WorldWideScience

Sample records for delivery basket functionality

  1. Functional characteristics of parvalbumin- and cholecystokinin-expressing basket cells.

    Science.gov (United States)

    Bartos, Marlene; Elgueta, Claudio

    2012-02-15

    Cortical neuronal network operations depend critically on the recruitment of GABAergic interneurons and the properties of their inhibitory output signals. Recent evidence indicates a marked difference in the signalling properties of two major types of perisomatic inhibitory interneurons, the parvalbumin- and the cholecystokinin-containing basket cells. Parvalbumin-expressing basket cells are rapidly recruited by excitatory synaptic inputs, generate high-frequency trains of action potentials, discharge single action potentials phase-locked to fast network oscillations and provide fast, stable and timed inhibitory output onto their target cells. In contrast, cholecystokinin-containing basket cells are recruited in a less reliable manner, discharge at moderate frequencies with single action potentials weakly coupled to the phases of fast network oscillations and generate an asynchronous, fluctuating and less timed inhibitory output. These signalling modes are based on cell type-dependent differences in the functional and plastic properties of excitatory input synapses, integrative qualities and in the kinetics and dynamics of inhibitory output synapses. Thus, the two perisomatic inhibitory interneuron types operate with different speed and precision and may therefore contribute differently to the operations of neuronal networks.

  2. Assembling Appliances Standards from a Basket of Functions

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. Bounds for Asian basket options

    Science.gov (United States)

    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.

  4. Implied Stopping Rules for American Basket Options from Markovian Projection

    KAUST Repository

    Bayer, Christian; Hä ppö lä , Juho; Tempone, Raul

    2017-01-01

    This work addresses the problem of pricing American basket options in a multivariate setting, which includes among others, the Bachelier and the Black-Scholes models. In high dimensions, nonlinear partial differential equation methods for solving the problem become prohibitively costly due to the curse of dimensionality. Instead, this work proposes to use a stopping rule that depends on the dynamics of a low-dimensional Markovian projection of the given basket of assets. It is shown that the ability to approximate the original value function by a lower-dimensional approximation is a feature of the dynamics of the system and is unaffected by the path-dependent nature of the American basket option. Assuming that we know the density of the forward process and using the Laplace approximation, we first efficiently evaluate the diffusion coefficient corresponding to the low-dimensional Markovian projection of the basket. Then, we approximate the optimal early-exercise boundary of the option by solving a Hamilton-Jacobi-Bellman partial differential equation in the projected, low-dimensional space. The resulting near-optimal early-exercise boundary is used to produce an exercise strategy for the high-dimensional option, thereby providing a lower bound for the price of the American basket option. A corresponding upper bound is also provided. These bounds allow to assess the accuracy of the proposed pricing method. Indeed, our approximate early-exercise strategy provides a straightforward lower bound for the American basket option price. Following a duality argument due to Rogers, we derive a corresponding upper bound solving only the low-dimensional optimal control problem. Numerically, we show the feasibility of the method using baskets with dimensions up to fifty. In these examples, the resulting option price relative errors are only of the order of few percent.

  5. Implied Stopping Rules for American Basket Options from Markovian Projection

    KAUST Repository

    Bayer, Christian

    2017-05-01

    This work addresses the problem of pricing American basket options in a multivariate setting, which includes among others, the Bachelier and the Black-Scholes models. In high dimensions, nonlinear partial differential equation methods for solving the problem become prohibitively costly due to the curse of dimensionality. Instead, this work proposes to use a stopping rule that depends on the dynamics of a low-dimensional Markovian projection of the given basket of assets. It is shown that the ability to approximate the original value function by a lower-dimensional approximation is a feature of the dynamics of the system and is unaffected by the path-dependent nature of the American basket option. Assuming that we know the density of the forward process and using the Laplace approximation, we first efficiently evaluate the diffusion coefficient corresponding to the low-dimensional Markovian projection of the basket. Then, we approximate the optimal early-exercise boundary of the option by solving a Hamilton-Jacobi-Bellman partial differential equation in the projected, low-dimensional space. The resulting near-optimal early-exercise boundary is used to produce an exercise strategy for the high-dimensional option, thereby providing a lower bound for the price of the American basket option. A corresponding upper bound is also provided. These bounds allow to assess the accuracy of the proposed pricing method. Indeed, our approximate early-exercise strategy provides a straightforward lower bound for the American basket option price. Following a duality argument due to Rogers, we derive a corresponding upper bound solving only the low-dimensional optimal control problem. Numerically, we show the feasibility of the method using baskets with dimensions up to fifty. In these examples, the resulting option price relative errors are only of the order of few percent.

  6. Laparoscopic retrieval of impacted Dormia basket

    Directory of Open Access Journals (Sweden)

    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.

  7. Spent nuclear fuel shipping basket

    International Nuclear Information System (INIS)

    Wells, A.H.

    1990-01-01

    This patent describes a basket for a cask for transporting nuclear fuel elements. It comprises: sleeve members, each of the sleeve members having interior cross-section dimensions for receiving a nuclear fuel assembly such that the assembly is restrained from lateral movement within the sleeve member, apertured disk members, means for axially aligning the apertures in the disk members, and means for maintaining the disk members in fixed spaced relationship to form a disk assembly, comprising an array of disks, the aligned apertures of the disks being adapted to receive the sleeve members and maintain them in fixed spaced relationship

  8. BASKET HASIL TANGKAPAN DAN KETERKAITANNYA DENGAN MUTU HASIL TANGKAPAN DAN SANITASI DI TPI PPN PALABUHANRATU

    Directory of Open Access Journals (Sweden)

    Anwar Bey Pane

    2008-12-01

    Full Text Available Fish basket has an important role in assisting efficacy of marketing and fish landing process at fishing port. Generally have been known the function of basket as place of fish conveyor. Basket that was used during the time in fishing port (FP and fish landing place (FLP, indication of apperance of uncleanness at port quay, fish auction place (FAP/TPI and it surrounding. The problem of sanitaion and also fish quality as ports at this period are very important for FP/FLP in Indonesia, especially for facing the era of globalization and free market. Including for FP such as PPN Palabuhanratu will be developed into ocean fishing port type; with one of function is to provide the fish for export purposes. This research was conducted at PPN Palabuhanratu at period of Sep-Nov 2007, the aims of this research are for knowing the effect of useful of basket to fish quality and the port quay sanitation, FAP and its surrounding. This research using study case method that is research the catch aspect in FP and fish basket aspect of catch landing and marketing activities and port quay and FAP. In PPN Palabuhanratu, the existing of fish basket are have so many type; plastic basket, bamboo basket, barrel, styrofoam box and container fibreglass (jolang. The use of its have affect to fish quality differently: assisting to maintain and degrade the quality of fish. Almost all type of fish basket have negative influence to sanitaion of port quay, FA and its surrounding, except box of styrofoam for layur. No one of the type of fish basket are able to provide only positive influence on fish quality and satation

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

    Science.gov (United States)

    Wang, Dongxiang; Wang, Xiaoxing; Song, Chunshan

    2017-11-17

    Polyallylamine (PAA)-based molecular basket sorbents (MBS) have been studied for CO 2 capture in comparison with polyethylenimine (PEI)-based MBS. The characterizations including N 2 physisorption, diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), and thermogravimetric analysis (TGA) showed that PAA (M n =15 000) is more rigid and has more steric hindrance inside SBA-15 pores than PEI owing mainly to its different polymer structure. The effects of temperature and PAA loading on the CO 2 sorption capacity of PAA-based MBS have been examined by TGA by using 100 % CO 2 gas stream and compared with PEI/SBA-15. It was found that the capacity of the PAA/SBA-15 sorbent increased with increasing temperature. The optimum capacity of 88 mg CO2  g sorb -1 was obtained at 140 °C for PAA(50)/SBA-15 whereas the optimum sorption temperature was 75 and 90 °C for PEI-I(50)/SBA-15 (PEI-I, M n =423) and PEI-II(50)/SBA-15 (PEI-II, M n =25 000), respectively. The capacity initially increased with the increase of PAA loading and then dropped at high amine contents, owing to the increased diffusion barrier. The highest CO 2 capacity of 109 mg CO2  g sorb -1 was obtained at a PAA loading of 65 wt %, whereas the PAA(50)/SBA-15 sorbent gave the best amine efficiency of 0.23 mol CO2  mol N -1 . The effect of moisture was examined in a fixed-bed flow system with simulated flue gas containing 15 % CO 2 and 4.5 % O 2 in N 2 . It was found that the presence of moisture significantly enhanced CO 2 sorption over PAA(50)/SBA-15 and greatly improved its cyclic stability and regenerability. Compared with PEI/SBA-15, PAA/SBA-15 possesses a better thermal stability and higher resistance to oxidative degradation. However, the CO 2 sorption rate over the PAA(50)/SBA-15 sorbent was much slower. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Removable cruciform for ice condenser ice basket

    International Nuclear Information System (INIS)

    Scrabis, C.M.; Mazza, G.E.; Golick, L.R.; Pomaibo, P.

    1987-01-01

    A removable cruciform for use in an ice basket having a generally cylindrical sidewall defining a central, vertical axis of the ice basket and plural, generally annular retaining rings secured to the interior of the cylindrical sidewall of the ice basket at predetermined, spaced elevations throughout the axial height of the ice basket is described comprising: a pair of brackets, each comprising a central, base portion having parallel longitudinal edges and a pair of integral legs extending at corresponding angles relative to the base portion from the perspective parallel longitudinal edges thereof; a pair of support plate assemblies secured to and extending in parallel, spaced relationship from one of the pair of brackets; a pair of slide support plates secured to the other of the pair of brackets and extending therefrom in spaced, parallel relationship; and spring means received within the housing and engaging the base portions of the brackets and applying a resilient biasing force thereto for maintaining the spaced relationship thereof

  11. Post-test fuel basket evaluations of the CASTOR-V/21 cask

    International Nuclear Information System (INIS)

    Anderson, R.T.; Kingsley, K.R.

    1986-01-01

    Following an extensive testing program of the CASTOR-V/21 cask at INEL, eight symmetrically positioned indications were observed on the fuel basket. Since the presence of fuel in the cask permitted only remote visual inspection, it could not be conclusively determined if the indications represented material failure. The cask was not functionally limited since vertical movement of various fuel assemblies was possible and the structure remained intact. The basket is a redundant structure and criticality safety is maintained by fluxtrap boxes which were not in affected regions of the basket. The indications were observed at plate joints, which are stitch-welded for basket-manufacturing purposes. An extensive analysis was made of the basket design, manufacture, and test sequence to determine the possible cause and nature of the indications. This test cask had been tested under stringent thermal operating conditions. The cask was held at a power level 45% over rated conditions (28.5 kW vs. 21 kW). Also, the cask was held for two days with a vacuum in the cavity rather than helium (a conductive, inert gas), which is used during fuel storage. An evaluation was performed which included the following considerations: history under similar conditions, unique aspects of the test, basket construction techniques, fatigue, metallurgy and welding, and thermal stress. The consensus of several experts was that high thermal stress due to constrained thermal expansion of the fuel basket components caused the indications. This situation was remedied for future baskets by ensuring that certain manufacturing tolerance be measured and controlled. These limiting dimensions were established to permit sufficient space for thermal expansion. An extensive stress analysis was performed to define the dimensional requirements and demonstrate that the resulting basket stresses are acceptably low

  12. Pricing for a basket of LCDS under fuzzy environments.

    Science.gov (United States)

    Wu, Liang; Liu, Jie-Fang; Wang, Jun-Tao; Zhuang, Ya-Ming

    2016-01-01

    This paper looks at both the prepayment risks of housing mortgage loan credit default swaps (LCDS) as well as the fuzziness and hesitation of investors as regards prepayments by borrowers. It further discusses the first default pricing of a basket of LCDS in a fuzzy environment by using stochastic analysis and triangular intuition-based fuzzy set theory. Through the 'fuzzification' of the sensitivity coefficient in the prepayment intensity, this paper describes the dynamic features of mortgage housing values using the One-factor copula function and concludes with a formula for 'fuzzy' pricing the first default of a basket of LCDS. Using analog simulation to analyze the sensitivity of hesitation, we derive a model that considers what the LCDS fair premium is in a fuzzy environment, including a pure random environment. In addition, the model also shows that a suitable pricing range will give investors more flexible choices and make the predictions of the model closer to real market values.

  13. Ex vivo cytosolic delivery of functional macromolecules to immune cells.

    Directory of Open Access Journals (Sweden)

    Armon Sharei

    Full Text Available Intracellular delivery of biomolecules, such as proteins and siRNAs, into primary immune cells, especially resting lymphocytes, is a challenge. Here we describe the design and testing of microfluidic intracellular delivery systems that cause temporary membrane disruption by rapid mechanical deformation of human and mouse immune cells. Dextran, antibody and siRNA delivery performance is measured in multiple immune cell types and the approach's potential to engineer cell function is demonstrated in HIV infection studies.

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

    Directory of Open Access Journals (Sweden)

    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. Design of a stationary-basket (microreactor)

    Energy Technology Data Exchange (ETDEWEB)

    Timidei, A; Raisa, L

    1977-05-01

    A continuous-flow stirred-tank microreactor (295 cc capacity) for kinetic studies in gas-solid heterogeneous catalysis has been designed to obtain an apparatus characterized by perfect mixing, absence of resistance to mass and heat transfer, and pressure tightness, and which would not require sophisticated machine-shop work. This reactor is suitable for operation at up to 300/sup 0/C and 20 atm, and has clear advantages over the spinning-basket or rotating reactor in studies of catalysts of low mechanical strength. Tests with nitrogen or ethane as tracer and helium as carrier gas, run with a thermal conductivity detector, gave a ''decadence'' curve with a -0.97 slope at all mixing speeds, compared with a -1.0 slope for perfect mixing. Thermal gradients between fluid and pellet were minimal for three different pellet positions within the annular bed, at 92/sup 0/C. In benzene hydrogenation over a nickel/kieselguhr catalyst, measurement of reaction rates as a function of mixing speeds showed that good results in kinetic studies were obtainable at 1500 rpm and above. Diagrams and graphs.

  16. Functionalization of protein-based nanocages for drug delivery applications.

    Science.gov (United States)

    Schoonen, Lise; van Hest, Jan C M

    2014-07-07

    Traditional drug delivery strategies involve drugs which are not targeted towards the desired tissue. This can lead to undesired side effects, as normal cells are affected by the drugs as well. Therefore, new systems are now being developed which combine targeting functionalities with encapsulation of drug cargo. Protein nanocages are highly promising drug delivery platforms due to their perfectly defined structures, biocompatibility, biodegradability and low toxicity. A variety of protein nanocages have been modified and functionalized for these types of applications. In this review, we aim to give an overview of different types of modifications of protein-based nanocontainers for drug delivery applications.

  17. Bait preference in basket trap fishing operation and heavy metal ...

    African Journals Online (AJOL)

    The bait preference of basket traps fishing operation and heavy metal contamination in the trap catches from Lagos Lagoon were carried out between January and June 2011. Sixty baskets traps were used for the fishing operation, twenty basket traps were baited each with soap, coconut and maize. Clibanarius africanus ...

  18. Primary Care Providers' Opening of Time-Sensitive Alerts Sent to Commercial Electronic Health Record InBaskets.

    Science.gov (United States)

    Cutrona, Sarah L; Fouayzi, Hassan; Burns, Laura; Sadasivam, Rajani S; Mazor, Kathleen M; Gurwitz, Jerry H; Garber, Lawrence; Sundaresan, Devi; Houston, Thomas K; Field, Terry S

    2017-11-01

    Time-sensitive alerts are among the many types of clinical notifications delivered to physicians' secure InBaskets within commercial electronic health records (EHRs). A delayed alert review can impact patient safety and compromise care. To characterize factors associated with opening of non-interruptive time-sensitive alerts delivered into primary care provider (PCP) InBaskets. We analyzed data for 799 automated alerts. Alerts highlighted actionable medication concerns for older patients post-hospital discharge (2010-2011). These were study-generated alerts sent 3 days post-discharge to InBaskets for 75 PCPs across a multisite healthcare system, and represent a subset of all urgent InBasket notifications. Using EHR access and audit logs to track alert opening, we performed bivariate and multivariate analyses calculating associations between patient characteristics, provider characteristics, contextual factors at the time of alert delivery (number of InBasket notifications, weekday), and alert opening within 24 h. At the time of alert delivery, the PCPs had a median of 69 InBasket notifications and had received a median of 379.8 notifications (IQR 295.0, 492.0) over the prior 7 days. Of the 799 alerts, 47.1% were opened within 24 h. Patients with longer hospital stays (>4 days) were marginally more likely to have alerts opened (OR 1.48 [95% CI 1.00-2.19]). Alerts delivered to PCPs whose InBaskets had a higher number of notifications at the time of alert delivery were significantly less likely to be opened within 24 h (top quartile >157 notifications: OR 0.34 [95% CI 0.18-0.61]; reference bottom quartile ≤42). Alerts delivered on Saturdays were also less likely to be opened within 24 h (OR 0.18 [CI 0.08-0.39]). The number of total InBasket notifications and weekend delivery may impact the opening of time-sensitive EHR alerts. Further study is needed to support safe and effective approaches to care team management of InBasket notifications.

  19. Nanoparticle functionalization for brain targeting drug delivery and diagnostic

    DEFF Research Database (Denmark)

    Gomes, Maria João; Mendes, Bárbara; Martins, Susana

    2016-01-01

    carriers to cross the BBB and achieve brain, and their functionalization strategies are described; and finally the delivery of nanoparticles to the target moiety, as diagnostics or therapeutics. Therefore, this chapter is focused on how the nanoparticle surface may be functionalized for drug delivery......Nanobiotechnology has been demonstrated to be an efficient tool for targeted therapy as well as diagnosis, with particular emphasis on brain tumor and neurodegenerative diseases. On this regard, the aim of this chapter is focused on engineered nanoparticles targeted to the brain, so that they have...... and diagnostics. Furthermore, it is also mentioned that some BBB targets were already used as transport mediators to central nervous system by functionalization on nanoparticles. It summarizes the nanoparticles potential in therapeutics and molecular targeting to BBB, and also an approach of the nanoparticle...

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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, N 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

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

    Directory of Open Access Journals (Sweden)

    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.

  2. A delivery transfer function (DTF) analysis for helical tomotherapy

    International Nuclear Information System (INIS)

    Kissick, Michael W; Mackie, Thomas Rockwell; Jeraj, Robert

    2007-01-01

    The previous theoretical work of a delivery transfer function (DTF) in radiotherapy is expanded to include the unique intensity modulation method of helical tomotherapy. In addition to the collimation of each beamlet, and the Gaussian scatter convolution spreading of the dose that other radiotherapy units have, helical tomotherapy uses 51 small arcs of varying lengths to adjust the intensity. The blurring from these arcs is not taken into account during treatment planning. A theoretical DTF is constructed, and a calculation is performed which includes this unique source motion in relation to the other DTF components. Various typical delivery parameters are used to generate resolution maps for a constant intensity projection. Near the isocenter, the transverse (to a given beam direction) blurring is small but at larger radii (>6 cm), the source blurring dominates over leaf size. For most clinical situations, this inherent source motion blurring is expected to be negligible

  3. Smoothing the payoff for efficient computation of Basket option prices

    KAUST Repository

    Bayer, Christian

    2017-07-22

    We consider the problem of pricing basket options in a multivariate Black–Scholes or Variance-Gamma model. From a numerical point of view, pricing such options corresponds to moderate and high-dimensional numerical integration problems with non-smooth integrands. Due to this lack of regularity, higher order numerical integration techniques may not be directly available, requiring the use of methods like Monte Carlo specifically designed to work for non-regular problems. We propose to use the inherent smoothing property of the density of the underlying in the above models to mollify the payoff function by means of an exact conditional expectation. The resulting conditional expectation is unbiased and yields a smooth integrand, which is amenable to the efficient use of adaptive sparse-grid cubature. Numerical examples indicate that the high-order method may perform orders of magnitude faster than Monte Carlo or Quasi Monte Carlo methods in dimensions up to 35.

  4. Functionalized mesoporous silicon for targeted-drug-delivery.

    Science.gov (United States)

    Tabasi, Ozra; Falamaki, Cavus; Khalaj, Zahra

    2012-10-01

    The present work concerns a preliminary step in the production of anticancer drug loaded porous silicon (PSi) for targeted-drug-delivery applications. A successful procedure for the covalent attachment of folic acid, polyethylene glycol (PEG) and doxorubicin to hydrophilic mesoporous silicon layers is presented. A systematic approach has been followed to obtain the optimal composition of the N,N'-dicyclohexylcarbodiimide (DCC)/N-hydroxysuccimide (NHS) in dimethylsulfoxide (DMSO) solution for the surface activation process of the undecylenic acid (UD) grafted molecules to take place with minimal undesired byproduct formation. The effect of reactant concentration and kind of solvent (aqueous or DMSO) on the attachment of folic acid to the activated PSi layer has been investigated. The covalent attachment of the doxorubicin molecules to the PSi layer functionalized with folic acid and PEG is discussed. The drug release kinetics as a function of pH has been studied. The functionalized PSi particles show a high cytotoxicity compared to the equivalent amount of free drug. Cell toxicity tests show clearly that the incorporation of folate molecules increases substantially the toxicity of the loaded PSi particles. Accordingly this new functionalized PSi may be considered a proper candidate for targeted drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Basket Option Pricing Using GP-GPU Hardware Acceleration

    KAUST Repository

    Douglas, Craig C.; Lee, Hyoseop

    2010-01-01

    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

  7. Smoothing the payoff for efficient computation of Basket option prices

    KAUST Repository

    Bayer, Christian; Siebenmorgen, Markus; Tempone, Raul

    2017-01-01

    We consider the problem of pricing basket options in a multivariate Black–Scholes or Variance-Gamma model. From a numerical point of view, pricing such options corresponds to moderate and high-dimensional numerical integration problems with non

  8. Alendronate functionalized mesoporous hydroxyapatite nanoparticles for drug delivery

    International Nuclear Information System (INIS)

    Li, Dongdong; Zhu, Yuntao; Liang, Zhiqiang

    2013-01-01

    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 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 3 + on the matrix and -COO − belongs to IBU. The system provides a new concept for improving the drug loading or slowing down the release rate

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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.

  11. Cardiopulmonary function and oxygen delivery during total liquid ventilation.

    Science.gov (United States)

    Tsagogiorgas, Charalambos; Alb, Markus; Herrmann, Peter; Quintel, Michael; Meinhardt, Juergen P

    2011-10-01

    Total liquid ventilation (TLV) with perfluorocarbons has shown to improve cardiopulmonary function in the injured and immature lung; however there remains controversy over the normal lung. Hemodynamic effects of TLV in the normal lung currently remain undetermined. This study compared changes in cardiopulmonary and circulatory function caused by either liquid or gas tidal volume ventilation. In a prospective, controlled study, 12 non-injured anesthetized, adult New Zealand rabbits were primarily conventionally gas-ventilated (CGV). After instrumentation for continuous recording of arterial (AP), central venous (CVP), left artrial (LAP), pulmonary arterial pressures (PAP), and cardiac output (CO) animals were randomized into (1) CGV group and (2) TLV group. In the TLV group partial liquid ventilation was initiated with instillation of perfluoroctylbromide (12 ml/kg). After 15 min, TLV was established for 3 hr applying a volume-controlled, pressure-limited, time-cycled ventilation mode using a double-piston configured TLV. Controls (CGV) remained gas-ventilated throughout the experiment. During TLV, heart rate, CO, PAP, MAP, CVP, and LAP as well as derived hemodynamic variables, arterial and mixed venous blood gases, oxygen delivery, PVR, and SVR did not differ significantly compared to CGV. Liquid tidal volumes suitable for long-term TLV in non-injured rabbits do not significantly impair CO, blood pressure, and oxygen dynamics when compared to CGV. Copyright © 2011 Wiley-Liss, Inc.

  12. Functionalized nanoparticles for AMF-induced gene and drug delivery

    Science.gov (United States)

    Biswas, Souvik

    The properties and broad applications of nano-magnetic colloids have generated much interest in recent years. Specially, Fe3O4 nanoparticles have attracted a great deal of attention since their magnetic properties can be used for hyperthermia treatment or drug targeting. For example, enhanced levels of intracellular gene delivery can be achieved using Fe3O4 nano-vectors in the presence of an external magnetic field, a process known as 'magnetofection'. The low cytotoxicity, tunable particle size, ease of surface functionalization, and ability to generate thermal energy using an external alternating magnetic field (AMF) are properties have propelled Fe3O4 research to the forefront of nanoparticle research. The strategy of nanoparticle-mediated, AMF-induced heat generation has been used to effect intracellular hyperthermia. One application of this 'magnetic hyperthermia' is heat activated local delivery of a therapeutic effector (e.g.; drug or polynucleotide). This thesis describes the development of a magnetic nano-vector for AMF-induced, heat-activated pDNA and small molecule delivery. The use of heat-inducible vectors, such as heat shock protein ( hsp) genes, is a promising mode of gene therapy that would restrict gene expression to a local region by focusing a heat stimulus only at a target region. We thus aimed to design an Fe3O4 nanoparticle-mediated gene transfer vehicle for AMF-induced localized gene expression. We opted to use 'click' oximation techniques to assemble the magnetic gene transfer vector. Chapter 2 describes the synthesis, characterization, and transfection studies of the oxime ether lipid-based nano-magnetic vectors MLP and dMLP. The synthesis and characterization of a novel series of quaternary ammonium aminooxy reagents (2.1--2.4) is described. These cationic aminooxy compounds were loaded onto nanoparticles for ligation with carbonyl groups and also to impart a net positive charge on the nanoparticle surface. Our studies indicated that the

  13. 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.

  14. A novel stone retrieval basket for more efficient lithotripsy procedures.

    Science.gov (United States)

    Salimi, N; Mahajan, A; Don, J; Schwartz, B

    2009-01-01

    This paper presents the development of an improved stone retrieval device that uses a newly designed cage of Nitinol wires encompassing a mesh basket made of a material that is laser resistant. Current methods to extract large stones involve imaging, using a laser to fragment the stones and then using existing cage-like baskets to trap the fragments individually and extracting them one at a time. These procedures are tedious, and may result in leaving some fragments behind that can reform causing the need for another procedure. The device presented in this paper will have a mesh-like sack which will consist of a laser resistant material of polytetrafluoroethylene (PTFE) enclosed within a newly designed Nitinol cage. Two alternate designs are provided for the cage in this paper. The handle of the device is revised to allow for a 3 Fr (1 mm) opening such that a laser's fiber optic cable can enter the device. Using this device a laser can be used to fragment the stone, and all the fragments are retained in the basket in both the design options. The basket can then be retracted allowing for the retrieval of all the fragments in one shot. The stone retrieval basket presented in this paper will significantly improve the efficiency and effectiveness of lithotripsy procedures for removal of large kidney and biliary tract stones.

  15. Functionalized linear poly(amidoamine)s are efficient vectors for intracellular protein delivery

    NARCIS (Netherlands)

    Coué, G.M.J.P.C.; Engbersen, Johannes F.J.

    2011-01-01

    An effective intracellular protein delivery system was developed based on functionalized linear poly(amidoamine)s (PAAs) that form self-assembled cationic nanocomplexes with oppositely charged proteins. Three differently functionalized PAAs were synthesized, two of these having repetitive disulfide

  16. Impact of a student's basket on work organization in schools

    OpenAIRE

    Zaleckienė, Lina; Šaparnis, Gintaras

    2006-01-01

    Support of the education system and its use of resources are being reformed in order to help the system to better adapt to free market and ensure its higher quality and better accessibility to it. Formation of a student's basket is assessed positively but head teachers do not consider it as a factor of changes in education so it is more often generalized as a possibility to plan and use finances and resources more efficiently. The formation of a student's basket is linked with in-service trai...

  17. Optimal Currency Basket Pegs for Developing and Emerging Economies

    OpenAIRE

    Joseph Daniels; Peter G. Toumanoff; Marc von der Ruhr

    2001-01-01

    The exchange rate arrangement represents an important policy choice for emerging and transitional economies as they strive to become stable and market-driven. A wide variety of arrangements have emerged, ranging from currency boards, basket-currency pegs and single-currency pegs to floating rates. Recently the IMF has recommended that, if the exchange value of a currency is to be pegged, it is better to peg to a basket of currencies rather than a single currency. Nonetheless, there has been l...

  18. Calculation of Permeability inside the Basket including one Fuel Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Seung Hwan; Bang, Kyung Sik; Lee, Ju an; Choi, Woo Seok [KAERI, Daejeon (Korea, Republic of)

    2016-05-15

    In general, the porous media model and the effective thermal conductivity were used to simply the fuel assembly. The methods of calculating permeability were compared considering the flow inside a basket which includes a nuclear fuel. Detailed fuel assembly was a computational modeling and the flow characteristics were investigated. The flow inside the basket which included a fuel assembly is analyzed by CFD. As the height of the fuel assembly increases, the pressure drop linearly increased. The inertia resistance could be neglected. Three methods to calculate the permeability were compared. The permeability by the friction factor is 50% less than the permeability by wall shear stress and pressure drop.

  19. MARKET BASKET ANALYSIS (MBA PADA SITUS WEB E-COMMERCE ZAKIYAH COLLECTION

    Directory of Open Access Journals (Sweden)

    Ari Muzakir

    2016-11-01

    Full Text Available E-commerce menghubungkan antara produsen dengan produsen, produsen dengan konsumen, konsumen dengan produsen, konsumen dengan konsumen. Untuk mengimplementasi e-commerce dalam mendukung bisnis organisasi perlu di perhatikan 5 komponen utama yaitu ; pengembangan produk, promosi, transaksi online, product delivery dan after sales support. Hal ini yang tengah diterapkan pada Zakiyah Collection. Zakiyah Collection bergerak dibidang penjualan aneka macam kain khas Palembang seperti songket, blongket,tanjung, dan lain sebagainya. Untuk melakukan analisis terhadap pangsa pasar yang ada agar dapat bersaing dengan toko online lainnya dilakukan dengan strategi pemasaran dengan menggunakan pendekatan market basket analysis (MBA. MBA merupakan salah satu teknik dari data mining yang digunakan untuk menentukan produk-produk manakah yang akan dibeli oleh pelanggan secara bersamaan dengan melakukan analisa terhadap daftar transaksi pelanggan. Dengan mengetahui produk-produk tersebut, maka sebuah sistem e-commerce dapat membuat maupun mengembangkan sebuah sistem customer profiles dan dapat menentukan layout katalog pelanggannya sendiri. Model pengembangan sistem yang dilakukan menggunakan prototype dimana pelanggan dan pengguna akan dilibatkan secara langsung dalam proses ini. Hasil akhir dalam penelitian ini adalah berupa analisis data transaksi menggunakan market basket analysis dengan dilakukan 4 kali kombinasi produk yang berdasarkan nilai support x confidence terbesar dengan hasil berupa angka-angka kemungkinan transasksi yang berkaitan dengan produk yang dijual. Jika dengan menggunakan 1 kali kombinasi, maka didapatkan blongket dengan nilai support sebesar 0.5625. Jika dilakukan 2 kali kombinasi diperoleh kombinasi blongket dan songket dengan nilai support 0.375. Kata kunci: e-commerce, market basket analysis, association rules.

  20. 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.

  1. The corbiculate bees arose from New World oil-collecting bees: implications for the origin of pollen baskets.

    Science.gov (United States)

    Martins, Aline C; Melo, Gabriel A R; Renner, Susanne S

    2014-11-01

    The economically most important group of bees is the "corbiculates", or pollen basket bees, some 890 species of honeybees (Apis), bumblebees (Bombus), stingless bees (Meliponini), and orchid bees (Euglossini). Molecular studies have indicated that the corbiculates are closest to the New World genera Centris, with 230 species, and Epicharis, with 35, albeit without resolving the precise relationships. Instead of concave baskets, these bees have hairy hind legs on which they transport pollen mixed with floral oil, collected with setae on the anterior and middle legs. We sampled two-thirds of all Epicharis, a third of all Centris, and representatives of the four lineages of corbiculates for four nuclear gene regions, obtaining a well-supported phylogeny that has the corbiculate bees nested inside the Centris/Epicharis clade. Fossil-calibrated molecular clocks, combined with a biogeographic reconstruction incorporating insights from the fossil record, indicate that the corbiculate clade arose in the New World and diverged from Centris 84 (72-95)mya. The ancestral state preceding corbiculae thus was a hairy hind leg, perhaps adapted for oil transport as in Epicharis and Centris bees. Its replacement by glabrous, concave baskets represents a key innovation, allowing efficient transport of plant resins and large pollen/nectar loads and freeing the corbiculate clade from dependence on oil-offering flowers. The transformation could have involved a novel function of Ubx, the gene known to change hairy into smooth pollen baskets in Apis and Bombus. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Handling and prevention of complications in stone basketing

    NARCIS (Netherlands)

    de La Rosette, Jean J. M. C. H.; Skrekas, Thomas; Segura, Joseph W.

    2006-01-01

    OBJECTIVE: To review the incidence, risk factors, and treatment options of intraoperative and postoperative complications of stone basketing in urology with emphasis on certain principles that must be upheld to prevent those complications. METHODS: A literature search was performed using the MEDLINE

  3. Typewriting: In-Basket Exercises for Production Typewriting

    Science.gov (United States)

    Stamps, Charles A.

    1977-01-01

    Describes the use of in-basket exercises, a nontraditional approach to teaching production typewriting, which (according to the author) enables students to increase their production typewriting speed, develop the ability to rely on their own decisions and interpretations of written instructions, learn the necessity for organization, and compose…

  4. Spatial variability in branchial basket meristics and morphology of ...

    African Journals Online (AJOL)

    We examined spatial variability in meristic and morphological characteristics of the branchial basket of sardine Sardinops sagax collected from four geographical regions around the southern African coast, namely Namibia and the South African west, south and east coasts. Our analysis tested the hypothesis of three putative ...

  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. Flexible power delivery system and its intelligent functions

    International Nuclear Information System (INIS)

    Glamochanin, Vlastimir; Andonov, Dragan

    1996-01-01

    This paper presents some of the features and capabilities of the novel energy distribution system called FRIENDS. The main FRIENDS objective is distribution system reliability, with flexible system structure reconfiguration, inclusion of dispersed energy generation systems. Altogether, it represents a new concept of reliable and economic electric power delivery to end users. The FRIENDS project is a challenge for future research and development, including new technology and devices for the implementation of such an integrated system. (author)

  7. Functionalized nanofibers as drug-delivery systems for osteochondral regeneration

    Czech Academy of Sciences Publication Activity Database

    Amler, Evžen; Filová, Eva; Buzgo, Matej; Prosecká, Eva; Rampichová, Michala; Nečas, A.; Nooeaid, P.; Boccaccini, A. R.

    2014-01-01

    Roč. 9, č. 7 (2014), s. 1083-1094 ISSN 1743-5889 Grant - others:GA MZd(CZ) NT12156; CEITEC CZ.1.05/1.1.00/02.0068; GA UK(CZ) 626012; GA UK(CZ) 384311; GA UK(CZ) 545313; GA UK(CZ) 424213; GA UK(CZ) 270513; GA MŠk(CZ) CZ.1.07/2.3.00/20.0092 Institutional support: RVO:68378041 Keywords : bone * cartilage * drug delivery Subject RIV: BO - Biophysics Impact factor: 5.413, year: 2014

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

    International Nuclear Information System (INIS)

    Gao Lin; Sun Jihong; Li Yuzhen

    2011-01-01

    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 f t =kt n 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. - Graphical abstract: Loading (A) and release profiles (B) of aspirin in N-BMMs and N-MCM-41 indicated that BMMs have more drug loading capacity and faster release rate than that MCM-41. Highlights: → Bimodal mesoporous silicas (BMMs) and MCM-41 modified with amino group via post-treatment procedure. → Loading and release profiles of aspirin in modified BMMs and MCM-41. → Modified BMMs have more drug loading capacity and faster release rate than that modified MCM-41.

  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. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Some topics in mathematical finance: Asian basket option pricing, Optimal investment strategies

    OpenAIRE

    Diallo, Ibrahima

    2010-01-01

    This thesis presents the main results of my research in the field of computational finance and portfolios optimization. We focus on pricing Asian basket options and portfolio problems in the presence of inflation with stochastic interest rates.In Chapter 2, we concentrate upon the derivation of 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 f...

  16. Separation of Electrolytic Reduction Product from Stainless Steel Wire Mesh Cathode Basket via Salt Draining and Reuse of the Cathode Basket

    Directory of Open Access Journals (Sweden)

    Eun-Young Choi

    2017-01-01

    Full Text Available We demonstrated that the metallic product obtained after electrolytic reduction (also called oxide reduction (OR can be simply separated from a stainless steel wire mesh cathode basket only by using a salt drain. First, the OR run of a simulated oxide fuel (0.6 kg/batch was conducted in a molten Li2O–LiCl salt electrolyte at 650°C. The simulated oxide fuel of the porous cylindrical pellets was used as a cathode by loading a stainless steel wire mesh cathode basket. Platinum was employed as an anode. After the electrolysis, the residual salt of the cathode basket containing the reduction product was drained by placing it at gas phase above the molten salt using a holder. Then, at a room temperature, the complete separation of the reduction product from the cathode basket was achieved by inverting it without damaging or deforming the basket. Finally, the emptied cathode basket obtained after the separation was reused for the second OR run by loading a fresh simulated oxide fuel. We also succeeded in the separation of the metallic product from the reused cathode basket for the second OR run.

