neurology.

    Science.gov (United States)

    Fernandes, Alinda R; Chari, Divya M

    2016-09-28

    Both neurotrophin-based therapy and neural stem cell (NSC)-based strategies have progressed to clinical trials for treatment of neurological diseases and injuries. Brain-derived neurotrophic factor (BDNF) in particular can confer neuroprotective and neuro-regenerative effects in preclinical studies, complementing the cell replacement benefits of NSCs. Therefore, combining both approaches by genetically-engineering NSCs to express BDNF is an attractive approach to achieve combinatorial therapy for complex neural injuries. Current genetic engineering approaches almost exclusively employ viral vectors for gene delivery to NSCs though safety and scalability pose major concerns for clinical translation and applicability. Magnetofection, a non-viral gene transfer approach deploying magnetic nanoparticles and DNA with magnetic fields offers a safe alternative but significant improvements are required to enhance its clinical application for delivery of large sized therapeutic plasmids. Here, we demonstrate for the first time the feasibility of using minicircles with magnetofection technology to safely engineer NSCs to overexpress BDNF. Primary mouse NSCs overexpressing BDNF generated increased daughter neuronal cell numbers post-differentiation, with accelerated maturation over a four-week period. Based on our findings we highlight the clinical potential of minicircle/magnetofection technology for therapeutic delivery of key neurotrophic agents.

  7. Association Between Sexual Health and Delivery Mode

    Directory of Open Access Journals (Sweden)

    Mihyon Song, MD

    2014-12-01

    Conclusion: This study suggests that routine episiotomies at delivery should be avoided to improve postpartum maternal sexual function. Maternal age and cesarean section were found to affect postpartum sexual health. Song M, Ishii H, Toda M, Tomimatsu T, Katsuyama H, Nakamura T, Nakai Y, and Shimoya K. Association between sexual health and delivery mode. Sex Med 2014;2:153–158.

  8. Extracellular vesicles for drug delivery

    NARCIS (Netherlands)

    Vader, Pieter; Mol, Emma A; Pasterkamp, Gerard; Schiffelers, Raymond M

    2016-01-01

    Extracellular vesicles (EVs) are cell-derived membrane vesicles, and represent an endogenous mechanism for intercellular communication. Since the discovery that EVs are capable of functionally transferring biological information, the potential use of EVs as drug delivery vehicles has gained consider

  9. 不同分娩方式对产后妇女盆底功能影响的临床分析%Clinical analysis of the effect of different delivery modes on the pelvic floor function of postpartum women

    Institute of Scientific and Technical Information of China (English)

    龚天柳

    2015-01-01

    Objective To evaluate postpartum pelvic floor disorder through assessing the pelvic floor func -tion and compare the effects of two kinds of delivery modes , cesarean section and vaginal delivery on postpartum pel-vic floor function and provide a theoretical basis for the prevention and treatment of pelvic floor dysfunction (PFD). Methods 800 postpartum women who revisited the outpatient department 6 to 8 weeks after childbirth were collected from January to June 2014 and divided into caesarean delivery group (n=288) and vaginal delivery group(n=512) according to the different modes of delivery .Routine assessment of pelvic floor function was retrospectively analyzed and compared between the two groups .Results Among 800 patients who were screened by the manual muscle test combined with the assessment of pelvic floor function .The damage of muscle fiber type Ⅰwas found in 185 cases and the damage of muscle fiber type Ⅱin 168 cases in the cesarean delivery group;the damage of muscle fiber type Ⅰwas found in 504 cases and the damage of muscl fibere type Ⅱin 502 cases in the vaginal delivery group .There was significant difference between the two groups (P<0.01).The impaired muscle strength, muscle injury, abnormal muscle fatigue and the vaginal dynamic pressure value <80 cmH2 O were more severe or higher in vagina delivery group than those in the caesarean delivery group (P<0.05).Conclusion Compared with vaginal delivery , cesarean section has less adverse effects on pelvic floor function .However , the impaired pelvic floor function can be recovered by carrying out postpartum rehabilitation exercise , so it should not be based on the choice of delivery modes .%目的:通过盆底功能评估了解产后妇女盆底功能障碍状况,分析比较剖宫产与阴道产两种分娩方式对产后盆底功能的影响,为盆底功能障碍性疾病( PFD)的防治提供理论依据。方法选取2014-01~2014-06间在该院分娩并于产后6~8

  10. 采运烤一体化烤房挂筐式烘烤烟叶的效应%Effects of Tobacco Harvesting Roast Integration Barn Basket Baking

    Institute of Scientific and Technical Information of China (English)

    刘久羽; 阚宏伟; 胡向丹; 张大斌; 孙建生; 邓泳; 张纪利

    2014-01-01

    In order to simplify the baking process of tobacco and reduce tobacco baking cost,the current widespread use of tobacco baking bulk curing barn was transformed and the tobacco harvesting roast basket type curing effect of hanging barn integration was studied in this paper.The results showed that logging roast integration barn basket baking could promote the transformation of tobacco inclusions and aroma precursors,promote the coordination of chemical composition,increase the content of neutral aroma substances and improve the proportion of high class leaf.it could save labor quantity 8.45,reduce baked cost 659.01 Yuan when baked fresh tobacco 4000 kg,and net income increased 939.01 Yuan each 600 kg dry tobacco.%为简化烟叶烘烤工作环节和降低烟叶烘烤成本,利用目前烟叶烘烤普遍使用的密集烤房进行改造,研究了烟叶采运烤一体化烤房的挂筐式烘烤效应。结果表明:采运烤一体化烤房挂筐式烘烤能够促进烟叶内含物和香气前体物质的转化,促进化学成分的协调性及中性香气物质的含量,提高上等烟叶比例。采烤4000 kg 鲜烟可节约用工数量8.45个,烟叶采烤成本降低659.01元;烤后干烟叶(600 kg)纯收入增加939.01元。

  11. Assisted Vaginal Delivery

    Science.gov (United States)

    ... be needed. What are the risks for my baby if I have assisted vaginal delivery? Although the overall rate of injury to the baby as a result of assisted vaginal delivery is low, there still is a risk of ...

  12. eDelivery

    Data.gov (United States)

    US Agency for International Development — eDelivery provides the electronic packaging and delivery of closed and complete OPM investigation files to government agencies, including USAID, in a secure manner....

  13. Assisted delivery with forceps

    Science.gov (United States)

    ... technique your doctor may use to deliver the baby is called vacuum assisted delivery . When is a Forceps Delivery Needed? Even after ... Problems with urinating or moving your bowels after delivery For the baby, the risks are: Bumps, bruises or marks on ...

  14. Hyaluronic acid functional amphipathic and redox-responsive polymer particles for the co-delivery of doxorubicin and cyclopamine to eradicate breast cancer cells and cancer stem cells

    Science.gov (United States)

    Hu, Kelei; Zhou, Huige; Liu, Ying; Liu, Zhu; Liu, Jing; Tang, Jinglong; Li, Jiayang; Zhang, Jiakun; Sheng, Wang; Zhao, Yuliang; Wu, Yan; Chen, Chunying

    2015-04-01

    Cancer stem cells (CSCs) have the ability to transform into bulk cancer cells, to promote tumor growth and establish tumor metastasis. To effectively inhibit tumor growth and prevent metastasis, treatments with conventional chemotherapy drugs should be combined with CSC targeted drugs. In this study, we describe the synthesis and characterization of a new amphiphilic polymer, hyaluronic acid-cystamine-polylactic-co-glycolic acid (HA-SS-PLGA), composed of a hydrophobic PLGA head and a hydrophilic HA segment linked by a bioreducible disulfide bond. With a double emulsion method, a nano delivery system was constructed to deliver doxorubicin (DOX) and cyclopamine (CYC, a primary inhibitor of the hedgehog signaling pathway of CSCs) to both a CD44-overexpressing breast CSC subpopulation and bulk breast cancer cells and allow an on-demand release. The resulting drug-loaded NPs exhibited a redox-responsive drug release profile. Dual drug-loaded particles potently diminished the number and size of tumorspheres and HA showed a targeting effect towards breast CSCs. In vivo combination therapy further demonstrated a remarkable synergistic anti-tumor effect and prolonged survival compared to mono-therapy using the orthotopic mammary fat pad tumor growth model. The co-delivery of drug and the CSC specific inhibitor towards targeted cancer chemotherapeutics provides an insight into anticancer strategy with facile control and high efficacy.Cancer stem cells (CSCs) have the ability to transform into bulk cancer cells, to promote tumor growth and establish tumor metastasis. To effectively inhibit tumor growth and prevent metastasis, treatments with conventional chemotherapy drugs should be combined with CSC targeted drugs. In this study, we describe the synthesis and characterization of a new amphiphilic polymer, hyaluronic acid-cystamine-polylactic-co-glycolic acid (HA-SS-PLGA), composed of a hydrophobic PLGA head and a hydrophilic HA segment linked by a bioreducible disulfide bond

  15. Synthesis, characterization and in vitro study of biocompatible cinnamaldehyde functionalized magnetite nanoparticles (CPGF Nps for hyperthermia and drug delivery applications in breast cancer.

    Directory of Open Access Journals (Sweden)

    Kirtee D Wani

    Full Text Available Cinnamaldehyde, the bioactive component of the spice cinnamon, and its derivatives have been shown to possess anti-cancer activity against various cancer cell lines. However, its hydrophobic nature invites attention for efficient drug delivery systems that would enhance the bioavailability of cinnamaldehyde without affecting its bioactivity. Here, we report the synthesis of stable aqueous suspension of cinnamaldehyde tagged Fe3O4 nanoparticles capped with glycine and pluronic polymer (CPGF NPs for their potential application in drug delivery and hyperthermia in breast cancer. The monodispersed superparamagnetic NPs had an average particulate size of ∼ 20 nm. TGA data revealed the drug payload of ∼ 18%. Compared to the free cinnamaldehyde, CPGF NPs reduced the viability of breast cancer cell lines, MCF7 and MDAMB231, at lower doses of cinnamaldehyde suggesting its increased bioavailability and in turn its therapeutic efficacy in the cells. Interestingly, the NPs were non-toxic to the non-cancerous HEK293 and MCF10A cell lines compared to the free cinnamaldehyde. The novelty of CPGF nanoparticulate system was that it could induce cytotoxicity in both ER/PR positive/Her2 negative (MCF7 and ER/PR negative/Her2 negative (MDAMB231 breast cancer cells, the latter being insensitive to most of the chemotherapeutic drugs. The NPs decreased the growth of the breast cancer cells in a dose-dependent manner and altered their migration through reduction in MMP-2 expression. CPGF NPs also decreased the expression of VEGF, an important oncomarker of tumor angiogenesis. They induced apoptosis in breast cancer cells through loss of mitochondrial membrane potential and activation of caspase-3. Interestingly, upon exposure to the radiofrequency waves, the NPs heated up to 41.6 °C within 1 min, suggesting their promise as a magnetic hyperthermia agent. All these findings indicate that CPGF NPs prove to be potential nano-chemotherapeutic agents in breast cancer.

  16. Service Delivery Platforms Developing and Deploying Converged Multimedia Services

    CERN Document Server

    Ahson, Syed A

    2011-01-01

    In the telecommunications industry, it is becoming increasingly important for operators to quickly provide a service delivery platform. This book discusses the fundamental requirements of service delivery platforms, evaluating their basic functions and feasibility. Starting with content and media in modern networks, the text presents the entire user experience, including requirements for the user terminal, supporting systems, broadcasting, and networks. Expert contributors explore the evolving role of service delivery platforms, explaining various applications and delivery mechanisms, providin

  17. 中医药联合Kegel训练对产后盆底功能康复的影响%Effect of traditional Chinese medicine combined with Kegel training on the rehabilitation of pelvic floor function after delivery

    Institute of Scientific and Technical Information of China (English)

    洪静娟; 吴霍曼; 向丽娟

    2011-01-01

    Objective: To explore the effect of traditional Chinese medicine combined with Kegel training on the rehabilitation of pelvic floor function after delivery. Methods: 360 full - term primiparous women ( head presentation, natural labor) were divided into observation group and control group randomly, 180 women in each group, the women in the two groups were treated with different methods for rehabilitation of pelvic floor function after delivery. The incidences of urinary incontinence and pelvic floor muscle tension scores in the two groups were evaluated at 42 days after delivery. Results: The incidence of urinary incontinence in observation group was significantly lower than that in control group, the pelvic floor muscle tension in observation group was better than that in control group ( P < 0. 05 ) . Conclusion : Early oral administration of traditional Chinese medicine combined with Kegel training can prevent and treat the occurrence and development of stress urinary incontinence effectively after delivery.%目的:探讨中医药联合Kegel训练对产后盆底功能康复的影响.方法:将360例足月、初产、头位自然分娩的产妇随机分观察组和对照组各180例,使用不同的方法进行产后盆底功能康复,以产后42天评价两组产妇尿失禁发生率及盆底肌张力强度评分.结果:观察组产妇尿失禁发生率低于对照组,盆底肌张力强度优于对照组,差异有统计学意义(P<0.05).结论:产后早期进行中药口服联合Kegel训练可以有效防治产后压力性尿失禁的发生和发展.