  17. 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.

  18. Basket call option pricing for CCVG using sparse grids

    KAUST Repository

    Crocce, Fabian; Hä ppö lä , Juho; Iania, Alessandro; Tempone, Raul

    2016-01-01

    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.

  19. Stability Analysis of Buffer Storage Large Basket and Temporary Storage Pre-packaging Basket Used in the Type B Radwaste Process Area

    International Nuclear Information System (INIS)

    Kim, Sung Kyun; Lee, Kune Woo; Moon, Jei Kwon

    2011-01-01

    The ITER radioactive waste (radwaste) treatment and storage systems are currently being designed to manage Type B, Type A and dust radwastes generated during the ITER machine operation. The Type B management system is to be in the hot cell building basement with temporary storage and the modular type storages outside the hot cell building for the pre-packed Type B radwaste during the ITER operation of 20 years. In order to store Type B radwaste components in onsite storage, the waste treatment chain process for Type B radwastes was developed as follows. First, Type B full components filled in a large basket are imported from Tokamak to the hot cell basement and they are stored in the buffer storage before treatment. Second, they are cut properly with a laser cutting machine or band saw machine and sliced waste parts are filled in a pre-packaging basket. Third, the sampling of Type B components is performed and then the tritium removal treatment is done in an oven to remove tritium from the waste surface and then the sampling is performed again. Forth, the characterization is performed by using a gamma spectrometry. Fifth, the pre-packaging operation is done to ensure the final packaging of the radwaste. Sixth, the pre-packaging baskets are stored in the temporary storage for 6 months and then they are sent to the extension storage and stored until export to host country. One of issues in the waste treatment scheme is to analyze the stacking stability of a stack of large baskets and pre-packaging baskets in the storage system. The baseline plan is to stack the large baskets in two layers in the buffer storage and to stack the pre-packaging baskets in three layers in the temporary storage and extension storage. In this study, the stacking stability analysis for the buffer storage large basket and temporary storage pre-packaging basket was performed for various stack failure modes

  20. Cummings Memorial Lecture - 1975. The market basket: food for thought.

    Science.gov (United States)

    Deichman, W B

    1975-06-01

    The world food crisis is as critical today as when it was debated at the 1974 World Food Conference in Rome. Since the United States and Canada-and to a lesser extent, Australia and New Zealand-lead in the production of corn, wheat and soybeans, the North American "bread basket" has become the "market basket" of the world. For welfare, economic, and political reasons, our energies, resources, and deliberations must be expanded toward optimum production of wholesome food products. I do not recommend that we permit food additives in "questionably" safe or excessive concentrations in our agricultural products. I do recommend, however, that tolerance limits for food additives be established based on a comprehensive review of all contributing factors-the world food crisis and the rational interpretation of both positive and negative animal data as they relate to man. As Dr. Herbert Stokinger put it so aptly: "Avoid the establishment of unnecessarily severe standards." 2. Funds for research and teaching of food and nutrition should be greatly increased, so that all who can read and write may be made aware of the daily dietary requirements for the maintenance of good health. 3. Unsubstantiated scare tactics in publications of the scientific and lay press can only lead to well-intended but often emotionally-inspired restrictions, ordinances, and laws. Such decisions are likely to either under- or over-define the requirements and standards for food additives and other chemicals which are important to the well-being of the populace.

  1. 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.

  2. 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.

  3. Reviewing Sexual Function After Delivery and Its Association with Some of the Demographic Marital Satisfaction Factors

    Directory of Open Access Journals (Sweden)

    Kh. Broumandfar

    2012-04-01

    Full Text Available Background: Desirable sexual function has an important role in strengthening the marital life of the couples. Sexual disorders can cause mental pressure and affect quality of life and marital relationship. Methods: This was a descriptive correlation study in one group and one phase covering multivariables. The study sample included 384 women after delivery period that had the following inclusion criteria: the age of at least 18 years, delivery in 38-42 pregnancy weeks, primiparous and multiparous women, living in the city, single pregnancy, and twelve months elapsed from the delivery. The required data such demographic, marital satisfaction and sexual function index were collected through reporting questionnaire. The data were analyzed using descriptive and inferential statistical methods using software SPSS. Results: The findings of the study indicated that the most prevalent disorder of the sexual relationship in postpartum was dyspareunia and the least prevalent was the sexual desire. There was no significant association between sexual function and, age, education degree , body mass index ,body size and job, but there was a significant association for other factors such as the economic, residence and marital satisfaction (p<0.01. Conclusion: It is recommended that sexual problems after delivery be placed on the list of health teaching issues to pass easily this period of time. Women should be assured that these problems gradually would be improved and they should learn using proper techniques to decrease dyspareunia which is a sexual disorder in postpartum period.

  4. Development of a Computerized In-Basket Exercise for the Classroom: A Sales Management Example

    Science.gov (United States)

    Pearson, Michael M.; Barnes, John W.; Onken, Marina H.

    2006-01-01

    This article follows the development of a sales management in-basket exercise for use in the classroom. The authors have computerized the exercise and added features to allow for additional and more quantitative input from the students. The exercise has evolved and been tested in numerous classroom situations. The computerized in-basket exercise…

  5. 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.

  6. MCO Engineering Test Report Fuel Basket Handling Grapple Acceptance Test

    International Nuclear Information System (INIS)

    CHENAULT, D.M.

    2000-01-01

    Acceptance testing of the production SNF Fuel Basket lift grapples to the required 150 percent maximum lift load is documented herein. The report shows the results affirming the proof test passage. The primary objective of this test was to confirm the load rating of the grapple per applicable requirements of ANSI 14 6 American National Standard For Radioactive Materials Special Lifting Devices for Shipping Containers Weighing 10,000 pounds (4500kg) or More. The above Standard requires a load test of 150% of the design load which must be held for a minimum of 10 minutes followed by a Liquid Penetrant or Magnetic Particle examination of critical areas and welds in accordance with the ANSI/ASME Boiler and Pressure Vessel Code 1989 Section 111 Division 1 section NF 5350

  7. Recent Progress in Functional Micellar Carriers with Intrinsic Therapeutic Activities for Anticancer Drug Delivery.

    Science.gov (United States)

    Qu, Ying; Chu, BingYang; Shi, Kun; Peng, JinRong; Qian, ZhiYong

    2017-12-01

    Polymeric micelles have presented superior delivery properties for poorly water-soluble chemotherapeutic agents. However, it remains discouraging that there may be some additional short or long-term toxicities caused by the metabolites of high quantities of carriers. If carriers had simultaneous therapeutic effects with the drug, these issues would not be a concern. For this, carriers not only simply act as drug carriers, but also exert an intrinsic therapeutic effect as a therapeutic agent. The functional micellar carriers would be beneficial to maximize the anticancer effect, overcome the drug resistance and reduce the systemic toxicity. In this review, we aim to summarize the recent progress on the development of functional micellar carriers with intrinsic anticancer activities for the delivery of anticancer drugs. This review focuses on the design strategies, properties of carriers and the drug loading behavior. In addition, the combinational therapeutic effects between carriers and chemotherapeutic agents are also discussed.

  8. Iterative photoinduced chain functionalization as a generic platform for advanced polymeric drug delivery systems

    Czech Academy of Sciences Publication Activity Database

    Al Samad, A.; Bethry, A.; Janoušková, Olga; Ciccione, J.; Wenk, C.; Coll, J.-L.; Subra, G.; Etrych, Tomáš; El Omar, F.; Bakkour, Y.; Coudane, J.; Nottelet, B.

    2018-01-01

    Roč. 39, č. 3 (2018), s. 1-5, č. článku 1700502. ISSN 1022-1336 R&D Projects: GA MŠk(CZ) LO1507; GA MŠk(CZ) LQ1604 Institutional support: RVO:61389013 Keywords : drug delivery systems * functionalization of polymers * photochemistry Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 4.265, year: 2016

  9. 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

  10. Intraspinal Delivery of Polyethylene Glycol-coated Gold Nanoparticles Promotes Functional Recovery After Spinal Cord Injury.

    Science.gov (United States)

    Papastefanaki, Florentia; Jakovcevski, Igor; Poulia, Nafsika; Djogo, Nevena; Schulz, Florian; Martinovic, Tamara; Ciric, Darko; Loers, Gabrielle; Vossmeyer, Tobias; Weller, Horst; Schachner, Melitta; Matsas, Rebecca

    2015-06-01

    Failure of the mammalian central nervous system (CNS) to regenerate effectively after injury leads to mostly irreversible functional impairment. Gold nanoparticles (AuNPs) are promising candidates for drug delivery in combination with tissue-compatible reagents, such as polyethylene glycol (PEG). PEG administration in CNS injury models has received interest for potential therapy, but toxicity and low bioavailability prevents clinical application. Here we show that intraspinal delivery of PEG-functionalized 40-nm-AuNPs at early stages after mouse spinal cord injury is beneficial for recovery. Positive outcome of hind limb motor function was accompanied by attenuated inflammatory response, enhanced motor neuron survival, and increased myelination of spared or regrown/sprouted axons. No adverse effects, such as body weight loss, ill health, or increased mortality were observed. We propose that PEG-AuNPs represent a favorable drug-delivery platform with therapeutic potential that could be further enhanced if PEG-AuNPs are used as carriers of regeneration-promoting molecules.

  11. Warehouse Plan for the Multi-Canister Overpacks (MC0) and Baskets

    International Nuclear Information System (INIS)

    MARTIN, M.K.

    2000-01-01

    The Multi-Canister Overpacks (MCO) will contain spent nuclear fuel (SNF) removed from the K East and West Basins. The SNF will be placed in fuel storage baskets that will be stacked inside the MCOs. Approximately 400 MCOs and 21 70 baskets will be fabricated for this purpose. These MCOs, loaded with SNF, will be placed in interim storage in the Canister Storage Building (CSB) located in the 200 Area of the Hanford Site. The MCOs consist of different components/sub-assemblies that will be manufactured by one or more vendors. All component/sub-assemblies will be shipped to the Hanford Site Central Stores Warehouse, 2355 Stevens Drive, Building 1163 in the 1100 Area, for inspection and storage until these components are required at the CSB and K Basins. The MCO fuel storage baskets will be manufactured in the MCO basket fabrication shop located in Building 328 of the Hanford Site 300 Area. The MCO baskets will be inspected at the fabrication shop before shipment to the Central Stores Warehouse for storage. The MCO components and baskets will be stored as received from the manufacturer with specified protective coatings, wrappings, and packaging intact to maintain mechanical integrity of the components and to prevent corrosion. The components and baskets will be shipped as needed from the warehouse to the CSB and K Basins. This warehouse plan includes the requirements for receipt of MCO components and baskets from the manufacturers and storage at the Hanford Site Central Stores Warehouse. Transportation of the MCO components and baskets from the warehouse, unwrapping, and assembly of the MCOs are the responsibility of SNF Operations and are not included in this plan

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

    International Nuclear Information System (INIS)

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

    2013-01-01

    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

  13. Pyramid-like basket cells in the granular layer of the dentate gyrus in the rat.

    Science.gov (United States)

    Seress, L

    1978-01-01

    Basket cells of the dentate gyrus were identified using Nissl (cresyl violet) staining. It has been found that the ratio between basket and granule cells is 1:150--210. Only a few glial cells, mainly astroglia, were found in the granular layer of the dentate gyrus. In accordance with earlier data it was found that the granule cells and glial cells originate mainly postnatally, but the basket cells, like the pyramidal cells of the hippocampus, originate prenatally. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:701192

  14. Local delivery of FTY720 in PCL membrane improves SCI functional recovery by reducing reactive astrogliosis.

    Science.gov (United States)

    Wang, Junjuan; Wang, Jiaqiu; Lu, Ping; Cai, Youzhi; Wang, Yafei; Hong, Lan; Ren, Hao; Heng, Boon Chin; Liu, Hua; Zhou, Jing; Ouyang, Hongwei

    2015-09-01

    FTY720 has recently been approved as an oral drug for treating relapsing forms of multiple sclerosis, and exerts its therapeutic effect by acting as an immunological inhibitor targeting the sphingosine-1-phosphate (S1P) receptor subtype (S1P1) of T cells. Recently studies demonstrated positive efficacy of this drug on spinal cord injury (SCI) in animal models after systemic administration, albeit with significant adverse side effects. We hereby hypothesize that localized delivery of FTY720 can promote SCI recovery by reducing pathological astrogliosis. The mechanistic functions of FTY720 were investigated in vitro and in vivo utilizing immunofluorescence, histology, MRI and behavioral analysis. The in vitro study showed that FTY720 can reduce astrocyte migration and proliferation activated by S1P. FTY720 can prolong internalization of S1P1 and exert antagonistic effects on S1P1. In vivo study of SCI animal models demonstrated that local delivery of FTY720 with polycaprolactone (PCL) membrane significantly decreased S1P1 expression and glial scarring compared with the control group. Furthermore, FTY720-treated groups exhibited less cavitation volume and neuron loss, which significantly improved recovery of motor function. These findings demonstrated that localized delivery of FTY720 can promote SCI recovery by targeting the S1P1 receptor of astrocytes, provide a new therapeutic strategy for SCI treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Variability in syringe components and its impact on functionality of delivery systems.

    Science.gov (United States)

    Rathore, Nitin; Pranay, Pratik; Eu, Bruce; Ji, Wenchang; Walls, Ed

    2011-01-01

    drug out of the syringe and into the site of administration. Complete understanding of the spring force, syringe barrel dimensions, needle size, and drug product properties is essential for robust device design. It is equally important to estimate the extent of variability that exists in these components and the resulting impact it could have on the performance of the device. In this work, we studied the impact of variability in syringe and device components on the delivery forces associated with syringe injection. More specifically, the effect of barrel size, needle size, autoinjector spring force, and frictional forces has been evaluated. An analytical model based on underlying physics is developed that can be used to predict the functionality of the autoinjector.

  16. Basket criticality design of a dual purpose cask for VVER 1000 spent fuel assemblies

    Energy Technology Data Exchange (ETDEWEB)

    Rezaeian, Mahdi [Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of); Kamali, Jamshid [Atomic Energy Organization of Iran (AEOI), Tehran (Iran, Islamic Republic of)

    2016-12-15

    Dual purpose cask technology is one of the most prominent options for interim storage of spent fuels following their removal from reactors. Criticality safety of the spent fuel assemblies are ensured by design of the basket within these casks. In this study, a set of criticality design calculations of a dual purpose cask for 12 VVER 1000 spent fuel assemblies of Bushehr nuclear power plant were carried out. The basket material of borated stainless steel with 0.5 to 2.5 wt% of boron and Boral (Al-B{sub 4}C) with 1.5 to 40 wt% of boron carbide, were investigated and the minimum required receptacle pitch of the basket was determined. Using the calculated receptacle pitch of the basket, the minimum required diameter of the cavity could be established.

  17. A food basket investigation during the autumn of 1994

    International Nuclear Information System (INIS)

    Moere, H.; Falk, R.; Svedjemark, G.A.; Becker, W.; Brugaard Konde, Aa.

    1995-10-01

    During the autumn of 1994 an investigation of foodstuffs has been accomplished to assess the average intake of 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 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 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 μSv. 6 refs, 10 tabs

  18. Separation of Electrolytic Reduction Product from Stainless Steel Wire Mesh Cathode Basket via Salt Draining and Reuse of the Cathode Basket

    OpenAIRE

    Choi, Eun-Young; Lee, Jeong; Heo, Dong Hyun; Hur, Jin-Mok

    2017-01-01

    We demonstrated that the metallic product obtained after electrolytic reduction (also called oxide reduction (OR)) can be simply separated from a stainless steel wire mesh cathode basket only by using a salt drain. First, the OR run of a simulated oxide fuel (0.6 kg/batch) was conducted in a molten Li2O–LiCl salt electrolyte at 650°C. The simulated oxide fuel of the porous cylindrical pellets was used as a cathode by loading a stainless steel wire mesh cathode basket. Platinum was employed as...

  19. Kinetics of lipid-nanoparticle-mediated intracellular mRNA delivery and function

    Science.gov (United States)

    Zhdanov, Vladimir P.

    2017-10-01

    mRNA delivery into cells forms the basis for one of the new and promising ways to treat various diseases. Among suitable carriers, lipid nanoparticles (LNPs) with a size of about 100 nm are now often employed. Despite high current interest in this area, the understanding of the basic details of LNP-mediated mRNA delivery and function is limited. To clarify the kinetics of mRNA release from LNPs, the author uses three generic models implying (i) exponential, (ii) diffusion-controlled, and (iii) detachment-controlled kinetic regimes, respectively. Despite the distinct differences in these kinetics, the associated transient kinetics of mRNA translation to the corresponding protein and its degradation are shown to be not too sensitive to the details of the mRNA delivery by LNPs (or other nanocarriers). In addition, the author illustrates how this protein may temporarily influence the expression of one gene or a few equivalent genes. The analysis includes positive or negative regulation of the gene transcription via the attachment of the protein without or with positive or negative feedback in the gene expression. Stable, bistable, and oscillatory schemes have been scrutinized in this context.

  20. Fibrin matrices with affinity-based delivery systems and neurotrophic factors promote functional nerve regeneration.

    Science.gov (United States)

    Wood, Matthew D; MacEwan, Matthew R; French, Alexander R; Moore, Amy M; Hunter, Daniel A; Mackinnon, Susan E; Moran, Daniel W; Borschel, Gregory H; Sakiyama-Elbert, Shelly E

    2010-08-15

    Glial-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) have both been shown to enhance peripheral nerve regeneration following injury and target different neuronal populations. The delivery of either growth factor at the site of injury may, therefore, result in quantitative differences in motor nerve regeneration and functional recovery. In this study we evaluated the effect of affinity-based delivery of GDNF or NGF from fibrin-filled nerve guidance conduits (NGCs) on motor nerve regeneration and functional recovery in a 13 mm rat sciatic nerve defect. Seven experimental groups were evaluated consisting of GDNF or NGF and the affinity-based delivery system (DS) within NGCs, control groups excluding the DS and/or growth factor, and nerve isografts. Groups with growth factor in the conduit demonstrated equivalent or superior performance in behavioral tests and relative muscle mass measurements compared to isografts at 12 weeks. Additionally, groups with GDNF demonstrated greater specific twitch and tetanic force production in extensor digitorum longus (EDL) muscle than the isograft control, while groups with NGF produced demonstrated similar force production compared to the isograft control. Assessment of motor axon regeneration by retrograde labeling further revealed that the number of ventral horn neurons regenerating across NGCs containing GDNF and NGF DS was similar to the isograft group and these counts were greater than the groups without growth factor. Overall, the GDNF DS group demonstrated superior functional recovery and equivalent motor nerve regeneration compared to the isograft control, suggesting it has potential as a treatment for motor nerve injury.

  1. Early effects of trimethyltin on the dentate gyrus basket cells: a morphological study

    Energy Technology Data Exchange (ETDEWEB)

    Chang, L.W.; Dyer, R.S.

    1985-01-01

    Electrophysiological evidence for reduction of recurrent inhibition in the dentate gyrus in animals exposed to trimethyltin (TMT) suggested alterations in the inhibitory neurons (basket cells) by TMT. The present study was designed to investigate the morphology of basket cells after TMT exposure. Long-Evans hooded rats were injected with TMT chloride in a dose of 6.0 mg/kg body weight (b.w.). Tissue samples from the dentate gyri were examined by both light and electron microscopy at 24 and 72 h after TMT exposure. Except for isolated basket cell damage at 72 h, no remarkable pathological changes were observed with light microscopy. Consistent with previous data, electron microscopy revealed that the basket cells of the dentate gyrus are large neurons situated just below the granule cell layer with characteristic large, infolded nuclei and intranuclear filamentous rods. Increased cytoplasmic density and degenerative changes of the Golgi complex were evident in the basket cells as early as 24 h after TMT exposure. By 72 h, neuronal vacuolation, accumulation of lysosomes, and occasional neuronal necrosis were observed. No significant pathological changes were found among the granule cells at this time. This report provides the first morphological evidence for early damage to the basket cells by TMT, which may account for the reduction of recurrent inhibition and hyperexcitability among the granule cells reported previously.

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

    International Nuclear Information System (INIS)

    Graves, C.E.

    1997-01-01

    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

  3. Carrier-free, functionalized pure drug nanorods as a novel cancer-targeted drug delivery platform

    International Nuclear Information System (INIS)

    Li Yanan; An Feifei; Zhang Xiaohong; Yang Yinlong; Liu Zhuang; Zhang Xiujuan

    2013-01-01

    A one-dimensional drug delivery system (1D DDS) is highly attractive since it has distinct advantages such as enhanced drug efficiency and better pharmacokinetics. However, drugs in 1D DDSs are all encapsulated in inert carriers, and problems such as low drug loading content and possible undesirable side effects caused by the carriers remain a serious challenge. In this paper, a novel, carrier-free, pure drug nanorod-based, tumor-targeted 1D DDS has been developed. Drugs are first prepared as nanorods and then surface functionalized to achieve excellent water dispersity and stability. The resulting drug nanorods show enhanced internalization rates mainly through energy-dependent endocytosis, with the shape-mediated nanorod (NR) diffusion process as a secondary pathway. The multiple endocytotic mechanisms lead to significantly improved drug efficiency of functionalized NRs with nearly ten times higher cytotoxicity than those of free molecules and unfunctionalized NRs. A targeted drug delivery system can be readily achieved through surface functionalization with targeting group linked amphipathic surfactant, which exhibits significantly enhanced drug efficacy and discriminates between cell lines with high selectivity. These results clearly show that this tumor-targeting DDS demonstrates high potential toward specific cancer cell lines. (paper)

  4. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Pulmonary dynamics and functional imaging with krypton-81m as related to generator delivery characteristics

    International Nuclear Information System (INIS)

    Kaplan, E.

    1985-01-01

    Krypton-81m supplied from a generator by continuous elution with air is used with a gamma-camera computer system to produce a sequence of images from multiple breaths, which reconstructed the time-activity images of the breathing human lung. Functional images are produced by subsequent derivation to show specific variables of the dynamic sequences. The dynamic, quantitative, and regional aspects of the respiratory cycle are thus made available in a single study. The need for the delivery of a constant ratio of /sub 81m/Kr to air is required to accurately produce these various studies

  6. 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. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Delivery Mode and the Transition of Pioneering Gut-Microbiota Structure, Composition and Predicted Metabolic Function

    Directory of Open Access Journals (Sweden)

    Noel T. Mueller

    2017-12-01

    Full Text Available Cesarean (C-section delivery, recently shown to cause excess weight gain in mice, perturbs human neonatal gut microbiota development due to the lack of natural mother-to-newborn transfer of microbes. Neonates excrete first the in-utero intestinal content (referred to as meconium hours after birth, followed by intestinal contents reflective of extra-uterine exposure (referred to as transition stool 2 to 3 days after birth. It is not clear when the effect of C-section on the neonatal gut microbiota emerges. We examined bacterial DNA in carefully-collected meconium, and the subsequent transitional stool, from 59 neonates [13 born by scheduled C-section and 46 born by vaginal delivery] in a private hospital in Brazil. Bacterial DNA was extracted, and the V4 region of the 16S rRNA gene was sequenced using the Illumina MiSeq (San Diego, CA, USA platform. We found evidence of bacterial DNA in the majority of meconium samples in our study. The bacterial DNA structure (i.e., beta diversity of meconium differed significantly from that of the transitional stool microbiota. There was a significant reduction in bacterial alpha diversity (e.g., number of observed bacterial species and change in bacterial composition (e.g., reduced Proteobacteria in the transition from meconium to stool. However, changes in predicted microbiota metabolic function from meconium to transitional stool were only observed in vaginally-delivered neonates. Within sample comparisons showed that delivery mode was significantly associated with bacterial structure, composition and predicted microbiota metabolic function in transitional-stool samples, but not in meconium samples. Specifically, compared to vaginally delivered neonates, the transitional stool of C-section delivered neonates had lower proportions of the genera Bacteroides, Parabacteroides and Clostridium. These differences led to C-section neonates having lower predicted abundance of microbial genes related to metabolism of

  8. Glucose Transporters at the Blood-Brain Barrier: Function, Regulation and Gateways for Drug Delivery.

    Science.gov (United States)

    Patching, Simon G

    2017-03-01

    Glucose transporters (GLUTs) at the blood-brain barrier maintain the continuous high glucose and energy demands of the brain. They also act as therapeutic targets and provide routes of entry for drug delivery to the brain and central nervous system for treatment of neurological and neurovascular conditions and brain tumours. This article first describes the distribution, function and regulation of glucose transporters at the blood-brain barrier, the major ones being the sodium-independent facilitative transporters GLUT1 and GLUT3. Other GLUTs and sodium-dependent transporters (SGLTs) have also been identified at lower levels and under various physiological conditions. It then considers the effects on glucose transporter expression and distribution of hypoglycemia and hyperglycemia associated with diabetes and oxygen/glucose deprivation associated with cerebral ischemia. A reduction in glucose transporters at the blood-brain barrier that occurs before the onset of the main pathophysiological changes and symptoms of Alzheimer's disease is a potential causative effect in the vascular hypothesis of the disease. Mutations in glucose transporters, notably those identified in GLUT1 deficiency syndrome, and some recreational drug compounds also alter the expression and/or activity of glucose transporters at the blood-brain barrier. Approaches for drug delivery across the blood-brain barrier include the pro-drug strategy whereby drug molecules are conjugated to glucose transporter substrates or encapsulated in nano-enabled delivery systems (e.g. liposomes, micelles, nanoparticles) that are functionalised to target glucose transporters. Finally, the continuous development of blood-brain barrier in vitro models is important for studying glucose transporter function, effects of disease conditions and interactions with drugs and xenobiotics.

  9. Thiol functionalized polymethacrylic acid-based hydrogel microparticles for oral insulin delivery.

    Science.gov (United States)

    Sajeesh, S; Vauthier, C; Gueutin, C; Ponchel, G; Sharma, Chandra P

    2010-08-01

    In the present study thiol functionalized polymethacrylic acid-polyethylene glycol-chitosan (PCP)-based hydrogel microparticles were utilized to develop an oral insulin delivery system. Thiol modification was achieved by grafting cysteine to the activated surface carboxyl groups of PCP hydrogels (Cys-PCP). Swelling and insulin loading/release experiments were conducted on these particles. The ability of these particles to inhibit protease enzymes was evaluated under in vitro experimental conditions. Insulin transport experiments were performed on Caco-2 cell monolayers and excised intestinal tissue with an Ussing chamber set-up. Finally, the efficacy of insulin-loaded particles in reducing the blood glucose level in streptozotocin-induced diabetic rats was investigated. Thiolated hydrogel microparticles showed less swelling and had a lower insulin encapsulation efficiency as compared with unmodified PCP particles. PCP and Cys-PCP microparticles were able to inhibit protease enzymes under in vitro conditions. Thiolation was an effective strategy to improve insulin absorption across Caco-2 cell monolayers, however, the effect was reduced in the experiments using excised rat intestinal tissue. Nevertheless, functionalized microparticles were more effective in eliciting a pharmacological response in diabetic animal, as compared with unmodified PCP microparticles. From these studies thiolation of hydrogel microparticles seems to be a promising approach to improve oral delivery of proteins/peptides. Copyright 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  10. 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.

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

    International Nuclear Information System (INIS)

    Feng, Guo-Hua; Hou, Sheng-You

    2015-01-01

    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. (paper)

  12. 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

  13. Semantic Web Service Delivery in Healthcare Based on Functional and Non-Functional Properties.

    Science.gov (United States)

    Schweitzer, Marco; Gorfer, Thilo; Hörbst, Alexander

    2017-01-01

    In the past decades, a lot of endeavor has been made on the trans-institutional exchange of healthcare data through electronic health records (EHR) in order to obtain a lifelong, shared accessible health record of a patient. Besides basic information exchange, there is a growing need for Information and Communication Technology (ICT) to support the use of the collected health data in an individual, case-specific workflow-based manner. This paper presents the results on how workflows can be used to process data from electronic health records, following a semantic web service approach that enables automatic discovery, composition and invocation of suitable web services. Based on this solution, the user (physician) can define its needs from a domain-specific perspective, whereas the ICT-system fulfills those needs with modular web services. By involving also non-functional properties for the service selection, this approach is even more suitable for the dynamic medical domain.

  14. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. A33 antibody-functionalized exosomes for targeted delivery of doxorubicin against colorectal Cancer.

    Science.gov (United States)

    Li, Yan; Gao, Yuan; Gong, Chunai; Wang, Zhuo; Xia, Qingming; Gu, Fenfen; Hu, Chuling; Zhang, Lijuan; Guo, Huiling; Gao, Shen

    2018-06-20

    Exosomes have emerged as a promising drug carrier with low immunogenicity, high biocompatibility and delivery efficiency. Here in, we isolated exosomes from A33-positive LIM1215 cells (A33-Exo) and loaded them with doxorubicin (Dox). Furthermore, we coated surface-carboxyl superparamagnetic iron oxide nanoparticles (US) with A33 antibodies (A33Ab-US), expecting that these A33 antibodies on the surface of the nanoparticles could bind to A33-positive exosomes and form a complex (A33Ab-US-Exo/Dox) to target A33-positive colon cancer cells. The results showed that A33Ab-US-Exo/Dox had good binding affinity and antiproliferative effect in LIM1215 cells, as shown by increased uptake of the complex. In vivo study showed that A33Ab-US-Exo/Dox had an excellent tumor targeting ability, and was able to inhibit tumor growth and prolong the survival of the mice with reduced cardiotoxicity. In summary, exosomes functionalized by targeting ligands through coating with high-density antibodies may prove to be a novel delivery system for targeted drugs against human cancers. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. 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.

  17. Synthesis and evaluation of functional alginate hydrogels based on click chemistry for drug delivery applications.

    Science.gov (United States)

    García-Astrain, Clara; Avérous, Luc

    2018-06-15

    Environment-sensitive alginate-based hydrogels for drug delivery applications are receiving increasing attention. However, most work in this field involves traditional cross-linking strategies which led to hydrogels with poor long-term stability. Herein, a series of chemically cross-linked alginate hydrogels was synthesized via click chemistry using Diels-Alder reaction by reacting furan-modified alginate and bifunctional cross-linkers. Alginate was successfully functionalized with furfurylamine. Then, 3D architectures were synthesized with water-soluble bismaleimides. Different substitution degrees were achieved in order to study the effect of alginate modification and the cross-linking extent over the behaviour of the hydrogels. The ensuing hydrogels were analysed in terms of microstructure, swelling, structure modification and rheological behaviour. The materials response to external stimuli such as pH was also investigated, revealing a pulsatile behaviour in a large pH range (1-13) and a clear pH-dependent swelling. Finally, vanillin release studies were conducted to demonstrate the potential of these biobased materials for drug delivery applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Assessment of Beta-Cell Function During Pregnancy and after Delivery

    Directory of Open Access Journals (Sweden)

    Genova M. P.

    2014-06-01

    Full Text Available The aim of the present study was to assess β-cell function using homeostasis model (HOMA-B and disposition index (DI in pregnant women with/without gestational diabetes, and after delivery. A total of 102 pregnant women between 24-28 gestational weeks (53 with gestational diabetes mellitus (GDM and 49 with normal glucose tolerance (NGT and 22 GDM postpartum women (8-12 weeks after delivery were included in the study. All postpartum women had a history of GDM. HOMA indexes (insulin resistance - HOMA-IR and HOMA-B for assessing β-cell function were calculated from fasting glucose and insulin concentrations. To estimate insulin secretion independent of insulin sensitivity, DI was calculated using glucose and insulin levels at 0 and 60 min during the course of a 2 h 75g oral glucose tolerance test (OGTT. In GDM pregnant women HOMA-B was significantly lower compared to NGT women (p = 0.017, but there was no significant difference compared to women after birth (NS. There was difference between NGT and postpartum women (p < 0.05. DI was significantly lower for GDM pregnant women in comparison to NGT and postpartum women (p < 0.0001; p = 0.011, between NGT and women after birth (p < 0.04. In our study, comparison of НОМА-В in NGT and GDM pregnant women demonstrated that the OR of developing GDM was 0.989 (95% CI, 0.980-0.998, P = 0.013, and comparison of DI in healthy pregnant and GDM showed that the OR of developing GDM was 0.967 (95% CI, 0.947-0.988, P = 0.002. Therefore, HOMA-B and DI appear to be protective factors in the risk of developing GDM. According to our results, assessment of β-cell function, using HOMA-B and DI, showed that they are lower in GDM than NGT group and postpartum women. It is important to note that HOMA-B did not show significant difference between GDM pregnant and women after delivery with a history for GDM. We assume that pregnant women with GDM have a pancreatic β-cell defect that remains after birth. These women

  19. Putting all your eggs in one basket: life-history strategies, bet hedging, and diversification.

    Science.gov (United States)

    White, Andrew Edward; Li, Yexin Jessica; Griskevicius, Vladas; Neuberg, Steven L; Kenrick, Douglas T

    2013-05-01

    Diversification of resources is a strategy found everywhere from the level of microorganisms to that of giant Wall Street investment firms. We examine the functional nature of diversification using life-history theory-a framework for understanding how organisms navigate resource-allocation trade-offs. This framework suggests that diversification may be adaptive or maladaptive depending on one's life-history strategy and that these differences should be observed under conditions of threat. In three studies, we found that cues of mortality threat interact with one index of life-history strategy, childhood socioeconomic status (SES), to affect diversification. Among those from low-SES backgrounds, mortality threat increased preferences for diversification. However, among those from high-SES backgrounds, mortality threat had the opposite effect, inclining people to put all their eggs in one basket. The same interaction pattern emerged with a potential biomarker of life-history strategy, oxidative stress. These findings highlight when, and for whom, different diversification strategies can be advantageous.

  20. Mud-plastered granary-baskets at a Celtic Oppidum near Čarnok (Vojvodina, Serbia

    Directory of Open Access Journals (Sweden)

    Medović Aleksandar

    2011-01-01

    Full Text Available In the Celtic Oppidum near Čarnok (Bačka, Vojvodina, Serbia remains of four mud-plastered granarybaskets were discovered. They are all dated to the period Gomolava VI-B (first half of the 1st century B.C.. Hulled barley and broomcorn millet were stored in the granary-baskets. The mesh of the granary-baskets was composed of young branches of oak tree (Quercus, common English elm tree (Ulmus cf. campestris L., poplar / willow (Populus / Salix, purgin buckthorn (Rhamnus cf. cathartica L., wayfaring tree (Viburnum cf. lantana L., spindle tree (Euonymus cf. europaeus L., barberry (Berberis vulgaris L. and a Pomoidae-tree. At least four different tree taxa were used for basket making. Construction of two-thousand-year old mud-plastered granary-baskets from the Pannonian plain is very similar to that of traditional granaries in some present-day villages in Africa. Additionally, one non-plastered basket was also discovered at Oppidum. It was build out of maple (Acer, barberry, buckthorn (Rhamnus and branches of a pomaceous fruits tree (Pomoidae. .

  1. Ballistic delivery of dyes for structural and functional studies of the nervous system

    Science.gov (United States)

    Gan, Wen-Biao; Grutzendler, Jaime; Wong, Rachel O.; Lichtman, Jeff W.

    2010-01-01

    This chapter describes a detail protocol for rapid labeling of cells in a variety of preparations by means of particle-mediated ballistic (gene gun) delivery of fluorescent dyes. This method has been used for rapid labeling of cells with either lipid or water-soluble dyes in a variety of preparations. In particular, carbocyanine lipophilic dyes such as DiI have been used to obtain Golgi-like labeling of neurons and glia in fixed and live cell cultures, brain slices, as well as fixed post-mortem human brain. Water-soluble calcium indicators such as calcium green-1 dextran have been used to image calcium dynamics in living brain slices and retinal explants. This ballistic labeling technique is thus useful for studying the structure and function of neurons and glia in both living and fixed specimens. PMID:20147144

  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. Functionalization of 3D scaffolds with protein-releasing biomaterials for intracellular delivery.

    Science.gov (United States)

    Seras-Franzoso, Joaquin; Steurer, Christoph; Roldán, Mònica; Vendrell, Meritxell; Vidaurre-Agut, Carla; Tarruella, Anna; Saldaña, Laura; Vilaboa, Nuria; Parera, Marc; Elizondo, Elisa; Ratera, Imma; Ventosa, Nora; Veciana, Jaume; Campillo-Fernández, Alberto J; García-Fruitós, Elena; Vázquez, Esther; Villaverde, Antonio

    2013-10-10

    Appropriate combinations of mechanical and biological stimuli are required to promote proper colonization of substrate materials in regenerative medicine. In this context, 3D scaffolds formed by compatible and biodegradable materials are under continuous development in an attempt to mimic the extracellular environment of mammalian cells. We have here explored how novel 3D porous scaffolds constructed by polylactic acid, polycaprolactone or chitosan can be decorated with bacterial inclusion bodies, submicron protein particles formed by releasable functional proteins. A simple dipping-based decoration method tested here specifically favors the penetration of the functional particles deeper than 300μm from the materials' surface. The functionalized surfaces support the intracellular delivery of biologically active proteins to up to more than 80% of the colonizing cells, a process that is slightly influenced by the chemical nature of the scaffold. The combination of 3D soft scaffolds and protein-based sustained release systems (Bioscaffolds) offers promise in the fabrication of bio-inspired hybrid matrices for multifactorial control of cell proliferation in tissue engineering under complex architectonic setting-ups. © 2013.