  18. 产前盆底肌功能锻炼对阴道分娩结局的影响%Effect of functional exercise of prenatal pelvic floor muscles on vaginal delivery outcome.

    Institute of Scientific and Technical Information of China (English)

    万忠艳

    2011-01-01

    Objective To investigate the effect of functional exercise ofprcnatal pelvic floor muscles on vaginal delivery outcome. Methods Pregnant women who voluntarily accepted functional exercise of prenatal pelvic floor muscles were selected as the study group (n=58). Pregnant women who didn't take part in functional exercise were selected as the control group (n=64). Before all women dehvering, tension of pelvic floor muscles were detected.Some information including the sage of labor and vaginal delivery were evaluated in two groups. Results There were significant differences between the study group and the control group, as to the tension of pelvic floor muscles (P<0.05), the time length of the active labor, second stage of labor and all stage of labor (P<O.0 l). The volume of vaginal bleeding and the rate of episiotomy or vaginal midwifery in the study group were lower than those in the control group (P<0.05). Conclusion Functional exercise ofprenaal pelvic floor muscles has a positive effect on vaginal delivery outcome, which may enhance the tension of pelvic floor muscles and shorten all stage of labor.%目的 探讨产前进行盆底肌功能锻炼对阴道分娩结局的影响.方法 选择自愿接受盆底肌功能锻炼的孕妇58例作为实验组,未进行功能锻炼的孕妇64例作为对照组.两组孕妇分娩前行盆底肌肉肌张力检测,并记录分娩产程时间和阴道分娩情况.结果 实验组孕妇盆底肌肉肌张力强于对照组(P<0.05),活跃期、第二产程和总产程时间均短于对照组(P<0.01);阴道助产率、会阴侧切率和阴道出血量均低于对照组(P<0.05).结论 孕妇产前进行盆底肌锻炼能够增强盆底肌张力、缩短产程,并且对于改善阴道分娩结局有积极的作用.

  19. Novopen Echo® for the delivery of insulin: a comparison of usability, functionality and preference among pediatric subjects, their parents, and health care professionals

    DEFF Research Database (Denmark)

    Olsen, Birthe S; Lilleøre, Søren Kruse; Korsholm, Conny Nøhr

    2010-01-01

    Despite advances in insulin pen design and functionality, the selection of pens available for children with diabetes is limited. This study assessed the usability, functionality and attitudes towards NovoPen Echo®, a new durable insulin pen designed for pediatric patients that combines a simple...... memory function with half-increment dosing, versus NovoPen® Junior and HumaPen® Luxura™ HD in pediatric subjects, their parents, and health care professionals (HCPs)....

  20. β-cyclodextrin functionalized poly (5-amidoisophthalicacid) grafted Fe{sub 3}O{sub 4} magnetic nanoparticles: A novel biocompatible nanocomposite for targeted docetaxel delivery

    Energy Technology Data Exchange (ETDEWEB)

    Tarasi, Roghayeh [Department of Chemistry, University of Zanjan, P.O. Box 45195-313, Zanjan (Iran, Islamic Republic of); Khoobi, Mehdi [Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Niknejad, Hassan [Department of Tissue Engineering, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Ramazani, Ali [Department of Chemistry, University of Zanjan, P.O. Box 45195-313, Zanjan (Iran, Islamic Republic of); Ma’mani, Leila [Department of Nanotechnology, Agricultural Biotechnology Research Institute of Iran (ABRII), Agricultural Research, Education and Extension Organization (AREEO), Karaj (Iran, Islamic Republic of); Bahadorikhalili, Saeed [Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Shafiee, Abbas, E-mail: ashafiee@ams.ac.ir [Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2016-11-01

    Thiol-lactam initiated radical polymerization (TLIRP) was successfully employed to prepare poly-N−5-acrylamidoisophthalicacid grafted onto Fe{sub 3}O{sub 4} magnetic nanoparticles (MNPs@PAIP). β-Cyclodextrin (CD) was then conjugated to the carboxylic groups of the prepared MNPs via carbodiimide activation. Subsequently, tumor-targeting folic acid (FA) was attached to the hydroxyl groups of CD on the surface of the latter MNPs to increase the site-specific intracellular delivery. The prepared MNPs were fully characterized by FTIR, VSM, TGA, XRD, FE-SEM and TEM. Docetaxel (DTX) as hydrophobic anticancer drug was loaded via host-guest inclusion complexation with CD and the release profile of the system was studied at different pH. The effect of MNPs on the cell viability was evaluated for the human embryonic kidney normal cell line (HEK293) as well as HeLa and MDA-MB-231 cancerous cell lines and the results did not show any apparent cytotoxic effect. In comparison, DTX loaded MNPs reduced the growth of HeLa and MDA-MB-231 cells more than free DTX. Intracellular uptake ability of DTX loaded MNPs was also studied using fluorescent microscopy and showed cellular uptake about 90% after 4 h treatment. - Highlights: • MNPs@PAIP-CD-FA nanoparticles as a carrier of Doctexal have excellent physical properties. • These nanoparticles are superparamagnetic, biocompatible and non-toxic. • The constructed nanocarrier showed suitable loading capacity and entrapment efficiency.

  1. β-cyclodextrin functionalized poly (5-amidoisophthalicacid) grafted Fe3O4 magnetic nanoparticles: A novel biocompatible nanocomposite for targeted docetaxel delivery

    Science.gov (United States)

    Tarasi, Roghayeh; Khoobi, Mehdi; Niknejad, Hassan; Ramazani, Ali; Ma'mani, Leila; Bahadorikhalili, Saeed; Shafiee, Abbas

    2016-11-01

    Thiol-lactam initiated radical polymerization (TLIRP) was successfully employed to prepare poly-N-5-acrylamidoisophthalicacid grafted onto Fe3O4 magnetic nanoparticles (MNPs@PAIP). β-Cyclodextrin (CD) was then conjugated to the carboxylic groups of the prepared MNPs via carbodiimide activation. Subsequently, tumor-targeting folic acid (FA) was attached to the hydroxyl groups of CD on the surface of the latter MNPs to increase the site-specific intracellular delivery. The prepared MNPs were fully characterized by FTIR, VSM, TGA, XRD, FE-SEM and TEM. Docetaxel (DTX) as hydrophobic anticancer drug was loaded via host-guest inclusion complexation with CD and the release profile of the system was studied at different pH. The effect of MNPs on the cell viability was evaluated for the human embryonic kidney normal cell line (HEK293) as well as HeLa and MDA-MB-231 cancerous cell lines and the results did not show any apparent cytotoxic effect. In comparison, DTX loaded MNPs reduced the growth of HeLa and MDA-MB-231 cells more than free DTX. Intracellular uptake ability of DTX loaded MNPs was also studied using fluorescent microscopy and showed cellular uptake about 90% after 4 h treatment.

  2. Comparison of different mode of delivery for women on postpartum hemorrhage and immune function%不同分娩方式对产妇产后出血及新生儿免疫功能的影响

    Institute of Scientific and Technical Information of China (English)

    夏红梅; 牟海波; 孟晓蓉; 李其香; 张彦

    2013-01-01

    目的 探讨阴道分娩与剖宫产对产后出血及新生儿免疫功能的影响.方法 选择健康初产妇120例,按照选择分娩方式的不同分为阴道分娩组和剖宫产组,每组各60例.检测两组产妇产后出血情况以及新生儿Apgar评分,脐带血免疫球蛋白(IgA、IgG和IgM)及C-反应蛋白(CRP)的变化水平.结果 剖宫分娩的产后出血率显著高于阴道分娩组(P< 0.05),而分娩方式对新生儿1 min和5 min Apgar评分结果并无显著影响(P>0.05).剖宫产组IgA、CRP水平显著高于阴道分娩(P<0.05),而IgG、IgM水平则低于阴道分娩组(P<0.05),且剖宫产男性新生儿IgA和IgM水平明显低于女性新生儿,IgG水平则高于女性新生儿,差异均有统计学意义(P<0.05).结论 阴道分娩与剖宫产对新生儿的Apgar评分无明显的影响,但剖宫产术可导致产后出血率增加并降低新生儿免疫力.%Objective To explore the vaginal delivery and cesarean section on the postpartum hemorrhage,Apgar score of newborns,and immune function by the primiparous women.Methods 120 cases of pregnant women were divided into vaginal delivery and cesarean section group,60 cases in each group.Apgar score,immunoglobulin (IgA,IgG and IgM) and C-reactive protein (CRP) level,and the levels of postpartum hemorrhage were detected in the two groups of newborns.Results The vaginal delivery mode showed significant lower rate of postpartum hemorrhage (P < 0.05).There were no significant differences on the 1 min and 5 min Apgar score results between the two groups (P =0.17; P=0.50).IgA,CRP level was significantly higher in cesarean section group than that of vaginal delivery group (P <0.05),while IgG,IgM level was lower than that of the vaginal delivery group (P < 0.05).Male newborns IgA and IgM levels were significantly lower in female newborns,but IgG was higher than the female newborns in the cesarean group (P < 0.05).Conclusion Vaginal delivery and cesarean have no

  3. 不同分娩方式对青年初产妇下尿路功能的远期影响%Impact of different delivery way on the youth primipara lower urinary tract long-term function

    Institute of Scientific and Technical Information of China (English)

    高金凤; 郑红枫

    2015-01-01

    目的:探讨不同分娩方式对青年初产妇下尿路功能的远期影响。方法收集2008年2月~2009年2月来我院分娩的健康初产妇175例,将其按照分娩的方式分为阴道分娩组(n=95)和剖宫产组(n=80),采用ICIQ-FLUTS调查初次分娩5年后阴道分娩及剖宫产两种分娩方式的初产妇下尿路功能,尿流率采用Laborite Spindle View TM尿流率仪进行检测。结果①阴道分娩组最大尿流率、平均尿流率高于剖宫产组,达最大尿流率时间短于剖宫产组,但差异无统计学意义(P>0.05)。②阴道分娩组尿频、夜尿增多、压力性尿失禁发生率低于剖宫产组,腹压排尿、间断排尿、排尿踌躇、混合性尿失禁发生率高于剖宫产组,但两组差异均无统计学意义(P>0.05)。尿急发生率高于剖宫产组,急迫性尿失禁发生率低于剖宫产组,两组差异有统计学意义(P<0.05)。③产后尿失禁组年龄、体质指数高于非产后尿失禁组,差异有统计学意义(P<0.05)。结论阴道分娩及剖宫产两种生产方式青年初产妇5年后均有较高的下尿路症状发生率,年龄及体质指数为产后尿失禁发生的影响因素。%Objective To investigate the effects of different delivery way on long-term youth primipara urinary tract function. Methods All 175 cases of health primipara were collected from February 2008 to February 2009 in our hospi-tal, they were divided into two groups according to the difference delivery manner:the vaginal delivery group (n=95), the cesarean group (n=80), the lower urinary tract function of the primipara five years after the initial delivery of vagi-nal delivery and cesarean delivery mode were surveyed with ICIQ-FLUTS , the urinary flow rate were tested with La-borite Spindle View TM flow rate meter. Results ①The Qmax, average flow rate of the vaginal delivery group was higher than that of the cesarean group , up to the maximum

  4. Project delivery system (PDS)

    CERN Document Server

    2001-01-01

    As business environments become increasingly competitive, companies seek more comprehensive solutions to the delivery of their projects. "Project Delivery System: Fourth Edition" describes the process-driven project delivery systems which incorporates the best practices from Total Quality and is aligned with the Project Management Institute and ISO Quality Standards is the means by which projects are consistently and efficiently planned, executed and completed to the satisfaction of clients and customers.

  5. Cesarean Delivery in Adolescents.

    Science.gov (United States)

    Katz Eriksen, Jennifer L; Melamed, Alexander; Clapp, Mark A; Little, Sarah E; Zera, Chloe

    2016-10-01

    To examine the effect of maternal age on indication for primary cesarean delivery in low-risk nulliparous women. Retrospective cohort study. Urban academic tertiary care center. Nulliparous women younger than 35 years of age delivering vertex-presenting singletons at term. Participants underwent spontaneous, operative or cesarean delivery. Mode of delivery, indication, and timing of cesarean delivery. Adolescents were half as likely to undergo cesarean delivery overall (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.43-0.54), and more than one-third less likely to undergo cesarean delivery in labor (OR, 0.59; 95% CI, 0.53-0.66). Adjustment for potential confounders did not alter the strength of these associations. Adolescents were half as likely to undergo cesarean delivery for failure to progress (OR, 0.49; 95% CI, 0.43-0.54). There was no difference in the odds of cesarean delivery for nonreassuring fetal status (OR, 0.91; 95% CI, 0.77-1.06), or genital herpes (OR, 1.44; 95% CI, 0.57-3.68). Induction, macrosomia, oxytocin augmentation, and any labor complication were all associated with increased risk of cesarean delivery. There was no difference in the duration of second stage for adolescents who delivered by cesarean delivery compared with adults (240.0 vs 237.7 minutes; P = .84), but adolescents who delivered vaginally had a second stage that was one-third shorter than adults (62.5 vs 100.3 minutes; P cesarean delivery overall, and 40% less likely to undergo a primary cesarean delivery in labor, even after adjustment for multiple maternal, neonatal, and labor characteristics. This difference is not explained by differences in the duration of the second stage of labor. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  6. Buccal drug delivery.

    Science.gov (United States)

    Smart, John D

    2005-05-01

    Buccal formulations have been developed to allow prolonged localised therapy and enhanced systemic delivery. The buccal mucosa, however, while avoiding first-pass effects, is a formidable barrier to drug absorption, especially for biopharmaceutical products (proteins and oligonucleotides) arising from the recent advances in genomics and proteomics. The buccal route is typically used for extended drug delivery, so formulations that can be attached to the buccal mucosa are favoured. The bioadhesive polymers used in buccal drug delivery to retain a formulation are typically hydrophilic macro-molecules containing numerous hydrogen bonding groups. Newer second-generation bioadhesives have been developed and these include modified or new polymers that allow enhanced adhesion and/or drug delivery, in addition to site-specific ligands such as lectins. Over the last 20 years a wide range of formulations has been developed for buccal drug delivery (tablet, patch, liquids and semisolids) but comparatively few have found their way onto the market. Currently, this route is restricted to the delivery of a limited number of small lipophilic molecules that readily cross the buccal mucosa. However, this route could become a significant means for the delivery of a range of active agents in the coming years, if the barriers to buccal drug delivery are overcome. In particular, patient acceptability and the successful systemic delivery of large molecules (proteins, oligonucleotides and polysaccharides) via this route remains both a significant opportunity and challenge, and new/improved technologies may be required to address these.

  7. Determination of Vanadyl Porphyrins by Liquid-liquid Microextraction and Nano-baskets of p-tert-Calix[4]arene Bearing Di-[N-(X)sulfonye Carboxamide] and Di-(1-propoxy) in Ortho-cone Conformation

    Institute of Scientific and Technical Information of China (English)

    MOKHTARI Bahram; POURABDOLLAH Kobra

    2012-01-01

    Dispersive liquid-liquid microextraction technique was introducd to remove the centrifuging step and conduct inclusion microextraction of charged porphyrins by nano-baskets.For nano-baskets ofp-tert-calix[4]arene bearing di-[N-(X)sulfonyl carboxamide] and di-(1-propoxy) in ortho-cone conformation was synthesized and used.The related parameters including ligand concentration,the volume of water disperser,salt effect,and extraction time were optimized.The linear range,detection limit(S/N=3) and precision(RSD,n=6) were determined to be 0.2-50,0.07 μg/L and 5.3%,respectively.The results reveal that the new approach is competitive analytical tool and an alternative of the traditional methods in the crude oil and related systems.

  8. Synthetic Lipoproteins as Carriers for Drug Delivery.

    Science.gov (United States)

    Huang, Gangliang; Liu, Yang; Huang, Hualiang

    2016-01-01

    Synthetic lipoprotein is an effective carrier of targeted delivery for drugs. It has the very small size, good biocompatibility, suitable half-life, and specific lipoprotein receptorbinding capacity. Compared with the traditional natural lipoprotein, synthetic lipoprotein not only retains the original biological characteristics and functions, but also exhibits the excellent characteristics in drug delivery. Herein, the advantages, development, applications, and prospect of synthetic lipoproteins as drug carriers were summarized.

  9. Influence of encapsulated functional lipids on crystal structure and chemical stability in solid lipid nanoparticles: Towards bioactive-based design of delivery systems.

    Science.gov (United States)

    Salminen, Hanna; Gömmel, Christina; Leuenberger, Bruno H; Weiss, Jochen

    2016-01-01

    We investigated the influence of physicochemical properties of encapsulated functional lipids--vitamin A, β-carotene and ω-3 fish oil--on the structural arrangement of solid lipid nanoparticles (SLN). The relationship between the crystal structure and chemical stability of the incorporated bioactive lipids was evaluated with different emulsifier compositions of a saponin-rich, food-grade Quillaja extract alone or combined with high-melting or low-melting lecithins. The major factors influencing the structural arrangement and chemical stability of functional lipids in solid lipid dispersions were their solubility in the aqueous phase and their crystallization temperature in relation to that of the carrier lipid. The results showed that the stabilization of the α-subcell crystals in the lattice of the carrier lipid is a key parameter for forming stable solid lipid dispersions. This study contributes to a better understanding of SLN as a function of the bioactive lipid. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Multifunctional non-viral delivery systems based on conjugated polymers.

    Science.gov (United States)

    Yang, Gaomai; Lv, Fengting; Wang, Bing; Liu, Libing; Yang, Qiong; Wang, Shu

    2012-12-01

    Multifunctional nanomaterials with simultaneous therapeutic and imaging functions explore new strategies for the treatment of various diseases. Conjugated polymers (CPs) are considered as novel candidates to serve as multifunctional delivery systems due to their high fluorescence quantum yield, good photostability, and low cytotoxicity. Highly sensitive sensing and imaging properties of CPs are well reviewed, while the applications of CPs as delivery systems are rarely covered. This feature article mainly focuses on CP-based multifunctional non-viral delivery systems for drug, protein, gene, and cell delivery. Promising directions for the further development of CP-based delivery systems are also discussed.

  11. Cu(In{sub 1-x}Ga{sub x})Se{sub 2} co-evaporated thin films from simple tungsten baskets-Influence of the gallium source

    Energy Technology Data Exchange (ETDEWEB)

    Drici, A. [LEREC, Departement de Physique, Universite Badji Mokhtar, BP 12, Annaba 23000 (Algeria)], E-mail: abdelaziz.drici@univ-annaba.org; Mekhnache, M.; Bouraoui, A. [LEREC, Departement de Physique, Universite Badji Mokhtar, BP 12, Annaba 23000 (Algeria); Kachouane, A.; Bernede, J.C. [LAMP, 2 Rue de la Houssiniere, BP 92208, 44322 Nantes Cedex (France); Amara, A.; Guerioune, M. [LEREC, Departement de Physique, Universite Badji Mokhtar, BP 12, Annaba 23000 (Algeria)

    2008-07-15

    Cu(In{sub 1-x}Ga{sub x})Se{sub 2} (CIGSe) thin films with 0 {<=} x {<=} 1 are grown by co-evaporation. Cu, In and Ga elements are evaporated from simple tungsten baskets, while Se is evaporated from broad Ta basket. Different combinations of the metal sources have been tested using three and two tungsten baskets. It is shown that, when deposited on a substrate heated at 500 deg. C, the Ga is present throughout the thickness of the films whatever the technique used. X-ray photoelectron spectroscopy (XPS measurements have shown that Ga depth profile is more reliable in that case. X-ray diffraction shows that the films crystallize in the expected chalcopyrite structure. The lattice parameters decrease with increasing Ga atomic percentage. It is revealed that the optical band gap increases with the Ga content and yielded a bowing parameter around 0.28. The best results have been obtained with the four sources technique. Thin film solar cells, Mo/CIGSe/In{sub 2}S{sub 3-x}O{sub 3x}/i-ZnO/ZnO:Al/Ni-Al grid, have been fabricated and probed. The efficiency of the cells depends strongly in the film composition but also in the metal source number.

  12. Dmp53, basket and drICE gene knockdown and polyphenol gallic acid increase life span and locomotor activity in a Drosophila Parkinson's disease model

    Directory of Open Access Journals (Sweden)

    Hector Flavio Ortega-Arellano

    2013-01-01

    Full Text Available Understanding the mechanism(s by which dopaminergic (DAergic neurons are eroded in Parkinson's disease (PD is critical for effective therapeutic strategies. By using the binary tyrosine hydroxylase (TH-Gal4/UAS-X RNAi Drosophila melanogaster system, we report that Dmp53, basket and drICE gene knockdown in dopaminergic neurons prolong life span (p < 0.05; log-rank test and locomotor activity (p < 0.05; χ² test in D. melanogaster lines chronically exposed to (1 mM paraquat (PQ, oxidative stress (OS generator compared to untreated transgenic fly lines. Likewise, knockdown flies displayed higher climbing performance than control flies. Amazingly, gallic acid (GA significantly protected DAergic neurons, ameliorated life span, and climbing abilities in knockdown fly lines treated with PQ compared to flies treated with PQ only. Therefore, silencing specific gene(s involved in neuronal death might constitute an excellent tool to study the response of DAergic neurons to OS stimuli. We propose that a therapy with antioxidants and selectively "switching off" death genes in DAergic neurons could provide a means for pre-clinical PD individuals to significantly ameliorate their disease condition.

  13. Dmp53, basket and drICE gene knockdown and polyphenol gallic acid increase life span and locomotor activity in a Drosophila Parkinson’s disease model

    Science.gov (United States)

    Ortega-Arellano, Hector Flavio; Jimenez-Del-Rio, Marlene; Velez-Pardo, Carlos

    2013-01-01

    Understanding the mechanism(s) by which dopaminergic (DAergic) neurons are eroded in Parkinson’s disease (PD) is critical for effective therapeutic strategies. By using the binary tyrosine hydroxylase (TH)-Gal4/UAS-X RNAi Drosophila melanogaster system, we report that Dmp53, basket and drICE gene knockdown in dopaminergic neurons prolong life span (p < 0.05; log-rank test) and locomotor activity (p < 0.05; χ2 test) in D. melanogaster lines chronically exposed to (1 mM) paraquat (PQ, oxidative stress (OS) generator) compared to untreated transgenic fly lines. Likewise, knockdown flies displayed higher climbing performance than control flies. Amazingly, gallic acid (GA) significantly protected DAergic neurons, ameliorated life span, and climbing abilities in knockdown fly lines treated with PQ compared to flies treated with PQ only. Therefore, silencing specific gene(s) involved in neuronal death might constitute an excellent tool to study the response of DAergic neurons to OS stimuli. We propose that a therapy with antioxidants and selectively “switching off” death genes in DAergic neurons could provide a means for pre-clinical PD individuals to significantly ameliorate their disease condition. PMID:24385865

  14. Delivery of siRNA silencing P-gp in peptide-functionalized nanoparticles causes efflux modulation at the blood-brain barrier

    DEFF Research Database (Denmark)

    Gomes, Maria João; Kennedy, Patrick J; Martins, Susana

    2017-01-01

    AIM: Explore the use of transferrin-receptor peptide-functionalized nanoparticles (NPs) targeting blood-brain barrier (BBB) as siRNA carriers to silence P-glycoprotein (P-gp). MATERIALS & METHODS: Permeability experiments were assessed through a developed BBB cell-based model; P-gp mRNA expressio...