  4. 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...... in each of the resulting five baskets was increased through limiting the relative share of individual foods. 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. Use of linear programming...

  5. 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

    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. 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...... in each of the resulting five baskets was increased through limiting the relative share of individual foods. 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...

  6. 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

  7. 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

  8. Functional nutrients in infants born by vaginal delivery or Cesarean section

    Directory of Open Access Journals (Sweden)

    Gianluca Lista

    2017-12-01

    Full Text Available The development of a proper neonatal microbiota is of great importance, especially for the effects that dysbiosis has in acute and chronic diseases’ onset. The microbiota, particularly the intestinal one, plays a crucial role in maintaining the health of the host, preventing colonization by pathogenic bacteria and significantly influencing the development and maturation of a normal gastrointestinal mucosal immunity. Several factors may interfere with the physiological development of microbiota, such as diseases during pregnancy, type of delivery, maternal nutrition, type of neonatal feeding, use of antibiotics, exposition to hospital environment (e.g., neonatal intensive care unit and genetic factors. Thanks to a proper maternal and neonatal supplementation with specific functional nutrients, it is now possible to correct dysbiosis, thus reducing the risks for the newborn’s health. In this review of the literature, we give an overview of the studies highlighting the composition of the maternal, fetal and neonatal microbiota, the factors potentially responsible for dysbiosis and the use of functional nutrients to prevent diseases’ onset.

  9. Recent developments in the nanostructured materials functionalized with ruthenium complexes for targeted drug delivery to tumors

    Directory of Open Access Journals (Sweden)

    Thangavel P

    2017-04-01

    Full Text Available Prakash Thangavel,1 Buddolla Viswanath,1 Sanghyo Kim1,2 1Department of Bionanotechnology, Gachon University, Bokjeong-Dong, Sujeong-Gu, Seongnam-Si, Gyeonggi-Do, 2Graduate Gachon Medical Research Institute, Gil Medical Center, Incheon, Republic of Korea Abstract: In recent years, the field of metal-based drugs has been dominated by other existing precious metal drugs, and many researchers have focused their attention on the synthesis of various ruthenium (Ru complexes due to their potential medical and pharmaceutical applications. The beneficial properties of Ru, which make it a highly promising therapeutic agent, include its variable oxidation states, low toxicity, high selectivity for diseased cells, ligand exchange properties, and the ability to mimic iron binding to biomolecules. In addition, Ru complexes have favorable adsorption properties, along with excellent photochemical and photophysical properties, which make them promising tools for photodynamic therapy. At present, nanostructured materials functionalized with Ru complexes have become an efficient way to administer Ru-based anticancer drugs for cancer treatment. In this review, the recent developments in the nanostructured materials functionalized with Ru complexes for targeted drug delivery to tumors are discussed. In addition, information on “traditional” (ie, non-nanostructured Ru-based cancer therapies is included in a precise manner. Keywords: metallodrugs, nanotechnology, cancer treatment, cell apoptosis, DNA damage, toxicity

  10. 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.

  11. A Universal Aptamer Chimera for the Delivery of Functional microRNA-126.

    Science.gov (United States)

    Rohde, Jan-H; Weigand, Julia E; Suess, Beatrix; Dimmeler, Stefanie

    2015-06-01

    microRNAs (miRs) regulate vascular diseases such as atherosclerosis and cancer. miR-126 is important for endothelial cell signaling and promotes angiogenesis, protects against atherosclerosis, and reduces breast cancer cell growth and metastasis. The overexpression of miR-126, therefore, may be an attractive therapeutic strategy for the treatment of cardiovascular disease or cancer. Here we report a novel strategy to deliver miR-126 to endothelial and breast cancer cells. We tested three different strategies to deliver miR-126 by linking the miR to an aptamer for the ubiquitously expressed transferrin receptor (transferrin receptor aptamer, TRA). Linking the precursor of miR-126 (pre-miR-126) to the TRA by annealing of a complementary stick led to efficient uptake and processing of miR-126, resulting in the delivery of 1.6×10(6)±0.3×10(6) copies miR-126-3p per ng RNA in human endothelial cells and 7.4×10(5)±2×10(5) copies miR-126-3p per ng in MCF7 breast cancer cells. The functionality of the active TRA-miR-126 chimera was further demonstrated by showing that the chimera represses the known miR-126 target VCAM-1 and improved endothelial cell sprouting in a spheroid assay. Moreover, the TRA-miR-126 chimera reduced proliferation and paracrine endothelial cell recruitment of breast cancer cells to a similar extent as miR-126-3p mimics introduced by conventional liposome-based transfection. Together, this data demonstrates that pre-miR-126 can be delivered by a non-specific aptamer to exert biological functions in two different cell models. The use of the TRA-miR-126 chimera or the combination of the delivery strategy with other endothelial or tumor specific aptamers may provide an interesting therapeutic option to treat vascular disease or cancers.

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

    NARCIS (Netherlands)

    Linden, van der E.; Ubbink, J.; Duchateau, G.

    2010-01-01

    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

  13. Pandora's picnic basket: the potential and hazards of genetically modified foods

    National Research Council Canada - National Science Library

    McHughen, Alan

    2000-01-01

    ... technologies in the them from with breeding whether examines and Picnic Basket subject, from potentially dangerous products. either use or about the regulatory processes established to protect us genetically other regulators modified "natural" the production. explains, in dear language, the technologies around the food, methods question of world of Researc...

  14. 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

    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 ...

  15. Many-core architectures boost the pricing of basket options on adaptive sparse grids

    DEFF Research Database (Denmark)

    Heinecke, Alexander; Jepsen, Jacob; Bungartz, Hans Joachim

    2013-01-01

    of the operator's parallelism, we are able to achieve nearly perfect strong scaling for the Black-Scholes solver. Our results show that typical problem sizes (5 dimensional basket options), require at least 4 NVIDIA K20X Kepler GPUs (inside a Cray XK7) in order to be faster than the Up-Down scheme running on 16...

  16. Handling of multiassembly sealed baskets between reactor storage and a remote handling facility

    International Nuclear Information System (INIS)

    Massey, J.V.; Kessler, J.H.; McSherry, A.J.

    1989-06-01

    The storage of multiple fuel assemblies in sealed (welded) dry storage baskets is gaining increasing use to augment at-reactor fuel storage capacity. Since this increasing use will place a significant number of such baskets on reactor sites, some initial downstream planning for their future handling scenarios for retrieving multi-assembly sealed baskets (MSBs) from onsite storage and transferring and shipping the fuel (and/or the baskets) to a federally operated remote handling facility (RHF). Numerous options or at-reactor and away-from-reactor handling were investigated. Materials handling flowsheets were developed along with conceptual designs for the equipment and tools required to handle and open the MSBs. The handling options were evaluated and compared to a reference case, fuel handling sequence (i.e., fuel assemblies are taken from the fuel pool, shipped to a receiving and handling facility and placed into interim storage). The main parameters analyzed are throughout, radiation dose burden and cost. In addition to evaluating the handling of MSBs, this work also evaluated handling consolidated fuel canisters (CFCs). In summary, the handling of MSBs and CFCs in the store, ship and bury fuel cycle was found to be feasible and, under some conditions, to offer significant benefits in terms of throughput, cost and safety. 14 refs., 20 figs., 24 tabs

  17. Kinetic enantioselectivity of a protonated bis(diamido)-bridged basket resorcin[4]arene towards alanine peptides.

    Science.gov (United States)

    Fraschetti, C; Montagna, M; Crestoni, M E; Calcaterra, A; Aiello, F; Santi, L; Filippi, A

    2017-02-01

    Efficient enantiodiscrimination of some alanine-containing di- and tri-peptides by using chiral protonated bis(diamido)-bridged basket resorcin[4]arenes depends on several factors, including the basicity of the amino acid residues at the C- and N-termini of the peptide.

  18. Re-Learning the Traditional Art of Inuit Grass Basket-Making

    Science.gov (United States)

    Cowan, Cindy

    2005-01-01

    This paper describes an adult learning project to revitalise the traditional Inuit art of weaving grass baskets. The participants involved in the project, all older women who speak an indigenous first language (Inuktitut) and who have limited experience with formal education, largely on their own initiative, undertook the process of successfully…

  19. Functionalized Carbon Nano-scale Drug Delivery Systems From Biowaste Sago Bark For Cancer Cell Imaging.

    Science.gov (United States)

    Abdul Manaf, Shoriya Aruni; Hegde, Gurumurthy; Mandal, Uttam Kumar; Wui, Tin Wong; Roy, Partha

    2017-01-01

    Nano-scale carbon systems are emerging alternatives in drug delivery and bioimaging applications of which they gradually replace the quantum dots characterized by toxic heavy metal content in the latter application. The work intended to use carbon nanospheres synthesized from biowaste Sago bark for cancer cell imaging applications. This study synthesised carbon nanospheres from biowaste Sago bark using a catalyst-free pyrolysis technique. The nanospheres were functionalized with fluorescent dye coumarin-6 for cell imaging. Fluorescent nanosytems were characterized by field emission scanning electron microscopy-energy dispersive X ray, photon correlation spectroscopy and fourier transform infrared spectroscopy techniques. The average size of carbon nanospheres ranged between 30 and 40 nm with zeta potential of -26.8 ± 1.87 mV. The percentage viability of cancer cells on exposure to nanospheres varied from 91- 89 % for N2a cells and 90-85 % for A-375 cells respectively. Speedy uptake of the fluorescent nanospheres in both N2a and A-375 cells was observed within two hours of exposure. Novel fluorescent carbon nanosystem design following waste-to-wealth approach exhibited promising potential in cancer cell imaging applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Polyglycerol-functionalized nanodiamond as a platform for gene delivery: Derivatization, characterization, and hybridization with DNA

    Directory of Open Access Journals (Sweden)

    Li Zhao

    2014-03-01

    Full Text Available A gene vector consisting of nanodiamond, polyglycerol, and basic polypeptide (ND-PG-BPP has been designed, synthesized, and characterized. The ND-PG-BPP was synthesized by PG functionalization of ND through ring-opening polymerization of glycidol on the ND surface, multistep organic transformations (–OH → –OTs (tosylate → –N3 in the PG layer, and click conjugation of the basic polypeptides (Arg8, Lys8 or His8 terminated with propargyl glycine. The ND-PG-BPP exhibited good dispersibility in water (>1.0 mg/mL and positive zeta potential ranging from +14.2 mV to +44.1 mV at neutral pH in Milli-Q water. It was confirmed by gel retardation assay that ND-PG-Arg8 and ND-PG-Lys8 with higher zeta potential hybridized with plasmid DNA (pDNA through electrostatic attraction, making them promising as nonviral vectors for gene delivery.

  1. 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.

  2. Polyglycerol-functionalized nanodiamond as a platform for gene delivery: Derivatization, characterization, and hybridization with DNA

    Science.gov (United States)

    Zhao, Li; Nakae, Yuki; Qin, Hongmei; Ito, Tadamasa; Kimura, Takahide; Kojima, Hideto; Chan, Lawrence

    2014-01-01

    Summary A gene vector consisting of nanodiamond, polyglycerol, and basic polypeptide (ND-PG-BPP) has been designed, synthesized, and characterized. The ND-PG-BPP was synthesized by PG functionalization of ND through ring-opening polymerization of glycidol on the ND surface, multistep organic transformations (–OH → –OTs (tosylate) → –N3) in the PG layer, and click conjugation of the basic polypeptides (Arg8, Lys8 or His8) terminated with propargyl glycine. The ND-PG-BPP exhibited good dispersibility in water (>1.0 mg/mL) and positive zeta potential ranging from +14.2 mV to +44.1 mV at neutral pH in Milli-Q water. It was confirmed by gel retardation assay that ND-PG-Arg8 and ND-PG-Lys8 with higher zeta potential hybridized with plasmid DNA (pDNA) through electrostatic attraction, making them promising as nonviral vectors for gene delivery. PMID:24778723

  3. Surface-functionalized polymethacrylic acid based hydrogel microparticles for oral drug delivery.

    Science.gov (United States)

    Sajeesh, S; Bouchemal, K; Sharma, C P; Vauthier, C

    2010-02-01

    Aim of the present work was to develop novel thiol-functionalized hydrogel microparticles based on poly(methacrylic acid)-chitosan-poly(ethylene glycol) (PCP) for oral drug delivery applications. PCP microparticles were prepared by a modified ionic gelation process in aqueous medium. Thiol modification of surface carboxylic acid groups of PCP micro particles was carried out by coupling l-cysteine with a water-soluble carbodiimide. Ellman's method was adopted to quantify the sulfhydryl groups, and dynamic light-scattering technique was used to measure the average particle size. Cytotoxicity of the modified particles was evaluated on Caco 2 cells by MTT assay. Effect of thiol modification on permeability of paracellular marker fluorescence dextran (FD4) was evaluated on Caco 2 cell monolayers and freshly excised rat intestinal tissue with an Ussing chamber set-up. Mucoadhesion experiments were carried out by an ex vivo bioadhesion method with excised rat intestinal tissue. The average size of the PCP microparticles was increased after thiol modification. Thiolated microparticles significantly improved the paracellular permeability of FD4 across Caco 2 cell monolayers, with no sign of toxicity. However, the efficacy of thiolated system remained low when permeation experiments were carried out across excised intestinal membrane. This was attributed to the high adhesion of the thiolated particles on the gut mucosa. Nevertheless, it can be concluded that surface thiolation is an interesting strategy to improve paracellular permeability of hydrophilic macromolecules. Copyright (c) 2009 Elsevier B.V. All rights reserved.

  4. 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

    2017-10-01

    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.

  5. An integrated fiber and stone basket device for use in Thulium fiber laser lithotripsy

    Science.gov (United States)

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

    2014-03-01

    The Thulium fiber laser (TFL) is being explored as an alternative laser lithotripter to the Holmium:YAG laser. The TFL's superior near-single mode beam profile enables higher power transmission through smaller fibers with reduced proximal fiber tip damage. Recent studies have also reported that attaching hollow steel tubing to the distal fiber tip decreases fiber degradation and burn-back without compromising stone ablation rates. However, significant stone retropulsion was observed, which increased with pulse rate. In this study, the hollow steel tip fiber design was integrated with a stone basket to minimize stone retropulsion during ablation. A device was constructed consisting of a 100-μm-core, 140-μm-OD silica fiber outfitted with 5-mm-long stainless steel tubing at the distal tip, and integrated with a 1.3-Fr (0.433-mm-OD) disposable nitinol wire basket, to form an overall 1.9-Fr (0.633-mm- OD) integrated device. This compact design may provide several potential advantages including increased flexibility, higher saline irrigation rates through the ureteroscope working channel, and reduced fiber tip degradation compared to separate fiber and stone basket manipulation. TFL pulse energy of 31.5 mJ with 500 μs pulse duration and pulse rate of 500 Hz was delivered through the integrated fiber/basket device in contact with human uric acid stones, ex vivo. TFL stone ablation rates measured 1.5 +/- 0.2 mg/s, comparable to 1.7 +/- 0.3 mg/s (P > 0.05) using standard bare fiber tips separately with a stone basket. With further development, this device may be useful for minimizing stone retropulsion, thus enabling more efficient TFL lithotripsy at higher pulse rates.

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

    Science.gov (United States)

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

    2016-01-01

    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. 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. 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. Use of linear programming facilitates the generation of low-cost food baskets that are nutritionally adequate, health promoting, and culturally acceptable.

  7. 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.

  8. 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.

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

    NARCIS (Netherlands)

    Chen, Wei; Meng, Fenghua; Cheng, R.; Deng, C.; Feijen, Jan; Zhong, Zhiyuan

    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

  10. Chloroplast-derived vaccine antigens and biopharmaceuticals: protocols for expression, purification, or oral delivery and functional evaluation.

    Science.gov (United States)

    Singh, N Dolendro; Ding, Yi; Daniell, Henry

    2009-01-01

    Many vaccine antigens and biopharmaceutical proteins have been expressed at high levels via the chloroplast genome and their functionality has been evaluated using in vitro assays in cell cultures (i.e., macrophage lysis assay, inhibition of vesicular stomatitis virus-induced cytopathicity in baby hamster kidney cells, or inhibition of human HIV infection in TZM-BL cells) as well as protection after challenge with bacterial or viral pathogens or antitumor assays or delay the onset of insulitis in suitable animal models. Production of therapeutic proteins in chloroplasts eliminates the expensive fermentation technology. Moreover, oral delivery of chloroplast-derived therapeutic proteins eliminates expensive purification steps, cold storage, cold transportation, and delivery via sterile needles, thereby further decreasing their cost. In this chapter, we describe detailed protocols for chloroplast transformation including the construction of chloroplast transformation vectors, delivery of DNA into plant cells using particle bombardment, selection and regeneration of transformants by tissue culture, confirmation of transgene integration into the chloroplast genome and homoplasmy, evaluation of foreign gene expression, purification of foreign protein, or oral delivery via bioencapsulation, functional evaluation using in vitro and in vivo assays, and evaluation of immunity after challenge with pathogens in suitable animal models.

  11. Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis.

    Science.gov (United States)

    Xiao, Bo; Xu, Zhigang; Viennois, Emilie; Zhang, Yuchen; Zhang, Zhan; Zhang, Mingzhen; Han, Moon Kwon; Kang, Yuejun; Merlin, Didier

    2017-07-05

    Overcoming adverse effects and selectively delivering drug to target cells are two major challenges in the treatment of ulcerative colitis (UC). Lysine-proline-valine (KPV), a naturally occurring tripeptide, has been shown to attenuate the inflammatory responses of colonic cells. Here, we loaded KPV into hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs). The resultant HA-KPV-NPs had a desirable particle size (∼272.3 nm) and a slightly negative zeta potential (∼-5.3 mV). These NPs successfully mediated the targeted delivery of KPV to key UC therapy-related cells (colonic epithelial cells and macrophages). In addition, these KPV-loaded NPs appear to be nontoxic and biocompatible with intestinal cells. Intriguingly, we found that HA-KPV-NPs exert combined effects against UC by both accelerating mucosal healing and alleviating inflammation. Oral administration of HA-KPV-NPs encapsulated in a hydrogel (chitosan/alginate) exhibited a much stronger capacity to prevent mucosa damage and downregulate TNF-α, thus they showed a much better therapeutic efficacy against UC in a mouse model, compared with a KPV-NP/hydrogel system. These results collectively demonstrate that our HA-KPV-NP/hydrogel system has the capacity to release HA-KPV-NPs in the colonic lumen and that these NPs subsequently penetrate into colitis tissues and enable KPV to be internalized into target cells, thereby alleviating UC. Copyright © 2016 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  12. 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

    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 hypoglycemic effect. The relative pharmacological bioavailability following oral administration of L/C NPs was 6.01%. Conclusion 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. PMID:26966360

  13. Delivery of Functionality in Complex Food Systems: Physically inspired approaches from nanoscale to microscale, Paris 14 to 17 July, 2015.

    Science.gov (United States)

    Relkin, Perla

    2016-10-01

    The 6th international symposium in the series "Delivery of Functionality in Complex Food Systems: Physically inspired approaches from nanoscale to microscal" was held in the heart of Paris from 14 to 17 July, 2015. It brought together PhD students, academic food researchers and industrials from diversified food sectors. The scientific sessions of this meeting were constructed around important topics dealing with 1) Engineering of tailored-made structures in bio-based systems; 2) Complexity and emergent phenomena in the integrative food science; 3) Investigation of nano and microstructures in the bulk and at interfaces; 4) Modeling approaches from bio-molecules and matrix structures to functionality; 5) Tuning binding & release of bioactive compounds by matrix modulation, and finally; 6) Tuning the delivery of functionality to the body. These topics were selected to cover different scientific fields and to show the contribution of food physical structures to development of health- and plaisure-supporting food functions. The oral communications were all introduced by key note speakers and they were all illustrated by outstanding high quality short communications. One of the most original features of this symposium was the increasing number of presentations using multiscale and modeling approaches illustrating the concept of complexity and emergent phenomena integrative food science. These highlighted the importance of studies on interactions between structure properties of engineered delivery systems and human body (sensory properties, digestion, release, bioavailability and bioaccessibility). Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. 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.

  15. Development of boronated aluminum alloy for basket of cask for nuclear spent fuel

    International Nuclear Information System (INIS)

    Sakaguchi, Y.; Saida, T.; Matsuoka, T.; Kuri, S.; Ohsono, K.; Hode, S.

    2001-01-01

    Since 1980's Mitsubishi Heavy Industries, Ltd. (MHI) has been contributing to develop metal cask technologies for utilities and competent authorities in Japan, and have established transport and storage cask design ''MSF series'' which realizes higher payload and reliability for long term storage. MSF series transport and storage cask uses new-developed boronated aluminum as basket material. This boronated aluminum has been developed to improve characteristics of material. To achieve this object, powder metallurgy method has been adopted for manufacturing boronated material. It is well known that this method provides excellent characteristics for the material and this boronated aluminum alloy has obtained excellent both mechanical and neutron absorbing characteristics. In addition, in order to maintain material properties for long-term use this boronated material is not strengthened by aging treatment. This paper summarizes an outline of the boronated aluminum alloy for basket assemblies by powder metallurgy. (author)

  16. A Nutritional Analysis of the Food Basket in BIH: A Linear Programming Approach

    Directory of Open Access Journals (Sweden)

    Arnaut-Berilo Almira

    2017-04-01

    Full Text Available This paper presents linear and goal programming optimization models for determining and analyzing the food basket in Bosnia and Herzegovina (BiH in terms of adequate nutritional needs according to World Health Organization (WHO standards and World Bank (WB recommendations. A linear programming (LP model and goal linear programming model (GLP are adequate since price and nutrient contents are linearly related to food weight. The LP model provides information about the minimal value and the structure of the food basket for an average person in BiH based on nutrient needs. GLP models are designed to give us information on minimal deviations from nutrient needs if the budget is fixed. Based on these results, poverty analysis can be performed. The data used for the models consisted of 158 food items from the general consumption of the population of BiH according to COICOP classifications, with average prices in 2015 for these products.

  17. The impact of using reduced capacity baskets on cask fleet size and cask fleet mix

    International Nuclear Information System (INIS)

    Joy, D.S.; Johnson, P.E.; Andress, D.A.

    1993-01-01

    The Civilian Radioactive Waste Management System transportation system will encounter a wide range of spent fuel characteristics. Since the Initiative I casks are being designed to transport 10-year-old fuel with a burnup of 35,000 MWd/MTU, there is a good likelihood that a number of the cask shipments will need to be derated in order to meet the Nuclear Regulatory Commission radiation guidelines. This report discusses the impact of cask derating by using reduced-capacity baskets. Cask derating, while enhancing the ability to move spent fuel with a wider range of age and burnup characteristics, increases the number of shipments; the amount of equipment (cask bodies, baskets, etc.); and the number of visits to both shipping and receiving sites required to transport a specific amount of spent fuel

  18. The impact of using reduced-capacity baskets on cask fleet size and cask fleet mix

    International Nuclear Information System (INIS)

    Joy, D.S.; Johnson, P.E.; Andress, D.A.

    1993-01-01

    The Civilian Radioactive Waste Management System transportation system will encounter a wide range of spent fuel characteristics. Since the Initiative I casks are being designed to transport 10-year-old fuel with a burnup of 35,000 MWd/MTU, there is a good likelihood that a number of the cask shipments will need to be derated in order to meet the Nuclear Regulatory Commission radiation guidelines. This report discusses the impact of cask derating by using reduced-capacity baskets. Cask derating, while enhancing the ability to move spent fuel with a wider range of age and burnup characteristics, increases the number of shipments; the amount of equipment (cask bodies, baskets, etc.); and the number of visits to both shipping and receiving sites required to transport a specific amount of spent fuel

  19. K Basins floor sludge retrieval system knockout pot basket fuel burn accident

    International Nuclear Information System (INIS)

    HUNT, J.W.

    1998-01-01

    The K Basins Sludge Retrieval System Preliminary Hazard Analysis Report (HNF-2676) identified and categorized a series of potential accidents associated with K Basins Sludge Retrieval System design and operation. The fuel burn accident was of concern with respect to the potential release of contamination resulting from a runaway chemical reaction of the uranium fuel in a knockout pot basket suspended in the air. The unmitigated radiological dose to an offsite receptor from this fuel burn accident is calculated to be much less than the offsite risk evaluation guidelines for anticipated events. However, because of potential radiation exposure to the facility worker, this accident is precluded with a safety significant lifting device that will prevent the monorail hoist from lifting the knockout pot basket out of the K Basin water pool

  20. An experiment framework to identify community functional components driving ecosystem processes and services delivery.

    NARCIS (Netherlands)

    Dias, A.; Berg, M.P.; de Bello, F.; van Oosten, A.R.; Bila, K.; Moretti, M.

    2013-01-01

    There is a growing consensus that the distribution of species trait values in a community can greatly determine ecosystem processes and services delivery. Two distinct components of community trait composition are hypothesized to chiefly affect ecosystem processes: (i) the average trait value of the

  1. 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...

  2. Delivery of pilot workshop on preserving and enhancing the functionality of highways in Texas.

    Science.gov (United States)

    2011-03-01

    This report summarizes the delivery and results of a one-day pilot workshop conducted at the Texas : Department of Transportation (TxDOT) Waco District office in August 2010. This workshop was based on : material developed for research project 0-6208...

  3. Advancing the design of a dynamic petro-dollar currency basket

    International Nuclear Information System (INIS)

    Elbeck, Matt

    2010-01-01

    This study offers Organization of Petroleum Exporting Countries (OPEC) member nations a crude oil pricing currency basket based on currency liquidity, in contrast with prior emphasis on OPEC trading patterns. Motivating the search for an alternative US dollar pricing of crude oil is the significant and inverse relationship (r=-0.82, p<0.01) between the US dollar major currencies index and crude oil price over the period January 1999-March 2009. A dynamically weighted petro-dollar currency basket is proposed based on the five currency claims (US dollar, Euro, British pound, Japanese yen and Swiss franc) and their varying proportions of foreign exchange reserves held by central banks. The major currencies US dollar index is compared against the proposed petro-dollar index to reveal an average US$8.1 billion annual gain in favor of the petro-dollar currency basket, offering OPEC members a revenue stream of diversified and highly liquid currencies to transition away from complete dependence on the US dollar crude oil pricing. The proposed petro-dollar crude oil pricing schema offers OPEC a crude oil price dynamically denominated in currencies reflecting the global use and importance of crude oil. This paper concludes with implementation issues facing a move toward the dynamically weighted petro-dollar crude oil pricing schema. (author)

  4. Preparation, Characterization and Adsorption Evaluation of old Newspaper Fibres using Basket Reactor (Nickel Removal by Adsorption)

    International Nuclear Information System (INIS)

    Ossman, M. E.; Abdelfatah, M.; Kiros, Y.

    2016-01-01

    In this work, old newspaper fibers bleached with H 2 O 2 , treated with KOH and treated with NaOCl were investigated as potential adsorbents. The characterization of the produced fibers using FTIR, SEM and particle size distribution have been carried out and tested for the removal of Ni (II) from aqueous solutions. The results indicated that the fibers treated with KOH give the highest %removal of Ni (II) with 88%. Two different reactor designs (batch and basket reactor) with different variables were studied. The results indicated that the equilibrium time was 30 min. and the removal of Ni (II) increased significantly as the p H increased from 2.0 to 6.0 and decreased at p H range of 6.5–8.0. The adsorption of Ni (II) onto old newspaper fibers treated with KOH using batch and basket reactors follows the Langmuir isotherm. The pseudo second order kinetic model provided good correlation for the adsorption of Ni (II) onto old newspaper fibers treated with KOH for both batch and basket reactors.

  5. Validation of the high performance leadership competencies as measured by an assessment centre in-basket

    Directory of Open Access Journals (Sweden)

    H. H. Spangenberg

    2003-10-01

    Full Text Available The purpose of this study was to validate Schroder’s High Performance Leadership Competencies (HPLCs, measured by a specially designed In-basket, against multiple criteria. These consisted of six measures of managerial success, representing managerial advancement and salary progress criteria, and a newly developed comprehensive measure of work unit performance, the Performance Index. An environmental dynamism and complexity questionnaire served as moderator variable. Results indicated disappointing predictive validity quotients for the HPLCs as measured by an In-basket, in contrast to satisfactory predictive and construct validity obtained in previous studies by means of a full assessment centre. The implications of the findings are discussed and suggestions are made for improving the validity of the In-basket. Opsomming Die doel van hierdie studie was die validering van Schroder se Hoëvlak Leierskapsbevoegdhede, gemeet deur ‘n spesiaal ontwerpte Posmandjie, teen veelvoudige kriteria. Dit behels ses metings van bestuursukses wat bestuursbevorderings- en salarisvorderingskriteria insluit, sowel as ‘n nuutontwikkelde, omvattende meting van werkeenheidsprestasie, die Prestasie indeks. ‘n Vraelys wat die dinamika en kompleksiteit van die omgewing meet, het as moderator veranderlike gedien. Resultate dui op teleurstellende geldigheidskwosiënte vir die Hoëvlak Leierskapsbevoegdhede soos gemeet deur ‘n posmandjie, in teenstelling met bevredigende voorspellings- en konstrukgeldigheid wat in vorige studies deur middel van ‘n volle takseersentrum verkry is. Die bevindinge word bespreek en voorstelle word gemaak om die geldigheidskwosiënte te verbeter.

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

    OpenAIRE

    Williams, Peter

    2010-01-01

    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 af...

  7. Physiological properties of anatomically identified basket and bistratified cells in the CA1 area of the rat hippocampus in vitro.

    Science.gov (United States)

    Buhl, E H; Szilágyi, T; Halasy, K; Somogyi, P

    1996-01-01

    Basket and bistratified cells form two anatomically distinct classes of GABAergic local-circuit neurons in the CA1 region of the rat hippocampus. A physiological comparison was made of intracellularly recorded basket (n = 13) and bistratified neurons (n = 6), all of which had been anatomically defined by their efferent target profile (Halasy et al., 1996). Basket cells had an average resting membrane potential of -64.2 +/- 7.2 vs. -69.2 +/- 4.6 mV in bistratified cells. The latter had considerably higher mean input resistances (60.2 +/- 42.1 vs. 31.3 +/- 10.9 M Ohms) and longer membrane time constants (18.6 +/- 8.1 vs. 9.8 +/- 4.5 ms) than basket cells. Differences were also apparent in the duration of action potentials, those of basket cells being 364 +/- 77 and those of bistratified cells being 527 +/- 138 microseconds at half-amplitude. Action potentials were generally followed by prominent, fast after-hyperpolarizing potentials which in basket cells were 13.5 +/- 6.7 mV in amplitude vs. 10.5 +/- 5.1 in bistratified cells. The differences in membrane time constant, resting membrane potential, and action potential duration reached statistical significance (P D-aspartate (NMDA) receptors, whereas the remaining slow-rise EPSP could be abolished by an NMDA receptor antagonist. Increasing stimulation intensity elicited biphasic inhibitory postsynaptic potentials (IPSPs) in both basket and bistratified cells. In conclusion, basket and bistratified cells in the CA1 area show prominent differences in several of their membrane and firing properties. Both cell classes are activated by Schaffer collateral/commissural axons in a feedforward manner and receive inhibitory input from other, as yet unidentified, local-circuit neurons.

  8. 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......D-optimal design and the desirability function were applied to optimize a self-microemulsifying drug delivery system (SMEDDS). The optimized key parameters were the following: 1) particle size of the dispersed emulsion, 2) solubility of the drug in the vehicle, and 3) the vehicle compatibility...

  9. Longitudinal comparison study of pelvic floor function between women with and without stress urinary incontinence after vaginal delivery.

    Science.gov (United States)

    Yoshida, Mikako; Murayama, Ryoko; Haruna, Megumi; Matsuzaki, Masayo; Yoshimura, Kenichi; Murashima, Sachiyo; Kozuma, Shiro

    2013-04-01

    To compare the pelvic floor function between women with and without stress urinary incontinence after vaginal delivery. Seventeen women (age 35.5 ± 3.5) were prospectively studied at about 6 weeks, 3 months, and 6 months after vaginal delivery. Urinary incontinence was assessed by the International Consultation on Incontinence Questionnaire - Short Form. Pelvic floor function was assessed by antero-posterior diameter of the levator hiatus using transperineal ultrasound. Five of 17 women experienced postpartum stress urinary incontinence. The antero-posterior diameter of the levator hiatus at rest was significantly longer in stress urinary incontinent women than in continent women until 3 months after delivery (p continent women and stress urinary incontinent women. Regardless of urinary incontinence, the antero-posterior diameter of the levator hiatus at rest shortened at 6 months postpartum, compared to 6 weeks postpartum (p continent women by 6 months postpartum (p = 0.02). The extended pelvic floor may be a cause of stress urinary incontinence in the postpartum period. Therefore, treatment to improve the extended pelvic floor should be developed for the prevention of stress urinary incontinence.

  10. Dual-Functionalized Graphene Oxide Based siRNA Delivery System for Implant Surface Biomodification with Enhanced Osteogenesis.

    Science.gov (United States)

    Zhang, Li; Zhou, Qing; Song, Wen; Wu, Kaimin; Zhang, Yumei; Zhao, Yimin

    2017-10-11

    Surface functionalization by small interfering RNA (siRNA) is a novel strategy for improved implant osseointegration. A gene delivery system with safety and high transfection activity is a crucial factor for an siRNA-functionalized implant to exert its biological function. To this end, polyethylene glycol (PEG) and polyethylenimine (PEI) dual-functionalized graphene oxide (GO; nGO-PEG-PEI) may present a promising siRNA vector. In this study, nanosized nGO-PEG-PEI was prepared and optimized for siRNA delivery. Titania nanotubes (NTs) fabricated by anodic oxidation were biomodified with nGO-PEG-PEI/siRNA by cathodic electrodeposition, designated as NT-GPP/siRNA. NT-GPP/siRNA possessed benign cytocompatibility, as evaluated by cell adhesion and proliferation. Cellular uptake and knockdown efficiency of the NT-GPP/siRNA were assessed by MC3T3-E1 cells, which exhibited high siRNA delivery efficiency and sustained target gene silencing. Casein kinase-2 interacting protein-1 (Ckip-1) is a negative regulator of bone formation. siRNA-targeting Ckip-1 (siCkip-1) was introduced to the implant, and a series of in vitro and in vivo experiments were carried out to evaluate the osteogenic capacity of NT-GPP/siCkip-1. NT-GPP/siCkip-1 dramatically improved the in vitro osteogenic differentiation of MC3T3-E1 cells in terms of improved osteogenesis-related gene expression, and increased alkaline phosphatase (ALP) production, collagen secretion, and extracellular matrix (ECM) mineralization. Moreover, NT-GPP/siCkip-1 led to apparently enhanced in vivo osseointegration, as indicated by histological staining and EDX line scanning. Collectively, these findings suggest that NT-GPP/siRNA represents a practicable and promising approach for implant functionalization, showing clinical potential for dental and orthopedic applications.

  11. Functionally engineered nanosized particles in pharmaceutics: improved oral delivery of poorly water-soluble drugs.

    Science.gov (United States)

    Ozeki, Tetsuya; Tagami, Tatsuaki

    2013-01-01

    The development of drug nanoparticles has attracted substantial attention because of their potential to improve the dissolution rate and oral availability of poorly water-soluble drugs. This review summarizes the recent articles that discussed nanoparticle-based oral drug delivery systems. The preparation methods were categorized as top-down and bottom-up methods, which are common methods for preparing drug nanoparticles. In addition, methods of handling drug nanoparticles (e.g., one-step preparation of nanocomposites which are microparticles containing drug nanoparticles) were introduced for the effective preservation of drug nanoparticles. The carrier-based preparation of drug nanoparticles was also introduced as a potentially promising oral drug delivery system.

  12. 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.

  13. Bucket elevator type continuous unloader; Basket elevator gata renzokushiki anroda

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-04-20

    This unloader was delivered to Wakayama branch of Sumikin Butsuryu in the site of Wakayama steel plant of Sumitomo Metal Industries Ltd. for landing sub-materials for ironworks. Main specifications: (1) Capacity: 400t/h for limestone, 280t/h for gypsum, (2) Kinds of ships: 5,000DWT maximum, (3) Boom swing radius: 20m. Features: (1) Simple light-weight unloader for not large ships for main materials but small coastal service ships which works with not swing motion but only traveling and normal-directional motion of the under structure of a bucket elevator unit, (2) Various useful functions such as ground conveyance, truck loading, back yard stacking and back yard shipment for handling of various sub-materials. (translated by NEDO)

  14. Polyethylene glycol and octa-arginine dual-functionalized nanographene oxide: an optimization for efficient nucleic acid delivery.

    Science.gov (United States)

    Imani, Rana; Prakash, Satya; Vali, Hojatollah; Faghihi, Shahab

    2018-05-29

    The successful application of nucleic acid-based therapy for the treatment of various cancers is largely dependent on a safe and efficient delivery system. A dual-functionalized graphene oxide (GO)-based nanocarrier with the conjugation of aminated-polyethylene glycol (PEG-diamine) and octa-arginine (R8) for the intracellular delivery of nucleic acids is proposed. The functionalized sites are covalently co-conjugated and the PEG : R8 molar ratio is optimized at 10 : 1 to achieve a hydrocolloidally stable size of 252 ± 2.0 nm with an effective charge of +40.97 ± 1.05 and an amine-rich content of 10.87 ± 0.4 μmol g-1. The uptake of the nanocarrier in breast cancer cell lines, MCF-7 and MDA-MB 231, is investigated. The siRNA and pDNA condensation ability in the presence and absence of enzymes and the endosomal buffering capacity, as well as the intracellular localization of the gene/nanocarrier complex are also evaluated. Furthermore, the delivery of functional genes associated with the nanocarrier is assessed using c-Myc protein knockdown and EGFP gene expression. The effective uptake of the nanocarrier by the cells shows superior cytocompatibility, and protects the siRNA and pDNA against enzyme degradation while inhibiting their migration with N : P ratios of 10 and 5, respectively. The co-conjugation of PEG-diamine and the cationic cell-penetrating peptide (CPP) into the GO nanocarrier also provides a superior internalization efficacy of 85% in comparison with a commercially available transfection reagent. The c-Myc protein knockdown and EGFP expression, which are induced by the nanocarrier, confirm that the optimized PEG-diamine/R8-functionalized GO could effectively deliver pDNA and siRNA into the cells and interfere with gene expression.

  15. 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.

  16. Pluronic-Functionalized Silica-Lipid Hybrid Microparticles: Improving the Oral Delivery of Poorly Water-Soluble Weak Bases.

    Science.gov (United States)

    Rao, Shasha; Richter, Katharina; Nguyen, Tri-Hung; Boyd, Ben J; Porter, Christopher J H; Tan, Angel; Prestidge, Clive A

    2015-12-07

    A Pluronic-functionalized silica-lipid hybrid (Plu-SLH) microparticle system for the oral delivery of poorly water-soluble, weak base drugs is reported for the first time. A highly effective Plu-SLH microparticle system was composed of Labrasol as the lipid phase, Pluronic F127 as the polymeric precipitation inhibitor (PPI), and silica nanoparticles as the solid carrier. For the model drug cinnarizine (CIN), the Plu-SLH delivery system was shown to offer significant biopharmaceutical advantages in comparison with unformulated drug and drug in the silica-lipid hybrid (SLH) system. In vitro two-phase dissolution studies illustrated significantly reduced pH provoked CIN precipitation and an 8- to 14-fold improvement in the extent of dissolution in intestinal conditions. In addition, under simulated intestinal digesting conditions, the Plu-SLH provided approximately three times more drug solubilization than the SLH. Oral administration in rats resulted in superior bioavailability for Plu-SLH microparticles, i.e., 1.6- and 2.1-fold greater than the SLH and the unformulated CIN, respectively. A physical mixture of Pluronic and SLH (Plu&SLH), having the same composition as Plu-SLH, was also evaluated, but showed no significant increase in CIN absorption when compared to unmodified CIN or SLH. This work represents the first study where different methods of incorporating PPI to formulate solid-state lipid-based formulations were compared for the impact on the biopharmaceutical performance. The data suggest that the novel physicochemical properties and structure of the fabricated Plu-SLH microparticle delivery system play an important role in facilitating the synergistic advantage of Labrasol and Pluronic F127 in preventing drug precipitation, and the Plu-SLH provides efficient oral delivery of poorly water-soluble weak bases.

  17. Use of the Escape nitinol stone retrieval basket facilitates fragmentation and extraction of ureteral and renal calculi: a pilot study.

    Science.gov (United States)

    Kesler, Stuart S; Pierre, Sean A; Brison, Daniel I; Preminger, Glenn M; Munver, Ravi

    2008-06-01

    Advances in ureteroscope and stone basket design have catapulted ureteroscopy to the forefront of surgical stone management; however, persistent problems such as stone migration continue to challenge urologists. The Escape nitinol stone retrieval basket (Boston Scientific, Natick, MA) is a stone basket designed to capture calculi and facilitate simultaneous laser lithotripsy in situ. We report our initial experience with the Escape basket for the management of urinary calculi and compare the use of this device with other methods of optimizing ureteroscopic stone management. A prospective evaluation of 23 patients undergoing ureteroscopic holmium:yttrium-aluminum-garnet laser lithotripsy of urinary calculi was performed at two institutions by two surgeons (R.M. and G.M.P). The Escape basket was used to prevent retrograde ureteral stone migration or to facilitate fragmentation and extraction of large renal calculi. Patient demographics and perioperative parameters were assessed. Twenty-three patients (16 men, 7 women), with a mean age of 55.5 years (range 33-74 yrs) were treated for renal (n = 9) or ureteral (n = 14) calculi. The mean stone diameter was 1.4 cm (range 0.4-2.5 cm), mean fragmentation time was 44.1 minutes (range 10-75 min), and mean energy used was 3.1 kJ (range 0.4-10.6 kJ). No complications were encountered. Eighty-seven percent (20/23) of patients were rendered completely stone free after ureteroscopic laser lithotripsy using the Escape basket. Of the three patients with residual calculi, one patient with a 2.5-cm renal calculus had residual fragments larger than 3 mm, and two patients with large renal calculi had residual fragments smaller than 3 mm. The Escape basket appears to be safe and effective in preventing stone migration and facilitating ureteroscopic laser lithotripsy and stone extraction.

  18. An experimental framework to identify community functional components driving ecosystem processes and services delivery

    Czech Academy of Sciences Publication Activity Database

    Dias, A. T. C.; Berg, M. P.; de Bello, Francesco; Oosten, A. R. V.; Bílá, Karolína; Morreti, M.

    2013-01-01

    Roč. 101, č. 1 (2013), s. 29-37 ISSN 0022-0477 R&D Projects: GA ČR GAP505/12/1296 Institutional support: RVO:67985939 ; RVO:67179843 Keywords : CWM * ecosystem functioning * ecosystem processes * ecosystem services * functional divergence * functional diversity * functional evenness * functional richness * mass ratio hypothesis * Rao index Subject RIV: EH - Ecology, Behaviour; EF - Botanics (BU-J) Impact factor: 5.694, year: 2013

  19. Gallic acid grafting effect on delivery performance and antiglaucoma efficacy of antioxidant-functionalized intracameral pilocarpine carriers.

    Science.gov (United States)

    Chou, Shih-Feng; Luo, Li-Jyuan; Lai, Jui-Yang

    2016-07-01

    Functionalization of therapeutic carrier biomaterials can potentially provide additional benefits in drug delivery for disease treatment. Given that this modification determines final therapeutic efficacy of drug carriers, here, we investigate systematically the role of grafting amount of antioxidant gallic acid (GA) onto GN in situ gelling copolymers made of biodegradable gelatin and thermo-responsive poly(N-isopropylacrylamide) for intracameral delivery of pilocarpine in antiglaucoma treatment. As expected, increasing redox reaction time increased total antioxidant activities and free radical scavenging abilities of synthesized carrier biomaterials. The hydrophilic nature of antioxidant molecules strongly affected physicochemical properties of carrier materials with varying GA grafting amounts, thereby dictating in vitro release behaviors and mechanisms of pilocarpine. In vitro oxidative stress challenges revealed that biocompatible carriers with high GA content alleviated lens epithelial cell damage and reduced reactive oxygen species. Intraocular pressure and pupil diameter in glaucomatous rabbits showed correlations with GA-mediated release of pilocarpine. Additionally, enhanced pharmacological treatment effects prevented corneal endothelial cell loss during disease progression. Increasing GA content increased total antioxidant level and decreased nitrite level in the aqueous humor, suggesting a much improved antioxidant status in glaucomatous eyes. This work significantly highlights the dependence of physicochemical properties, drug release behaviors, and bioactivities on intrinsic antioxidant capacities of therapeutic carrier biomaterials for glaucoma treatment. Development of injectable biodegradable polymer depots and functionalization of carrier biomaterials with antioxidant can potentially provide benefits such as improved bioavailability, controlled release pattern, and increased therapeutic effect in intracameral pilocarpine administration for glaucoma

  20. Antiseptic cyclodextrin-functionalized hydrogels and gauzes for loading and delivery of benzalkonium chloride.

    Science.gov (United States)

    Garcia-Fernandez, Maria José; Brackman, Gilles; Coenye, Tom; Concheiro, Angel; Alvarez-Lorenzo, Carmen

    2013-01-01

    Prevention and management of wound infections receive a lot of attention, since the presence of micro-organisms interferes with the wound-healing process. The aim of this work was to use cyclodextrins (CDs) to endow hydrogels and gauzes with the ability to take up antiseptics and sustain their delivery for several hours. Benzalkonium chloride (BzCl) can form inclusion complexes with cross-linked CDs that regulate the release through an affinity-driven mechanism. Grafting of CDs to cotton gauzes using citric acid as the linker, at 190 °C and for 15 min, led to grafting yields of about 148%, much larger than those obtained at 180 °C or with shorter reaction times. Microbiological tests revealed that the BzCl-loaded networks can inhibit the growth of Staphylococcus epidermidis and Escherichia coli both on agar plates and in liquid medium. Furthermore, the antiseptic-loaded gauzes were able to inhibit biofilm formation by Staphylococcus aureus RN1HG pMV158GFP when applied in early stages of biofilm formation and could reduce the number of living cells in preformed biofilms grown in a chronic wound biofilm model. These findings highlight the role of CDs as main components of hydrogels and gauzes for the efficient delivery of antiseptics.

  1. 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

  2. Water-soluble ferrocene complexes (WFCs) functionalized silica nanospheres for WFC delivery in HepG2 tumor therapy.

    Science.gov (United States)

    Yan, Saisai; Hu, Fan; Hong, Xia; Shuai, Qi

    2018-09-01

    Silica-encapsulated nanospheres of water-soluble ferrocene complexes WFCs@SiO 2 and WFCs@SiO 2 @glutaraldehyde (GA) were first synthesized by a facile inverse-microemulsion method. The surface functional groups, particle size, and morphologies of nanospheres were characterized by IR spectra, UV-vis absorption spectra, dynamic light scattering (DLS) and SEM images. Single-crystal X-ray diffraction was used to confirm the molecular structure of free ferrocenyl-pyrazol ligand (L) and three WFCs, namely, [Ni(C 22 H 14 F 6 FeN 4 O 4 )(H 2 O) 4 ] (5a), [Mg(C 22 H 14 F 6 FeN 4 O 4 )(H 2 O) 4 ]·3H 2 O (5b), and [Ba(C 22 H 14 F 6 FeN 4 O 4 )(H 2 O) 3 ] (5c). The electrochemical properties of 5a-5c were explored by cyclic voltammetry. The WFCs-loading capacities of 5a-5c in WFCs@SiO 2 were found to be 38.4, 38.2, and 38.1 μg/mg, respectively. Cell studies under two drug delivery modes (free diffusion and endocytosis) were carried out by MTT cell-survival assays and morphological observation of HepG2 cells. It's interesting that the cytotoxicity of WFCs against HepG2 was increased by applying silica nanocarriers. Compared to WFCs@SiO 2 , the modification of GA on the spherical surface provided not only the better water-dispersity but also additional functional groups for further modification of other pharmacophores. The novel nanocarrier system for WFC delivery present a novel concept-of-proof method to protect varieties of affordable metal-based anticancer agents in physiological conditions and provided experimental basis for future studies focusing on drug delivery of other WFCs. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. 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.

  4. Perancangan Dan Pembuatan Modul Data Mining Market Basket Analysis Pada Odoo Dengan Studi Kasus Supermarket X

    OpenAIRE

    Hendratha, Stefani Natalia; Yulia, Yulia; Budhi, Gregorius Satia

    2016-01-01

    Odoo Enterprise Resource Planning (ERP) system storing company's transaction data. However, Odoo doesn't have a module for managing data. It takes a module for managing data into useful information.Based on the above problems, a module for data mining Market Basket Analysis is being designed. This module uses FP-Growth algorithm by utilizing the sales transaction data.For the testing, this module using data from X Supermarket. The final result of this module is an association rule from data m...

  5. Functionalized tetrapod-like ZnO nanostructures for plasmid DNA purification, polymerase chain reaction and delivery

    International Nuclear Information System (INIS)

    Nie Leng; Gao Lizeng; Yan Xiyun; Wang Taihong

    2007-01-01

    Functionalized tetrapodal ZnO nanostructures are tested in plasmid DNA experiments (1) as a solid-phase adsorbent for plasmid DNA purification (2) as improving reagents in a polymerase chain reaction (PCR) and (3) as novel carriers for gene delivery. The amino-modification, the tetrapod-like shape of the nanostructure and its high biocompatibility all contribute to measurements showing promise for applications. A sol-gel method is used for silica coating and amino-modification. Plasmid DNA is purified through reversible conjugations of amino-modified ZnO tetrapods with DNA. Also, as additional reagents, functionalized tetrapods are shown to improve the amount of PCR product. For transfection, ZnO tetrapods provide some protection against deoxyribonuclease cleavage of plasmid DNA and deliver plasmid DNA into cells with little cytotoxicity

  6. 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.

  7. Monitoring the affordability of healthy eating: a case study of 10 years of the Illawarra Healthy Food Basket.

    Science.gov (United States)

    Williams, Peter

    2010-11-01

    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.

  8. Application of an amine functionalized biopolymer in the colonic delivery of glycyrrhizin: a design and in vivo efficacy study.

    Science.gov (United States)

    Kumar De, Amit; Datta, Sriparna; Mukherjee, Arup

    2013-01-01

    In our current study, a newer amine functionalized guar gum derivative was studied for its efficacy in colonic drug delivery. Glycyrrhizic acid mono-ammonium salt was used as the model drug. Drug-loaded microparticles were formulated by ionic crosslinking using sodium tripolyphosphate. The Scanning Electron Microscopic study revealed spherical particles of sizes from 4.9 ± 3.8 μm to 6.9 ± 3.9 μm. The FT-IR studies presented a possible interaction between the drug and the polymer. The drug was encapsulated in amorphous form as observed from the powder X-Ray Diffraction studies. A cumulative drug release study was carried out in simulated gastric, intestinal, and colonic fluids. The cumulative drug release studies presented a burst release followed by a sustained release of the drug in simulated colonic fluid containing rat cecal contents. The drug-polymer ratio was optimised using a 3(2) factorial design by taking the amounts of glycyrrhizic acid (X1) and guar gum alkyl amine (X2) as the independant variables. The percent cumulative drug release at 240 mins (Q240), 720 mins (Q720), and at 1,440 mins (Q1440) were considered as the dependant variables. The efficacy of the optimized formulation was studied in a 2,4,6-trinitrobenzene sulfonic acid-induced rat colitis model. The tissue's nitric oxide, malondialdehyde, and myeloperoxidase activities were found to be much lower in the microparticle-treated group compared to free drug-treated group. The histology of the colonic tissue from the treated group of animals revealed almost no infiltration of inflammatory cells in the tissue for the microparticle-treated group of animals. The synthesized amine derivative of guar gum was found to be better in vitro with a better in vivo efficacy in the colonic delivery of glycyrrhizic acid monoammonium salt and can be considered as a newer modified biopolymer for colonic drug delivery.

  9. Organic saffron position in the future household consumption basket and effective structures (Case study

    Directory of Open Access Journals (Sweden)

    Ahmadreza Shahpouri

    2014-09-01

    Full Text Available Considering the importance of planning at the production level, it is necessary to identify the consumer's future behavior towards organic products. Thus, using seemingly unrelated regression and data of 2012 for 200 households in mashhad, in the present study we have tried to determine the future share of these products in the household's basket and also survey the effective factors on this share in organic saffron. The results showed that households in mashhad tend to allocate an average of 34 percent of their future consumption basket for organic saffron. The regression results illustrated that while children below 10 years old in the households, willingness to pay the price differential compared with non-organic products and organic labeling positively affected the willingness to pay for organic products, environmental concerns variables created by non-organic products had a negative effect on their willingness. Considering the research results, helping to raise people's awareness about food through different educational and advertising approaches, providing a mechanism to label organic products and assessing the strengths and weaknesses of producing and distributing the organic products are provided as suggestions.

  10. Cross-correlations between Renminbi and four major currencies in the Renminbi currency basket

    Science.gov (United States)

    Wang, Gang-Jin; Xie, Chi

    2013-03-01

    We investigate the cross-correlations between Renminbi (CNY) and four major currencies (USD, EUR, JPY, and KRW) in the Renminbi currency basket, i.e., the cross-correlations of CNY-USD, CNY-EUR, CNY-JPY, and CNY-KRW. Qualitatively, using a statistical test in analogy to the Ljung-Box test, we find that cross-correlations significantly exist in CNY-USD, CNY-EUR, CNY-JPY, and CNY-KRW. Quantitatively, employing the detrended cross-correlation analysis (DCCA) method, we find that the cross-correlations of CNY-USD, CNY-EUR, CNY-JPY, and CNY-KRW are weakly persistent. We use the DCCA cross-correlation coefficient ρ to quantify the level of cross-correlations and find the currency weight in the Renminbi currency basket is arranged in the order of USD>EUR>JPY >KRW. Using the method of rolling windows, which can capture the time-varying cross-correlation scaling exponents, we find that: (i) CNY and USD are positively cross-correlated over time, but the cross-correlations of CNY-USD are anti-persistent during the US sub-prime crisis and the European debt crisis. (ii) The cross-correlation scaling exponents of CNY-EUR have the cyclical fluctuation with a nearly two-year cycle. (iii) CNY-JPY has long-term negative cross-correlations, during the European debt crisis, but CNY and KRW are positively cross-correlated.

  11. Clostridium difficile in retail baskets, trolleys, conveyor belts, and plastic bags in Saudi Arabia.

    Science.gov (United States)

    Alqumber, Mohammed A

    2014-10-01

    To determine Clostridium difficile (C. difficile) prevalence on retail surfaces and shoppers plastic bags. From 20 June to 10 August 2011, in a cross-sectional epidemiological study, 17 supermarkets from 2 cities, Albaha and Altaif, Saudi Arabia were sampled. A total of 800 samples, which comprised 200 samples per surveyed surface, were studied. These included baskets, trolleys, conveyer belts, and outgoing shoppers' plastic bags. Clostridium difficile strains were isolated. The isolates were characterized using ribotyping and  polymerase chain reaction for the detection of toxin A (tcdA), toxin B (tcdB), binary toxin (cdtB), and toxin C (tcdC) genes. Susceptibility to antibiotics was determined on a Muller-Hinton agar with 5% sheep blood agar using E-tests. Overall, the C. difficile prevalence on sampled surfaces was 0.75%. The highest prevalence was found on retail baskets and trolleys, followed by plastic bags. A total of 5 different ribotypes were identified. Alterations in tcdC were detected in ribotype 027 and BT1. All the identified isolates were susceptible to vancomycin, but resistant to levofloxacin. In this study, C. difficile was present at a rate of 0.75% on supermarket surfaces. Spore disinfection of implicated surfaces may be necessary to control any community-acquired infections caused by this pathogen. 

  12. Handling tool for, and method of use of, ice basket removable cruciform

    International Nuclear Information System (INIS)

    Scrabis, C.M.; Mazza, G.E.; Golick, L.R.; Pomaibo, P.

    1987-01-01

    This patent describes a method for selectively installing and removing a removable cruciform of a resiliently compressible type, in and from the interior of a generally cylindrical, elongated and vertically oriented ice containment structure, which interior is accessible from an open, upper and thereof. Each such removable cruciform comprises a central housing defining an axis of compression and expansion, means normally biasing the housing in the direction of expansion, legs extending from the housing in a generally radially oriented direction and means on the outer edges of the legs configured to engage a corresponding stiffenning ring rigidly secured on the interior of the cylindrical sidewall of the ice basket, comprising: providing a handling tool having an elongated frame defining an axis, guide means connected to the frame and comprising at least first and second guide fingers extending radially from the axis and angularly displaced thereabout and selectively moveable between retracted and extended positions, and clamping means mounted to the frame and extending axially outwardly therefrom, positioning the tool, with the clamping shoes in the disengaged positions, in axial alignment with and disposed radially outwardly about the central housing of a removable cruciform of the resiliently compressible type; selectively actuating the clamping means to the engaged positions of the clamping shoes for engaging and compressing the central housing of the cruciform and retracting the legs thereof; lowering the tool with the cruciform engaged thereby, axially downwardly through the ice basket to a desired elevation

  13. Plant basket hydraulic structures (PBHS) as a new river restoration measure.

    Science.gov (United States)

    Kałuża, Tomasz; Radecki-Pawlik, Artur; Szoszkiewicz, Krzysztof; Plesiński, Karol; Radecki-Pawlik, Bartosz; Laks, Ireneusz

    2018-06-15

    River restoration has become increasingly attractive worldwide as it provides considerable benefits to the environment as well as to the economy. This study focuses on changes of hydromorphological conditions in a small lowland river recorded during an experiment carried out in the Flinta River, central Poland. The proposed solution was a pilot project of the construction of vegetative sediment traps (plant basket hydraulic structures - PBHS). A set of three PBSH was installed in the riverbed in one row and a range of hydraulic parameters were recorded over a period of three years (six measurement sessions). Changes of sediment grain size were analysed, and the amount and size of plant debris in the plant barriers were recorded. Plant debris accumulation influencing flow hydrodynamics was detected as a result of the installation of vegetative sediment traps. Moreover, various hydromorphological processes in the river were initiated. Additional simulations based on the detected processes showed that the proposed plant basket hydraulic structures can improve the hydromorphological status of the river. Copyright © 2018 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Kroemer, Jeremy A.; Bonning, Bryony C.; Harrison, Robert L.

    2015-01-01

    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. PMID:25609310

  15. A delivery device for presentation of tactile stimuli during functional magnetic resonance imaging.

    Science.gov (United States)

    Dykes, Robert W; Miqueé, Aline; Xerri, Christian; Zennou-Azogui, Yoh'i; Rainville, Constant; Dumoulin, André; Marineau, Daniel

    2007-01-30

    We describe a novel stimulus delivery system designed to present tactile stimuli to a subject in the tunnel of a magnetic resonance imaging (MRI) system. Using energy from an air-driven piston to turn a wheel, the device advances a conveyor belt with a pre-determined sequence of stimuli that differ in their spatial features into the tunnel of the MRI. The positioning of one or several stimulus objects in a window near the subject's hand is controlled by a photoelectric device that detects periodic openings in the conveyor belt. Using this electric signal to position each presentation avoids cumulative positioning errors and provides a signal related to the progression of the experiment. We used a series of shapes that differed in their spatial features but the device could carry stimuli with a diversity of shapes and textures. This flexibility allows the experimenter to design a wide variety of psychophysical experiments in the haptic world and possibly to compare and contrast these stimuli with the cognitive treatment of similar stimuli delivered to the other senses. Appropriate experimental design allows separation of motor, sensory and memory storage phases of mental processes.

  16. 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.

  17. 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.

  18. 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.

  19. 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 , transport authority, functions, capacity building, funding, institutional strengthening, legislative mandates, South Africa 224 1 INTRODUCTION Since the advent of the democratic political dispensation in South Africa in 1994, the nature and functions... in that it influences the quality and style of life, the range and location of productive and leisure activities, and the goods and services which will be available for consumption (Morlok, 1978; Fuller, 2004). Given that transport plays this important triple role...

  20. MCM-41 functionalized with YVO{sub 4}:Eu{sup 3+}: a novel drug delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Yang Piaoping [Key Laboratory of Rare Earth Chemistry and Physics, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Quan Zewei [Key Laboratory of Rare Earth Chemistry and Physics, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Lu Lanlan [Key Laboratory of Rare Earth Chemistry and Physics, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Huang Shanshan [Key Laboratory of Rare Earth Chemistry and Physics, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Lin Jun [Key Laboratory of Rare Earth Chemistry and Physics, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Fu Honggang [School of Chemistry and Materials Science, Heilongjiang University, Harbin 150080 (China)

    2007-06-13

    Luminescence functionalization of ordered mesoporous MCM-41 silica was realized by depositing a YVO{sub 4}:Eu{sup 3+} phosphor layer on its surface via the Pechini sol-gel process. This material, which combines the mesoporous structure of MCM-41 and the strong red luminescence property of YVO{sub 4}:Eu{sup 3+}, has been studied as a host carrier for drug delivery/release systems. The structure, morphology, texture and optical properties of Materials were well characterized by x-ray diffraction (XRD), Fourier infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), N{sub 2} adsorption and photoluminescence (PL) spectra. The results indicated that the specific surface area and pore volume of MCM-41, which were directly correlated to the drug-loading amount and ibuprofen (IBU) release rate, decreased in sequence after deposition of YVO{sub 4}:Eu{sup 3+} and loading of IBU as expected. The IBU-loaded YVO{sub 4}:Eu{sup 3+}MCM-41 system still showed red luminescence under UV irradiation (365 nm) and a controlled release property for IBU. In addition, the emission intensity of Eu{sup 3+} increases with an increase in the cumulative released amount of IBU, making the extent of drug release easily identified, tracked and monitored by the change of luminescence, which demonstrates its potential application in drug delivery/release systems.

  1. Fluorinated ionic liquids for protein drug delivery systems: Investigating their impact on the structure and function of lysozyme.

    Science.gov (United States)

    Alves, Márcia; Vieira, Nicole S M; Rebelo, Luís Paulo N; Araújo, João M M; Pereiro, Ana B; Archer, Margarida

    2017-06-30

    Since the approval of recombinant human insulin by FDA in 1982, more than 200 proteins are currently available for pharmaceutical use to treat a wide range of diseases. However, innovation is still required to develop effective approaches for drug delivery. Our aim is to investigate the potential use of fluorinated ionic liquids (FILs) as drug delivery systems (DDS) for therapeutic proteins. Some initial parameters need to be assessed before further studies can proceed. This work evaluates the impact of FILs on the stability, function, structure and aggregation state of lysozyme. Different techniques were used for this purpose, which included differential scanning fluorimetry (DSF), spectrophotometric assays, circular dichroism (CD), dynamic light scattering (DLS), and scanning and transmission electron microscopy (SEM/TEM). Ionic liquids composed of cholinium-, imidazolium- or pyridinium- derivatives were combined with different anions and analysed at different concentrations in aqueous solutions (below and above the critical aggregation concentration, CAC). The results herein presented show that the addition of ionic liquids had no significant effect on the stability and hydrolytic activity of lysozyme. Moreover, a distinct behaviour was observed in DLS experiments for non-surfactant and surfactant ionic liquids, with the latter encapsulating the protein at concentrations above the CAC. These results encourage us to further study ionic liquids as promising tools for DDS of protein drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Cytosolic and Nuclear Delivery of CRISPR/Cas9-ribonucleoprotein for Gene Editing Using Arginine Functionalized Gold Nanoparticles.

    Science.gov (United States)

    Mout, Rubul; Rotello, Vincent M

    2017-10-20

    In this protocol, engineered Cas9-ribonucleoprotein (Cas9 protein and sgRNA, together called Cas9-RNP) and gold nanoparticles are used to make nanoassemblies that are employed to deliver Cas9-RNP into cell cytoplasm and nucleus. Cas9 protein is engineered with an N-terminus glutamic acid tag (E-tag or En, where n = the number of glutamic acid in an E-tag and usually n = 15 or 20), C-terminus nuclear localizing signal (NLS), and a C-terminus 6xHis-tag. [Cas9En hereafter] To use this protocol, the first step is to generate the required materials (gold nanoparticles, recombinant Cas9En, and sgRNA). Laboratory-synthesis of gold nanoparticles can take up to a few weeks, but can be synthesized in large batches that can be used for many years without compromising the quality. Cas9En can be cloned from a regular SpCas9 gene (Addgene plasmid id = 47327), and expressed and purified using standard laboratory procedures which are not a part of this protocol. Similarly, sgRNA can be laboratory-synthesized using in vitro transcription from a template gene (Addgene plasmid id = 51765) or can be purchased from various sources. Once these materials are ready, it takes about ~30 min to make the Cas9En-RNP complex and 10 min to make the Cas9En-RNP/nanoparticles nanoassemblies, which are immediately used for delivery (Figure 1). Complete delivery (90-95% cytoplasmic and nuclear delivery) is achieved in less than 3 h. Follow-up editing experiments require additional time based on users' need. Synthesis of arginine functionalized gold nanoparticles (ArgNPs) (Yang et al ., 2011), expression of recombinant Cas9En, and in vitro synthesis of sgRNA is reported elsewhere (Mout et al ., 2017). We report here only the generation of the delivery vehicle i.e. , the fabrication of Cas9En-RNP/ArgNPs nanoassembly.

  3. Structure-function correlation of chloroquine and analogues as transgene expression enhancers in nonviral gene delivery.

    Science.gov (United States)

    Cheng, Jianjun; Zeidan, Ryan; Mishra, Swaroop; Liu, Aijie; Pun, Suzie H; Kulkarni, Rajan P; Jensen, Gregory S; Bellocq, Nathalie C; Davis, Mark E

    2006-11-02

    To understand how chloroquine (CQ) enhances transgene expression in polycation-based, nonviral gene delivery systems, a number of CQ analogues with variations in the aliphatic amino side chain or in the aromatic ring are synthesized and investigated. Our studies indicate that the aliphatic amino moiety of CQ is essential to provide increased gene expression. Further, the enhancements are more dramatically affected by changes to the aromatic ring and are positively correlated to the strength of intercalation between DNA and the CQ analogues. Quinacrine (QC), a CQ analogue with a fused acridinyl structure that can strongly intercalate DNA, enhances transfection similarly to CQ at a concentration 10 times lower, while N(4)-(4-pyridinyl)-N(1),N(1)-diethyl-1,4-pentanediamine (CP), a CQ analogue that has a weakly intercalating pyridinyl ring, shows no effect on gene expression. Subtle change on the 7-substituent of the chloroquine aromatic structure can also greatly affect the ability of the CQ analogues to enhance transgene expression. Transfection in the presence of N(4)-(7-trifluoromethyl-4-quinolinyl)-N(1),N(1)-diethyl-1,4-pentanediamin e (CQ7a) shows expression efficiency 10 times higher than in the presence of CQ at same concentration, while transfection in the presence of N(4)-(4-quinolinyl)-N(1),N(1)-diethyl-1,4-pentanediamine (CQ7b) does not reveal any enhancing effects on expression. Through a number of comparative studies with CQ and its analogues, we conclude that there are at least three mechanistic features of CQ that lead to the enhancement in gene expression: (i) pH buffering in endocytic vesicles, (ii) displacement of polycations from the nucleic acids in polyplexes, and (iii) alteration of the biophysical properties of the released nucleic acid.

  4. Hydrosilylated Porous Silicon Particles Function as an Intravitreal Drug Delivery System for Daunorubicin

    Science.gov (United States)

    Hartmann, Kathrin I.; Nieto, Alejandra; Wu, Elizabeth C.; Freeman, William R.; Kim, Jae Suk; Chhablani, Jay; Sailor, Michael J.

    2013-01-01

    Abstract Purpose To evaluate in vivo ocular safety of an intravitreal hydrosilylated porous silicon (pSi) drug delivery system along with the payload of daunorubicin (DNR). Methods pSi microparticles were prepared from the electrochemical etching of highly doped, p-type Si wafers and an organic linker was attached to the Si-H terminated inner surface of the particles by thermal hydrosilylation of undecylenic acid. DNR was bound to the carboxy terminus of the linker as a drug-loading strategy. DNR release from hydrosilylated pSi particles was confirmed in the excised rabbit vitreous using liquid chromatography–electrospray ionization–multistage mass spectrometry. Both empty and DNR-loaded hydrosilylated pSi particles were injected into the rabbit vitreous and the degradation and safety were studied for 6 months. Results The mean pSi particle size was 30×46×15 μm with an average pore size of 15 nm. Drug loading was determined as 22 μg per 1 mg of pSi particles. An ex vivo drug release study showed that intact DNR was detected in the rabbit vitreous. An in vivo ocular toxicity study did not reveal clinical or pathological evidence of any toxicity during a 6-month observation. Hydrosilylated pSi particles, either empty or loaded with DNR, demonstrated a slow elimination kinetics from the rabbit vitreous without ocular toxicity. Conclusions Hydrosilylated pSi particles can host a large quantity of DNR by a covalent loading strategy and DNR can be slowly released into the vitreous without ocular toxicity, which would appear if an equivalent quantity of free drug was injected. PMID:23448595

  5. Transdermal drug delivery

    Science.gov (United States)

    Prausnitz, Mark R.; Langer, Robert

    2009-01-01

    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 of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

  6. Importance of public participation in decision-making process in healthcare system illustarted with an example of the development of American and Polish scope of health benefit basket.

    Science.gov (United States)

    Kolasa, Katarzyna; Hermanowski, Tomasz; Borek, Ewa

    2013-01-01

    The process of the development of health benefit basket may serve as a good example of decision-making process in the healthcare system which is based on public participation. Comparative analysis of development and implementation of health benefit basket in Poland and the USA. On a basis of the literature review, following questions were studied, i.e.: What is the origin of health benefit basket development in the USA and Poland? What was the role of pubic opinion in determining the range of health benefit basket in both countries? What criteria were employed to determine the range of health benefit basket in both countries? What conclusions can be drawn for Poland from the USA experience of determining the range of health benefit basket? Irrespective of the similarities in the origin of health benefit basket development, both countries approached this issue differently. In the USA, the approach based on social dialogue and patient's perspective was selected while in Poland the perspective of public payer predominated. The transparency of principles and social dialogue constitute the fundamental elements of effective process of health benefit basket development and implementation which is both required and generally unpopular modification.

  7. Formulation of curcumin delivery with functionalized single-walled carbon nanotubes: characteristics and anticancer effects in vitro.

    Science.gov (United States)

    Li, Haixia; Zhang, Nan; Hao, Yongwei; Wang, Yali; Jia, Shasha; Zhang, Hongling; Zhang, Yun; Zhang, Zhenzhong

    2014-08-01

    Single-walled carbon nanotubes (SWCNTs), an important class of artificial nanomaterials with unique physicochemical properties, were used as novel carriers of curcumin. Formulation and evaluation of curcumin-loaded SWCNTs systems for utilizing the curcumin's anticancer potential by circumventing conventional limitations of extremely low aqueous solubility and instability under physiological conditions, and combining SWCNTs photothermal therapy enabled by the strong optical absorbance of SWCNTs in the 0.8-1.4 μm resulting in excessive local heating. After functionalized SWCNTs were confirmed, they were conjugated with curcumin (SWCNT-Cur). Subsequently, the formulation was analyzed for size, zeta-potential and morphology. And the solubility, stability and release of curcumin were assessed using spectrofluorometer, and the solid state of the curcumin was determined using X-ray diffraction and UV spectroscopy. Furthermore, in PC-3 cells, photothermal response was further determined by irradiating laser after the antitumor effect of SWCNT-Cur was evaluated. SWCNTs were functionalized, and subsequent SWCNT-Cur conjugates were found to possess an average size of 170.4 nm, a zeta potential of -12.5 mV and to significantly enhance the solubility and stability of curcumin, overcoming the barriers to adequate curcumin delivery. Moreover, curcumin in SWCNT-Cur was in an amorphous form and could be rapidly released. In PC-3 cells, improved inhibition efficacy was achieved by SWCNT-Cur compared with native curcumin. Meanwhile, the SWCNTs in SWCNT-Cur served not only as scaffolds but also as thermal ablation agents, further inhibiting PC-3 cell growth. SWCNT-Cur assemblies may provide a promising delivery system for curcumin for use in cancer therapy.

  8. Effect of home and hospital delivery on long-term cognitive function.

    Science.gov (United States)

    Sørensen, H T; Steffensen, F H; Rothman, K J; Gillman, M W; Fischer, P; Sabroe, S; Olsen, J

    2000-11-01

    We examined the relation between place of birth and cognitive function in young adult life in a historical cohort study based upon birth data from the computerized Danish Medical Birth Registry and cognitive function as measured at time of drafting for military service in two Danish counties. The cohort included 4,296 Danish conscripts born between 1973 and 1976, 123 born at home and 4,173 born in hospital or at a birth clinic. Cognitive function was measured by the Boerge Prien test in men, 18 to 20 years of age. The highest possible score is 78. The mean Boerge Prien test score was 43.1 for conscripts born in specialized hospital departments, 2.4 higher for conscripts born in a birth clinic (95% confidence interval = 0.9-4.0), and 2.1 lower for conscripts born at home (95% confidence limits = -3.8 to -0.4) after adjusting for birth weight, length at birth, birth order, gestational age, maternal age, and marital and occupational status. Our findings raise the possibility that home birth can lead to lower cognitive function in adulthood; however, from our data we could not distinguish between planned and unplanned births at home.

  9. Tissue-engineered matrices as functional delivery systems: adsorption and release of bioactive proteins from degradable composite scaffolds.

    Science.gov (United States)

    Cushnie, Emily K; Khan, Yusuf M; Laurencin, Cato T

    2010-08-01

    A tissue-engineered bone graft should imitate the ideal autograft in both form and function. However, biomaterials that have appropriate chemical and mechanical properties for grafting applications often lack biological components that may enhance regeneration. The concept of adding proteins such as growth factors to scaffolds has therefore emerged as a possible solution to improve overall graft design. In this study, we investigated this concept by loading porous hydroxyapatite-poly(lactide-co-glycolide) (HA-PLAGA) scaffolds with a model protein, cytochrome c, and then studying its release in a phosphate-buffered saline solution. The HA-PLAGA scaffold has previously been shown to be bioactive, osteoconductive, and to have appropriate physical properties for tissue engineering applications. The loading experiments demonstrated that the HA-PLAGA scaffold could also function effectively as a substrate for protein adsorption and release. Scaffold protein adsorptive loading (as opposed to physical entrapment within the matrix) was directly related to levels of scaffold HA-content. The HA phase of the scaffold facilitated protein retention in the matrix following incubation in aqueous buffer for periods up to 8 weeks. Greater levels of protein retention time may improve the protein's effective activity by increasing the probability for protein-cell interactions. The ability to control protein loading and delivery simply via composition of the HA-PLAGA scaffold offers the potential of forming robust functionalized bone grafts. (c) 2010 Wiley Periodicals, Inc.