  15. Prediction of preterm delivery

    NARCIS (Netherlands)

    Wilms, F.F.

    2014-01-01

    Preterm delivery is in quantity and in severity an important issue in the obstetric care in the Western world. There is considerable knowledge on maternal and obstetric risk factors of preterm delivery. Of the women presenting with preterm labor, the majority is pregnant with a male fetus and in

  16. Prediction of preterm delivery

    NARCIS (Netherlands)

    Wilms, F.F.

    2014-01-01

    Preterm delivery is in quantity and in severity an important issue in the obstetric care in the Western world. There is considerable knowledge on maternal and obstetric risk factors of preterm delivery. Of the women presenting with preterm labor, the majority is pregnant with a male fetus and in Cau

  17. Delivery by Cesarean Section

    Science.gov (United States)

    ... often when: The mother has had a previous baby by Cesarean delivery The obstetrician feels that the baby’s health might ... lost time. Don’t be surprised if your baby is still affected by the anesthesia for six to twelve hours after delivery and appears a little sleepy. If you’re ...

  18. Vacuum-assisted delivery

    Science.gov (United States)

    ... a handle on the cup to move the baby through the birth canal. When is Vacuum-assisted Delivery Needed? Even after your cervix is fully dilated ( ... delivers the baby's head, you will push the baby the rest of the way out. After delivery, you can hold your baby on your tummy ...

  19. Impact of different methods of delivery on the postpartum sexual function of primipara%不同分娩方式对初产妇产后性功能影响的临床对比研究

    Institute of Scientific and Technical Information of China (English)

    祖丽菲娅·阿布力克木; 米热阿依·尕依提

    2015-01-01

    Objectives:To explore the impact of nature birth,episiotomy and cesarean on the postpartum sexual function of primipara.Methods:The 300 primipara in our hospital from March 201 1 to February 201 4 were selected and divided into three groups according to their mode of delivery,i.e.nature birth group (80 cases),epi-siotomy group (1 05 cases),and cesarean section group (1 1 5 cases).Their sexual functions were surveyed 2 months,5 months and 8 months after,to analyze and compare the differences among the three groups.Results:The occurrence rate of sexual dysfunction was the highest 2 months after delivery,with significant difference from those at 5 or 8 months after delivery (P 0.05),so as the difference among the three groups 8 months after deliv-ery (P >0.05).At two months after delivery,the recovery rate of sexual function in the nature birth group and ce-sarean group were 75.0% and 73.9% respectively,higher than that in the episiotomy group,with significant differ-ence (P 0.05).Conclusion:Primipara adopting nature birth delivery has the lowest incidence rate of sexual dysfunction,highest level of sexual function and recovery rate,followed by cesarean section and episiotomy orderly.Therefore,nature birth is a better choice for primipara.%目的:探究分析顺产、会阴侧切与剖宫产三种分娩方式对初产妇产后性功能的影响。方法:选择2011年3月至2014年2月来我院分娩的300例初产妇,按照其分娩方式分为顺产组80例,会阴侧切组105例,剖宫产组115例。分别在产后2个月、5个月以及8个月对所有初产妇进行性功能状况调查,分析比较三组患者性功能状况的差异性。结果:产后2个月、5个月、8个月时的性功能障碍发生率相比,三组患者均在产后2个月后发生性功能障碍的比例最高,产后5个月、8个月后均明显降低,具有明显差异性(P <0.05)。NVD/epi 组与其他两组比较,产后2个月、5个月、8个月时的性

  20. Lactic acid bacteria as a cell factory for the delivery of functional biomolecules and ingredients in cereal-based beverages: a review.

    Science.gov (United States)

    Waters, Deborah M; Mauch, Alexander; Coffey, Aidan; Arendt, Elke K; Zannini, Emanuele

    2015-01-01

    In this review, we aim to describe the mechanisms by which LAB can fulfil the novel role of efficient cell factory for the production of functional biomolecules and food ingredients to enhance the quality of cereal-based beverages. LAB fermentation is a safe, economical, and traditional method of food preservation foremost, as well as having the additional benefits of flavor, texture, and nutrition amelioration. Additionally, LAB fermentation in known to render cereal-based foods and beverages safe, in a chemical-free, consumer-friendly manner, from an antinutrient and toxigenic perspective. Huge market opportunities and potential exist for food manufacturers who can provide the ideal functional beverage fulfilling consumer needs. Newly developed fermented cereal-based beverages must address markets globally including, high-nutrition markets (developing countries), lifestyle choice consumers (vegetarian, vegan, low-fat, low-salt, low-calorie), food-related non-communicable disease sufferers (cardiovascular disease, diabetes), and green label consumers (Western countries). To fulfil these recommendations, a suitable LAB starter culture and cereal-based raw materials must be developed. These strains would be suitable for the biopreservation of cereal beverages and, ideally, would be highly antifungal, anti-mycotoxigenic, mycotoxin-binding and proteolytic (neutralize toxic peptides and release flavor-contributing amino acids) with an ability to ferment cereals, whilst synthesizing oligosaccharides, thus presenting a major opportunity for the development of safe cereal-based prebiotic functional beverages to compete with and replace the existing dairy versions.

  1. Deep-Eutectic Solvents as MWCNT Delivery Vehicles in the Synthesis of Functional Poly(HIPE) Nanocomposites for Applications as Selective Sorbents.

    Science.gov (United States)

    Carranza, Arturo; Pérez-García, María G; Song, Kunlin; Jeha, George M; Diao, Zhenyu; Jin, Rongying; Bogdanchikova, Nina; Soltero, Armando F; Terrones, Mauricio; Wu, Qinglin; Pojman, John A; Mota-Morales, Josué D

    2016-11-16

    We report an alternative green strategy based on deep-eutectic solvents (DES) to deliver multiwalled carbon nanotubes (MWCNTs) for a bottom-up approach that allows for the selective interfacial functionalization of nonaqueous poly(high internal phase emulsions), poly(HIPEs). The formation and polymerization of methacrylic and styrenic HIPEs were possible through stabilization with nitrogen doped carbon nanotube (CNX) and surfactant mixtures using a urea-choline chloride DES as a delivering phase. Subtle changes in CNX concentration (less than 0.2 wt % to the internal phase) produced important changes in the macroporous monolith functionalization, which in turn led to increased monolith hydrophobicity and pore openness. These materials displayed great oleophilicity with water contact angles as high as 140° making them apt for biodiesel, diesel, and gasoline fuel sorption applications. Overall, styrene divinylbenzene (StDvB) based poly(HIPEs) showed hydrophobicity and fuel sorption capacities as high as 4.8 (g/g). Pore hierarchy, namely pore openness, regulated sorption capacity, and sorption times where greater openness resulted in faster sorption and increased sorption capacity. Monoliths were subject to 20 sorption-desorption cycles demonstrating recyclability and stable sorption capacity. Finally, CNX/surfactant hybrids made it possible to reduce surfactant requirements for successful HIPE formation and stabilization during polymerization. All poly(HIPEs) retained acceptable conversion as a function of CNX loading nearing 90% or better with thermal stability as high as 283 °C.

  2. Correlation between self-ignition of a dust layer on a hot surface and in baskets in an oven

    OpenAIRE

    2008-01-01

    International audience; Evaluation of self-ignition hazard of bulk materials requires experimental determination of self-ignition temperatures as a function of volume. There are two standardised methods : determination of the self-ignition temperature of dust samples in oven and measurement of the self-ignition temperature of a dust layer deposited on a hot surface. Sometimes, the sample behaviour during these tests makes the second method difficult to apply. The self-ignition phenomena in th...

  3. 产后盆底肌肉功能测评及康复护理%Nursing analysis of pelvic floor muscle function assessment and rehabilitation after delivery

    Institute of Scientific and Technical Information of China (English)

    纪淑春

    2016-01-01

    Objective To investigate the level of pelvic floor muscle function and its related factors in pregnancy and childbirth for the female patients. Methods A total of 169 outpatients medical records were collected who visited the Pelvic Floor Muscle Rehabilitation Clinic, Postpartum Rehabilitation Center in ourhospital from January 2014 to December 2014. Results There were 135 women ( 75. 0%) showing symptoms associated with pelvic floor dysfunction during the inquiry. 167 patients showed different degrees of pelvic floor muscle function damage under receiving the pelvic floor muscle function evaluation. Maternal times, newborn birth body mass and fetal position affected maternal pelvic floor muscle function damage degree. Whether to choose the pelvic floor muscles biofeedback therapy was impacted by three factors: the increasing of body mass during pregnancy, whether experienced stress urinary incontinence and the time when received postpartum pelvic floor muscle function assessment. Conclusions Many maternal experience postpartum pelvic floor muscle function damage which has not gained awareness. It should be reinforced that health education and guidance on strengthening the pelvic floor muscles to female patients in pregnancy.%目的 了解就诊女性的盆底肌肌肉功能水平及其在妊娠及分娩中受损的相关影响因素.方法 选择2014年1—12月在产后康复中心盆底肌康复门诊就诊的孕产妇,对其门诊病历资料进行整理,共计169人.结果 在临床症状问诊中发现,共计135名产妇在孕产期间表现出与盆底功能受损相关的症状,比例达75.0%.而在盆底肌肌肉功能检测评估中,167名显示盆底肌肉功能存在不同程度的损伤.孕产次数、新生儿出生体质量和胎位影响孕产妇的盆底肌肌肉功能损伤程度;而孕期体质量增长水平、孕产期是否存在压力性尿失禁现象以及产后的盆底肌肉功能评估时间影响孕产妇是否选择进行

  4. A first-principles study of functionalized clusters and carbon nanotubes or fullerenes with 5-Aminolevulinic acid as vehicles for drug delivery

    Science.gov (United States)

    Kia, Majid; Golzar, Maryam; Mahjoub, Kosar; Soltani, Alireza

    2013-10-01

    At present work, we explore the adsorption properties of the 5-Aminolevulinic acid (5ALA) interacting with SWCNTs, C60, and C24 by density functional ab initio (DFT) calculations. It was found that the electronic structure of C60 is more sensitive to the presence of 5ALA in comparison with C24, (5, 5), and (9, 0) SWCNT. Our results demonstrate that the interactions between 5ALA and the nanostructures are chemisorption. The natural bond orbital (NBO) and density of states (DOSs) analyses represent that the nature of 5ALA adsorption on the applied nanostructures is permanently electrostatic rather than covalent.

  5. Obesity appears to be associated with altered muscle protein synthetic and breakdown responses to increased nutrient delivery in older men, but not reduced muscle mass or contractile function.

    OpenAIRE

    Andrew J Murton; Marimuthu, Kanagaraj; Mallinson, Joanne E.; Selby, Anna L.; Smith, Kenneth; Rennie, Michael J; Greenhaff, Paul L.

    2015-01-01

    Obesity is increasing, yet despite the necessity to maintain muscle mass and function with age, the effect of obesity on muscle protein turnover in older adults remains unknown. Eleven obese (BMI 31.9 ±1.1) and 15 healthy weight (HW; BMI 23.4 ±0.3) older men (55-75 years old) participated in a study that determined muscle protein synthesis (MPS) and leg protein breakdown (LPB) under post-absorptive (hypoinsulinaemic euglycaemic clamp) and post-prandial (hyperinsulinemic hyperaminoacidaemic eu...

  6. Antioxidant Nanoplatforms for Dermal Delivery: Melatonin.

    Science.gov (United States)

    Milán, Aroha Belen Sánchez; Campmany, Ana C Calpena; Naveros, Beatriz Clares

    2017-02-22

    Melatonin (MLT) is emerging as a promising therapeutic agent, mainly due to its role as antioxidant. Substantial evidences show that melatonin is potentially effective on a variety of diseases as cancer, inflammation and neurodegenerative diseases. The excellent antioxidant capacity with pharmacokinetics characteristics and the emerging search for new pharmaceutical nanotechnology based systems, make it particularly attractive to elaborate nanoplatforms based on MLT for biomedical or cosmetic dermal applications. Different nanosystems for dermal delivery have been investigated. These nanosystems are expected to play a significant role in the protection of therapeutic functions of MLT, enhanced transdermal permeability and dermal delivery profiles. These nanocarriers not only transport MLT, but also increase the solubility, bioavailability, half-life and antioxidant activity. In the current review, we will focus on nanocarrier production strategies, dermal MLT application and delivery advances in vivo and in vitro. Equally, future perspectives of this assisted MLT delivery will be also discussed.