  10. Potential functional bakery products as delivery systems for prebiotics and probiotics health enhancers.

    Science.gov (United States)

    Longoria-García, S; Cruz-Hernández, M A; Flores-Verástegui, M I M; Contreras-Esquivel, J C; Montañez-Sáenz, J C; Belmares-Cerda, R E

    2018-03-01

    Several health benefits have been associated to probiotics and prebiotics, most of these are involved in the regulation of the host's gut microbiome. Their incorporation to diverse food products has been done to develop potential functional foods. In the case of bakery products, their incorporation has been seen to improve several technological parameters such as volume, specific volume, texture along with sensorial parameters such as flavor and aroma. Scientific literature in this topic has been divided in three main research branches: nutrition, physical quality and sensory analyzes, however, studies rarely cover all of them. Due to the harsh thermal stress during baking, sourdough technology along with microencapsulation of probiotics, has been studied as an alternative to enhance its nutritional values and increase cell viability, though in few occasions. The potential functional baked goods have maintained acceptable physical characteristics and sensorial acceptability, while in some cases an improvement is seen due to the effect of probiotics and prebiotics. The results obtained from several studies done, have shown the viability of developing functional bakery products by applying prebiotics or probiotics. This could be used as an encouragement for more research to be done in this topic.

  11. In vitro head-to-head comparison of the durability, versatility and efficacy of the NGage and novel Dakota stone retrieval baskets.

    Science.gov (United States)

    Bechis, Seth K; Abbott, Joel E; Sur, Roger L

    2017-12-01

    To compare head to head two end-engaging nitinol stone retrieval devices available to urologists, in terms of durability, versatility and efficacy. For durability testing, 30 NGage and Dakota baskets were cycled 20 times between grasping and releasing synthetic stone models and evaluated for damage or device failure. For versatility and efficacy testing, baskets were assessed in their ability to capture and release stone models from 1 to 11 mm. Each stone was raised above the capture site and the basket was opened to passively release the stone. If the stone did not release, the basket handle was shaken and the OpenSure feature employed if needed. Manual release was used as a last resort. Durability-the Cook NGage demonstrated a statistically significant increased rate of visible device breakdown (P=0.0046) in 8 of 30 (26.7%) devices vs. 0 of 30 Dakota devices, with mean damage at 13.5 cycles. Versatility and efficacy-both 8 mm baskets successfully captured stones from 1-8 mm. The Dakota more effectively released 7-8 mm stones (PDakota. For 11 mm baskets, the Dakota released all stones up to 10 mm with simple opening, while the NGage released 10 of 15 (67%) of 9 mm stones and 1 of 15 (7%) of 10 mm stones by simple opening. For 11 mm stones, the Dakota captured 100% whereas NGage could not capture any. Both baskets showed similar durability characteristics. The Dakota basket more effectively captured and released stones over 7 mm, as compared to the NGage basket. The OpenSure aspect conferred an advantage in handling and release of larger stones. These in vitro results demonstrate potential versatility, durability and efficacy of the Dakota basket.

  12. Schwann cell-mediated delivery of glial cell line-derived neurotrophic factor restores erectile function after cavernous nerve injury.

    Science.gov (United States)

    May, Florian; Buchner, Alexander; Schlenker, Boris; Gratzke, Christian; Arndt, Christian; Stief, Christian; Weidner, Norbert; Matiasek, Kaspar

    2013-03-01

    To evaluate the time-course of functional recovery after cavernous nerve injury using glial cell line-derived neurotrophic factor-transduced Schwann cell-seeded silicon tubes. Sections of the cavernous nerves were excised bilaterally (5 mm), followed by immediate bilateral surgical repair. A total of 20 study nerves per group were reconstructed by interposition of empty silicon tubes and silicon tubes seeded with either glial cell line-derived neurotrophic factor-overexpressing or green fluorescent protein-expressing Schwann cells. Control groups were either sham-operated or received bilateral nerve transection without nerve reconstruction. Erectile function was evaluated by relaparotomy, electrical nerve stimulation and intracavernous pressure recording after 2, 4, 6, 8 and 10 weeks. The animals underwent re-exploration only once, and were killed afterwards. The nerve grafts were investigated for the maturation state of regenerating nerve fibers and the fascular composition. Recovery of erectile function took at least 4 weeks in the current model. Glial cell line-derived neurotrophic factor-transduced Schwann cell grafts restored erectile function better than green fluorescent protein-transduced controls and unseeded conduits. Glial cell line-derived neurotrophic factor-transduced grafts promoted an intact erectile response (4/4) at 4, 6, 8 and 10 weeks that was overall significantly superior to negative controls (P cell line-derived neurotrophic factor-transduced grafts compared with negative controls (P = 0.018) and unseeded tubes (P = 0.034). Return of function was associated with the electron microscopic evidence of preganglionic myelinated nerve fibers and postganglionic unmyelinated axons. Schwann cell-mediated delivery of glial cell line-derived neurotrophic factor presents a viable approach for the treatment of erectile dysfunction after cavernous nerve injury. © 2013 The Japanese Urological Association.

  13. 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)

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

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Robertson, Aileen; Hondru, Gabriela

    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...... every day is unrealistic and too monotonous to be maintained, so this novel approach is used to select a wide range of diverse foods that can be recommended for a period of up to, for example, one month. The following are the key findings of this report. • The simplest version of the Romanian food.......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...

  15. A basket two-part model to analyze medical expenditure on interdependent multiple sectors.

    Science.gov (United States)

    Sugawara, Shinya; Wu, Tianyi; Yamanishi, Kenji

    2018-05-01

    This study proposes a novel statistical methodology to analyze expenditure on multiple medical sectors using consumer data. Conventionally, medical expenditure has been analyzed by two-part models, which separately consider purchase decision and amount of expenditure. We extend the traditional two-part models by adding the step of basket analysis for dimension reduction. This new step enables us to analyze complicated interdependence between multiple sectors without an identification problem. As an empirical application for the proposed method, we analyze data of 13 medical sectors from the Medical Expenditure Panel Survey. In comparison with the results of previous studies that analyzed the multiple sector independently, our method provides more detailed implications of the impacts of individual socioeconomic status on the composition of joint purchases from multiple medical sectors; our method has a better prediction performance.

  16. 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

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

    International Nuclear Information System (INIS)

    Avegliano, Roseane P.; Maihara, Vera A.; Silva, Fabio F. da

    2009-01-01

    To establish a Market Basket of Sao Paulo state seventy-one foods, with a mean consumption of more than 2 g day -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)

  18. Structural analysis on the open basket type instrumented capsule for fuel irradiation tests in HANARO

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Do Sik; Kang, Y. H.; Kim, B. G.; Cho, M. S.; Sohn, J. M.; Choo, K. N.; Oh, J. M.; Shin, Y. T.; Park, S. J. [Korea Atomic Energy Research Institute, Taejeon (Korea)

    2002-05-01

    To develop the open basket type instrumented capsule to be used for the irradiation test of various nuclear fuels, it is necessary to ensure the compatibility of the capsule with HANARO and the structural integrity of the capsule. The dimensions of the open basket type instrumented capsule were determined in the basis of the pressure drop criteria in OR test hole of HANARO(mass flow rate <12.7kg/s, pressure drop {delta}P>200kPa). From the buckling stability analysis for this capsule, the critical buckling load P{sub cr} was 7.5kN. The vertical impact stress of the capsule under unit impact load was evaluated by the transient analysis, and the maximum vertical impact load calculated from the impact stress and the allowable stress was 60.5kN. Under the loading of the calculated Pcr, the maximum vertical impact stress was 20.4MPa. The structural integrity of the capsule under a horizontal impact loading was also examined. The mechanical stresses occurred by the pressure difference at the inner and outer surface of cladding and by the coolant pressure at the surface of cladding were 3.1MPa and 43.3MPa, respectively. These stress values were lower than the allowable stress in each case. Therefore, it was ensured that the instrumented capsule for the irradiation test of various nuclear fuels met the criteria on the structural integrity during installing and testing the capsule in HANARO. 8 refs., 61 figs., 3 tabs. (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. 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

  1. Development of mannose functionalized dendrimeric nanoparticles for targeted delivery to macrophages: use of this platform to modulate atherosclerosis.

    Science.gov (United States)

    He, Hongliang; Yuan, Quan; Bie, Jinghua; Wallace, Ryan L; Yannie, Paul J; Wang, Jing; Lancina, Michael G; Zolotarskaya, Olga Yu; Korzun, William; Yang, Hu; Ghosh, Shobha

    2018-03-01

    Dysfunctional macrophages underlie the development of several diseases including atherosclerosis where accumulation of cholesteryl esters and persistent inflammation are 2 of the critical macrophage processes that regulate the progression as well as stability of atherosclerotic plaques. Ligand-dependent activation of liver-x-receptor (LXR) not only enhances mobilization of stored cholesteryl ester but also exerts anti-inflammatory effects mediated via trans-repression of proinflammatory transcription factor nuclear factor kappa B. However, increased hepatic lipogenesis by systemic administration of LXR ligands (LXR-L) has precluded their therapeutic use. The objective of the present study was to devise a strategy to selectively deliver LXR-L to atherosclerotic plaque-associated macrophages while limiting hepatic uptake. Mannose-functionalized dendrimeric nanoparticles (mDNP) were synthesized to facilitate active uptake via the mannose receptor expressed exclusively by macrophages using polyamidoamine dendrimer. Terminal amine groups were used to conjugate mannose and LXR-L T091317 via polyethylene glycol spacers. mDNP-LXR-L was effectively taken up by macrophages (and not by hepatocytes), increased expression of LXR target genes (ABCA1/ABCG1), and enhanced cholesterol efflux. When administered intravenously to LDLR-/- mice with established plaques, significant accumulation of fluorescently labeled mDNP-LXR-L was seen in atherosclerotic plaque-associated macrophages. Four weekly injections of mDNP-LXR-L led to significant reduction in atherosclerotic plaque progression, plaque necrosis, and plaque inflammation as assessed by expression of nuclear factor kappa B target gene matrix metalloproteinase 9; no increase in hepatic lipogenic genes or plasma lipids was observed. These studies validate the development of a macrophage-specific delivery platform for the delivery of anti-atherosclerotic agents directly to the plaque-associated macrophages to attenuate plaque

  2. Biological functionalization of drug delivery carriers to bypass size restrictions of receptor-mediated endocytosis independently from receptor targeting.

    Science.gov (United States)

    Ansar, Maria; Serrano, Daniel; Papademetriou, Iason; Bhowmick, Tridib Kumar; Muro, Silvia

    2013-12-23

    Targeting of drug carriers to cell-surface receptors involved in endocytosis is commonly used for intracellular drug delivery. However, most endocytic receptors mediate uptake via clathrin or caveolar pathways associated with ≤200-nm vesicles, restricting carrier design. We recently showed that endocytosis mediated by intercellular adhesion molecule 1 (ICAM-1), which differs from clathrin- and caveolae-mediated pathways, allows uptake of nano- and microcarriers in cell culture and in vivo due to recruitment of cellular sphingomyelinases to the plasmalemma. This leads to ceramide generation at carrier binding sites and formation of actin stress-fibers, enabling engulfment and uptake of a wide size-range of carriers. Here we adapted this paradigm to enhance uptake of drug carriers targeted to receptors associated with size-restricted pathways. We coated sphingomyelinase onto model (polystyrene) submicro- and microcarriers targeted to clathrin-associated mannose-6-phosphate receptor. In endothelial cells, this provided ceramide enrichment at the cell surface and actin stress-fiber formation, modifying the uptake pathway and enhancing carrier endocytosis without affecting targeting, endosomal transport, cell-associated degradation, or cell viability. This improvement depended on the carrier size and enzyme dose, and similar results were observed for other receptors (transferrin receptor) and cell types (epithelial cells). This phenomenon also enhanced tissue accumulation of carriers after intravenous injection in mice. Hence, it is possible to maintain targeting toward a selected receptor while bypassing natural size restrictions of its associated endocytic route by functionalization of drug carriers with biological elements mimicking the ICAM-1 pathway. This strategy holds considerable promise to enhance flexibility of design of targeted drug delivery systems.

  3. Nanoemulsion-based delivery systems to improve functionality of lipophilic components

    Directory of Open Access Journals (Sweden)

    ISABEL eODRIOZOLA-SERRANO

    2014-12-01

    Full Text Available The use of active lipophilic substances such as antimicrobials and health-related compounds in the food industry still is a challenge due to their poor water-solubility and instability in food formulations. Nano-sized structures such as nanoemulsions of oil-in-water are regarded as useful tools with a great potential in the food sector to incorporate food ingredients. Reducing the size of the active compounds incorporated within a solution would increase the surface area per mass unit of nanoemulsions thus enhancing solubility and stability in foods. In addition, the ability of the active lipids to penetrate across biological membranes is also enhanced, thus boosting their biological functionality. An overview of the most significant studies reporting data about the potential benefits of active lipid nanoemulsions over conventional emulsions is presented.

  4. Functionalized PLA-PEG nanoparticles targeting intestinal transporter PepT1 for oral delivery of acyclovir.

    Science.gov (United States)

    Gourdon, Betty; Chemin, Caroline; Moreau, Amélie; Arnauld, Thomas; Baumy, Philippe; Cisternino, Salvatore; Péan, Jean-Manuel; Declèves, Xavier

    2017-08-30

    Targeting intestinal di- and tri-peptide transporter PepT1 with prodrugs is a successful strategy to improve oral drug bioavailability, as demonstrated with valacyclovir, a prodrug of acyclovir. The aim of this new drug delivery strategy is to over-concentrate a poorly absorbed drug on the intestinal membrane surface by targeting PepT1 with functionalized polymer nanoparticles. In the present study, poly(lactic acid)-poly(ethylene glycol)-ligand (PLA-PEG-ligand) nanoparticles were obtained by nanoprecipitation. A factorial experimental design allowed us to identify size-influent parameters and to obtain optimized ≈30nm nanoparticles. Valine, Glycylsarcosine, Valine-Glycine, and Tyrosine-Valine were chemically linked to PLA-PEG. In Caco-2 cell monolayer model, competition between functionalized nanoparticles and [ 3 H]Glycylsarcosine, a strong substrate of PepT1, reduced [ 3 H]Glycylsarcosine transport from 22 to 46%. Acyclovir was encapsulated with a drug load of ≈10% in valine-functionalized nanoparticles, resulting in a 2.7-fold increase in permeability as compared to the free drug. An in vivo pharmacokinetic study in mice compared oral absorption of acyclovir after administration of 25mg/kg of valacyclovir, free or encapsulated acyclovir in functionalized nanoparticles. Acyclovir encapsulation did not statistically modify AUC or C max , but increased t 1/2 and MRT 1.3-fold as compared to free acyclovir. This new strategy is promising for poorly absorbed drugs by oral administration. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. 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

  6. Localized Intrathecal Delivery of Mesenchymal Stromal Cells Conditioned Medium Improves Functional Recovery in a Rat Model of Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Dasa Cizkova

    2018-03-01

    Full Text Available It was recently shown that the conditioned medium (CM of mesenchymal stem cells can enhance viability of neural and glial cell populations. In the present study, we have investigated a cell-free approach via CM from rat bone marrow stromal cells (MScCM applied intrathecally (IT for spinal cord injury (SCI recovery in adult rats. Functional in vitro test on dorsal root ganglion (DRG primary cultures confirmed biological properties of collected MScCM for production of neurosphere-like structures and axon outgrowth. Afterwards, rats underwent SCI and were treated with IT delivery of MScCM or vehicle at postsurgical Days 1, 5, 9, and 13, and left to survive 10 weeks. Rats that received MScCM showed significantly higher motor function recovery, increase in spared spinal cord tissue, enhanced GAP-43 expression and attenuated inflammation in comparison with vehicle-treated rats. Spared tissue around the lesion site was infiltrated with GAP-43-labeled axons at four weeks that gradually decreased at 10 weeks. Finally, a cytokine array performed on spinal cord extracts after MScCM treatment revealed decreased levels of IL-2, IL-6 and TNFα when compared to vehicle group. In conclusion, our results suggest that molecular cocktail found in MScCM is favorable for final neuroregeneration after SCI.

  7. 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

  8. Thioether profragrances: parameters influencing the performance of precursor-based fragrance delivery in functional perfumery.

    Science.gov (United States)

    Maddalena, Umberto; Trachsel, Alain; Fankhauser, Peter; Berthier, Damien L; Benczédi, Daniel; Wang, Wei; Xi, Xiujuan; Shen, Youqing; Herrmann, Andreas

    2014-11-01

    A series of thioether profragrances was prepared by reaction of different sulfanylalkanoates with δ-damascone and tested for their release efficiencies in a fabric-softener and an all-purpose cleaner application. Dynamic headspace analysis on dry cotton and on a ceramic plate revealed that the performance of the different precursors depended on the structure, but also on the particular conditions encountered in different applications. Moreover, profragrances derived from other α,β-unsaturated fragrance aldehydes and ketones were synthesized analogously and evaluated using the same test protocol. Thioethers were found to be suitable precursors to release the corresponding fragrances, but neither the quantity of profragrance deposited from an aqueous environment onto the target surface, nor the amount of fragrance released after deposition could be linearly correlated to the hydrophilicity or hydrophobicity of the compounds. Different sets of compounds were found to be the best performers for different types of applications. Only one of the compounds evaluated in the present work, namely the thiolactic acid derivative of δ-damascone, efficiently released the corresponding fragrance in both of the tested applications. Profragrance development for functional perfumery thus remains a partially empirical endeavour. More knowledge (and control) of the various application conditions are required for an efficient profragrance design. Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.

  9. Synthesis, Characterization, and Atenolol Delivery Application of Functionalized Mesoporous Hydroxyapatite Nanoparticles Prepared by Microwave-Assisted Co-precipitation Method.

    Science.gov (United States)

    Mortazavi-Derazkola, Sobhan; Naimi-Jamal, Mohammad Reza; Ghoreishi, Seyedeh Masoumeh

    2016-01-01

    Atenolol has been used to treat angina and hypertension, either alone or with other antihypertensives. Despite its usefulness, it shows some side effects such as diarrhea and nausea in some patients. A method for slow release of atenolol in intestine is helpful to prevent such side effects. A facile co-precipitation microwave-assisted method was used to fabricate mesoporous hydroxyapatite nanoparticles (mHAp). It was then functionalized to have SO3H groups. The synthesized material was used for storage/slow release study of atenolol. Atenolol loaded mHAp shows immediate release of atenolol in pH 8, whileafter functionalizing shows up to ca. 30% release at the beginning. In pH 1, 50% of drug was released after 10 h from AT@mHAp and after 18h the drug was almost completely released.The drug release profiles of functionalized HAp at pH value 1 and 8reveals the complete release of atenolol in intestine pH, while no complete release is observed in stomach environment. The aims of this work were synthesis and characterization of mesoporous HAp through the microwave-assisted co-precipitation method and elucidate the underlying drug release capability of mesoporous HAp nanoparticles. The SO3H group was incorporated into the mesoporous HAp and then used as drug delivery carriers using atenolol as a model drug to investigate their drug storage/release properties in simulated body fluid (SBF). Increasing pH value to 8 causes increase in the drug release.

  10. 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

  11. 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.

  12. Biopolymers/poly(ε-caprolactone)/polyethylenimine functionalized nano-hydroxyapatite hybrid cryogel: Synthesis, characterization and application in gene delivery.

    Science.gov (United States)

    Simionescu, Bogdan C; Drobota, Mioara; Timpu, Daniel; Vasiliu, Tudor; Constantinescu, Cristina Ana; Rebleanu, Daniela; Calin, Manuela; David, Geta

    2017-12-01

    Nano-hydroxyapatite (nHAp), surface functionalized with linear polyethylenimine (LPEI), was used for the preparation of biocomposites in combination with biopolymers and poly(ε-caprolactone) (PCL), by cryogelation technique, to yield biomimetic scaffolds with controlled interconnected macroporosity, mechanical stability, and predictable degradation behavior. The structural characteristics, swelling and degradation behavior of hydroxyapatite and hydroxyapatite/β-tricalcium phosphate (β-TCP) filled matrices were investigated as compared to the corresponding naked polymer 3D system. It was found that the homogeneity and cohesivity of the composite are significantly dependent on the size and amount of the included inorganic particles, which are thus determining the structural parameters. Surface modification with LPEI and nanodimensions favored the nHAp integration in the organic matrix, with preferential location along protein fibers, while β-TCP microparticles induced an increased disorder in the hybrid system. The biocomposite including nHAp only was further investigated targeting biomedical uses, and proved to be non-cytotoxic and capable of acting as gene-activated matrix (GAM). It allowed sustained delivery over time (until 22days) of embedded PEI 25 -pDNA polyplexes at high levels of transgene expression, while insuring a decrease in cytotoxicity as compared to polyplexes alone. Experimental data recommend such biocomposite as an attractive material for regenerative medicine. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Formulation, functional evaluation and ex vivo performance of thermoresponsive soluble gels - A platform for therapeutic delivery to mucosal sinus tissue.

    Science.gov (United States)

    Pandey, Preeti; Cabot, Peter J; Wallwork, Benjamin; Panizza, Benedict J; Parekh, Harendra S

    2017-01-01

    Mucoadhesive in situ gelling systems (soluble gels) have received considerable attention recently as effective stimuli-transforming vectors for a range of drug delivery applications. Considering this fact, the present work involves systematic formulation development, optimization, functional evaluation and ex vivo performance of thermosensitive soluble gels containing dexamethasone 21-phosphate disodium salt (DXN) as the model therapeutic. A series of in situ gel-forming systems comprising the thermoreversible polymer poloxamer-407 (P407), along with hydroxypropyl methyl cellulose (HPMC) and chitosan were first formulated. The optimized soluble gels were evaluated for their potential to promote greater retention at the mucosal surface, for improved therapeutic efficacy, compared to existing solution/suspension-based steroid formulations used clinically. Optimized soluble gels demonstrated a desirable gelation temperature with Newtonian fluid behaviour observed under storage conditions (4-8°C), and pseudoplastic fluid behaviour recorded at nasal cavity/sinus temperature (≈34°C). The in vitro characterization of formulations including rheological evaluation, textural analysis and mucoadhesion studies of the gel form were investigated. Considerable improvement in mechanical properties and mucoadhesion was observed with incorporation of HPMC and chitosan into the gelling systems. The lead poloxamer-based soluble gels, PGHC4 and PGHC7, which were carried through to ex vivo permeation studies displayed extended drug release profiles in conditions mimicking the human nasal cavity, which indicates their suitability for treating a range of conditions affecting the nasal cavity/sinuses. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Evaluation of gene delivery strategies to efficiently overexpress functional HLA-G on human bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    Joana S Boura

    2014-01-01

    Full Text Available Mesenchymal stromal cells (MSC constitutively express low levels of human leukocyte antigen-G (HLA-G, which has been shown to contribute to their immunomodulatory and anti-inflammatory properties. Here, we hypothesized that overexpression of HLA-G on bone marrow-derived MSC would improve their immunomodulatory function, thus increasing their therapeutic potential. Therefore, we investigated which gene transfer system is best suited for delivering this molecule while maintaining its immunomodulatory effects. We performed a side-by-side comparison between three nonviral plasmid-based platforms (pmax-HLA-G1; MC-HLA-G1; pEP-HLA-G1 and a viral system (Lv-HLA-G1 using gene transfer parameters that yielded similar levels of HLA-G1-expressing MSC. Natural killer (NK cell–mediated lysis assays and T cell proliferation assays showed that MSC modified with the HLA-G1 expressing viral vector had significantly lower susceptibility to NK-lysis and significantly reduced T cell proliferation when compared to nonmodified cells or MSC modified with plasmid. We also show that, in plasmid-modified MSC, an increase in Toll-like receptor (TLR9 expression is the mechanism responsible for the abrogation of HLA-G1's immunomodulatory effect. Although MSC can be efficiently modified to overexpress HLA-G1 using viral and nonviral strategies, only viral-based delivery of HLA-G1 is suitable for improvement of MSC's immunomodulatory properties.

  15. Luminescent GdVO4:Eu3+ functionalized mesoporous silica nanoparticles for magnetic resonance imaging and drug delivery.

    Science.gov (United States)

    Huang, Shanshan; Cheng, Ziyong; Ma, Ping'an; Kang, Xiaojiao; Dai, Yunlu; Lin, Jun

    2013-05-14

    Luminescent GdVO4:Eu(3+) nanophosphor functionalized mesoporous silica nanoparticles (MSN) were prepared (denoted as GdVO4:Eu(3+)@MSN). The in vitro cytotoxicity tests show that the sample has good biocompatibility, which indicates that the nanocomposite could be a promising candidate for drug delivery. Flow cytometry and confocal laser scanning microscopy (CLSM) confirm that the sample can be effectively taken up by SKOV3 ovarian cancer cells and A549 lung adenocarcinoma cells. It was also shown that the GdVO4:Eu(3+)@MSN brightened the T1-weighted images and enhanced the r1 relaxivity of water protons, which suggested that they could act as T1 contrast agents for magnetic resonance (MR) imaging. It was found that the carriers present a pH-dependent drug release behavior for doxorubicin (DOX). The composites show a red emission under UV irradiation due to the GdVO4:Eu(3+) nanophosphors. Furthermore, the PL intensity of the composite shows correlation with the cumulative release of DOX. These results suggest that the composite can potentially act as a multifunctional drug carrier system with luminescent tagging, MR imaging and pH-controlled release property for DOX.

  16. 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.

  17. Delivery presentations

    Science.gov (United States)

    Pregnancy - delivery presentation; Labor - delivery presentation; Occiput posterior; Occiput anterior; Brow presentation ... The mother can walk, rock, and try different delivery positions during labor to help encourage the baby ...

  18. Optimization of self-microemulsifying drug delivery system for telmisartan using Box-Behnken design and desirability function.

    Science.gov (United States)

    Cho, Hyuk Jun; Lee, Dong Won; Marasini, Nirmal; Poudel, Bijay Kumar; Kim, Jeong Hwan; Ramasamy, Thiruganesh; Yoo, Bong Kyu; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2013-10-01

    To develop and optimize the novel self-microemulsifying drug delivery system (SMEDDS) formulation for enhanced water solubility and bioavailability of telmisartan (TMS) using the Box-Behnken design (BBD) and desirability function. TMS-SMEDDS formulation consisted of the mixture of oil (Peceol), surfactant (Labrasol), co-surfactant (Transcutol), TMS and triethanolamine. A three-level BBD was applied to explore the main effect, interaction effect and quadratic effect of three independent variables, including the amount of Peceol (X1 ), Labrasol (X2 ) and Transcutol (X3 ). Determined conditions were 20 < X1  < 40, 50 < X2  < 80 and 5 < X3  < 30. The response variables were droplet size (Y1 ), polydispersity index (Y2 ) and dissolution percentage of TMS after 15 min (Y3 ). The optimized conditions were 28.93, 80 and 28.08 (mg) for X1 , X2 and X3 , respectively, and the response variables were predicted to be 159.8 nm, 0.241 and 85.8% for Y1 , Y2 and Y3 , respectively. The actual values from the optimized formulation showed good agreement with predicted values. The optimized TMS-SMEDDS formulation showed faster drug dissolution rate and higher bioavailability than TMS powder. Our results suggest that response surface methodology using BBD and desirability function is a promising approach to understand the effect of SMEDDS variables and to optimize the formulation. © 2013 Royal Pharmaceutical Society.

  19. Novel functionalized nanoparticles for tumor-targeting co-delivery of doxorubicin and siRNA to enhance cancer therapy

    Directory of Open Access Journals (Sweden)

    Xia Y

    2017-12-01

    Full Text Available Yu Xia, Tiantian Xu, Changbing Wang, Yinghua Li, Zhengfang Lin, Mingqi Zhao, Bing Zhu Central Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China Abstract: Human homeobox protein (Nanog is highly expressed in most cancer cells and has gradually emerged as an excellent target in cancer therapy, owing to its regulation of cancer cell proliferation, metastasis and apoptosis. In this study, we prepared tumor-targeting functionalized selenium nanoparticles (RGDfC-SeNPs to load chemotherapeutic doxorubicin (DOX and Nanog siRNA. Herein, RGDfC peptide was used as a tumor-targeting moiety which could specifically bind to αvβ3 integrins overexpressed on various cancer cells. The sizes of RGDfC-SeNPs@DOX nanoparticles (~12 nm were confirmed by both dynamic light scattering and transmission electron microscopy. The chemical structure of RGDfC-SeNPs@DOX was characterized via Fourier-transform infrared spectroscopy. The RGDfC-SeNPs@DOX was compacted with siRNA (anti-Nanog by electrostatic interaction to fabricate the RGDfC-SeNPs@DOX/siRNA complex. The RGDfC-SeNPs@DOX/siRNA complex nanoparticles could efficiently enter into HepG2 cells via clathrin-associated endocytosis, and showed high gene transfection efficiency that resulted in enhanced gene silencing. The in vivo biodistribution experiment indicated that RGDfC-SeNPs@DOX/siRNA nanoparticles were capable of specifically accumulating in the tumor site. Furthermore, treatment with RGDfC-SeNPs@DOX/siRNA resulted in a more significant anticancer activity than the free DOX, RGDfC-SeNPs@DOX or RGDfC-SeNPs/siRNA in vitro and in vivo. In summary, this study shows a novel type of DOX and siRNA co-delivery system, thereby providing an alternative route for cancer treatment. Keywords: nanoparticles, tumor targeting, drug delivery, doxorubicin, Nanog siRNA

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

    International Nuclear Information System (INIS)

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

    2016-01-01

    The functionalization and surface engineering of CoFe 2 O 4 and ZnFe 2 O 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 2 O 4 and ZnFe 2 O 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.

  2. 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

    available foods. The study was designed to obtain healthy, affordable, and socially acceptable diets for three European countries (Denmark, Slovenia, and Romania) and in three regions within Canada, Argentina, and Switzerland. Moreover, the costs for the “limiting” micronutrients and relative price......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...

  3. In vitro release of ketoprofen suppositories using the USP basket and the flow-through cell dissolution methods.

    Science.gov (United States)

    Medina, José Raúl; Padilla, Adrián Roberto; Hurtado, Marcela; Cortés, Alma Rosa; Domínguez-Ramírez, Adriana Miriam

    2014-05-01

    In order to study the release characteristics of ketoprofen suppositories under the hydrodynamic environment generated by USP Apparatus 1 and 4, the dissolution profiles of the Mexican reference product (100 mg) were determined. Phosphate buffer pH 8 and 1% sodium lauryl sulfate (SLS) aqueous solutions were proved as dissolution mediums. Baskets were rotated at 100 rpm with USP Apparatus 1 and different flow rates from 16-32 mL/min with USP Apparatus 4 were used. Drug samples were taken and quantified during 60 min by UV analysis at 260 nm. Mean dissolution time (MDT) and dissolution efficiency (DE) were calculated by model-independent methods. Data were also fitted to several kinetic models. Poor dissolution was found in both dissolution mediums when USP basket method was used ( 0.99). The results suggest the need to establish an adequate dissolution method to evaluate the release kinetics of ketoprofen from suppositories.

  4. 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.

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

    International Nuclear Information System (INIS)

    Kim, Young Hwan; Ko, Sung Min; Kim, Mi Jung; Kwon, Jung Hyeok; Sohn, Cheol Ho; Choi, Jin Soo; Park, Kyung Sik; Kim, Yong Joo

    2006-01-01

    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 (ρ = 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 (ρ = 0.871). Percutaneous treatment of thrombosed native arteriovenous

  6. 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

  7. Real purchasing power of oil revenues for OPEC Member Countries: a broad currency basket and dynamic trade pattern approach

    International Nuclear Information System (INIS)

    Mazraati, M.

    2005-01-01

    The purpose of this paper is to examine the real purchasing power of OPEC Member Countries' oil revenues, which are subject to 'the value of the US dollar vis-a-vis other major currencies' and 'world imported inflation'. The exponential weighting average formula with a broad basket of currencies is suggested. The basket of currencies is labelled as a broad currency basket and includes the major trading partners of OPEC Member Countries. The weights are normalized OPEC import shares of the countries of the basket and are updated and adjusted every year to incorporate a gradual change in the trade pattern. In other words, the dynamic trade pattern approach is incorporated in the calculations. The nominal dollar oil revenues of OPEC Member Countries are about $5,099 billion during 1970 to 2004, of which $3,725 bn (73 per cent) have been lost due to imported inflation and the dollar's depreciation. Imported inflation and dollar depreciation have had a respective 78.6 per cent and 21.4 per cent contribution to the losses of the purchasing power of OPEC Member Countries. The imported inflation rate approaches a stable low level, but OPEC still has a lot of concerns on dollar swings. The euro offers opportunities for many oil-exporting nations that have extensive trade relations with Euro-zone countries. Payments for oil exports can be invoked in euros at the prevailing dollar-euro rate on the day of a given contract, or any other trigger formula. This would immunize a major portion of OPEC oil revenues from dollar depreciation. (author)

  8. National Beef Market Basket Survey - 2006: External fat thickness measurements and separable component determinations for beef from US retail establishments.

    Science.gov (United States)

    Mason, C L; Nicholson, K L; Brooks, J C; Delmore, R J; Henning, W R; Johnson, D D; Lorenzen, C L; Maddock, R J; Miller, R K; Morgan, J B; Wasser, B E; Gwartney, B L; Harris, K B; Griffin, D B; Hale, D S; Savell, J W

    2009-02-01

    A market basket survey for beef retail cut composition at the retail level (four stores each from two chains in each city) was conducted in 11 US cities from January to March 2006. Beef cuts (n=17,495) were measured for external fat thickness with cuts from the chuck (0.05cm), round (0.05cm), and miscellaneous (0.04cm) having less (Pmarketing purposes.

  9. 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.

  10. STS-95 crew members Duque and Mukai check out slidewire basket

    Science.gov (United States)

    1998-01-01

    At Launch Pad 39-B, STS-95 Mission Specialist Pedro Duque of Spain (left) and Payload Specialist Chiaki Mukai look over the gate for the slidewire basket, part of the emergency egress system on the pad. Mukai represents the National Space Development Agency of Japan (NASDA), and Duque the European Space Agency (ESA). The STS-95 crew are at KSC to participate in a Terminal Countdown Demonstration Test (TCDT) which includes mission familiarization activities, emergency egress training, and a simulated main engine cut-off exercise. Other STS-95 crew members are Mission Specialist Stephen K. Robinson, Mission Commander Curtis L. Brown, Pilot Steven W. Lindsey, Payload Specialists John H. Glenn Jr., senator from Ohio, and Mission Specialist Scott E. Parazynski. The STS-95 mission, targeted for liftoff on Oct. 29, includes research payloads such as the Spartan solar-observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as the SPACEHAB single module with experiments on space flight and the aging process. Following the TCDT, the crew will be returning to Houston for final flight preparations.

  11. 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.

  12. A Refined Basket of Goods Approach for Comparing Construction Costs between Countries

    Directory of Open Access Journals (Sweden)

    Rick Best

    2012-11-01

    Full Text Available Most comparisons of construction industry performance requirethat construction costs be converted to a common base. Existingmechanisms for such conversions produce unreliable results.A proposed method for producing industry-specifi c conversionfactors was tested using a single building type. A basket ofmaterials and labour was identifi ed and weighted to refl ect the costshare of each item in a completed project. Prices for the basketwere gathered in three cities and simple construction specifi cconversion indices were calculated based on the constructionpurchasing power of each currency. The construction purchasingpower parities (CPPPs showed marked differences from otheravailable conversion mechanisms such as exchange rates andgeneral purchasing power parities (PPPs that have been used inprevious international comparison studies. While the study waslimited in scope, and is only the fi rst stage of a longer process, thesubstantial differences in comparative costs based on purchasingpower illustrate the problems inherent in international costcomparisons. For example, comparing Singapore and Sydney,Singapore costs appear to be only 40% of those in Sydney (basedon exchange rates about two-thirds the cost of Sydney (usinggeneral PPPs or almost the same (using the preliminary CPPPs.These results illustrate the problems of converting costs fromlocal currencies to a single base currency and suggest that furtherdevelopment is needed to improve the reliability of outcomes.

  13. A market basket survey of As, Zn and Se in rice imports in Qatar: health implications.

    Science.gov (United States)

    Rowell, Candace; Kuiper, Nora; Al-Saad, Khalid; Nriagu, Jerome; Shomar, Basem

    2014-08-01

    Qatar is dependent on importation of rice, its staple dish, and is therefore susceptible to compromises of food quality in the global market. This market basket study assesses potential health risks of As exposure from rice consumption in Qatar and examines its contribution to the recommended nutritional intakes (RNI) for Zn and Se. Fifty-six rice types and 12 products sold in Qatar were analyzed by ICP/MS. Mean concentrations and ranges were 96.2±54.1μg/kg (9.76-258μg/kg) for As; 12.5±5.35mg/kg (2.79-29.9mg/kg) for Zn and 103±113μg/kg (Qatar is not a significant route of As exposure but can contribute up to 100% and 50% of the RNI for Se and Zn, respectively. Results indicate that children in Qatar may be at elevated risk of arsenic exposure from rice-based infant cereals but more data is needed to obtain a definitive assessment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Design of Product Placement Layout In Retail Shop Using Market Basket Analysis

    Directory of Open Access Journals (Sweden)

    Isti Surjandari

    2010-10-01

    Full Text Available Retailing is an industry with high level of competition.  It is a customer-based industry which depends on how it could be aware of what the customers' needs and requirements are. One technique most used in supermarkets is the mix merchandise. The purpose of this paper is to identify associated products, which then grouped in mix merchandise with the use of market basket analysis. This association between products then will be applied in the design layout of the product in the supermarket. The process of identifying the related products bought together in one transaction is done by using data mining  technique. Apriori algorithm is chosen as a method in the data mining process. Using WEKA (Waikato Environment for Knowledge Analysis software, the association rule between products is calculated. The results found five category association rules and fourteen sub-category association rules. These associations then will be interpreted as confidence and support to become consideration for the product layout.

  15. Scoping corrosion tests on candidate waste package basket materials for the Yucca Mountain project

    International Nuclear Information System (INIS)

    Konynenburg, R.A. van; Curtis, P.G.; Summers, T.S.E.

    1998-03-01

    A scoping corrosion test was performed on candidate waste package basket materials. The corrosion medium was a pH-buffered solution of chemical species expected to be produced by radiolysis. The test was conducted at 90 C for 96 hours. Samples included aluminum-, copper-, stainless steel- and zirconium-based metallic materials and several ceramics, incorporating neutron-absorbing elements. Sample weight losses and solution chemical changes were measured. Both corrosion of the host materials and dissolution of the neutron-absorbing elements were studied. The ceramics and the zirconium-based materials underwent only minor corrosion. The stainless steel-based materials performed well except for a welded sample. The aluminum- and copper-based materials exhibited the highest corrosion rates. Boron dissolution depends on its chemical form. Boron oxide and many metal borides dissolve readily in acidic solutions while high-chromium borides and boron carbide, though thermodynamically unstable, exhibit little dissolution in short times. The results of solution chemical analyses were consistent with this. Gadolinium did not dissolve significantly from monazite, and hafnium showed little dissolution from a variety of host materials, in keeping with its low solubility

  16. Functionalizing Ascl1 with Novel Intracellular Protein Delivery Technology for Promoting Neuronal Differentiation of Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Robinson, Meghan; Chapani, Parv; Styan, Tara; Vaidyanathan, Ranjani; Willerth, Stephanie Michelle

    2016-08-01

    Pluripotent stem cells can become any cell type found in the body. Accordingly, one of the major challenges when working with pluripotent stem cells is producing a highly homogenous population of differentiated cells, which can then be used for downstream applications such as cell therapies or drug screening. The transcription factor Ascl1 plays a key role in neural development and previous work has shown that Ascl1 overexpression using viral vectors can reprogram fibroblasts directly into neurons. Here we report on how a recombinant version of the Ascl1 protein functionalized with intracellular protein delivery technology (Ascl1-IPTD) can be used to rapidly differentiate human induced pluripotent stem cells (hiPSCs) into neurons. We first evaluated a range of Ascl1-IPTD concentrations to determine the most effective amount for generating neurons from hiPSCs cultured in serum free media. Next, we looked at the frequency of Ascl1-IPTD supplementation in the media on differentiation and found that one time supplementation is sufficient enough to trigger the neural differentiation process. Ascl1-IPTD was efficiently taken up by the hiPSCs and enabled rapid differentiation into TUJ1-positive and NeuN-positive populations with neuronal morphology after 8 days. After 12 days of culture, hiPSC-derived neurons produced by Ascl1-IPTD treatment exhibited greater neurite length and higher numbers of branch points compared to neurons derived using a standard neural progenitor differentiation protocol. This work validates Ascl1-IPTD as a powerful tool for engineering neural tissue from pluripotent stem cells.

  17. Biocompatible nanogel derived from functionalized dextrin for targeted delivery of doxorubicin hydrochloride to MG 63 cancer cells.

    Science.gov (United States)

    Das, Dipankar; Rameshbabu, Arun Prabhu; Ghosh, Paulomi; Patra, Priyapratim; Dhara, Santanu; Pal, Sagar

    2017-09-01

    The present article demonstrates the targeted delivery of doxorubicin hydrochloride to human osteosarcoma cancer cell lines (MG 63) using functionalized dextrin based crosslinked, pH responsive and biocompatible nanogel. The nanogel has been prepared through Michael-type addition reaction using dextrin (Dxt), N, N'-methylene bisacrylamide (MBA, as crosslinker), acrylic acid (AA, as monomer) and potassium persulfate (KPS, as initiator). The structure, composition, morphology of the nanogel have been explored using FTIR and 1 H NMR spectroscopy, XRD, TGA, DSC, CHN and AFM analyses. The TEM analysis confirmed that the size of nanogel appeared within 100nm, while DLS study indicates that the diameter of the nanogel remained between 113 and 126nm. The AFM study implied the porous morphology of the synthesized nanogel. The rheological study suggests the gel behaviour of the synthesized nanogel at 37±0.1°C. Difference in% swelling at pH 5.5 and 7.4 indicates pH-responsiveness of the nanogel. The in vitro cytocompatibility results ascertained that the nanogel is non-toxic to human mesenchymal stem cells (hMSCs). In vitro cellular uptake study confirmed that FITC-loaded nanogel can cross the cellular membrane and be well uptake by the cell cytoplasm. The nanogel could efficiently encapsulate doxorubicin hydrochloride (Dox) with the loading efficiency of 27±0.2% after 72h. The Dox-loaded nanogel demonstrates anti-cancer activity towards MG 63 cancer cells and release the encapsulated drug in a controlled way. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Recovery of HPA Axis Function After Successful Gonadotropin-Induced Pregnancy and Delivery in a Woman With Panhypopituitarism: Case Report and Review.

    Science.gov (United States)

    Wang, Yi; Zhang, Qiongyue; Yang, Jianzhi; Zhao, Xiaolong; He, Min; Shou, Xuefei; Li, Shiqi; Li, Yiming; Wang, Yongfei; Ye, Hongying

    2015-09-01

    Hypopituitarism is defined as the partial or complete defect of anterior pituitary hormone secretion. Patients with hypopituitarism usually need life-long hormone replacement therapy. However, in this case, we report a patient with panhypopituitarism whose hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered after pregnancy and delivery. In this case study, we reported the case management and conducted a review of literature to identify the possible mechanism of pituitary function recovery. The patient who suffered from secondary amenorrhea was found a nonfunctioning pituitary macroadenoma, and the hormone test showed serum cortisol, FT3, FT4, thyrotropic hormone, and prolactin were at normal range. After surgical removal of the tumor which invasion in the sellar region, the patient had panhypopituitarism confirmed by the routine hormone test. Though spontaneous pregnancy is impossible in female patients with panhypopituitarism, the patient was restored fertility by the help of artificial reproductive techniques. After the confirmation of the pregnancy, levothyroixine was increased to 75 μg daily and readjusted to 150 μg daily before delivery according to the monthly measurement thyroid function. Hydrocortisone 10 mg daily replaced cortisone acetate; the dose was increased according to the symptoms of morning sickness. A single stress dose of hydrocortisone (200 mg) was used before elective cesarean delivery and was tapered to the dose of 10 mg per day in 1 week. Levothyroixine was reduced to 75 μg daily after delivery. During follow-up, her hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered. The peak serum cortisol level could increase to 19.08 μg/dL by insulin-induced hypoglycemia. However, growth hormone remained unresponsive to the insulin-tolerance test, and thyroid hormone still needed exogenous supplementation. Hormone replacement therapy needed closely followed by endocrinologist and multidisciplinary

  19. Development of high-strength aluminum alloys for basket in transport and storage cask for high burn-up spent fuel

    International Nuclear Information System (INIS)

    Maeguchi, T.; Sakaguchi, Y.; Kamiwaki, Y.; Ishii, M.; Yamamoto, T.

    2004-01-01

    Mitsubishi Heavy Industries, Ltd. (MHI) has developed high-strength borated aluminum alloys (high-strength B-Al alloys), suitable for application to baskets in transport and storage casks for high burn-up spent fuels. Aluminum is a suitable base material for the baskets due to its low density and high thermal conductivity. The aluminum basket would reduce weight of the cask, and effectively release heat generated by spent fuels. MHI had already developed borated aluminum alloys (high-toughness B-Al alloy), and registered them as ASME Code Case ''N-673''. However, there has been a strong demand for basket materials with higher strength in the case of MSF (Mitsubishi Spent Fuel) casks for high-burn up spent fuels, since the basket is required to stand up to higher stress at higher temperature. The high-strength basket material enables the design of a compact cask under a limitation of total size and weight. MHI has developed novel high-strength B-Al alloys which meet these requirements, based on a new manufacturing process. The outline of mechanical and metallurgical characteristics of the high-strength B-Al alloys is described in this paper

  20. Low-cost production of proinsulin in tobacco and lettuce chloroplasts for injectable or oral delivery of functional insulin and C-peptide.

    Science.gov (United States)

    Boyhan, Diane; Daniell, Henry

    2011-06-01

    Current treatment for type I diabetes includes delivery of insulin via injection or pump, which is highly invasive and expensive. The production of chloroplast-derived proinsulin should reduce cost and facilitate oral delivery. Therefore, tobacco and lettuce chloroplasts were transformed with the cholera toxin B subunit fused with human proinsulin (A, B, C peptides) containing three furin cleavage sites (CTB-PFx3). Transplastomic lines were confirmed for site-specific integration of transgene and homoplasmy. Old tobacco leaves accumulated proinsulin up to 47% of total leaf protein (TLP). Old lettuce leaves accumulated proinsulin up to 53% TLP. Accumulation was so stable that up to ~40% proinsulin in TLP was observed even in senescent and dried lettuce leaves, facilitating their processing and storage in the field. Based on the yield of only monomers and dimers of proinsulin (3 mg/g leaf, a significant underestimation), with a 50% loss of protein during the purification process, one acre of tobacco could yield up to 20 million daily doses of insulin per year. Proinsulin from tobacco leaves was purified up to 98% using metal affinity chromatography without any His-tag. Furin protease cleaved insulin peptides in vitro. Oral delivery of unprocessed proinsulin bioencapsulated in plant cells or injectable delivery into mice showed reduction in blood glucose levels similar to processed commercial insulin. C-peptide should aid in long-term treatment of diabetic complications including stimulation of nerve and renal functions. Hyper-expression of functional proinsulin and exceptional stability in dehydrated leaves offer a low-cost platform for oral and injectable delivery of cleavable proinsulin. © 2010 The Authors. Plant Biotechnology Journal © 2010 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  1. Аpplication of markowitz portfolios based on currency baskets to commodity trade

    OpenAIRE

    Duda, T.; Augustynek, А.

    2012-01-01

    Розглянуто оптимальну структуру кошика валют для мінімізації ризиків торговельних операцій. Проаналізовано принципи побудови оптимального кошика валют, розроблено засадні положення оптимального портфеля Марковіца. Надано пропозиції щодо урахування периферійних валют у структурі платіжного кошика. The article proposes an application of currency basket payments together with Markovitz portfolio idea, to reduce a foreword transactions risk in commodity trade. It follows the line of earlier pa...

  2. Pesticide contamination of fruits and vegetables - A market basket survey from selected regions in Ghana

    International Nuclear Information System (INIS)

    Asiedu, Eric

    2013-07-01

    A market - basket survey was carried out with the aim of determining the concentration levels of pesticides, in lettuce, garden eggs, pineapple and mango from some selected regions in Ghana and to assess the potential health risk associated with exposure to the pesticide residues from fruits and vegetables consumption. A total of 192 fresh samples of fruits and vegetables were randomly collected under normal purchase conditions from 12 major towns and cities in the three regions of Ghana. The samples were extracted and analyzed for organophosphates, synthetic pyrethroids and organo chlorine pesticides. The percentage of samples of fruits and vegetables with pesticide residues in Lettuce, Garden eggs, Pineapple and Mango were 52%, 40%, 45%, 48% respectively and concentrations of pesticides did not vary significantly in samples as well as the sampling areas (p>0.05) even though there were differences in residual concentrations of pesticides . The differences in residual concentrations of pesticides could be due to different agricultural practices adopted by farmers and also accessibility of the pesticides. The average residue concentrations range from 0.01-0.45 mg/kg, 0.01-0.30 mg/kg and 0.01-1.27 mg/kg for organophosphates, synthetic pyrethroids and organo chlorine pesticides respectively. Lindane, chloropyrifos and cypermethrin were the most frequent organo chlorine, organophosphate and synthetic pyrethroid pesticides respectively while lettuce was the most frequently contaminated sample. Comparing the concentration levels of organo chlorine pesticides residue with the maximum residue limits (MRLs) adopted by the FAO/WHO Codex Alimentarious Commission shows that some of the fruits and vegetables sold on Ghanaian markets are contaminated even though the levels are generally low. Health risk analysis indicates that heptachlor in particular may be of public concern since its concentration levels exceeded the reference dose in all the four different types of samples

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

    Science.gov (United States)

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

    2013-01-01

    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 environmental disaster can be

  4. 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

  5. Design and development of hyaluronan-functionalized polybenzofulvene nanoparticles as CD44 receptor mediated drug delivery system

    Science.gov (United States)

    Licciardi, Mariano; Scialabba, Cinzia; Giammona, Gaetano; Paolino, Marco; Razzano, Vincenzo; Grisci, Giorgio; Giuliani, Germano; Makovec, Francesco; Cappelli, Andrea

    2017-06-01

    A tri-component polymer brush (TCPB ), composed of a polybenzofulvene copolymer bearing low molecular weight hyaluronic acid (HA) on the surface of its cylindrical brush-like backbone and oligo-PEG fractions, was employed in the preparation of 350 nm nanostructured drug delivery systems capable of delivering the anticancer drug doxorubicin. The obtained drug delivery systems were characterized on the basis of drug loading and release, dimensions and zeta potential, morphology and in vitro cell activity, and uptake on three different human cell lines, namely the bronchial epithelial 16HBE, the breast adenocarcinoma MCF-7, and the colon cancer HCT116 cells. Finally, the ability of doxorubicin-loaded TCPB nanoparticles (DOXO-TCPB) to be internalized into cancer cells by CD44 receptor mediated uptake was assessed by means of uptake studies in HCT cells. These data were supported by anti-CD44-FITC staining assay. The proposed TCPB nanostructured drug delivery systems have many potential applications in nanomedicine, including cancer targeted drug delivery.

  6. Chondroitin sulfate-functionalized polyamidoamine as a tumor-targeted carrier for miR-34a delivery.

    Science.gov (United States)

    Chen, Wenqi; Liu, Yong; Liang, Xiao; Huang, Yu; Li, Quanshun

    2017-07-15

    Chondroitin sulfate (CS) was modified on a polyamidoamine dendrimer (PAMAM) through Michael addition to construct a tumor-targeted carrier CS-PAMAM for miR-34a delivery. The derivative CS-PAMAM was demonstrated to achieve an efficient cellular uptake of miR-34a in a CD44-dependent endocytosis way and further facilitate the endosomal escape of miR-34a after 4h. Through the miR-34a delivery, obvious inhibition of cell proliferation could be detected which was attributed to the enhancement of cell apoptosis and cell cycle arrest, and meanwhile the cell migration and invasion has been observed to be inhibited. Finally, the intravenous injection of CS-PAMAM/miR-34a formulation into mice bearing human lung adenocarcinoma cell A549 xenografts could efficiently inhibit the tumor growth and induce the tumor apoptosis owing to the enhanced accumulation of miR-34a in tumor tissue. Overall, CS-PAMAM is potential to be used as a tumor-targeted oligonucleotide carrier for achieving tumor gene therapy. The cationic dendrimer PAMAM was modified by chondroitin sulfate (CS) through Michael addition to construct a tumor-targeted carrier CS-PAMAM for miR-34a delivery. The introduction of CS could achieve an efficient cellular uptake and intracellular transfection of miR-34a in a CD44-dependent endocytosis manner. The miR-34a delivery could execute the anti-proliferation activity by simultaneously inducing cell apoptosis and cell cycle arrest, and also the anti-migration activity. The CS-PAMAM-mediated systemic delivery of miR-34a showed significant inhibition of tumor growth and induction of tumor apoptosis using a mice model of subcutaneously implanted tumors. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  7. Operative vaginal delivery in case of persistent occiput posterior position after manual rotation failure: a 6-month follow-up on pelvic floor function.

    Science.gov (United States)

    Guerby, Paul; Parant, Olivier; Chantalat, Elodie; Vayssiere, Christophe; Vidal, Fabien

    2018-05-21

    To compare the short- and long-term perineal consequences (at 6 months postpartum) and short-term neonatal consequences of instrumental rotation (IR) to those induced by assisted delivery (AD) in the occiput posterior (OP) position, in case of manual rotation failure. A prospective observational cohort study; tertiary referral hospital including all women presenting with persistent OP position who delivered vaginally after manual rotation failure with attempted IR or AD in OP position from September 2015 to October 2016. Maternal and neonatal outcomes of all attempted IR deliveries were compared with OP operative vaginal deliveries. Main outcomes measured were pelvic floor function at 6 months postpartum including Wexner score for anal incontinence and ICIQ-FLUTS for urinary symptoms. Perineal morbidity comprised severe perineal tears, corresponding to third and fourth degree lacerations. Fetal morbidity parameters comprised low neonatal Apgar scores, acidaemia, major and minor fetal injuries and neonatal intensive care unit admissions. Among 5265 women, 495 presented with persistent OP positions (9.4%) and 111 delivered after manual rotation failure followed by AD delivery: 58 in the IR group and 53 in the AD in OP group. The incidence of anal sphincter injuries was significantly reduced after IR attempt (1.7% vs. 24.5%; p < 0.001) without increasing neonatal morbidity. At 6 months postpartum, AD in OP position was associated with higher rate of anal incontinence (30% vs. 5.5%, p = 0.001) and with more urinary symptoms, dyspareunia and perineal pain. OP operative deliveries are associated with significant perineal morbidity and pelvic floor dysfunction at 6 months postpartum.

  8. 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.

  9. FUNCTIONALIZATION OF 3D FIBROUS SCAFFOLDS PREPARED USING CENTRIFUGAL SPINNING WITH LIPOSOMES AS A SIMPLE DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Michala Rampichová

    2017-06-01

    Full Text Available 3D materials supporting cell adhesion, infiltration and proliferation are crucial for bone tissue engineering. In the current study we combined PCL fibers prepared using centrifugal spinning with adhered liposomes filled with platelet lysate as a natural source of growth factors. The scaffold was seeded with MG-63 cells and tested in vitro as a potential drug delivery system for bone tissue engineering.

  10. Evaluation of soil thermal potential under Tunisian climate using a new conic basket geothermal heat exchanger: Energy and exergy analysis

    International Nuclear Information System (INIS)

    Boughanmi, Hassen; Lazaar, Mariem; Farhat, Abdelhamid; Guizani, Amenallah

    2017-01-01

    Highlights: • Conic geothermal basket heat exchanger (CBGHE) is experimentally investigated. • Charging and discharging processes of CBGHE are evaluated. • Energy and exergy efficiencies of CBGHE are performed. • High and stable performance of surface geothermal energy in Tunisia is established. - Abstract: Geothermal heat exchangers system composed of two conic baskets serially connected is designed and realized. Both heat exchangers are made in polyethylene high-density material and have a length of 3 m each one. They will be used for greenhouse cooling and heating through a geothermal heat pump. Its conical geometry is selected to reduce the operation cost and the exploited area, compared to vertical and horizontal geothermal heat exchangers often used. It also assures the maximum of heat exchange with the soil. The aim of this study is to determine the thermal performance of one Conic Basket Geothermal Heat Exchanger (CBGHE), buried at 3 m deep, in the exploitation of the soil thermal potential, in summer. A rate of heat exchange with the soil is determined and the global heat exchange of the CBGHE is assessed. Its energy and exergy efficiencies are also evaluated using both first and second law of thermodynamic. Results show that the specific heat exchange ranges between 20 W m"−"1 and 50 W m"−"1. Maximal energetic and exergetic efficiencies of the CBGHE, equal to 62% and 37% respectively, are reached for a mass flow rate of 0.1 kg s"−"1. For this value of mass flow rate, the overall heat exchange coefficient is of 52 W m"−"2 K"−"1.

  11. Tracing artificial trans fat in popular foods in Europe: a market basket investigation.

    Science.gov (United States)

    Stender, Steen; Astrup, Arne; Dyerberg, Jørn

    2014-05-20

    To minimise the intake of industrial artificial trans fat (I-TF), nearly all European countries rely on food producers to voluntarily reduce the I-TF content in food. The objective of this study was to investigate the effect of this strategy on I-TF content in prepackaged biscuits/cakes/wafers in 2012-2013 in 20 European countries. The I-TF content was assessed in a market basket investigation. Three large supermarkets were visited in each capital, and in some countries, three additional ethnic shops were included. A total of 598 samples of biscuits/cakes/wafers with 'partially hydrogenated vegetable fat' or a similar term high on the list of ingredients were analysed, 312 products had more than 2% of fat as I-TF, exceeding the legislatively determined I-TF limit in Austria and Denmark; the mean (SD) was 19 (7)%. In seven countries, no I-TF was found, whereas nine predominantly Eastern European countries had products with very high I-TF content, and the remaining four countries had intermediate levels. Of the five countries that were examined using the same procedure as in 2006, three had unchanged I-TF levels in 2013, and two had lower levels. The 18 small ethnic shops examined in six Western European countries sold 83 products. The mean (SD) was 23 (12)% of the fat as I-TF, all imported from countries in Balkan. In Sweden, this type of food imported from Balkan was also available in large supermarkets. The findings suggest that subgroups of the population in many countries in Europe still consume I-TF in amounts that increase their risk of coronary heart disease. Under current European Union (EU) legislation, the sale of products containing I-TF is legal but conflicts with the WHO recommendation to minimise the intake of I-TF. An EU-legislative limit on I-TF content in foods is expected to be an effective strategy to achieve this goal. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

  12. Polydopamine-Functionalized CA-(PCL-ran-PLA) Nanoparticles for Target Delivery of Docetaxel and Chemo-photothermal Therapy of Breast Cancer

    Science.gov (United States)

    Kong, Na; Deng, Mei; Sun, Xiu-Na; Chen, Yi-Ding; Sui, Xin-Bing

    2018-01-01

    Current limitations of cancer therapy include the lack of effective strategy for target delivery of chemotherapeutic drugs, and the difficulty of achieving significant efficacy by single treatment. Herein, we reported a synergistic chemo-photothermal strategy based on aptamer (Apt)-polydopamine (pD) functionalized CA-(PCL-ran-PLA) nanoparticles (NPs) for effective delivery of docetaxel (DTX) and enhanced therapeutic effect. The developed DTX-loaded Apt-pD-CA-(PCL-ran-PLA) NPs achieved promising advantages, such as (i) improved drug loading content (LC) and encapsulation efficiency (EE) initiated by star-shaped copolymer CA-(PCL-ran-PLA); (ii) effective target delivery of drugs to tumor sites by incorporating AS1411 aptamers; (iii) significant therapeutic efficacy caused by synergistic chemo-photothermal treatment. In addition, the pD coating strategy with simple procedures could address the contradiction between targeting modification and maintaining formerly excellent bio-properties. Therefore, with excellent bio-properties and simple preparation procedures, the DTX-loaded Apt-pD-CA-(PCL-ran-PLA) NPs effectively increased the local drug concentration in tumor sites, minimized side effects, and significantly eliminated tumors, indicating the promising application of these NPs for cancer therapy. PMID:29527167

  13. Recirculating cardiac delivery of AAV2/1SERCA2a improves myocardial function in an experimental model of heart failure in large animals.

    Science.gov (United States)

    Byrne, M J; Power, J M; Preovolos, A; Mariani, J A; Hajjar, R J; Kaye, D M

    2008-12-01

    Abnormal excitation-contraction coupling is a key pathophysiologic component of heart failure (HF), and at a molecular level reduced expression of the sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA2a) is a major contributor. Previous studies in small animals have suggested that restoration of SERCA function is beneficial in HF. Despite this promise, the means by which this information might be translated into potential clinical application remains uncertain. Using a recently established cardiac-directed recirculating method of gene delivery, we administered adeno-associated virus 2 (AAV2)/1SERCA2a to sheep with pacing-induced HF. We explored the effects of differing doses of AAV2/1SERCA2a (low 1 x 10(10) d.r.p.; medium 1 x 10(12) d.r.p. and high 1 x 10(13) d.r.p.) in conjunction with an intra-coronary delivery group (2.5 x 10(13) d.r.p.). At the end of the study, haemodynamic, echocardiographic, histopathologic and molecular biologic assessments were performed. Cardiac recirculation delivery of AAV2/1SERCA2a elicited a dose-dependent improvement in cardiac performance determined by left ventricular pressure analysis, (+d P/d t(max); low dose -220+/-70, P>0.05; medium dose 125+/-53, P0.05; medium dose 1+/-2, P>0.05; high dose 6.5+/-3.9, Preversal of the HF molecular phenotype. In contrast, direct intra-coronary infusion did not elicit any effect on ventricular function. As such, AAV2/1SERCA2a elicits favourable functional and molecular actions when delivered in a mechanically targeted manner in an experimental model of HF. These observations lay a platform for potential clinical translation.

  14. Functional Expression of P-glycoprotein and Organic Anion Transporting Polypeptides at the Blood-Brain Barrier: Understanding Transport Mechanisms for Improved CNS Drug Delivery?

    Science.gov (United States)

    Abdullahi, Wazir; Davis, Thomas P; Ronaldson, Patrick T

    2017-07-01

    Drug delivery to the central nervous system (CNS) is greatly limited by the blood-brain barrier (BBB). Physical and biochemical properties of the BBB have rendered treatment of CNS diseases, including those with a hypoxia/reoxygenation (H/R) component, extremely difficult. Targeting endogenous BBB transporters from the ATP-binding cassette (ABC) superfamily (i.e., P-glycoprotein (P-gp)) or from the solute carrier (SLC) family (i.e., organic anion transporting polypeptides (OATPs in humans; Oatps in rodents)) has been suggested as a strategy that can improve delivery of drugs to the brain. With respect to P-gp, direct pharmacological inhibition using small molecules or selective regulation by targeting intracellular signaling pathways has been explored. These approaches have been largely unsuccessful due to toxicity issues and unpredictable pharmacokinetics. Therefore, our laboratory has proposed that optimization of CNS drug delivery, particularly for treatment of diseases with an H/R component, can be achieved by targeting Oatp isoforms at the BBB. As the major drug transporting Oatp isoform, Oatp1a4 has demonstrated blood-to-brain transport of substrate drugs with neuroprotective properties. Furthermore, our laboratory has shown that targeting Oatp1a4 regulation (i.e., TGF-β signaling mediated via the ALK-1 and ALK-5 transmembrane receptors) represents an opportunity to control Oatp1a4 functional expression for the purpose of delivering therapeutics to the CNS. In this review, we will discuss limitations of targeting P-gp-mediated transport activity and the advantages of targeting Oatp-mediated transport. Through this discussion, we will also provide critical information on novel approaches to improve CNS drug delivery by targeting endogenous uptake transporters expressed at the BBB.

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

    International Nuclear Information System (INIS)

    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-B_4C) were investigated, and the minimum required receptacle pitch of the basket was determined. - Highlights: • Criticality safety analysis for a dual purpose cask was carried out. • The basket material of borated stainless steel and Boral were investigated. • Minimum receptacle pitch was determined for 12, 18, or 19 VVER 1000 spent fuel assemblies.

  16. 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

  17. Highly efficient delivery of functional cargoes by the synergistic effect of GAG binding motifs and cell-penetrating peptides.

    Science.gov (United States)

    Dixon, James E; Osman, Gizem; Morris, Gavin E; Markides, Hareklea; Rotherham, Michael; Bayoussef, Zahia; El Haj, Alicia J; Denning, Chris; Shakesheff, Kevin M

    2016-01-19

    Protein transduction domains (PTDs) are powerful nongenetic tools that allow intracellular delivery of conjugated cargoes to modify cell behavior. Their use in biomedicine has been hampered by inefficient delivery to nuclear and cytoplasmic targets. Here we overcame this deficiency by developing a series of novel fusion proteins that couple a membrane-docking peptide to heparan sulfate glycosaminoglycans (GAGs) with a PTD. We showed that this GET (GAG-binding enhanced transduction) system could deliver enzymes (Cre, neomycin phosphotransferase), transcription factors (NANOG, MYOD), antibodies, native proteins (cytochrome C), magnetic nanoparticles (MNPs), and nucleic acids [plasmid (p)DNA, modified (mod)RNA, and small inhibitory RNA] at efficiencies of up to two orders of magnitude higher than previously reported in cell types considered hard to transduce, such as mouse embryonic stem cells (mESCs), human ESCs (hESCs), and induced pluripotent stem cells (hiPSCs). This technology represents an efficient strategy for controlling cell labeling and directing cell fate or behavior that has broad applicability for basic research, disease modeling, and clinical application.

  18. 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.

  19. Novel non-viral vectors for gene delivery: synthesis of a second-generation library of mono-functionalized poly-(guanidinium)amines and their introduction into cationic lipids.

    Science.gov (United States)

    Byk, G; Soto, J; Mattler, C; Frederic, M; Scherman, D

    1998-01-01

    The development of new gene delivery technologies is a prerequisite towards gene therapy clinical trials. Because gene delivery mediated by viral vectors remains of limited scope due to immunological and propagation risks, the development of new non-viral gene delivery systems is of crucial importance. We have synthesized a secondary library of mono-functionalized poly-(guanidinium)amines generated from a library of mono-functionalized polyamines applying the concept of "libraries from libraries." The method allows a quick and easy access to mono-functionalized geometrically varied poly-(guanidinium)amines. The new building blocks were introduced into cationic lipids to obtain novel poly-(guanidinium)amine lipids, which are potential DNA vectors for gene delivery. Copyright 1998 John Wiley & Sons, Inc.

  20. Engineered exosome-mediated delivery of functionally active miR-26a and its enhanced suppression effect in HepG2 cells

    Directory of Open Access Journals (Sweden)

    Liang G

    2018-01-01

    Full Text Available Gaofeng Liang,1,2,* Shu Kan,2,* Yanliang Zhu,3 Shuying Feng,1 Wenpo Feng,1 Shegan Gao1,4 1Medical College, Henan University of Science and Technology, Luoyang, China; 2Department of Biomedical Engineering, University of California Berkeley, California, CA, USA; 3State Key laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 4Henan Key Laboratory of Cancer Epigenetics, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China *These authors contributed equally to this work Introduction: Exosomes are closed-membrane nanovesicles that are secreted by a variety of cells and exist in most body fluids. Recent studies have demonstrated the potential of exosomes as natural vehicles that target delivery of functional small RNA and chemotherapeutics to diseased cells. Methods: In this study, we introduce a new approach for the targeted delivery of exosomes loaded with functional miR-26a to scavenger receptor class B type 1-expressing liver cancer cells. The tumor cell-targeting function of these engineered exosomes was introduced by expressing in 293T cell hosts, the gene fusion between the transmembrane protein of CD63 and a sequence from Apo-A1. The exosomes harvested from these 293T cells were loaded with miR-26a via electroporation. Results: The engineered exosomes were shown to bind selectively to HepG2 cells via the scavenger receptor class B type 1–Apo-A1 complex and then internalized by receptor-mediated endocytosis. The release of miR-26a in exosome-treated HepG2 cells upregulated miR-26a expression and decreased the rates of cell migration and proliferation. We also presented evidence that suggest cell growth was inhibited by miR-26a-mediated decreases in the amounts of key proteins that regulate the cell cycle. Conclusion: Our gene delivery strategy can be adapted to treat a broad spectrum of cancers by expressing proteins on the surface of mi

  1. Wide-field lifetime-based FRET imaging for the assessment of early functional distribution of transferrin-based delivery in breast tumor-bearing small animals

    Science.gov (United States)

    Sinsuebphon, Nattawut; Rudkouskaya, Alena; Barroso, Margarida; Intes, Xavier

    2016-02-01

    Targeted drug delivery is a critical aspect of successful cancer therapy. Assessment of dynamic distribution of the drug provides relative concentration and bioavailability at the target tissue. The most common approach of the assessment is intensity-based imaging, which only provides information about anatomical distribution. Observation of biomolecular interactions can be performed using Förster resonance energy transfer (FRET). Thus, FRET-based imaging can assess functional distribution and provide potential therapeutic outcomes. In this study, we used wide-field lifetime-based FRET imaging for the study of early functional distribution of transferrin delivery in breast cancer tumor models in small animals. Transferrin is a carrier for cancer drug delivery. Its interaction with its receptor is within a few nanometers, which is suitable for FRET. Alexa Fluor® 700 and Alexa Fluor® 750 were conjugated to holo-transferrin which were then administered via tail vein injection to the mice implanted with T47D breast cancer xenografts. Images were continuously acquired for 60 minutes post-injection. The results showed that transferrin was primarily distributed to the liver, the urinary bladder, and the tumor. The cellular uptake of transferrin, which was indicated by the level of FRET, was high in the liver but very low in the urinary bladder. The results also suggested that the fluorescence intensity and FRET signals were independent. The liver showed increasing intensity and increasing FRET during the observation period, while the urinary bladder showed increasing intensity but minimal FRET. Tumors gave varied results corresponding to their FRET progression. These results were relevant to the biomolecular events that occurred in the animals.

  2. 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.

  3. Dynamic Effect of a Change in the Exchange Rate System: From a Fixed Regime to a Basket-Peg or a Floating Regime

    OpenAIRE

    Yoshino, Naoyuki; Kaji, Sahoko; Asonuma, Tamon

    2015-01-01

    This paper theoretically evaluates the dynamic effects of a shift in an exchange rate system from a fixed regime to a basket peg, or to a floating regime, and obtains transition paths for the shift based on a dynamic stochastic general equilibrium model of a small open economy. We apply quantitative analysis using data from the People's Republic of China and Thailand and find that a small open country would be better off shifting to a basket peg or to a floating regime than maintaining a doll...

  4. Surface functionalization of inorganic nano-crystals with fibronectin and E-cadherin chimera synergistically accelerates trans-gene delivery into embryonic stem cells

    International Nuclear Information System (INIS)

    Kutsuzawa, K.; Chowdhury, E.H.; Nagaoka, M.; Maruyama, K.; Akiyama, Y.; Akaike, T.

    2006-01-01

    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

  5. 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.

  6. Cationic lipid-based nanoparticles mediate functional delivery of acetate to tumor cells in vivo leading to significant anticancer effects

    Directory of Open Access Journals (Sweden)

    Brody LP

    2017-09-01

    Full Text Available Leigh P Brody,1,* Meliz Sahuri-Arisoylu,1,* James R Parkinson,1 Harry G Parkes,2 Po Wah So,3 Nabil Hajji,4 E Louise Thomas,1 Gary S Frost,5 Andrew D Miller,6,* Jimmy D Bell1,* 1Department of Life Sciences, Faculty of Science and Technology, University of Westminster, 2CR-UK Clinical MR Research Group, Institute of Cancer Research, Sutton, Surrey, 3Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, 4Department of Medicine, Division of Experimental Medicine, Centre for Pharmacology & Therapeutics, Toxicology Unit, Imperial College London, 5Faculty of Medicine, Nutrition and Dietetic Research Group, Division of Diabetes, Endocrinology and Metabolism, Department of Investigative Medicine, Imperial College London, Hammersmith Hospital, 6Institute of Pharmaceutical Science, King’s College London, London, UK *These authors contributed equally to this work Abstract: Metabolic reengineering using nanoparticle delivery represents an innovative therapeutic approach to normalizing the deregulation of cellular metabolism underlying many diseases, including cancer. Here, we demonstrated a unique and novel application to the treatment of malignancy using a short-chain fatty acid (SCFA-encapsulated lipid-based delivery system – liposome-encapsulated acetate nanoparticles for cancer applications (LITA-CAN. We assessed chronic in vivo administration of our nanoparticle in three separate murine models of colorectal cancer. We demonstrated a substantial reduction in tumor growth in the xenograft model of colorectal cancer cell lines HT-29, HCT-116 p53+/+ and HCT-116 p53-/-. Nanoparticle-induced reductions in histone deacetylase gene expression indicated a potential mechanism for these anti-proliferative effects. Together, these results indicated that LITA-CAN could be used as an effective direct or adjunct therapy to treat malignant transformation in vivo. Keywords: lipid-based nanoparticles, liposomes

  7. 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

  8. Targeted delivery of polyamidoamine-paclitaxel conjugate functionalized with anti-human epidermal growth factor receptor 2 trastuzumab

    Directory of Open Access Journals (Sweden)

    Ma P

    2015-03-01

    Full Text Available Pengkai Ma,1 Xuemei Zhang,1 Ling Ni,2 Jinming Li,2 Fengpu Zhang,1 Zheng Wang,1 Shengnan Lian,1 Kaoxiang Sun1 1School of Pharmacy, Yantai University, Yantai, Shandong Province, People’s Republic of China; 2State Key Laboratory of Long-acting and Targeting Drug Delivery System, Yantai, Shandong Province, People’s Republic of China Background: Antibody-dendrimer conjugates have the potential to improve the targeting and release of chemotherapeutic drugs at the tumor site while reducing adverse side effects caused by drug accumulation in healthy tissues. In this study, trastuzumab (TMAB, which binds to human epidermal growth factor receptor 2 (HER2, was used as a targeting agent in a TMAB-polyamidoamine (PAMAM conjugate carrying paclitaxel (PTX specifically to cells overexpressing HER2. Methods: TMAB was covalently linked to a PAMAM dendrimer via bifunctional polyethylene glycol (PEG. PTX was conjugated to PAMAM using succinic anhydride as a cross-linker, yielding TMAB-PEG-PAMAM-PTX. Dynamic light scattering and transmission electron microscopy were used to characterize the conjugates. The cellular uptake and in vivo biodistribution were studied by fluorescence microscopy, flow cytometry, and Carestream In Vivo FX, respectively. Results: Nuclear magnetic resonance spectroscopy demonstrated that PEG, PTX, fluorescein isothiocyanate, and cyanine7 were conjugated to PAMAM. Ultraviolet-visible spectroscopy and sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrated that TMAB was conjugated to PEG-PAMAM. Dynamic light scattering and transmission electron microscopy measurements revealed that the different conjugates ranged in size between 10 and 35 nm and had a spherical shape. In vitro cellular uptake demonstrated that the TMAB-conjugated PAMAM was taken up by HER2-overexpressing BT474 cells more efficiently than MCF-7 cells that expressed lower levels of HER2. Co-localization experiments indicated that TMAB-conjugated PAMAM was

  9. 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

  10. Percutaneous Retrieval of a Dislodged Guide Wire by Dormia Basket in a 98-year-old Patient, Still a Safe and Feasible Approach

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    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.