  7. Novel biodegradable nanocarriers for enhanced drug delivery.

    Science.gov (United States)

    Gagliardi, Mariacristina

    2016-12-01

    With the refinement of functional properties, the interest around biodegradable materials, in biorelated applications and, in particular, in their use as controlled drug-delivery systems, increased in the last decades. Biodegradable materials are an ideal platform to obtain nanoparticles for spatiotemporal controlled drug delivery for the in vivo administration, thanks to their biocompatibility, functionalizability, the control exerted on delivery rates and the complete degradation. Their application in systems for cancer treatment, brain and cardiovascular diseases is already a consolidated practice in research, while the bench-to-bedside translation is still late. This review aims at summarizing reported applications of biodegradable materials to obtain drug-delivery nanoparticles in the last few years, giving a complete overview of pros and cons related to degradable nanomedicaments.

  8. Global Delivery Models

    DEFF Research Database (Denmark)

    Manning, Stephan; Larsen, Marcus M.; Bharati, Pratyush

    2013-01-01

    This article examines antecedents and performance implications of global delivery models (GDMs) in global business services. GDMs require geographically distributed operations to exploit both proximity to clients and time-zone spread for efficient service delivery. We propose and empirically show...... that service providers who differentiate based on speed of service delivery are likely to set up GDM structures, and that these structures positively affect deal renewal rates if speed is important for clients in selecting vendors. Findings imply that, as co-location becomes less necessary for providing...... digitalized services, time zones increasingly affect....

  9. Global Delivery Models

    DEFF Research Database (Denmark)

    Manning, Stephan; Møller Larsen, Marcus; Bharati, Pratyush

    We investigate antecedents and contingencies of location configurations supporting global delivery models (GDMs) in global outsourcing. GDMs are a new form of IT-enabled client-specific investment promoting services provision integration with clients by exploiting client proximity and time......-zone spread allowing for 24/7 service delivery and access to resources. Based on comprehensive data we show that providers are likely to establish GDM configurations when clients value access to globally distributed talent pools and speed of service delivery, and in particular when services are highly...

  10. Global Delivery Models

    DEFF Research Database (Denmark)

    Manning, Stephan; Møller Larsen, Marcus; Bharati, Pratyush

    We investigate antecedents and contingencies of location configurations supporting global delivery models (GDMs) in global outsourcing. GDMs are a new form of IT-enabled client-specific investment promoting services provision integration with clients by exploiting client proximity and time......-zone spread allowing for 24/7 service delivery and access to resources. Based on comprehensive data we show that providers are likely to establish GDM configurations when clients value access to globally distributed talent pools and speed of service delivery, and in particular when services are highly...... commoditized. Findings imply that coordination across time zones increasingly affects international operations in business-to-business and born-global industries....

  11. Focus on Delivery

    DEFF Research Database (Denmark)

    Hasman, Kirsten; Barfoed, Anne

    2016-01-01

    (2). It is, however, not clarified which of the multifaceted aspects of preventing perineal injury that might explain the decrease (3). Aims: We hypothesized that the use of structured reflection on a clinical practice by midwives and midwifery students would increase both parts’ knowledge on how...... attended a delivery. The tool was developed based on five categories: communication, pace, ergonomic positions, perineal support in the chosen birth position and delivery of the shoulders, and five predefined questions guided an overall reflection upon practice. After a delivery a project midwife, who had...

  12. A redox-sensitive, oligopeptide-guided, self-assembling, and efficiency-enhanced (ROSE) system for functional delivery of microRNA therapeutics for treatment of hepatocellular carcinoma.

    Science.gov (United States)

    Hu, Qida; Wang, Kai; Sun, Xu; Li, Yang; Fu, Qihan; Liang, Tingbo; Tang, Guping

    2016-10-01

    Lack of efficient adjuvant therapy contributes to a high incidence of recurrence and metastasis of hepatocellular carcinoma (HCC). A novel therapeutic is required for adjuvant treatment of HCC. We developed a polymer-based nanosystem (ROSE) for functional gene therapy by synthesizing a supramolecular complex self-assembled from polycations and functional adamantyl modules. The ROSE system condensing tumor suppressor microRNA-34a (miR-34a) therapeutics becomes ROSE/miR-34a nanoparticles that could facilitate gene transfection in HCC cells with satisfied stability and efficiency, possibly due to proton sponge effect by polycations, PEGlyation protection, and controlled release by breakdown of disulfide bonds. Meanwhile, modification with a targeting oligopeptide SP94 in ROSE/miR-34a enables approximately higher affinity for LM3 HCC cells than hepatocytes in vitro and greater HCC specificity in vivo. Furthermore, ROSE/miR-34a nanoparticles significantly inhibits HCC cell proliferation and in vivo tumor growth, representing a notable effect improvement over conventional gene delivery strategies. ROSE/miR-34a, featuring redox-responsiveness, oligopeptide-guided specificity, self-assembly, and enhanced transfection, is therefore a potential therapeutic agent in future adjuvant therapy for HCC treatment.

  13. The incorporation of water-soluble gel matrix into bile acid-based microcapsules for the delivery of viable β-cells of the pancreas, in diabetes treatment: biocompatibility and functionality studies.

    Science.gov (United States)

    Mooranian, Armin; Negrulj, Rebecca; Al-Salami, Hani

    2016-02-01

    In recent studies, we microencapsulated pancreatic β-cells using sodium alginate (SA) and poly-L-ornithine (PLO) and the bile acid, ursodeoxycholic acid (UDCA), and tested the morphology and cell viability post-microencapsulation. Cell viability was low probably due to limited strength of the microcapsules. This study aimed to assess a β-cell delivery system which consists of UDCA-based microcapsules incorporated with water-soluble gel matrix. The polyelectrolytes, water-soluble gel (WSG), polystyrenic sulphate (PSS), PLO and polyallylamine (PAA) at ratios 4:1:1:2.5 with or without 4% UDCA, were incorporated into our microcapsules, and cell viability, metabolic profile, cell functionality, insulin production, levels of inflammation, microcapsule morphology, cellular distribution, UDCA partitioning, biocompatibility, thermal and chemical stabilities and the microencapsulation efficiency were examined. The incorporation of UDCA with PSS, PAA and WSG enhanced cell viability per microcapsule (p < 0.05), cellular metabolic profile (p < 0.01) and insulin production (p < 0.01); reduced the inflammatory release TNF-α (p < 0.01), INF-gamma (p < 0.01) and interleukin-6 (IL-6) (p < 0.01); and ceased the production of IL-1β. UDCA, PSS, PAA and WSG addition did not change the microencapsulation efficiency and resulted in biocompatible microcapsules. Our designed microcapsules showed good morphology and desirable insulin production, cell functionality and reduced inflammatory profile suggesting potential applications in diabetes.

  14. 聚酰胺-胺型树枝状大分子及其衍生物在基因传递中的应用%Functionalized Polyamidoamine Dendrimer as Gene Delivery Vectors

    Institute of Scientific and Technical Information of China (English)

    董博; 闫熙博; 牛玉洁; 王欣; 王连永; 王燕铭

    2012-01-01

    Gene therapy has emerged as the most promising therapeutic strategy for various human diseases such as cardiovascular disorders, neurological disease, and cancers by introducing functional gene into body via gene vectors. For the successful advancement of gene therapy, the further development of safer and more efficient gene delivery vectors has been an advanced topic in the researches of bioactive materials and gene delivery. Recently, polyamidoamine (PAMAM) dendrimers have been intensively studied because of their well-defined three-dimensional structures, relatively lower toxicity, possibility of facile modification, and capacity of carrying large gene segments. However, the applications of such molecules in gene delivery have been restricted by the complicated synthetic procedures and the laborious purification steps, as well as its lower transfection efficiency than virus. It is noted that surface modification of PAMAM dendrimers with series of bioactive molecules should intensively improve the transfection efficiency and biorecognition capacity. In this paper, an overview is presented with a focus on the PAMAM derivatives design and synthesis to enhance the gene delivery both in vitro and in vivo. We hope it may provide helpful insights for the further development of safe and efficient non-viral vectors.%基因治疗通过基因载体将治病基因导入病患的特异细胞以治疗心血管、神经系统疾病和癌症等。寻找安全高效的非病毒基因载体一直是基因治疗以及生物材料领域中的前沿课题。聚酰胺-胺型(PAMAM)树枝状高分子作为一类三维的、结构高度有序的新型载体,由于具有安全性好、易于修饰、携带外源基因容量大等特点,已经引起了广泛的关注。但是另一方面,合成步骤相对繁琐、后期产物纯化困难以及转染效率相对较低等问题限制了这类载体的进一步发展。本文结合本课题组的研究情况,针对如何提

  15. Transdermal delivery of proteins.

    Science.gov (United States)

    Kalluri, Haripriya; Banga, Ajay K

    2011-03-01

    Transdermal delivery of peptides and proteins avoids the disadvantages associated with the invasive parenteral route of administration and other alternative routes such as the pulmonary and nasal routes. Since proteins have a large size and are hydrophilic in nature, they cannot permeate passively across the skin due to the stratum corneum which allows the transport of only small lipophilic drug molecules. Enhancement techniques such as chemical enhancers, iontophoresis, microneedles, electroporation, sonophoresis, thermal ablation, laser ablation, radiofrequency ablation and noninvasive jet injectors aid in the delivery of proteins by overcoming the skin barrier in different ways. In this review, these enhancement techniques that can enable the transdermal delivery of proteins are discussed, including a discussion of mechanisms, sterility requirements, and commercial development of products. Combination of enhancement techniques may result in a synergistic effect allowing increased protein delivery and these are also discussed.

  16. A model of long-term memory storage in the cerebellar cortex: a possible role for plasticity at parallel fiber synapses onto stellate/basket interneurons.

    Science.gov (United States)

    Kenyon, G T

    1997-12-09

    By evoking changes in climbing fiber activity, movement errors are thought to modify synapses from parallel fibers onto Purkinje cells (pf*Pkj) so as to improve subsequent motor performance. Theoretical arguments suggest there is an intrinsic tradeoff, however, between motor adaptation and long-term storage. Assuming a baseline rate of motor errors is always present, then repeated performance of any learned movement will generate a series of climbing fiber-mediated corrections. By reshuffling the synaptic weights responsible for any given movement, such corrections will degrade the memories for other learned movements stored in overlapping sets of synapses. The present paper shows that long-term storage can be accomplished by a second site of plasticity at synapses from parallel fibers onto stellate/basket interneurons (pf*St/Bk). Plasticity at pf*St/Bk synapses can be insulated from ongoing fluctuations in climbing fiber activity by assuming that changes in pf*St/Bk synapses occur only after changes in pf*Pkj synapses have built up to a threshold level. Although climbing fiber-dependent plasticity at pf*Pkj synapses allows for the exploration of novel motor strategies in response to changing environmental conditions, plasticity at pf*St/Bk synapses transfers successful strategies to stable long-term storage. To quantify this hypothesis, both sites of plasticity are incorporated into a dynamical model of the cerebellar cortex and its interactions with the inferior olive. When used to simulate idealized motor conditioning trials, the model predicts that plasticity develops first at pf*Pkj synapses, but with additional training is transferred to pf*St/Bk synapses for long-term storage.