  11. A study on recovery of uranium in the anode basket residues delivered from the pyrochemical process of used nuclear fuel

    Science.gov (United States)

    Eun, H. C.; Kim, T. J.; Jang, J. H.; Kim, G. Y.; Park, S. B.; Yoon, D. S.; Kim, S. H.; Paek, S. W.; Lee, S. J.

    2018-04-01

    In this study, the chlorination of uranium oxide (UO2) using ammonium chloride and zirconium as chemical agents was conducted to recover the uranium in the anode basket residues from the pyrochemical process of used nuclear fuel. The chlorination of UO2 was predicted using thermodynamic equilibrium calculations. The experimental conditions for the chlorination were determined using a chlorination test with cerium oxide (CeO2). In the chlorination test, it was confirmed that UO2 was chlorinated into UCl3 at 320 °C, some UO2 remained without changes in the chemical form, and ZrO2, Zr2O, and ZrCl2 were generated as byproducts.

  12. Tumor cell-targeted delivery of CRISPR/Cas9 by aptamer-functionalized lipopolymer for therapeutic genome editing of VEGFA in osteosarcoma.

    Science.gov (United States)

    Liang, Chao; Li, Fangfei; Wang, Luyao; Zhang, Zong-Kang; Wang, Chao; He, Bing; Li, Jie; Chen, Zhihao; Shaikh, Atik Badshah; Liu, Jin; Wu, Xiaohao; Peng, Songlin; Dang, Lei; Guo, Baosheng; He, Xiaojuan; Au, D W T; Lu, Cheng; Zhu, Hailong; Zhang, Bao-Ting; Lu, Aiping; Zhang, Ge

    2017-12-01

    Osteosarcoma (OS) is a highly aggressive pediatric cancer, characterized by frequent lung metastasis and pathologic bone destruction. Vascular endothelial growth factor A (VEGFA), highly expressed in OS, not only contributes to angiogenesis within the tumor microenvironment via paracrine stimulation of vascular endothelial cells, but also acts as an autocrine survival factor for tumor cell themselves, thus making it a promising therapeutic target for OS. CRISPR/Cas9 is a versatile genome editing technology and holds tremendous promise for cancer treatment. However, a major bottleneck to achieve the therapeutic potential of the CRISPR/Cas9 is the lack of in vivo tumor-targeted delivery systems. Here, we screened an OS cell-specific aptamer (LC09) and developed a LC09-functionalized PEG-PEI-Cholesterol (PPC) lipopolymer encapsulating CRISPR/Cas9 plasmids encoding VEGFA gRNA and Cas9. Our results demonstrated that LC09 facilitated selective distribution of CRISPR/Cas9 in both orthotopic OS and lung metastasis, leading to effective VEGFA genome editing in tumor, decreased VEGFA expression and secretion, inhibited orthotopic OS malignancy and lung metastasis, as well as reduced angiogenesis and bone lesion with no detectable toxicity. The delivery system simultaneously restrained autocrine and paracrine VEGFA signaling in tumor cells and could facilitate translating CRISPR-Cas9 into clinical cancer treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Synergistic effect of pH-responsive folate-functionalized poloxamer 407-TPGS-mixed micelles on targeted delivery of anticancer drugs

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    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

  14. After Delivery

    Science.gov (United States)

    ... Rights Employment Discrimination Health Care Professionals Law Enforcement Driver's License For Lawyers Food & Fitness Home Food MyFoodAdvisor ... A Listen En Español After Delivery After your baby arrives, your body begins to recover from the ...

  15. Aminopropyl groups of the functionalized Mobil Crystalline Material 41 as a carrier for controlled diclofenac sodium and piroxicam delivery.

    Science.gov (United States)

    Khodaverdi, Elham; Ahmadi, Mina; Kamali, Hossein; Hadizadeh, Farzin

    2017-01-01

    Synthetic Mobil Crystalline Material 41 (MCM-41) as a mesoporous material and functionalized MCM-41 using aminopropyl groups were studied in order to investigate their ability to encapsulate and to control the release of diclofenac sodium and piroxicam. MCM-41 was synthesized through sol-gel procedure and functionalized with aminopropyl groups. The physicochemical properties of MCM-41 were studied through particle size analysis, infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and carbon-hydrogen-nitrogen analysis. Diclofenac sodium and piroxicam were loaded into the MCM-41 matrix using the filtration and solvent evaporation methods. The drug-loading capacity was determined by ultraviolet, Fourier transform infrared, X-ray diffraction, and Brunauer-Emmett-Teller analysis. According to the results for pure drug release, >57% was released in the 1 st h, but when these drugs were loaded into pure Mobil Crystalline Material 41 (MCM-41) and functionalized MCM-41, the release into the simulated gastrointestinal medium was less, continuous, and slower. The release of piroxicam from functionalized MCM-41 was slower than that from MCM-41 in the simulated intestinal medium because of the formation of electrostatic bonds between piroxicam and the aminopropyl groups of the functionalized MCM-41. However, in the case of diclofenac sodium, there was no significant difference between pure MCM-41 and functionalized MCM-41. The difference between piroxicam and diclofenac sodium was due to the high solubility of diclofenac sodium in the intestinal medium (pH 6.8), which caused more rapid release from the matrixes than for piroxicam. Our findings indicate that, after functionalization of MCM-41, it could offer a good means of delivering controlled diclofenac sodium and piroxicam.

  16. 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

  17. Functional intercalated nanocomposites with chitosan-glutathione-glycylsarcosine and layered double hydroxides for topical ocular drug delivery.

    Science.gov (United States)

    Xu, Tingting; Xu, Xiaoyue; Gu, Yan; Fang, Lei; Cao, Feng

    2018-01-01

    To enhance ocular bioavailability, the traditional strategies have focused on prolonging precorneal retention and improving corneal permeability by nano-carriers with positive charge, thiolated polymer, absorption enhancer and so on. Glycylsarcosine (GS) as an active target ligand of the peptide tranpsporter-1 (PepT-1), could specific interact with the PepT-1 on the cornea and guide the nanoparticles to the treating site. The objective of the study was to explore the active targeting intercalated nanocomposites based on chitosan-glutathione-glycylsarcosine (CG-GS) and layered double hydroxides (LDH) as novel carriers for the treatment of mid-posterior diseases. CG-GS-LDH intercalated nanocomposites were prepared by the coprecipitation hydrothermal method. In vivo precorneal retention study, ex vivo fluorescence images, in vivo experiment for distribution and irritation were studied in rabbits. The cytotoxicity and cellular uptake were studied in human corneal epithelial primary cells (HCEpiC). CG-GS-LDH nanocomposites were prepared successfully and characterized by FTIR and XRD. Experiments with rabbits showed longer precorneal retention and higher distribution of fluorescence probe/model drug. In vitro cytological study, CG-GS-LDH nanocomposites exhibited enhanced cellular uptake compared to pure drug solution. Furthermore, the investigation of cellular uptake mechanisms demonstrated that both the active transport by PepT-1 and clathrin-mediated endocytosis were involved in the internalization of CG-GS-LDH intercalated nanocomposites. An ocular irritation study and a cytotoxicity test indicated that these nanocomposites produced no significant irritant effects. The active targeting intercalated nanocomposites could have great potential for topical ocular drug delivery due to the capacity for prolonging the retention on the ocular surface, enhancing the drug permeability through the cornea, and efficiently delivering the drug to the targeted site.

  18. Functionalized graphene oxide mediated adriamycin delivery and miR-21 gene silencing to overcome tumor multidrug resistance in vitro.

    Directory of Open Access Journals (Sweden)

    Feng Zhi

    Full Text Available Multidrug resistance (MDR is a major impediment to successful cancer chemotherapy. Co-delivery of novel MDR-reversing agents and anticancer drugs to cancer cells holds great promise for cancer treatment. MicroRNA-21 (miR-21 overexpression is associated with the development and progression of MDR in breast cancer, and it is emerging as a novel and promising MDR-reversing target. In this study, a multifunctional nanocomplex, composed of polyethylenimine (PEI/poly(sodium 4-styrenesulfonates (PSS/graphene oxide (GO and termed PPG, was prepared using the layer-by-layer assembly method to evaluate the reversal effects of PPG as a carrier for adriamycin (ADR along with miR-21 targeted siRNA (anti-miR-21 in cancer drug resistance. ADR was firstly loaded onto the PPG surface (PPGADR by physical mixing and anti-miR-21 was sequentially loaded onto PPGADR through electric absorption to form (anti-miR-21PPGADR. Cell experiments showed that PPG significantly enhanced the accumulation of ADR in MCF-7/ADR cells (an ADR resistant breast cancer cell line and exhibited much higher cytotoxicity than free ADR, suggesting that PPG could effectively reverse ADR resistance of MCF-7/ADR. Furthermore, the enhanced therapeutic efficacy of PPG could be correlated with effective silencing of miR-21 and with increased accumulation of ADR in drug-resistant tumor cells. The endocytosis study confirmed that PPG could effectively carry drug molecules into cells via the caveolae and clathrin-mediated endocytosis pathways. These results suggest that this PPG could be a potential and efficient non-viral vector for reversing MDR, and the strategy of combining anticancer drugs with miRNA therapy to overcome MDR could be an attractive approach in cancer treatment.

  19. Noninvasive Assessment of Losartan-Induced Increase in Functional Microvasculature and Drug Delivery in Pancreatic Ductal Adenocarcinoma.

    Science.gov (United States)

    Kumar, Vidhya; Boucher, Yves; Liu, Hao; Ferreira, Diego; Hooker, Jacob; Catana, Ciprian; Hoover, Andrew J; Ritter, Tobias; Jain, Rakesh K; Guimaraes, Alexander R

    2016-10-01

    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. 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 18 F-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. 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 18 F-5FU by 53% (P<.0001). 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 18 F-5FU. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Food Protein Based Core-Shell Nanocarriers for Oral Drug Delivery: Effect of Shell Composition on in Vitro and in Vivo Functional Performance of Zein Nanocarriers.

    Science.gov (United States)

    Alqahtani, Mohammed S; Islam, M Saiful; Podaralla, Satheesh; Kaushik, Radhey S; Reineke, Joshua; Woyengo, Tofuko; Perumal, Omathanu

    2017-03-06

    The study was aimed at systematically investigating the influence of shell composition on the particle size, stability, release, cell uptake, permeability, and in vivo gastrointestinal distribution of food protein based nanocarriers for oral delivery applications. Three different core-shell nanocarriers were prepared using food-grade biopolymers including zein-casein (ZC) nanoparticles, zein-lactoferrin (ZLF), nanoparticles and zein-PEG (ZPEG) micelles. Nile red was used as a model hydrophobic dye for in vitro studies. The nanocarriers had negative, positive, and neutral charge, respectively. All three nanocarriers had a particle size of less than 200 nm and a low polydispersity index. The nanoparticles were stable at gastrointestinal pH (2-9) and ionic strength (10-200 mM). The nanocarriers sustained the release of Nile red in simulated gastric and intestinal fluids. ZC nanoparticles showed the slowest release followed by ZLF nanoparticles and ZPEG micelles. The nanocarriers were taken up by endocytosis in Caco-2 cells. ZPEG micelles showed the highest cell uptake and transepithelial permeability followed by ZLF and ZC nanoparticles. ZPEG micelles also showed P-gp inhibitory activity. All three nanocarriers showed bioadhesive properties. Cy 5.5, a near IR dye, was used to study the in vivo biodistribution of the nanocarriers. The nanocarriers showed longer retention in the rat gastrointestinal tract compared to the free dye. Among the three formulations, ZC nanoparticles was retained the longest in the rat gastrointestinal tract (≥24 h). Overall, the outcomes from this study demonstrate the structure-function relationship of core-shell protein nanocarriers. The findings from this study can be used to develop food protein based oral drug delivery systems with specific functional attributes.

  1. 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

  2. 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.

  3. Amino-functionalized poloxamer 407 with both mucoadhesive and thermosensitive properties: preparation, characterization and application in a vaginal drug delivery system

    Directory of Open Access Journals (Sweden)

    Liqian Ci

    2017-09-01

    Full Text Available Lack of mucoadhesive properties is the major drawback to poloxamer 407 (F127-based in situ hydrogels for mucosal administration. The objective of the present study was to construct a novel mucoadhesive and thermosensitive in situ hydrogel drug delivery system based on an amino-functionalized poloxamer for vaginal administration. First, amino-functionalized poloxamer 407 (F127-NH2 was synthesized and characterized with respect to its micellization behavior and interaction with mucin. Then using acetate gossypol (AG as model drug, AG-loaded F127-NH2-based in situ hydrogels (NFGs were evaluated with respect to rheology, drug release, ex vivo vaginal mucosal adhesion, in vivo intravaginal retention and local irritation after vaginal administration to healthy female mice. The results show that F127-NH2 is capable of forming a thermosensitive in situ hydrogel with sustained drug release properties. An interaction between positively charged F127-NH2 and negatively charged mucin was revealed by changes in the particle size and zeta potential of mucin particles as well as an increase in the complex modulus of NFG caused by mucin. Ex vivo and in vivo fluorescence imaging and quantitative analysis of the amount of AG remaining in mouse vaginal lavage all demonstrated greater intravaginal retention of NFG than that of an unmodified F127-based in situ hydrogel. In conclusion, amino group functionalization confers valuable mucoadhesive properties on poloxamer 407.

  4. Functional and unmodified MWNTs for delivery of the water-insoluble drug Carvedilol - A drug-loading mechanism

    International Nuclear Information System (INIS)

    Li Yuting; Wang Tianyi; Wang Jing; Jiang Tongying; Cheng Gang; Wang Siling

    2011-01-01

    The purpose of this study was to develop carboxyl multi-wall carbon nanotubes (MWNTs) and unmodified MWNTs loaded with a poorly water-soluble drug, intended to improve the drug loading capacity, dissolubility and study the drug-loading mechanism. MWNTs were modified with a carboxyl group through the acid treatment. MWNTs as well as the resulting functionalized MWNTs were investigated as scaffold for loading the model drug, Carvedilol (CAR), using three different methods (the fusion method, the incipient wetness impregnation method, and the solvent method). The effects of different pore size, specific surface area and physical state were systematically studied using scanning electron microscopy (SEM), thermogravimetric analysis (TGA), Fourier transformation infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), nitrogen adsorption, X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The functional MWNTs allowed a higher drug loading than the unmodified preparations. The methods used to load the drug had a marked effect on the drug-loading, dissolution, and physical state of the drug as well as its distribution. In addition, the solubility of the drug was increased when carried by both MWNTs and functional MWNTs, and this might help to improve the bioavailability.

  5. A54 peptide-mediated functionalized gold nanocages for targeted delivery of DOX as a combinational photothermal-chemotherapy for liver cancer

    Directory of Open Access Journals (Sweden)

    Huang S

    2017-07-01

    Full Text Available Shengnan Huang,1,* Chunming Li,2,* Weiping Wang,1 Huanjie Li,1 Zhi Sun,3 Chengzhi Song,4 Benyi Li,5 Shaofeng Duan,6,7 Yurong Hu1,8,9 1Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Pharmacy, Chongqing Cancer Institute & Hospital & Cancer Center, Chongqing, People’s Republic of China; 3Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 4School of Physical Sciences, University of Science and Technology of China, Hefei, People’s Republic of China; 5Department of Urology and Cancer Center, the University of Kansas Medical Center, Kansas City, KS, USA; 6College of Pharmacy, Henan University, Kaifeng, People’s Republic of China; 7Department of Orthopedics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 8Key Laboratory of Key Technology of Drug Preparation, Ministry of Education, Institute of Drug Discovery & Development, Zhengzhou University, Zhengzhou, People’s Republic of China; 9Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, People’s Republic of China *These authors contributed equally to this work Abstract: The combination of photothermal therapy and chemotherapy (photothermal–­chemotherapy is a promising strategy for cancer therapy. Gold nanocages (AuNCs, with hollow and porous structures and unique optical properties, have become a rising star in the field of drug delivery. Here, we designed a novel targeted drug delivery system based on functionalized AuNCs and evaluated their therapeutic effects in vitro and in vivo. We then loaded doxorubicin into this promising system, designated as DHTPAuNCs consisting of hyaluronic acid-grafted and A54 peptide-targeted PEGylated AuNCs. Its formation was corroborated by ultraviolet

  6. 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. PMID:26099034

  7. Anhydrous polymer-based coating with sustainable controlled release functionality for facile, efficacious impregnation, and delivery of antimicrobial peptides.

    Science.gov (United States)

    Lim, Kaiyang; Saravanan, Rathi; Chong, Kelvin K L; Goh, Sharon H M; Chua, Ray R Y; Tambyah, Paul A; Chang, Matthew W; Kline, Kimberly A; Leong, Susanna S J

    2018-04-17

    Anhydrous polymers are actively explored as alternative materials to overcome limitations of conventional hydrogel-based antibacterial coating. However, the requirement for strong organic solvent in polymerization reactions often necessitates extra protection steps for encapsulation of target biomolecules, lowering encapsulation efficiency, and increasing process complexity. This study reports a novel coating strategy that allows direct solvation and encapsulation of antimicrobial peptides (HHC36) into anhydrous polycaprolactone (PCL) polymer-based dual layer coating. A thin 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) film is layered onto the peptide-impregnated PCL as a diffusion barrier, to modulate and enhance release kinetics. The impregnated peptides are eventually released in a controlled fashion. The use of 2,2,2-trifluoroethanol (TFE), as polymerization and solvation medium, induces the impregnated peptides to adopt highly stable turned conformation, conserving peptide integrity, and functionality during both encapsulation and subsequent release processes. The dual layer coating showed sustained antibacterial functionality, lasting for 14 days. In vivo assessment using an experimental mouse wounding model demonstrated good biocompatibility and significant antimicrobial efficacy of the coating under physiological conditions. The coating was translated onto silicone urinary catheters and showed promising antibacterial efficacy, even outperforming commercial silver-based Dover cather. This anhydrous polymer-based platform holds immense potential as an effective antibacterial coating to prevent clinical device-associated infections. The simplicity of the coating process enhances its industrial viability. © 2018 Wiley Periodicals, Inc.

  8. Applying the International Classification of Functioning, Disability and Health to guide home health care services planning and delivery in Thailand.

    Science.gov (United States)

    Pimdee, Atipong; Nualnetr, Nomjit

    2017-01-01

    Home health care is an essential service for home-bound patients in Thailand. In this action research study, we used the International Classification of Functioning, Disability and Health (ICF) framework to modify home health care services provided by a university hospital. Staff responsible for delivering the services (physical therapist, nurses, and Thai traditional medicine practitioners) participated in the development of an ICF-based assessment tool and home health care service procedure. After an 8-month trial of implementing these changes, professional satisfaction and empowerment were high among the home health care team members. Patients and their caregivers were also satisfied with the services. In conclusion, the ICF is an effective means of guiding home health care.

  9. Functional nanoparticles exploit the bile acid pathway to overcome multiple barriers of the intestinal epithelium for oral insulin delivery

    DEFF Research Database (Denmark)

    Fan, Weiwei; Xia, Dengning; Zhu, Quanlei

    2018-01-01

    , especially to avoid lysosomal degradation, and basolateral release. Here, the functional material, deoxycholic acid-conjugated chitosan, is synthesized and loaded with the model protein drug insulin into deoxycholic acid-modified nanoparticles (DNPs). The DNPs designed in this study are demonstrated......Oral absorption of protein/peptide-loaded nanoparticles is often limited by multiple barriers of the intestinal epithelium. In addition to mucus translocation and apical endocytosis, highly efficient transepithelial absorption of nanoparticles requires successful intracellular trafficking...... to endolysosomal escape of DNPs. Additionally, DNPs can interact with a cytosolic ileal bile acid-binding protein that facilitates the intracellular trafficking and basolateral release of insulin. In rats, intravital two-photon microscopy also reveals that the transport of DNPs into the intestinal villi...

  10. Electron transfer function versus oxygen delivery: a comparative study for several hexacoordinated globins across the animal kingdom.

    Science.gov (United States)

    Kiger, Laurent; Tilleman, Lesley; Geuens, Eva; Hoogewijs, David; Lechauve, Christophe; Moens, Luc; Dewilde, Sylvia; Marden, Michael C

    2011-01-01

    Caenorhabditis elegans globin GLB-26 (expressed from gene T22C1.2) has been studied in comparison with human neuroglobin (Ngb) and cytoglobin (Cygb) for its electron transfer properties. GLB-26 exhibits no reversible binding for O(2) and a relatively low CO affinity compared to myoglobin-like globins. These differences arise from its mechanism of gaseous ligand binding since the heme iron of GLB-26 is strongly hexacoordinated in the absence of external ligands; the replacement of this internal ligand, probably the E7 distal histidine, is required before binding of CO or O(2) as for Ngb and Cygb. Interestingly the ferrous bis-histidyl GLB-26 and Ngb, another strongly hexacoordinated globin, can transfer an electron to cytochrome c (Cyt-c) at a high bimolecular rate, comparable to those of inter-protein electron transfer in mitochondria. In addition, GLB-26 displays an unexpectedly rapid oxidation of the ferrous His-Fe-His complex without O(2) actually binding to the iron atom, since the heme is oxidized by O(2) faster than the time for distal histidine dissociation. These efficient mechanisms for electron transfer could indicate a family of hexacoordinated globin which are functionally different from that of pentacoordinated globins.

  11. Functionalized liposomes and phytosomes loading Annona muricata L. aqueous extract: Potential nanoshuttles for brain-delivery of phenolic compounds.

    Science.gov (United States)

    Mancini, Simona; Nardo, Luca; Gregori, Maria; Ribeiro, Inês; Mantegazza, Francesco; Delerue-Matos, Cristina; Masserini, Massimo; Grosso, Clara

    2018-03-15

    Multi-target drugs have gained significant recognition for the treatment of multifactorial diseases such as depression. Under a screening study of multi-potent medicinal plants with claimed antidepressant-like activity, the phenolic-rich Annona muricata aqueous extract (AE) emerged as a moderate monoamine oxidase A (hMAO-A) inhibitor and a strong hydrogen peroxide (H 2 O 2 ) scavenger. In order to protect this extract from gastrointestinal biotransformation and to improve its permeability across the blood-brain barrier (BBB), four phospholipid nanoformulations of liposomes and phytosomes functionalized with a peptide ligand promoting BBB crossing were produced. AE and nanoformulations were characterized by HPLC-DAD-ESI-MS n , HPLC-DAD, spectrophotometric, fluorescence and dynamic light scattering methods. Cytotoxicity and permeability studies were carried out using an in vitro transwell model of the BBB, composed of immortalized human microvascular endothelial cells (hCMEC/D3), and in vitro hMAO-A inhibition and H 2 O 2 scavenging activities were performed with all samples. The encapsulation/binding of AE was more efficient with phytosomes, while liposomes were more stable, displaying a slower extract release over time. In general, phytosomes were less toxic than liposomes in hCMEC/D3 cells and, when present, cholesterol improved the permeability across the cell monolayer of all tested nanoformulations. All nanoformulations conserved the antioxidant potential of AE, while phosphatidylcholine interfered with MAO-A inhibition assay. Overall, phytosome formulations registered the best performance in terms of binding efficiency, enzyme inhibition and scavenging activity, thus representing a promising multipotent phenolic-rich nanoshuttle for future in vivo depression treatment. Copyright © 2018 Elsevier GmbH. All rights reserved.

  12. Polyethylenimine-functionalized silver nanoparticle-based co-delivery of paclitaxel to induce HepG2 cell apoptosis

    Directory of Open Access Journals (Sweden)

    Li Y

    2016-12-01

    Full Text Available Yinghua Li,1,* Min Guo,1,* Zhengfang Lin,1 Mingqi Zhao,1 Misi Xiao,1 Changbing Wang,1 Tiantian Xu,1 Tianfeng Chen,2 Bing Zhu1 1Center Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 2Department of Chemistry, Jinan University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Hepatocarcinoma is the third leading cause of cancer-related deaths around the world. Recently, a novel emerging nanosystem as anticancer therapeutic agents with intrinsic therapeutic properties has been widely used in various medical applications. In this study, surface decoration of functionalized silver nanoparticles (AgNPs by polyethylenimine (PEI and paclitaxel (PTX was synthesized. The purpose of this study was to evaluate the effect of Ag@PEI@PTX on cytotoxic and anticancer mechanism on HepG2 cells. The transmission electron microscope image and 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay showed that Ag@PEI@PTX had satisfactory size distribution and high stability and selectivity between cancer and normal cells. Ag@PEI@PTX-induced HepG2 cell apoptosis was confirmed by accumulation of the sub-G1 cells population, translocation of phosphatidylserine, depletion of mitochondrial membrane potential, DNA fragmentation, caspase-3 activation, and poly(ADP-ribose polymerase cleavage. Furthermore, Ag@PEI@PTX enhanced cytotoxic effects on HepG2 cells and triggered intracellular reactive oxygen species; the signaling pathways of AKT, p53, and MAPK were activated to advance cell apoptosis. In conclusion, the results reveal that Ag@PEI@PTX may provide useful information on Ag@PEI@PTX-induced HepG2 cell apoptosis and as appropriate candidate for chemotherapy of cancer. Keywords: silver nanoparticles, polyethylenimine, paclitaxel, reactive oxygen species, apoptosis

  13. 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

    Energy Technology Data Exchange (ETDEWEB)

    Anandhakumar, S., E-mail: rsanandhakumar@gmail.com [SRM Research Institute, SRM University, Kattankulathur, Chennai 603203 (India); Krishnamoorthy, G.; Ramkumar, K.M. [SRM Research Institute, SRM University, Kattankulathur, Chennai 603203 (India); Raichur, A.M. [Department of Materials Engineering, Indian Institute of Science, Bangalore 560012 (India)

    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 100 nm 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. - Highlights: • Preparation of collagen peptide functionalized chitosan nanoparticles • Hydrogen bonding plays a key role in particle formation. • Electrostatic interaction plays a key role in drug encapsulation. • Functionalized chitosan particles are more stable than chitosan NPs.

  14. 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.

  15. Quantum mechanical design and structure of the Li@B10H14 basket with a remarkably enhanced electro-optical response.

    Science.gov (United States)

    Muhammad, Shabbir; Xu, Hongliang; Liao, Yi; Kan, Yuhe; Su, Zhongmin

    2009-08-26

    An innovative type of lithium decahydroborate (Li@B(10)H(14)) complex with a basketlike complexant of decaborane (B(10)H(14)) has been designed using quantum mechanical methods. As Li atom binds in a handle fashion to terminal electrophilic boron atoms of the decaborane basket, its NBO charge q (Li) is found to be 0.876, close to +1. This shows that the Li atom has been ionized to form a cation and an anion at the open end of B(10)H(14). The most fascinating feature of this Li doping is its loosely bound valence electron, which has been pulled into the cavity of the B(10)H(14) basket and become diffuse by the electron-deficient morphological features of the open end of the B(10)H(14) basket. Strikingly, the first hyperpolarizability (beta(0)) of Li@B(10)H(14) is about 340 times larger than that of B(10)H(14), computed to be 23,075 au (199 x 10(-30) esu) and 68 au, respectively. Besides this, the intercalation of the Li atom to the B(10)H(14) basket brings some distinctive changes in its Raman, (11)B NMR, and UV-vis spectra along with its other electronic properties that might be used by the experimentalists to identify this novel kind of Li@B(10)H(14) complex with a large electro-optical response. This study may evoke the possibility to explore a new thriving area, i.e., alkali metal-boranes for NLO application.

  16. Empowering families by engaging and relating Murri way: a grounded theory study of the implementation of the Cape York Baby Basket program.

    Science.gov (United States)

    McCalman, Janya; Searles, Andrew; Bainbridge, Roxanne; Ham, Rachael; Mein, Jacki; Neville, Johanna; Campbell, Sandra; Tsey, Komla

    2015-05-21

    Evaluating program outcomes without considering how the program was implemented can cause misunderstandings and inefficiencies when initiating program improvements. In conjunction with a program evaluation, reported elsewhere, this paper theorises the process of implementing an Indigenous Australian maternal and child health program. The Baby Basket program was developed in 2009 for the remote Cape York region and aimed to improve the attendance and engagement of Indigenous women at antenatal and postnatal clinics through providing three baskets of maternal and baby goods and associated health education. Constructivist grounded theory methods were used to generate and analyse data from qualitative interviews and focus groups with Indigenous women who received the baskets, their extended family members, and healthcare workers who delivered them. Data was coded in NVivo with concepts iteratively compared until higher order constructs and their relationships could be modelled to explain the common purpose for participants, the process involved in achieving that purpose, key strategies, conditions and outcomes. Theoretical terms are italicised. Program implementation entailed empowering families through a process of engaging and relating Murri (Queensland Indigenous) way. Key influencing conditions of the social environment were the remoteness of communities, keeping up with demand, families' knowledge, skills and roles and organisational service approaches and capacities. Engaging and relating Murri way occurred through four strategies: connecting through practical support, creating a culturally safe practice, becoming informed and informing others, and linking at the clinic. These strategies resulted in women and families taking responsibility for health through making healthy choices, becoming empowered health consumers and advocating for community changes. The theoretical model was applied to improve and revise Baby Basket program implementation, including

  17. 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. Copyright © 2015 the authors 0270-6474/15/353616-09$15.00/0.

  18. Multi-institutional Evaluation of Upper Urinary Tract Biopsy Using Backloaded Cup Biopsy Forceps, a Nitinol Basket, and Standard Cup Biopsy Forceps.

    Science.gov (United States)

    Lama, Daniel J; Safiullah, Shoaib; Patel, Roshan M; Lee, Thomas K; Balani, Jyoti P; Zhang, Lishi; Okhunov, Zhamshid; Margulis, Vitaly; Savage, Stephen J; Uchio, Edward; Landman, Jaime

    2018-04-06

    To compare the performance of 3 contemporary ureteroscopic biopsy devices for the histopathologic diagnosis of upper tract urothelial carcinoma (UTUC). We retrospectively reviewed 145 patients who underwent 182 urothelial biopsies using 2.4F backloaded cup biopsy forceps, a nitinol basket, or 3F standard cup biopsy forceps at 3 tertiary academic centers between 2011 and 2016. Experienced genitourinary pathologists provided an assessment of each specimen without knowledge of the device used for biopsy. For patients who underwent nephroureterectomy without neoadjuvant chemotherapy within 3 months of biopsy-proven UTUC diagnosis, the biopsy grade was compared with both the grade and stage of the surgical specimen. Biopsy utilization varied among the 3 institutions (P cup forceps was rated similarly to the nitinol basket (P >.05) and was favored over standard cup forceps specimens. Grade concordance was not affected by specimen size (P >.05), morphology (P >.1), or location (P >.5). No difference existed among the devices in the rate of acquiring a grade concordant biopsy; however, the backloaded cup forceps provided concordant biopsies that could be distinguished as low- and high-grade (P = .02). The backloaded cup forceps and nitinol basket obtained a higher quality urothelial specimen compared with standard cup forceps. Ureteroscopic biopsy device selection did not significantly impact the accuracy of the histologic diagnosis of UTUC. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. 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.

  20. Regulation of RNA-binding proteins affinity to export receptors enables the nuclear basket proteins to distinguish and retain aberrant mRNAs.

    Science.gov (United States)

    Soheilypour, M; Mofrad, M R K

    2016-11-02

    Export of messenger ribonucleic acids (mRNAs) into the cytoplasm is a fundamental step in gene regulation processes, which is meticulously quality controlled by highly efficient mechanisms in eukaryotic cells. Yet, it remains unclear how the aberrant mRNAs are recognized and retained inside the nucleus. Using a new modelling approach for complex systems, namely the agent-based modelling (ABM) approach, we develop a minimal model of the mRNA quality control (QC) mechanism. Our results demonstrate that regulation of the affinity of RNA-binding proteins (RBPs) to export receptors along with the weak interaction between the nuclear basket protein (Mlp1 or Tpr) and RBPs are the minimum requirements to distinguish and retain aberrant mRNAs. Our results show that the affinity between Tpr and RBPs is optimized to maximize the retention of aberrant mRNAs. In addition, we demonstrate how the length of mRNA affects the QC process. Since longer mRNAs spend more time in the nuclear basket to form a compact conformation and initiate their export, nuclear basket proteins could more easily capture and retain them inside the nucleus.

  1. Acetal-Linked Paclitaxel Polymeric Prodrug Based on Functionalized mPEG-PCL Diblock Polymer for pH-Triggered Drug Delivery

    Directory of Open Access Journals (Sweden)

    Yinglei Zhai

    2017-12-01

    Full Text Available The differences in micro-environment between cancer cells and the normal ones offer the possibility to develop stimuli-responsive drug-delivery systems for overcoming the drawbacks in the clinical use of anticancer drugs, such as paclitaxel, doxorubicin, and etc. Hence, we developed a novel endosomal pH-sensitive paclitaxel (PTX prodrug micelles based on functionalized poly(ethylene glycol-poly(ε-caprolactone (mPEG-PCL diblock polymer with an acid-cleavable acetal (Ace linkage (mPEG-PCL-Ace-PTX. The mPEG-PCL-Ace-PTX5 with a high drug content of 23.5 wt % was self-assembled in phosphate buffer (pH 7.4, 10 mM into nanosized micelles with an average diameter of 68.5 nm. The in vitro release studies demonstrated that mPEG-PCL-Ace-PTX5 micelles was highly pH-sensitive, in which 16.8%, 32.8%, and 48.2% of parent free PTX was released from mPEG-PCL-Ace-PTX5 micelles in 48 h at pH 7.4, 6.0, and 5.0, respectively. Thiazolyl Blue Tetrazolium Bromide (MTT assays suggested that the pH-sensitive PTX prodrug micelles displayed higher therapeutic efficacy against MCF-7 cells compared with free PTX. Therefore, the PTX prodrug micelles with acetal bond may offer a promising strategy for cancer therapy.

  2. A carrier for non-covalent delivery of functional beta-galactosidase and antibodies against amyloid plaques and IgM to the brain.

    Directory of Open Access Journals (Sweden)

    Gobinda Sarkar

    Full Text Available BACKGROUND: Therapeutic intervention of numerous brain-associated disorders currently remains unrealized due to serious limitations imposed by the blood-brain-barrier (BBB. The BBB generally allows transport of small molecules, typically <600 daltons with high octanol/water partition coefficients, but denies passage to most larger molecules. However, some receptors present on the BBB allow passage of cognate proteins to the brain. Utilizing such receptor-ligand systems, several investigators have developed methods for delivering proteins to the brain, a critical requirement of which involves covalent linking of the target protein to a carrier entity. Such covalent modifications involve extensive preparative and post-preparative chemistry that poses daunting limitations in the context of delivery to any organ. Here, we report creation of a 36-amino acid peptide transporter, which can transport a protein to the brain after routine intravenous injection of the transporter-protein mixture. No covalent linkage of the protein with the transporter is necessary. APPROACH: A peptide transporter comprising sixteen lysine residues and 20 amino acids corresponding to the LDLR-binding domain of apolipoprotein E (ApoE was synthesized. Transport of beta-galactosidase, IgG, IgM, and antibodies against amyloid plques to the brain upon iv injection of the protein-transporter mixture was evaluated through staining for enzyme activity or micro single photon emission tomography (micro-SPECT or immunostaining. Effect of the transporter on the integrity of the BBB was also investigated. PRINCIPAL FINDINGS: The transporter enabled delivery to the mouse brain of functional beta-galactosidase, human IgG and IgM, and two antibodies that labeled brain-associated amyloid beta plaques in a mouse model of Alzheimer's disease. SIGNIFICANCE: The results suggest the transporter is able to transport most or all proteins to the brain without the need for chemically linking the

  3. Assisted Vaginal Delivery

    Science.gov (United States)

    ... Education & Events Advocacy For Patients About ACOG Assisted Vaginal Delivery Home For Patients Search FAQs Assisted Vaginal ... Vaginal Delivery FAQ192, February 2016 PDF Format Assisted Vaginal Delivery Labor, Delivery, and Postpartum Care What is ...