  17. Functionalization of Strongly Interacting Magnetic Nanocubes with (Thermo)responsive Coating and their Application in Hyperthermia and Heat-Triggered Drug Delivery

    KAUST Repository

    Kakwere, Hamilton

    2015-04-03

    Herein we prepare nanohybrids by incorporating iron oxide nanocubes (cubic-IONPs) within a thermo-responsive polymer shell that can act as drug carriers for doxorubicin(doxo). The cubic-shaped nanoparticles employed are at the interface between superparamagnetic and ferromagnetic behavior and have an exceptionally high specific absorption rate (SAR) but their functionalization is extremely challenging compared to bare superparamagnetic iron oxide nanoparticles as they strongly interact with each other. By conducting the polymer grafting reaction using reversible addition-fragmentation chain transfer (RAFT) polymerization in a viscous solvent medium, we have here developed a facile approach to decorate the nanocubes with stimuli-responsive polymers. When the thermo-responsive shell is composed of poly(N-isopropyl acrylamide-co-polyethylene glycolmethylether acrylate), nanohybrids have a phase transition temperature, the lower critical solution temperature (LCST), above 37 °C in physiological conditions. Doxo loaded nanohybrids exhibited a negligible drug release below 37 °C but showed a consistent release of their cargo on demand by exploiting the capability of the nanocubes to generate heat under an alternating magnetic field (AMF). Moreover, the drug free nanocarrier does not exhibit cytotoxicity even when administered at high concentration of nanocubes (1g/L of iron) and internalized at high extent (260 pg of iron per cell). We have also implemented the synthesis protocol to decorate the surface of nanocubes with poly(vinylpyridine) polymer and thus prepare pH-responsive shell coated nanocubes.

  18. Obesity Appears to Be Associated With Altered Muscle Protein Synthetic and Breakdown Responses to Increased Nutrient Delivery in Older Men, but Not Reduced Muscle Mass or Contractile Function.

    Science.gov (United States)

    Murton, Andrew J; Marimuthu, Kanagaraj; Mallinson, Joanne E; Selby, Anna L; Smith, Kenneth; Rennie, Michael J; Greenhaff, Paul L

    2015-09-01

    Obesity is increasing, yet despite the necessity of maintaining muscle mass and function with age, the effect of obesity on muscle protein turnover in older adults remains unknown. Eleven obese (BMI 31.9 ± 1.1 kg · m(-2)) and 15 healthy-weight (BMI 23.4 ± 0.3 kg · m(-2)) older men (55-75 years old) participated in a study that determined muscle protein synthesis (MPS) and leg protein breakdown (LPB) under postabsorptive (hypoinsulinemic-euglycemic clamp) and postprandial (hyperinsulinemic hyperaminoacidemic-euglycemic clamp) conditions. Obesity was associated with systemic inflammation, greater leg fat mass, and patterns of mRNA expression consistent with muscle deconditioning, whereas leg lean mass, strength, and work done during maximal exercise were no different. Under postabsorptive conditions, MPS and LPB were equivalent between groups, whereas insulin and amino acid administration increased MPS in only healthy-weight subjects and was associated with lower leg glucose disposal (LGD) (63%) in obese men. Blunting of MPS in the obese men was offset by an apparent decline in LPB, which was absent in healthy-weight subjects. Lower postprandial LGD in obese subjects and blunting of MPS responses to amino acids suggest that obesity in older adults is associated with diminished muscle metabolic quality. This does not, however, appear to be associated with lower leg lean mass or strength.

  19. Enhanced oral delivery of paclitaxel using acetylcysteine functionalized chitosan-vitamin E succinate nanomicelles based on a mucus bioadhesion and penetration mechanism.

    Science.gov (United States)

    Lian, He; Zhang, Tianhong; Sun, Jin; Liu, Xiaohong; Ren, Guolian; Kou, Longfa; Zhang, Youxi; Han, Xiaopeng; Ding, Wenya; Ai, Xiaoyu; Wu, Chunnuan; Li, Lin; Wang, Yongjun; Sun, Yinghua; Wang, Siling; He, Zhonggui

    2013-09-03

    In addition to being a physiological protective barrier, the gastrointestinal mucosal membrane is also a primary obstacle that hinders the oral absorption of many therapeutic compounds, especially drugs with a poor permeability. In order to resolve this impasse, we have designed multifunctional nanomicelles based on the acetylcysteine functionalized chitosan-vitamin E succinate copolymer (CS-VES-NAC, CVN), which exhibit marked bioadhesion, possess the ability to penetrate mucus, and enhance the oral absorption of a hydrophobic drug with a poor penetrative profile, paclitaxel. The intestinal absorption (Ka = 0.38 ± 0.04 min(-1), Papp = 0.059 cm · min(-1)) of CVN nanomicelles was greatly improved (4.5-fold) in comparison with paclitaxel solution, and CLSM (confocal laser scanning microscope) pictures also showed not only enhanced adhesion to the intestinal surface but improved accumulation within intestinal villi. The in vivo pharmacokinetics indicated that the AUC0-t (586.37 ng/mL · h) of CVN nanomicelles was markedly enhanced compared with PTX solution. In summary, the novel multifunctional CVN nanomicelles appear to be a promising nanocarrier for insoluble and poorly permeable drugs due to their high bioadhesion and permeation-enhancing capability.

  20. A smart magnetic nanoplatform for synergistic anticancer therapy: manoeuvring mussel-inspired functional magnetic nanoparticles for pH responsive anticancer drug delivery and hyperthermia

    Science.gov (United States)

    Sasikala, Arathyram Ramachandra Kurup; Ghavaminejad, Amin; Unnithan, Afeesh Rajan; Thomas, Reju George; Moon, Myeongju; Jeong, Yong Yeon; Park, Chan Hee; Kim, Cheol Sang

    2015-10-01

    We report the versatile design of a smart nanoplatform for thermo-chemotherapy treatment of cancer. For the first time in the literature, our design takes advantage of the outstanding properties of mussel-inspired multiple catecholic groups - presenting a unique copolymer poly(2-hydroxyethyl methacrylate-co-dopamine methacrylamide) p(HEMA-co-DMA) to surface functionalize the superparamagnetic iron oxide nanoparticles as well as to conjugate borate containing anticancer drug bortezomib (BTZ) in a pH-dependent manner for the synergistic anticancer treatment. The unique multiple anchoring groups can be used to substantially improve the affinity of the ligands to the surfaces of the nanoparticles to form ultrastable iron oxide nanoparticles with control over their hydrodynamic diameter and interfacial chemistry. Thus the BTZ-incorporated-bio-inspired-smart magnetic nanoplatform will act as a hyperthermic agent that delivers heat when an alternating magnetic field is applied while the BTZ-bound catechol moieties act as chemotherapeutic agents in a cancer environment by providing pH-dependent drug release for the synergistic thermo-chemotherapy application. The anticancer efficacy of these bio-inspired multifunctional smart magnetic nanoparticles was tested both in vitro and in vivo and found that these unique magnetic nanoplatforms can be established to endow for the next generation of nanomedicine for efficient and safe cancer therapy.We report the versatile design of a smart nanoplatform for thermo-chemotherapy treatment of cancer. For the first time in the literature, our design takes advantage of the outstanding properties of mussel-inspired multiple catecholic groups - presenting a unique copolymer poly(2-hydroxyethyl methacrylate-co-dopamine methacrylamide) p(HEMA-co-DMA) to surface functionalize the superparamagnetic iron oxide nanoparticles as well as to conjugate borate containing anticancer drug bortezomib (BTZ) in a pH-dependent manner for the synergistic

  1. Combining Low Price, Low Climate Impact and High Nutritional Value in One Shopping Basket through Diet Optimization by Linear Programming

    Directory of Open Access Journals (Sweden)

    Corné van Dooren

    2015-09-01

    Full Text Available Background: This study aims to find diets with low price and low climate impact, yet fulfilling all nutritional requirements. Methods: Optimization by linear programming. The program constrains 33 nutrients to fulfill Dutch dietary requirements. In a second cycle, the upper boundary for climate impact through greenhouse gas emissions (GHGE is set to 1.6 kg carbon dioxide equivalents/day (CO2eq. In a third cycle, the costs are set on €2.50 as a constraint. The objective function of the optimization maximized the most consumed food products (n = 206 for male and female adults separately (age 31–50. Results: A diet of 63 popular and low priced basic products was found to deliver all required nutrients at an adequate level for both male and female adults. This plant-based, carbohydrate and fiber-rich diet consists mainly of wholegrain bread, potatoes, muesli, open-field vegetables and fruits. The climate impact of this diet is very low (1.59 kg CO2eq/day compared to the average Dutch diet. By constraining costs, a low carbon diet of €2.59/day is possible. Conclusions: A two-person diet consisting of 63 products and costing €37 per week can simultaneously be healthy and yet have half the average climate impact. Linear programming is a promising tool to combine health and sustainability on both societal and individual levels.

  2. Correlation between self-ignition of a dust layer on a hot surface and in baskets in an oven.

    Science.gov (United States)

    Janes, A; Carson, D; Accorsi, A; Chaineaux, J; Tribouilloy, B; Morainvillers, D

    2008-11-30

    Evaluation of self-ignition hazard of bulk materials requires experimental determination of self-ignition temperatures as a function of volume. There are two standardised methods: (1) determination of the self-ignition temperature of dust samples in oven and (2) measurement of the self-ignition temperature of a dust layer deposited on a hot surface. Sometimes, the sample behaviour during these tests makes the second method difficult to apply. The self-ignition phenomena in these two tests rely on the same principles. Their results are interpreted with the help of theoretical relations. The correlation described in this paper can be considered acceptable to deduce self-ignition temperature of a dust layer, based on results of self-ignition of the same dust in heating ovens, if the Biot number (alpha) can be estimated. Uncertainty on the correlation is near 30K. This uncertainty is on the same order of magnitude as the difference in the self-ignition temperature on a hot surface for thickness between 5 and 15 mm.

  3. Enhanced laser thermal ablation for the in vitro treatment of liver cancer by specific delivery of multiwalled carbon nanotubes functionalized with human serum albumin

    Directory of Open Access Journals (Sweden)

    Cornel Iancu

    2011-01-01

    process. These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating.Keywords: carbon nanotubes, albumin, HepG2 cells, noncovalent functionalization, laser irradiation, Gp60 receptor

  4. COMPARATIVE THERAPEUTIC EFFECTS OF VARIOUS MORPHOLOGICAL FORMS OF NASYA (NASAL ROUTE OF DRUG DELIVERY IN PRATISHYAYA (RHINOSINUSITIS WITH REFERENCE TO NASAL MUCO-CILIARY FUNCTION

    Directory of Open Access Journals (Sweden)

    Bhardwaj Atul

    2012-10-01

    Full Text Available Different morphological forms of Nasyas (Nasal route of drug administration in Ayurveda like Taila and Ghrita (lipid based nasal drops, churna (dry fine powder and Avpeeda nasya (Aqueous based medicated decoction nasal drops are commonly used as nasal drugs for the management of rhinological disorders in Ayurveda and they distinctly behave differently in the nasal cavity when introduced. This present study explores how these different morphological forms of Nasyas effects the nasal health and mucociliary mechanism in the patients of Pratishyaya i.e. Rhinosinusitis with the help of Goldman’s saccharin test which is carried out at various stages of this study. Clinically, endoscopically and radiologically diagnosed patients of Pratishyaya i.e. rhinosinusitis, satisfying the inclusion criteria were divided randomly by table method into four groups. A total of 40 patients were subjected in this trial after ramification into four trial groups with 10 patients in each group. Anu taila nasya, Shadbindu ghrita nasya, Katphala churna nasya and Pippali Avapeeda nasya respectively were selected for the present study in trial groups I – IV as they are the most frequently prescribed drugs in Ayurveda (Indian system of medicine for the management of the disease Pratishyaya i.e. Rhinosinusitis. These selected drugs subtly represent medicated oils/lipids, powder insufflations (errhines and medicated aqueous base decoction form of nasal drug administration when visualized in morphological appearance and modern perspective. Goldman’s saccharin test, which is used for the present study is a gold standard test for the evaluation of nasal mucociliary function and is directly related to nasal health. Powder form of nasal administered drug i.e. Katphala Churna nasya (powder form was found to be most effective in improvement of endoscopic and radiological parameters of rhinosinusitis. Mucoadhesive properties of Anu Taila nasya and Shadbindu ghrita nasya (both

  5. Hydroxypropyl-β-cyclodextrin functionalized calcium carbonate microparticles as a potential carrier for enhancing oral delivery of water-insoluble drugs

    Directory of Open Access Journals (Sweden)

    Zhang L

    2015-04-01

    Full Text Available Lihua Zhang,1 Wufu Zhu,2 Qisi Lin,1 Jin Han,1 Liqun Jiang,1 Yanzhuo Zhang1,3 1Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, Xuzhou, People’s Republic of China; 2School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang, People’s Republic of China; 3Department of Pharmaceutics, School of Pharmacy, Xuzhou Medical College, Xuzhou, People’s Republic of China Abstract: The objective of the present study was to demonstrate that a novel hydroxypropyl-β-cyclodextrin functionalized calcium carbonate (HP-β-CD/CC based amorphous solid dispersion (ASD can be used to increase the solubility and oral bioavailability of water-insoluble drugs. Irbesartan (IRB was selected as a model compound and loaded into the nanoporous HP-β-CD/CC matrix using an immersion method. The IRB-loaded HP-β-CD/CC formulation was characterized by various analytical techniques, such as specific surface area analysis, scanning electron microscopy (SEM, dynamic light scattering (DLS, powder X-ray diffraction (PXRD, and differential scanning calorimetry (DSC. Analyses with PXRD and DSC confirmed that IRB was fully converted into the amorphous form in the nanopores of HP-β-CD/CC. From the solubility and dissolution tests, it was observed that the aqueous solubility and dissolution rate of IRB-loaded HP-β-CD/CC were increased significantly compared with those of pure IRB and IRB-loaded mesoporous silica. Likewise, the IRB-loaded HP-β-CD/CC formulation exhibited better absorption compared with that of the commercially available IRB capsules in beagle dogs. The mean peak plasma concentration (Cmax and the area under the mean plasma concentration–time curve (AUC[0→48] of IRB-loaded HP-β-CD/CC were 1.56- and 1.52-fold higher than that of the commercial product, respectively. Furthermore, the IRB-loaded HP-β-CD/CC formulation exhibited excellent stability against re-crystallization. These results clearly

  6. Effect of Different Delivery Mode on the Post-partum Mental State and Physiological Function of Puerpera%不同分娩方式对产妇产后心理和生理的影响

    Institute of Scientific and Technical Information of China (English)

    段利停; 沈宗姬; 黄沁; 于芳芳; 沈宇

    2013-01-01

    Objective:To analyze the effect of different delivery modes on the post-partum mental state and physiological function of puerperal.Methods:400 cases of primipara admitted in first affiliated hospital of Soochow university from January 2011 to December 2011 were randomly selected,including cesarean section and vaginal natural childbirth,200 cases in each group,the maternal postpartum 42 days psychological status,lochia duration,lactation were observed and compared between two groups.Results:There was no statistically significant difference between two groups (P>0.05),vaginal natural childbirth is better than cesarean section on physiological function of puerperal:vaginal natural childbirth group of postpartum lochia duration is shorter than cesarean section group (P<0.01).The initial time of lactation of puerperal with depression and anxiety was significantly longer than that of normal puerperal,while the quantity of lactation in 24h was significantly fewer (P<0.01).Conclusion:The impact of cesarean delivery on the physilogical and psycological situations of primipara was more serious than natural childbirth.The indication of cesarean delivery should be strictly controlled,while natural childbirth should be encouraged.%目的:探讨不同分娩方式对产妇产后心理和生理的影响.方法:随机选择2011年1月~2011年12月在苏大附一院分娩的初产妇400例,其中剖宫产、阴道自然分娩各200例,对两组产妇产后42天心理状况、恶露持续时间、泌乳情况进行调查.结果:两种分娩方式对产妇产后42天发生焦虑和抑郁心理的影响无明显差别(P>0.05);阴道自然分娩组产后恶露持续时间短于剖宫产组,差异有显著意义(P<0.01).有抑郁、焦虑情绪的产妇泌乳始动时间显著长于正常产妇,24h泌乳量显著少于正常产妇(P<0.01).结论:剖宫产对产妇身体生理创伤大过阴道自然分娩,应严格控制剖宫产的适应症,鼓励阴道自然分娩.

  7. Role of neuropsin in parvalbumin immunoreactivity changes in hippocampal basket terminals of mice reared in various environments

    Directory of Open Access Journals (Sweden)

    Harumitsu eSuzuki

    2014-12-01

    Full Text Available In vitro approaches have suggested that neuropsin (or kallikrein 8/KLK8, which controls gamma-aminobutyric acid (GABA neurotransmission through neuregulin-1 and its receptor (ErbB4, is involved in neural plasticity (Tamura et al., 2012, 2013. In the present study, we examined whether parvalbumin (PV-positive neuronal networks, the majority of which are ErbB4-positive GABAergic interneurons, are controlled by neuropsin in tranquil and stimulated voluntarily behaving mice.PV-immunoreactive fibers surrounding hippocampal pyramidal and granular neurons in mice reared in their home cage were decreased in neuropsin-deficient mice, suggesting that neuropsin controls PV immunoreactivity. One- or two-week exposures of wild mice to novel environments, in which they could behave freely and run voluntarily in a wheel resulted in a marked upregulation of both neuropsin mRNA and protein in the hippocampus. To elucidate the functional relevance of the increase in neuropsin during exposure to a rich environment, the intensities of PV-immunoreactive fibers were compared between neuropsin-deficient and wild-type mice under environmental stimuli. When mice were transferred into novel cages (large cages with toys, the intensity of PV-immunoreactive fibers increased in wild-type mice and neuropsin-deficient mice. Therefore, behavioral stimuli control a neuropsin-independent form of PV immunoreactivity. However, the neuropsin-dependent part of the change in PV-immunoreactive fibers may occur in the stimulated hippocampus because increased levels of neuropsin continued during these enriched conditions.

  8. 不同分娩方式对女性盆底功能影响的研究进展%Research progress on the effects of different delivery modes on female pelvic floor function

    Institute of Scientific and Technical Information of China (English)

    王淑静; 邓晓岚; 陈德新; 何荣霞

    2015-01-01

    女性骨盆底由多层肌肉和筋膜构成,它封闭骨盆出口,主要作用为承托并保持盆腔脏器于正常的位置。妊娠过程中,子宫重量的增加、激素水平的变化、胎先露部对盆底组织的过度压迫以及基因水平决定的胶原纤维和结缔组织的脆弱均会造成盆底组织松弛。不同分娩方式会对女性盆底肌肉、纤维、神经等造成不同程度的损伤,进而在产后及老年期导致盆底肌肌力下降、压力性尿失禁(SUI)、盆腔脏器脱垂(POP)和大便失禁(FI)等盆底功能障碍性疾病(PFD),严重影响女性生活质量。随着肌电图、超声、动态MRI技术的发展,产后盆底功能的筛查已被予以重视,女性产后都应进行盆底功能的筛查,并根据自身情况选择盆底肌肉训练、生物电刺激或生物反馈训练等方式恢复盆底功能。不同分娩方式对女性产后盆底功能的影响将在以下做一综述。%Female pelvic floor consists of layers of muscle and fascia, which closed the pelvis exports and the main role is retainering and keeping the pelvic cavity viscera on the normal position. During pregnancy, the increase of uterus weight, the change of hormone level, the excessive oppression of fetal presentation on pelvic floor organization and the fragility of collagen fibers and the connective tissue which is decided by genetic level will cause the relaxation of pelvic floor tissues. Different delivery modes will lead to different degree of damage on female pelvic floor muscles, fibers and nerve, which will lead to the decrease of the pelvic floor muscle strength, stress urinary incontinence (SUI), pelvic organ prolapse (POP), fecal incontinence (FI), and pelvic floor functional disorder (PFD) in postpartum and old period, and this will seriously affect the female postpartum quality of life. With the development of electromyography, ultrasonic and dynamic magnetic resonance imaging (MRI), the

  9. LSPS/Optogenetics to Improve Synaptic Connectivity Mapping: Unmasking the Role of Basket Cell-Mediated Feedforward Inhibition

    Science.gov (United States)

    Brill, Julia; Mattis, Joanna; Deisseroth, Karl

    2016-01-01

    Abstract Neocortical pyramidal cells (PYRs) receive synaptic inputs from many types of GABAergic interneurons. Connections between parvalbumin (PV)-positive, fast-spiking interneurons (“PV cells”) and PYRs are characterized by perisomatic synapses and high-amplitude, short-latency IPSCs. Here, we present novel methods to study the functional influence of PV cells on layer 5 PYRs using optogenetics combined with laser-scanning photostimulation (LSPS). First, we examined the strength and spatial distribution of PV-to-PYR inputs. To that end, the fast channelrhodopsin variant AAV5-EF1α-DIO-hChR2(E123T)-eYFP (ChETA) was expressed in PV cells in somatosensory cortex of mice using an adeno-associated virus-based viral construct. Focal blue illumination (100–150 µm half-width) was directed through the microscope objective to excite PV cells along a spatial grid covering layers 2–6, while IPSCs were recorded in layer 5 PYRs. The resulting optogenetic input maps showed evoked PV cell inputs originating from an ∼500-μm-diameter area surrounding the recorded PYR. Evoked IPSCs had the short-latency/high-amplitude characteristic of PV cell inputs. Second, we investigated how PV cell activity modulates PYR output in response to synaptic excitation. We expressed halorhodopsin (eNpHR3.0) in PV cells using the same strategy as for ChETA. Yellow illumination hyperpolarized eNpHR3.0-expressing PV cells, effectively preventing action potential generation and thus decreasing the inhibition of downstream targets. Synaptic input maps onto layer 5 PYRs were acquired using standard glutamate-photolysis LSPS either with or without full-field yellow illumination to silence PV cells. The resulting IPSC input maps selectively lacked short-latency perisomatic inputs, while EPSC input maps showed increased connectivity, particularly from upper layers. This indicates that glutamate uncaging LSPS-based excitatory synaptic maps will consistently underestimate connectivity. PMID

  10. Drug delivery system using functional PLGA nanoparticle prepared by emulsification-diffusion method%应用由乳化-扩散方法制备的功能PLGA纳米颗粒的药物发送系统

    Institute of Scientific and Technical Information of China (English)

    J.H 金; S.W 崔; W.S 金

    2004-01-01

    Drug delivery system using functional nanoparticle is a promising way for the reduction of side effects and the sustained release. Poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles with size 80 nm were prepared through emulsification-diffusion method using Poloxamer 188 as a stabilizer. The prepared nanoparticles have the hydrophobic core for drug loading and the hydrophilic surface corona for avoidance of reticuloendocellial system (RES). First example of biomedical applications is the localization of PLGA nanoparticle containing estrogen for the inhibition of restenosis after balloon injury. In vivo study demonstrated that locally delivered PLGA nanoparticles with estrogen drastically decrease the degree of neointimal formation. Secondly, bone-specific drug delivery was carried out using PLGA nanoparticles modified with alendronate which have a high affinity to bone. It was shown that PLGA nanoparticles conjugated with bisphosphonate were accumulated into bone after intravenous administration into rats.%运用功能纳米颗粒的药物发送系统是一种具有发展前景的途径,因为它减少了副反应并减轻病痛.Poly(D,L-lactide-co- glycolide) (PLGA)纳米颗粒的尺寸是80nm,它的制备是通过乳化扩散方法,并应用Poloxamer188作为稳定剂.所制备的纳米颗粒具有疏水核作为药物的载体,而其冠状亲水表面可避免形成网状内皮系统(RES).作为生物医学应用的第一个例子是PLAG纳米颗粒包含雌激素,它对于受到意外伤害而抑制不安情绪具有局限性.研究指出:局部地发送具有雌激素的PLGA纳米颗粒将激烈减少新内膜的形成程度.其次是应用经过修改的PLAG纳米颗粒发送系统专用于骨治疗的药已经实现,它与骨有高度的相似.已经证明:与双磷酸(bisphosphonate)相结合的PLGA纳米颗粒,参入到鼠的静脉内之后,将可累积在鼠骨内.

  11. Protein-Based Drug-Delivery Materials

    Directory of Open Access Journals (Sweden)

    Dave Jao

    2017-05-01

    Full Text Available There is a pressing need for long-term, controlled drug release for sustained treatment of chronic or persistent medical conditions and diseases. Guided drug delivery is difficult because therapeutic compounds need to survive numerous transport barriers and binding targets throughout the body. Nanoscale protein-based polymers are increasingly used for drug and vaccine delivery to cross these biological barriers and through blood circulation to their molecular site of action. Protein-based polymers compared to synthetic polymers have the advantages of good biocompatibility, biodegradability, environmental sustainability, cost effectiveness and availability. This review addresses the sources of protein-based polymers, compares the similarity and differences, and highlights characteristic properties and functionality of these protein materials for sustained and controlled drug release. Targeted drug delivery using highly functional multicomponent protein composites to guide active drugs to the site of interest will also be discussed. A systematical elucidation of drug-delivery efficiency in the case of molecular weight, particle size, shape, morphology, and porosity of materials will then be demonstrated to achieve increased drug absorption. Finally, several important biomedical applications of protein-based materials with drug-delivery function—including bone healing, antibiotic release, wound healing, and corneal regeneration, as well as diabetes, neuroinflammation and cancer treatments—are summarized at the end of this review.

  12. Global Delivery Models

    DEFF Research Database (Denmark)

    Manning, Stephan; Møller Larsen, Marcus; Bharati, Pratyush M.

    2015-01-01

    Global delivery models (GDMs) are transforming the global IT and business process outsourcing industry. GDMs are a new form of client-specific investment promoting service integration with clients by combining client proximity with time-zone spread for 24/7 service operations. We investigate...... antecedents and contingencies of setting up GDM structures. Based on comprehensive data we show that providers are likely to establish GDM location configurations when clients value access to globally distributed talent and speed of service delivery, in particular when services are highly commoditized...

  13. Ethical issues in cesarean delivery.

    Science.gov (United States)

    Chervenak, Frank A; McCullough, Laurence B

    2017-08-01

    Cesarean delivery is the most common and important surgical intervention in obstetric practice. Ethics provides essential guidance to obstetricians for offering, recommending, recommending against, and performing cesarean delivery. This chapter provides an ethical framework based on the professional responsibility model of obstetric ethics. This framework is then used to address two especially ethically challenging clinical topics in cesarean delivery: patient-choice cesarean delivery and trial of labor after cesarean delivery. This chapter emphasizes a preventive ethics approach, designed to prevent ethical conflict in clinical practice. To achieve this goal, a preventive ethics approach uses the informed consent process to offer cesarean delivery as a medically reasonable alternative to vaginal delivery, to recommend cesarean delivery, and to recommend against cesarean delivery. The limited role of shared decision making is also described. The professional responsibility model of obstetric ethics guides this multi-faceted preventive ethics approach. Copyright © 2017. Published by Elsevier Ltd.

  14. Nanochemistry of protein-based delivery agents

    Directory of Open Access Journals (Sweden)

    Subin R.C.K. Rajendran

    2016-07-01

    Full Text Available The past decade has seen an increased interest in the conversion of food proteins into functional biomaterials, including their use for loading and delivery of physiologically active compounds such as nutraceuticals and pharmaceuticals. Proteins possess a competitive advantage over other platforms for the development of nanodelivery systems since they are biocompatible, amphipathic, and widely available. Proteins also have unique molecular structures and diverse functional groups that can be selectively modified to alter encapsulation and release properties. A number of physical and chemical methods have been used for preparing protein nanoformulations, each based on different underlying protein chemistry. This review focuses on the chemistry of the reorganization and/or modification of proteins into functional nanostructures for delivery, from the perspective of their preparation, functionality, stability and physiological behavior.

  15. Nanochemistry of protein-based delivery agents

    Science.gov (United States)

    Rajendran, Subin; Udenigwe, Chibuike; Yada, Rickey

    2016-07-01

    The past decade has seen an increased interest in the conversion of food proteins into functional biomaterials, including their use for loading and delivery of physiologically active compounds such as nutraceuticals and pharmaceuticals. Proteins possess a competitive advantage over other platforms for the development of nanodelivery systems since they are biocompatible, amphipathic, and widely available. Proteins also have unique molecular structures and diverse functional groups that can be selectively modified to alter encapsulation and release properties. A number of physical and chemical methods have been used for preparing protein nanoformulations, each based on different underlying protein chemistry. This review focuses on the chemistry of the reorganization and/or modification of proteins into functional nanostructures for delivery, from the perspective of their preparation, functionality, stability and physiological behavior.

  16. Basket weaving and social weaving

    DEFF Research Database (Denmark)

    Olwig, Mette Fog; Gough, Katherine

    2013-01-01

    An important topic in climate change discourse is the question of ``climate refugees'' and climate-related mobility, which is often presented as failed adaptation. This discourse feeds into, and reinvigorates, anti-mobility sentiments, especially concerning youth, among nongovernmental...... artisans' narratives of mobility, related in the aftermath of flooding attributed to climate change, we show, firstly, that mobility among young people is commonplace and that the decision to either stay or move is typically an active choice associated with the artisans' fabric of relations. Secondly, we...

  17. Insurance:The Third Basket

    Institute of Scientific and Technical Information of China (English)

    Yang Wei

    2007-01-01

    @@ For the general public,instead of focusing on a simple increase in income,their investment and finance decisions should pay much more attention to the rise of actual living standards and managing risk.

  18. [Complications of cesarean deliveries].

    Science.gov (United States)

    Valgeirsdottir, Heiddis; Hardardottir, Hildur; Bjarnadottir, Ragnheidur I

    2010-01-01

    The objective of the study was to determine the rate of complications which accompany cesarean sections at Landspitali University Hospital (LSH). All deliveries by cesarean section from July 1st 2001 to December 31st 2002 were examined in a retrospective manner. Information was collected from maternity records regarding the operation and its complications if they occurred, during or following the operation. During this period 761 women delivered by cesarean section at LSH. The overall complication rate was 35,5%. The most common complications were; blood loss > or =1000 ml (16.5%), post operative fever (12.2%), extension from the uterine incision (7.2%) and need for blood transfusion (4.3%). Blood transfusion was most common in women undergoing cesarean section after attempted instrumental vaginal delivery (20%). Fever and extension from the uterine incision were most common in women undergoing cesarean section after full cervical dilation without attempt of instrumental delivery (19,4%). These complications were least likely to occur if the patient underwent an elective cesarean section. Complications following cesarean section are common, especially if labor is advanced. Each indication for an operative delivery should be carefully weighed and the patient informed accordingly.

  19. A Medical Delivery Device

    DEFF Research Database (Denmark)

    2010-01-01

    The present invention relates to a medical delivery device comprising at least two membrane electrode assembly units each of which comprises three layers: an upper and a lower electrode and a selective ionic conductive membrane provided there-between. At least one of the three layers are shared...

  20. Recovering from Delivery

    Science.gov (United States)

    ... suicidal thoughts, or any thoughts of harming your baby While recovering from delivery can be a lot to handle, things will get easier. Before you know it, you will be able to fully focus on enjoying your new baby. Reviewed by: Larissa Hirsch, MD Date reviewed: June ...

  1. A Medical Delivery Device

    DEFF Research Database (Denmark)

    2010-01-01

    The present invention relates to a medical delivery device comprising at least two membrane electrode assembly units each of which comprises three layers: an upper and a lower electrode and a selective ionic conductive membrane provided there-between. At least one of the three layers are shared...

  2. Protease-triggered siRNA delivery vehicles.

    Science.gov (United States)

    Rozema, David B; Blokhin, Andrei V; Wakefield, Darren H; Benson, Jonathan D; Carlson, Jeffrey C; Klein, Jason J; Almeida, Lauren J; Nicholas, Anthony L; Hamilton, Holly L; Chu, Qili; Hegge, Julia O; Wong, So C; Trubetskoy, Vladimir S; Hagen, Collin M; Kitas, Eric; Wolff, Jon A; Lewis, David L

    2015-07-10

    The safe and efficacious delivery of membrane impermeable therapeutics requires cytoplasmic access without the toxicity of nonspecific cytoplasmic membrane lysis. We have developed a mechanism for control of cytoplasmic release which utilizes endogenous proteases as a trigger and results in functional delivery of small interfering RNA (siRNA). The delivery approach is based on reversible inhibition of membrane disruptive polymers with protease-sensitive substrates. Proteolytic hydrolysis upon endocytosis restores the membrane destabilizing activity of the polymers thereby allowing cytoplasmic access of the co-delivered siRNA. Protease-sensitive polymer masking reagents derived from polyethylene glycol (PEG), which inhibit membrane interactions, and N-acetylgalactosamine, which targets asialoglycoprotein receptors on hepatocytes, were synthesized and used to formulate masked polymer-siRNA delivery vehicles. The size, charge and stability of the vehicles enable functional delivery of siRNA after subcutaneous administration and, with modification of the targeting ligand, have the potential for extrahepatic targeting.

  3. Self-nanoemulsifying drug delivery systems for oral insulin delivery

    DEFF Research Database (Denmark)

    Li, Ping; Tan, Angel; Prestidge, Clive A

    2014-01-01

    This study aims at evaluating the combination of self-nanoemulsifying drug delivery systems (SNEDDS) and enteric-coated capsules as a potential delivery strategy for oral delivery of insulin. The SNEDDS preconcentrates, loaded with insulin-phospholipid complex at different levels (0, 2.5 and 10% w...

  4. Mammalian cell delivery via aerosol deposition.

    Science.gov (United States)

    Veazey, William S; Anusavice, Kenneth J; Moore, Karen

    2005-02-15

    The objective of this study was to test the hypothesis that bovine dermal fibroblasts can survive aerosol delivery via an airbrush with mean cell survival rates greater than 50%. This technology has great implications for burn and other wound therapies, for delivery of genetically altered cells in gene therapies, and for tissue engineering with tissue scaffolds. Bovine dermal fibroblasts were suspended at a concentration of 200,000 cells/mL in Hank's Balanced Salt Solution, and delivered into six-well tissue culture plates using a Badger 100G airbrush. Cells were delivered through three nozzle diameters (312, 484, and 746 microm) at five different air pressures (41, 55, 69, 96, and 124 kPa). Nine repetitions were performed for each treatment group, and cell viability was measured using trypan blue exclusion assay. Mean cell viability ranged from 37 to 94%, and depended on the combination of nozzle diameter and delivery pressure (p < 0.0001). Linear regression analysis was used to develop a stochastic model of cell delivery viability as a function of nozzle diameter and delivery air pressure. This study demonstrates the feasibility of using an airbrush to deliver viable cells in an aerosol to a substrate.

  5. Aptamers for Targeted Drug Delivery

    Directory of Open Access Journals (Sweden)

    Partha Ray

    2010-05-01

    Full Text Available Aptamers are a class of therapeutic oligonucleotides that form specific three-dimensional structures that are dictated by their sequences. They are typically generated by an iterative screening process of complex nucleic acid libraries employing a process termed Systemic Evolution of Ligands by Exponential Enrichment (SELEX. SELEX has traditionally been performed using purified proteins, and cell surface receptors may be challenging to purify in their properly folded and modified conformations. Therefore, relatively few aptamers have been generated that bind cell surface receptors. However, improvements in recombinant fusion protein technology have increased the availability of receptor extracellular domains as purified protein targets, and the development of cell-based selection techniques has allowed selection against surface proteins in their native configuration on the cell surface. With cell-based selection, a specific protein target is not always chosen, but selection is performed against a target cell type with the goal of letting the aptamer choose the target. Several studies have demonstrated that aptamers that bind cell surface receptors may have functions other than just blocking receptor-ligand interactions. All cell surface proteins cycle intracellularly to some extent, and many surface receptors are actively internalized in response to ligand binding. Therefore, aptamers that bind cell surface receptors have been exploited for the delivery of a variety of cargoes into cells. This review focuses on recent progress and current challenges in the field of aptamer-mediated delivery.

  6. Integrin Targeted Delivery of Chemotherapeutics

    Directory of Open Access Journals (Sweden)

    Kai Chen, Xiaoyuan Chen

    2011-01-01

    Full Text Available Targeted delivery of chemotherapeutics is defined in the sense, that is, to maximize the therapeutic index of a chemotherapeutic agent by strictly localizing its pharmacological activity to the site or tissue of action. Integrins are a family of heterodimeric transmembrane glycoproteins involved in a wide range of cell-to-extracellular matrix (ECM and cell-to-cell interactions. As cell surface receptors, integrins readily interact with extracellular ligands and play a vital role in angiogenesis, leukocytes function and tumor development, which sets up integrins as an excellent target for chemotherapy treatment. The peptide ligands containing the arginine-glycine-aspartic acid (RGD, which displays a strong binding affinity and selectivity to integrins, particularly to integrin αvβ3, have been developed to conjugate with various conventional chemotherapeutic agents, such as small molecules, peptides and proteins, and nanoparticle-carried drugs for integtrin targeted therapeutic studies. This review highlights th