  4. Sexual function and postpartum depression 6 months after attempted operative vaginal delivery according to fetal head station: A prospective population-based cohort study.

    Directory of Open Access Journals (Sweden)

    Guillaume Ducarme

    Full Text Available To evaluate the effect of the fetal head station at attempted operative vaginal delivery (aOVD, and specifically midpelvic or low aOVD, on female and male sexual function and symptoms of postpartum depression (PPD at 6 months.Prospective population-based cohort study.1,941 women with singleton term fetuses in vertex presentation with midpelvic or low aOVD between 2008 and 2013 in a tertiary care university hospital.Symptoms of female sexual dysfunction using the Pelvic Organ Prolapse/Urinary Incontinence/Sexual Function Short Form Questionnaire (PISQ-12, symptoms of PPD using the Edinburgh Postnatal Depression Scale (EPDS score, symptoms of male sexual dysfunction using the International Index of Erectile Function (IIEF-15 and perineal pain were assessed 6 months after aOVD. We measured the association between midpelvic or low aOVD and symptoms of female and male sexual function and symptoms of PPD at 6 months using multiple regression and adjusting for demographics, and risk factors of sexual dysfunction, symptoms of PPD and perineal pain with adjusted odds ratios (aORs and 95% confidence intervals (95% CI.The study included 907 women (46.7% who responded to the questionnaire; 18.4% (167/907 had midpelvic aOVD, and 81.6% (740/907 low. Most women (873/907 [96.3%] of those with partners reported sexual activity at 6 months. No significant difference was observed for PISQ-12, EPDS, IIEF-15 scores and perineal pain between mid and low pelvic groups. Compared with low pelvic aOVD, midpelvic aOVD was not significantly associated with either female or male sexual dysfunction (p = 0.89 and p = 0.76, respectively, or maternal symptoms of PPD (p = 0.83. Perineal pain significantly increased the risk of male and female sexual dysfunction and maternal symptoms of PPD at 6 months (p = 0.02, p = 0.006, and p = 0.02, respectively.Midpelvic compared with low pelvic aOVD was not associated with an increase in sexual dysfunction, nor with symptoms of PPD at 6

  5. Intracavernous Delivery of a Designed Angiopoietin-1 Variant Rescues Erectile Function by Enhancing Endothelial Regeneration in the Streptozotocin-Induced Diabetic Mouse

    Science.gov (United States)

    Jin, Hai-Rong; Kim, Woo Jean; Song, Jae Sook; Piao, Shuguang; Choi, Min Ji; Tumurbaatar, Munkhbayar; Shin, Sun Hwa; Yin, Guo Nan; Koh, Gou Young; Ryu, Ji-Kan; Suh, Jun-Kyu

    2011-01-01

    OBJECTIVE Patients with diabetic erectile dysfunction often have severe endothelial dysfunction and respond poorly to oral phosphodiesterase-5 inhibitors. We examined the effectiveness of the potent angiopoietin-1 (Ang1) variant, cartilage oligomeric matrix protein (COMP)-Ang1, in promoting cavernous endothelial regeneration and restoring erectile function in diabetic animals. RESEARCH DESIGN AND METHODS Four groups of mice were used: controls; streptozotocin (STZ)-induced diabetic mice; STZ-induced diabetic mice treated with repeated intracavernous injections of PBS; and STZ-induced diabetic mice treated with COMP-Ang1 protein (days −3 and 0). Two and 4 weeks after treatment, we measured erectile function by electrical stimulation of the cavernous nerve. The penis was harvested for histologic examinations, Western blot analysis, and cGMP quantification. We also performed a vascular permeability test. RESULTS Local delivery of the COMP-Ang1 protein significantly increased cavernous endothelial proliferation, endothelial nitric oxide (NO) synthase (NOS) phosphorylation, and cGMP expression compared with that in the untreated or PBS-treated STZ-induced diabetic group. The changes in the group that received COMP-Ang1 restored erectile function up to 4 weeks after treatment. Endothelial protective effects, such as marked decreases in the expression of p47phox and inducible NOS, in the generation of superoxide anion and nitrotyrosine, and in the number of apoptotic cells in the corpus cavernosum tissue, were noted in COMP-Ang1–treated STZ-induced diabetic mice. An intracavernous injection of COMP-Ang1 completely restored endothelial cell-cell junction proteins and decreased cavernous endothelial permeability. COMP-Ang1–induced promotion of cavernous angiogenesis and erectile function was abolished by the NOS inhibitor, N-nitro-L-arginine methyl ester, but not by the NADPH oxidase inhibitor, apocynin. CONCLUSIONS These findings support the concept of cavernous

  6. 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

  7. 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.

  8. Colon-targeted delivery of cyclosporine A using dual-functional Eudragit® FS30D/PLGA nanoparticles ameliorates murine experimental colitis.

    Science.gov (United States)

    Naeem, Muhammad; Bae, Junhwan; Oshi, Murtada A; Kim, Min-Soo; Moon, Hyung Ryong; Lee, Bok Luel; Im, Eunok; Jung, Yunjin; Yoo, Jin-Wook

    2018-01-01

    Colon-targeted oral nanoparticles (NPs) have emerged as an ideal, safe, and effective therapy for ulcerative colitis (UC) owing to their ability to selectively accumulate in inflamed colonic mucosa. Cyclosporine A (CSA), an immunosuppressive agent, has long been used as rescue therapy in severe steroid-refractory UC. In this study, we developed CSA-loaded dual-functional polymeric NPs composed of Eudragit ® FS30D as a pH-sensitive polymer for targeted delivery to the inflamed colon, and poly(lactic-co-glycolic acid) (PLGA) as a sustained-release polymer. CSA-loaded Eudragit FS30D nanoparticles (ENPs), PLGA nanoparticles (PNPs), and Eudragit FS30D/PLGA nanoparticles (E/PNPs) were prepared using the oil-in-water emulsion method. Scanning electron microscope images and zeta size data showed successful preparation of CSA-loaded NPs. PNPs exhibited a burst drug release of >60% at pH 1.2 (stomach pH) in 0.5 h, which can lead to unwanted systemic absorption and side effects. ENPs effectively inhibited the burst drug release at pH 1.2 and 6.8 (proximal small intestine pH); however, nearly 100% of the CSA in ENPs was released rapidly at pH 7.4 (ileum-colon pH) owing to complete NP dissolution. In contrast to single-functional PNPs and ENPs, the dual-functional E/PNPs minimized burst drug release (only 18%) at pH 1.2 and 6.8, and generated a sustained release at pH 7.4 thereafter. Importantly, in distribution studies in the gastrointestinal tracts of mice, E/PNPs significantly improved CSA distribution to the colon compared with PNPs or ENPs. In a mouse model of colitis, E/PNP treatment improved weight loss and colon length, and decreased rectal bleeding, spleen weight, histological scoring, myeloperoxidase activity, macrophage infiltration, and expression of proinflammatory cytokines compared with PNPs or ENPs. Overall, this work confirms the benefits of CSA-loaded E/PNPs for efficiently delivering CSA to the colon, suggesting their potential for UC therapy.

  9. Targeted Delivery of TrkB Receptor to Phrenic Motoneurons Enhances Functional Recovery of Rhythmic Phrenic Activity after Cervical Spinal Hemisection

    Science.gov (United States)

    Gransee, Heather M.; Zhan, Wen-Zhi; Sieck, Gary C.; Mantilla, Carlos B.

    2013-01-01

    Progressive recovery of rhythmic phrenic activity occurs over time after a spinal cord hemisection involving unilateral transection of anterolateral funiculi at C2 (SH). Brain-derived neurotrophic factor (BDNF) acting through its full-length tropomyosin related kinase receptor subtype B (TrkB.FL) contributes to neuroplasticity after spinal cord injury, but the specific cellular substrates remain unclear. We hypothesized that selectively targeting increased TrkB.FL expression to phrenic motoneurons would be sufficient to enhance recovery of rhythmic phrenic activity after SH. Several adeno-associated virus (AAV) serotypes expressing GFP were screened to determine specificity for phrenic motoneuron transduction via intrapleural injection in adult rats. GFP expression was present in the cervical spinal cord 3 weeks after treatment with AAV serotypes 7, 8, and 9, but not with AAV2, 6, or rhesus-10. Overall, AAV7 produced the most consistent GFP expression in phrenic motoneurons. SH was performed 3 weeks after intrapleural injection of AAV7 expressing human TrkB.FL-FLAG or saline. Delivery of TrkB.FL-FLAG to phrenic motoneurons was confirmed by FLAG protein expression in the phrenic motor nucleus and human TrkB.FL mRNA expression in microdissected phrenic motoneurons. In all SH rats, absence of ipsilateral diaphragm EMG activity was confirmed at 3 days post-SH, verifying complete interruption of ipsilateral descending drive to phrenic motoneurons. At 14 days post-SH, all AAV7-TrkB.FL treated rats (n = 11) displayed recovery of ipsilateral diaphragm EMG activity compared to 3 out of 8 untreated SH rats (pphrenic motoneurons is sufficient to enhance recovery of ipsilateral rhythmic phrenic activity after SH, indicating that selectively targeting gene expression in spared motoneurons below the level of spinal cord injury may promote functional recovery. PMID:23724091

  10. Effect of subsequent vaginal delivery on bowel symptoms and anorectal function in women who sustained a previous obstetric anal sphincter injury.

    Science.gov (United States)

    Jordan, Polly A; Naidu, Madhu; Thakar, Ranee; Sultan, Abdul H

    2018-03-29

    Our primary objective was to prospectively evaluate anorectal symptoms, anal manometry and endoanal ultrasound (EAUS) in women who followed the recommended mode of subsequent delivery following index obstetric anal sphincter injuries (OASIs) using our unit's standardised protocol. Our secondary objectives were to evaluate the role of internal anal sphincter defects and also to compare outcomes in a subgroup of symptomatic women with normal anorectal physiology. This is a prospective follow-up study of pregnant women with previous OASIs who were counselled regarding subsequent mode of delivery between January 2003 and December 2014. Assessment involved the St Mark's Incontinence Score (SMIS), anal manometry and EAUS at both antepartum and 3-month postpartum visits. Data were analysed using Wilcoxon and Mann-Whitney U tests. Three hundred and fifty women attended the perineal clinic over the study period, of whom 122 met the inclusion criteria (99 vaginal delivery [VD], 23 caesarean section). No significant worsening of anorectal symptoms was observed following subsequent delivery in the VD group (p = 0.896), although a reduced squeeze pressure was observed at 3 months postpartum (p delivery. In the absence of a randomised study, use of this protocol can aid clinicians in their decision-making.

  11. (02.2) Scoping experiments; (02.3) long-term corrosion testing and properties evaluation of candidate waste package basket material

    International Nuclear Information System (INIS)

    VanKonynenburg, R. A.

    1996-01-01

    The work described in this activity plan addresses Information Need 2.7.3 of the Yucca Mountain Site Characterization Plan (l), which reads Determination that the design criteria in lOCFR60.130 through 60.133 and any appropriate additional design objectives pertaining to criticality control have been met. This work falls under section WBS 1.2.2.5 2 (Basket Materials) of WBS 1.2.2.5 (Waste Package Materials) in the Work Breakdown Structure of the Yucca Mountain Site Characterization Project

  12. From baskets to baking

    OpenAIRE

    Taylor, Clare

    2016-01-01

    Whilst ‘occupation’ and the links between occupation and health have been central tenets of occupational therapy since its inception (Reilly 1961), the place and meaning of occupation within our therapeutic repertoire has evolved and changed as the profession has developed (Wilcock & Hocking, 2015). Utilising the principles of auto/biography and autoethnography (Adams, et al 2015), this poster will explore the nature of ‘occupation’ from a professional and personal perspective across a 40 yea...

  13. Deproteinized bovine bone functionalized with the slow delivery of BMP-2 for the repair of critical-sized bone defects in sheep.

    Science.gov (United States)

    Liu, Tie; Wu, Gang; Wismeijer, Daniel; Gu, Zhiyuan; Liu, Yuelian

    2013-09-01

    As an alternative to an autologous bone graft, deproteinized bovine bone (DBB) is widely used in the clinical dentistry. Although DBB provides an osteoconductive scaffold, it is not capable of enhancing bone regeneration because it is not osteoinductive. In order to render DBB osteoinductive, bone morphogenetic protein 2 (BMP-2) has previously been incorporated into a three dimensional reservoir (a biomimetic calcium phosphate coating) on DBB, which effectively promoted the osteogenic response by the slow delivery of BMP-2. The aim of this study was to investigate the therapeutic effectiveness of such coating on the DBB granules in repairing a large cylindrical bone defect (8 mm diameter, 13 mm depth) in sheep. Eight groups were randomly assigned to the bone defects: (i) no graft material; (ii) autologous bone; (iii) DBB only; (iv) DBB mixed with autologous bone; (v) DBB bearing adsorbed BMP-2; (vi) DBB bearing a coating but no BMP-2; (vii) DBB bearing a coating with adsorbed BMP-2; and (viii) DBB bearing a coating-incorporated depot of BMP-2. 4 and 8 weeks after implantation, samples were withdrawn for a histological and a histomorphometric analysis. Histological results confirmed the excellent biocompatibility and osteoconductivity of all the grafts tested. At 4 weeks, DBB mixed with autologous bone or functionalized with coating-incorporated BMP-2 showed more newly-formed bone than the other groups with DBB. At 8 weeks, the volume of newly-formed bone around DBB that bore a coating-incorporated depot of BMP-2 was greatest among the groups with DBB, and was comparable to the autologous bone group. The use of autologous bone and BMP-2 resulted in more bone marrow formation. Multinucleated giant cells were observed in the resorption process around DBB, whereas histomorphometric analysis revealed no significant degradation of DBB. In conclusion, it was shown that incorporating BMP-2 into the calcium phosphate coating of DBB induced strong bone formation around DBB

  14. 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.

  15. Assisted delivery with forceps

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000509.htm Assisted delivery with forceps To use the sharing features on ... called vacuum assisted delivery . When is a Forceps Delivery Needed? Even after your cervix is fully dilated ( ...

  16. 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...

  17. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Design and evaluation of mPEG-PLA micelles functionalized with drug-interactive domains as improved drug carriers for docetaxel delivery.

    Science.gov (United States)

    Qi, Dingqing; Gong, Feirong; Teng, Xin; Ma, Mingming; Wen, Huijing; Yuan, Weihao; Cheng, Yi; Lu, Chong

    2017-10-01

    Polymeric micelles are very attractive drug delivery systems for hydrophobic agents, owing to their readily tailorable chemical structure and ease for scale-up preparation. However, the intrinsic poor stability of drug-loaded micelles presents one of the major challenges for most micellar systems in the translation to clinical applications. In this study, a simple, well-defined, and easy-to-scale up 9-Fluorenylmethoxycarbonyl (Fmoc) and tert-butoxycarbonyl (Boc) containing lysine dendronized mPEG-PLA (mPEG-PLA-Lys(FB) 2 ) micellar formulation was designed and prepared for docetaxel (DTX) delivery, in an effort to improve the stability of the micelles, and its physicochemical properties, pharmacokinetics, and anti-tumor efficacy against SKOV-3 ovarian cancer were evaluated. MPEG-PLA-Lys(FB) 2 was synthesized via a three-step synthetic route, and it actively interacted with DTX in aqueous media to form stable micelles with small particle sizes (~17-19 nm) and narrow size distribution (PI PLA-Lys(FB) 2 micelles achieved delayed and sustained release manner of DTX in comparison with mPEG-PLA micelles. Further in vivo xenograft tumor model in nude mice DTX/mPEG-PLA-Lys(FB) 2 micelles demonstrated significantly higher inhibitory effect on tumor growth than the marketed formulation Taxotere. Thus, our system may hold promise as a simple and effective delivery system for DTX with a potential for translation into clinical study.

  19. 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 ...

  20. Assessment of the adsorption mechanism of Flutamide anticancer drug on the functionalized single-walled carbon nanotube surface as a drug delivery vehicle: An alternative theoretical approach based on DFT and MD

    Science.gov (United States)

    Kamel, Maedeh; Raissi, Heidar; Morsali, Ali; Shahabi, Mahnaz

    2018-03-01

    In the present work, we have studied the drug delivery performance of the functionalized (5, 5) single-walled carbon nanotube with a carboxylic acid group for Flutamide anticancer drug in the gas phase as well as water solution by means of density functional theory calculations. The obtained results confirmed the energetic stability of the optimized geometries and revealed that the nature of drug adsorption on the functionalized carbon nanotube is physical. Our computations showed that the hydrogen bonding between active sites of Flutamide molecule and the carboxyl functional group of the nanotube plays a vital role in the stabilization of the considered configurations. The natural bond orbital analysis suggested that the functionalized nanotube plays the role of an electron donor and Flutamide molecule acts as an electron acceptor at the investigated complexes. In addition, molecular dynamics simulation is also utilized to investigate the effect of functionalized carbon nanotube chirality on the dynamic process of drug molecule adsorption on the nanotube surface. Simulation results demonstrated that drug molecules are strongly adsorbed on the functionalized nanotube surface with (10,5) chirality, as reflected by the most negative van der Waals interaction energy and a high number of hydrogen bonds between the functionalized nanotube and drug molecules.

  1. Fabrication of Reductive-Responsive Prodrug Nanoparticles with Superior Structural Stability by Polymerization-Induced Self-Assembly and Functional Nanoscopic Platform for Drug Delivery.

    Science.gov (United States)

    Zhang, Wen-Jian; Hong, Chun-Yan; Pan, Cai-Yuan

    2016-09-12

    A highly efficient strategy, polymerization-induced self-assembly (PISA) for fabrication of the polymeric drug delivery systems in cancer chemotherapy is reported. Diblock prodrug copolymer, PEG-b-P(MEO2MA-co-CPTM) was used as the macro-RAFT agent to fabricate prodrug nanoparticles through PISA. The advantages of fabricating intelligent drug delivery system via this approach are as following: (1) Simultaneous fulfillment of polymerization, self-assembly, and drug encapsulation in one-pot at relatively high concentration (100 mg/mL); (2) Almost complete monomer conversion allows direct application of the resultant prodrug nanoparticles without further purification; (3) Robust structures of the resultant prodrug nanoparticles, because the cross-linker was used as the comonomer, resulted in core-cross-linking simultaneously with the formation of the prodrug nanoparticles; (4) The drug content in the resultant prodrug nanoparticles can be accurately modulated just via adjusting the feed molar ratio of MEO2MA/CPTM in the synthesis of PEG-b-P(MEO2MA-co-CPTM). The prodrug nanoparticles with similar diameters but various drug contents were obtained using different prodrug macro-CTA. In consideration of the long-term biological toxicity, the prodrug nanoparticles with higher drug content exhibit more excellent anticancer efficiency due to that lower dosage of them are enough for effectively killing HeLa cells.

  2. Synthesis of a basket-shaped C56H38 hydrocarbon as a precursor toward an end-cap template for carbon [6,6]nanotubes.

    Science.gov (United States)

    Cui, Hu; Akhmedov, Novruz G; Petersen, Jeffrey L; Wang, Kung K

    2010-03-19

    A basket-shaped C(56)H(38) hydrocarbon (3) possessing a 30-carbon difluorenonaphthacenyl core that can be mapped onto the surface of C(78) was synthesized from 4-bromo-1-indanone. The first stage of the synthesis involved the preparation of tetraketone 10 as a key intermediate. The use of cascade cyclization reactions of benzannulated enyne-allenes as key features in the next stage of the synthetic sequence provides an efficient route to 3 from 4-bromo-1-indanone in 12 steps. The all-cis relationship among the methyl groups and the methine hydrogens causes the two benzofluorenyl units in 3 to be in an essentially perpendicular orientation to each other. Hydrocarbon 3 and its derivatives could serve as attractive precursors leading to a geodesic C(68)H(26) end-cap template for carbon [6,6]nanotubes.

  3. Puebla Territory-Specific Basket of Goods Strategies and Their Local Repercussions for Employment and Profit: the Case of Xicotepec de Juárez, Puebla

    Directory of Open Access Journals (Sweden)

    Mario del Roble Pensado Leglise

    2015-07-01

    Full Text Available Developing a basket of land goods means a systemic strateg y for small farmers because it allows reaching multiple objectives in order to promote territorial competitiveness to access market niches with varied rural goods, strengthen social capital and generate better local levels in employment and income, together with increasing and preserving the environment. This analysis implied the application of a system dynamics model which produced possible future scenarios (through Ve n s i m®DSS 5.8 about employment and income obtained by smallholder coffee farmers from Xicotepec de Juárez municipality in Puebla, regarding the setting of the above mentioned strateg y for rural development. Results showed that this strateg y was implemented successfully and also revealed opportunities for: a improving the development capacity of small farmers; b making the institutional context favorable; c The reinforcement of social capital essential to implement this land strategy.

  4. Thoracoamniotic shunting for fetal pleural effusion with hydropic change using a double-basket catheter: An insight into the preoperative determinants of shunting efficacy.

    Science.gov (United States)

    Hidaka, Nobuhiro; Kido, Saki; Sato, Yuka; Murata, Masaharu; Fujita, Yasuyuki; Kato, Kiyoko

    2018-02-01

    Although the efficacy of thoracoamniotic shunting (TAS) for fetal hydrothorax is well-recognized, the coexistence of hydrops fetalis is still a clinical challenge. The preoperative determinants of shunting efficacy are not fully understood. In this study, we aimed to investigate the perinatal and postnatal outcomes of hydrops fetalis with pleural effusion treated by TAS using a double-basket catheter, and to discuss the preoperative factors predictive of patients who will benefit from TAS. We conducted a retrospective study in hydropic fetuses with pleural effusion treated by TAS between 2007 and 2015. We extracted information regarding postnatal survival and pretherapeutic sonographic findings, including skin-edema thickness, pleural-effusion pocket size, and Doppler readings. Twelve subjects underwent TAS at a median gestational age of 29 +5 weeks (range, 25 +5 -33 +2 weeks). Skin edema disappeared or regressed in 7. Three experienced early neonatal death and the other 9 ultimately survived after a live birth at a median gestational age of 33 +4 weeks (range, 29 +1 -38 +2 weeks). All surviving children, except for 1, had a pretherapeutic pleural-effusion pocket greater than the precordial-edema thickness. All 3 children that died had precordial-edema thickness equal to or greater than the size of the pleural-effusion pocket. We achieved a high survival rate (75%) using the double-basket technique. A greater pretherapeutic width of skin edema compared with the pleural-effusion pocket is possibly suggestive of a treatment-resistant condition and subsequent poor postnatal outcome. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. 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.

  6. 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....

  7. Vacuum-assisted delivery

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000514.htm Vacuum-assisted delivery To use the sharing features on this page, ... through the birth canal. When is Vacuum-assisted Delivery Needed? Even after your cervix is fully dilated ( ...

  8. 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)....

  9. Articulating feedstock delivery device

    Science.gov (United States)

    Jordan, Kevin

    2013-11-05

    A fully articulable feedstock delivery device that is designed to operate at pressure and temperature extremes. The device incorporates an articulating ball assembly which allows for more accurate delivery of the feedstock to a target location. The device is suitable for a variety of applications including, but not limited to, delivery of feedstock to a high-pressure reaction chamber or process zone.

  10. Influencia del tamaño del balón y la altura de la canasta en la eficacia del lanzamiento en categoría pre-infantil (11-12 años femenina.[Influence of ball size and basket height in the effectiveness of the shooting in femalepre-child level (11-12 years

    Directory of Open Access Journals (Sweden)

    María Teresa Gutiérrez Colón

    2010-03-01

    Abstract The aim of this study is to know which are learning best conditions of the shooting basketball in the phase pre-child. In this phase is a sharp change for the boy depending on the size of the equipment, that demands to carry out a progressive adaptation process of dimensions of the ball and of the basket, allowing that players have a more suitable and adapted learning to his characteristics. The sample was formed by 12 players pre-child (11-12 years, belonging an equipment from feminine basketball. The effectiveness of the releases was analyzed to basket depending on the size of the ball and the height of the basket, as well as of the position of the shooting, before and after an intervention process. Results showed that at the start of the process were differences in the effectiveness of shooting. Players were more effective shooting with ball of minibasket (number 5 and basket of minibasket that with those of the full-grown game (number 6. Finally, after the intervention process results showed as players increase their effectiveness when they shoot with big ball and basket with respect to the beginning of the process. Besides, in the post-test obtained great effectiveness values with this material that with the small ball and basket. Key words:  basketball, pre-child, effectiveness, shooting, ball size, basket

  11. Functional correction of neurological and somatic disorders at later stages of disease in MPS IIIA mice by systemic scAAV9-hSGSH gene delivery

    Directory of Open Access Journals (Sweden)

    Haiyan Fu

    2016-01-01

    Full Text Available The reversibility of neuropathic lysosomal storage diseases, including MPS IIIA, is a major goal in therapeutic development, due to typically late diagnoses and a large population of untreated patients. We used self-complementary adeno-associated virus (scAAV serotype 9 vector expressing human N-sulfoglucosamine sulfohydrolase (SGSH to test the efficacy of treatment at later stages of the disease. We treated MPS IIIA mice at 1, 2, 3, 6, and 9 months of age with an intravenous injection of scAAV9-U1a-hSGSH vector, leading to restoration of SGSH activity and reduction of glycosaminoglycans (GAG throughout the central nervous system (CNS and somatic tissues at a dose of 5E12 vg/kg. Treatment up to 3 months age improved learning ability in the Morris water maze at 7.5 months, and lifespan was normalized. In mice treated at 6 months age, behavioral performance was impaired at 7.5 months, but did not decline further when retested at 12 months, and lifespan was increased, but not normalized. Treatment at 9 months did not increase life-span, though the GAG storage pathology in the CNS was improved. The study suggests that there is potential for gene therapy intervention in MPS IIIA at intermediate stages of the disease, and extends the clinical relevance of our systemic scAAV9-hSGSH gene delivery approach.

  12. AAV serotype 2/1-mediated gene delivery of anti-inflammatory interleukin-10 enhances neurogenesis and cognitive function in APP+PS1 mice.

    Science.gov (United States)

    Kiyota, T; Ingraham, K L; Swan, R J; Jacobsen, M T; Andrews, S J; Ikezu, T

    2012-07-01

    Brain inflammation is a double-edged sword. It is required for brain repair in acute damage, whereas chronic inflammation and autoimmune disorders are neuropathogenic. Certain proinflammatory cytokines and chemokines are closely related to cognitive dysfunction and neurodegeneration. Representative anti-inflammatory cytokines, such as interleukin (IL)-10, can suppress neuroinflammation and have significant therapeutic potentials in ameliorating neurodegenerative disorders such as Alzheimer's disease (AD). Here, we show that adeno-associated virus (AAV) serotype 2/1 hybrid-mediated neuronal expression of the mouse IL-10 gene ameliorates cognitive dysfunction in amyloid precursor protein+ presenilin-1 bigenic mice. AAV2/1 infection of hippocampal neurons resulted in sustained expression of IL-10 without its leakage into the blood, reduced astro/microgliosis, enhanced plasma amyloid-β peptide (Aβ) levels and enhanced neurogenesis. Moreover, increased levels of IL-10 improved spatial learning, as determined by the radial arm water maze. Finally, IL-10-stimulated microglia enhanced proliferation but not differentiation of primary neural stem cells in the co-culture system, whereas IL-10 itself had no effect. Our data suggest that IL-10 gene delivery has a therapeutic potential for a non-Aβ-targeted treatment of AD.

  13. 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.

  14. UAV Delivery Monitoring System

    Directory of Open Access Journals (Sweden)

    San Khin Thida

    2018-01-01

    Full Text Available UAV-based delivery systems are increasingly being used in the logistics field, particularly to achieve faster last-mile delivery. This study develops a UAV delivery system that manages delivery order assignments, autonomous flight operation, real time control for UAV flights, and delivery status tracking. To manage the delivery item assignments, we apply the concurrent scheduler approach with a genetic algorithm. The present paper describes real time flight data based on a micro air vehicle communication protocol (MAVLink. It also presents the detailed hardware components used for the field tests. Finally, we provide UAV component analysis to choose the suitable components for delivery in terms of battery capacity, flight time, payload weight and motor thrust ratio.

  15. Effects of PEG tethering chain length of vitamin E TPGS with a Herceptin-functionalized nanoparticle formulation for targeted delivery of anticancer drugs.

    Science.gov (United States)

    Zhao, Jing; Feng, Si-Shen

    2014-03-01

    Drug formulation by ligand conjugated nanoparticles of biodegradable polymers has become one of the most important strategies in drug targeting. We have developed in our previous work nanoparticles of a mixture of two vitamin E TPGS based copolymers PLA-TPGS and TPGS-TOOH with the latter for Herceptin conjugation for targeted delivery of anticancer drugs such as docetaxel to the cancer cells of human epidermal growth factor receptor 2 (HER2) overexpression. In this research, we investigated the effects of the PEG chain length in TPGS, which is in fact a PEGylated vitamin E, on the cellular uptake and cytotoxicity of the drug formulated in the Herceptin-conjugated nanoparticles of PLA-TPGS/TPGS-COOH blend (NPs). Such NPs of PEG1000, PEG2000, PEG3350 and PEG5000, i.e. the PEG of molecule weight 1000, 2000, 3350 and 5000, were prepared by the nanoprecipitation method and characterized for their size and size distribution, drug loading, surface morphology, surface charge and surface chemistry as well as in vitro drug release profile, cellular uptake and cytotoxicity. We found among such nanoparticles, those of PEG1000, i.e. of the shortest PEG tethering chain length, could result in the best therapeutic effects, which are 24.1%, 37.3%, 38.1% more efficient in cellular uptake and 68.1%, 90%, 92.6% lower in IC50 (thus higher in cytotoxicity) than the Herceptin-conjugated nanoparticles of PLA-TPGS/TPGS-COOH blend of PEG2000, PEG3350 and PEG5000 respectively in treatment of SK-BR-3 cancer cells which are of high HER2 overexpression. We provided a theoretical explanation from surface mechanics and thermodynamics for endocytosis of nanoparticles. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. 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.

  17. 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 expression...

  18. A Study to Identify Functions Which Inhibit or Facilitate the Health Care Delivery Process on Ward 51 at Walter Reed Army Medical Center, Washington, D.C.

    Science.gov (United States)

    1980-08-01

    system for distribution of supplies and linen on mobile supply carts has become a manual system because of design flaws in the monorail which was desigred...end is a function of the facility design and related fire and safety codes. Traffic flow patterns, including patient transport ser- vice, prohibit

  19. 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.

  20. Physisorbed o-carborane onto lyso-phosphatidylcholine-functionalized, single-walled carbon nanotubes: a potential carrier system for the therapeutic delivery of boron

    International Nuclear Information System (INIS)

    Yannopoulos, S N; Bouropoulos, N; Zouganelis, G D; Nurmohamed, S; Smith, J R; Fatouros, D G; Tsibouklis, J; Calabrese, G

    2010-01-01

    A combination of data from ICP-MS, Raman spectroscopy, UV-vis spectrometry, atomic force microscopy, ζ-potential measurements and gel electorphoresis studies has shown that o-carborane may be immobilized on stable aqueous dispersions of lyso-phosphatidylcholine-functionalized single-walled carbon nanotubes, which in turn indicates the potential of such structures for deployment as carrier vehicles in boron neutron capture therapy.

  1. IGF-1 delivery to CNS attenuates motor neuron cell death but does not improve motor function in type III SMA mice.

    Science.gov (United States)

    Tsai, Li-Kai; Chen, Yi-Chun; Cheng, Wei-Cheng; Ting, Chen-Hung; Dodge, James C; Hwu, Wuh-Liang; Cheng, Seng H; Passini, Marco A

    2012-01-01

    The efficacy of administering a recombinant adeno-associated virus (AAV) vector encoding human IGF-1 (AAV2/1-hIGF-1) into the deep cerebellar nucleus (DCN) of a type III SMA mouse model was evaluated. High levels of IGF-1 transcripts and protein were detected in the spinal cord at 2 months post-injection demonstrating that axonal connections between the cerebellum and spinal cord were able to act as conduits for the viral vector and protein to the spinal cord. Mice treated with AAV2/1-hIGF-1 and analyzed 8 months later showed changes in endogenous Bax and Bcl-xl levels in spinal cord motor neurons that were consistent with IGF-1-mediated anti-apoptotic effects on motor neurons. However, although AAV2/1-hIGF-1 treatment reduced the extent of motor neuron cell death, the majority of rescued motor neurons were non-functional, as they lacked axons that innervated the muscles. Furthermore, treated SMA mice exhibited abnormal muscle fibers, aberrant neuromuscular junction structure, and impaired performance on motor function tests. These data indicate that although CNS-directed expression of IGF-1 could reduce motor neuron cell death, this did not translate to improvements in motor function in an adult mouse model of type III SMA. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Calcium phosphate ceramics in drug delivery

    Science.gov (United States)

    Bose, Susmita; Tarafder, Solaiman; Edgington, Joe; Bandyopadhyay, Amit

    2011-04-01

    Calcium phosphate (CaP) particulates, cements and scaffolds have attracted significant interest as drug delivery vehicles. CaP systems, including both hydroxyapaptite and tricalcium phosphates, possess variable stoichiometry, functionality and dissolution properties which make them suitable for cellular delivery. Their chemical similarity to bone and thus biocompatibility, as well as variable surface charge density contribute to their controlled release properties. Among specific research areas, nanoparticle size, morphology, surface area due to porosity, and chemistry controlled release kinetics are the most active. This article discusses CaP systems in their particulate, cements, and scaffold forms for drug, protein, and growth factor delivery toward orthopedic and dental applications.

  3. Influence of dissolution media pH and USP1 basket speed on erosion and disintegration characteristics of immediate release metformin hydrochloride tablets.

    Science.gov (United States)

    Desai, Divyakant; Wong, Benjamin; Huang, Yande; Tang, Dan; Hemenway, Jeffrey; Paruchuri, Srinivasa; Guo, Hang; Hsieh, Daniel; Timmins, Peter

    2015-01-01

    To investigate the influence of the pH of the dissolution medium on immediate release 850 mg metformin hydrochloride tablets. A traditional wet granulation method was used to manufacture metformin hydrochloride tablets with or without a disintegrant. Tablet dissolution was conducted using the USP apparatus I at 100 rpm. In spite of its pH-independent high solubility, metformin hydrochloride tablets dissolved significantly slower in 0.1 N HCl (pH 1.2) and 50 mM pH 4.5 acetate buffer compared with 50 mM pH 6.8 phosphate buffer, the dissolution medium in the USP. Metformin hydrochloride API compressed into a round 1200 mg disk showed a similar trend. When basket rotation speed was increased from 100 to 250 rpm, the dissolution of metformin hydrochloride tablets was similar in all three media. Incorporation of 2% w/w crospovidone in the tablet formulation improved the dissolution although the pH-dependent trend was still evident, but incorporation of 2% w/w croscarmellose sodium resulted in rapid pH-independent tablet dissolution. In absence of a disintegrant in the tablet formulation, the dissolution was governed by the erosion-diffusion process. Even for a highly soluble drug, a super-disintegrant was needed in the formulation to overcome the diffusion layer limitation and change the dissolution mechanism from erosion-diffusion to disintegration.

  4. 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.

  5. Heart rate at discharge and long-term prognosis following percutaneous coronary intervention in stable and acute coronary syndromes--results from the BASKET PROVE trial.

    Science.gov (United States)

    Jensen, Magnus Thorsten; Kaiser, Christoph; Sandsten, Karl Erik; Alber, Hannes; Wanitschek, Maria; Iversen, Allan; Jensen, Jan Skov; Pedersen, Sune; Soerensen, Rikke; Rickli, Hans; Zurek, Marzena; Fahrni, Gregor; Bertel, Osmund; De Servi, Stefano; Erne, Paul; Pfisterer, Matthias; Galatius, Søren

    2013-10-09

    Elevated heart rate (HR) is associated with mortality in a number of heart diseases. We examined the long-term prognostic significance of HR at discharge in a contemporary population of patients with stable angina (SAP), non-ST-segment elevation acute coronary syndromes (NSTE-ACS), and ST-segment elevation myocardial infarction (STEMI) revascularized with percutaneous coronary intervention (PCI). Patients from the BASKET-PROVE trial, an 11-center randomized all-comers trial comparing bare-metal and drug-eluting stenting in large coronary vessels, were included. Discharge HR was determined from a resting ECG. Long-term outcomes (7 days to 2 years) were evaluated for all-cause mortality and cardiovascular death and non-fatal myocardial infarction. A total of 2029 patients with sinus rhythm were included, 722 (35.6%) SAP, 647 (31.9%) NSTE-ACS, and 660 (32.5%) STEMI. Elevated discharge HR was associated significantly with all-cause mortality: when compared to a reference of 90 bpm. For cardiovascular death/myocardial infarction, a discharge HR >90 bpm was associated with a hazard ratio of 6.2 (2.5-15.5, pacute coronary syndromes an elevated discharge HR was independently associated with poor prognosis. Conversely, a HR <60 bpm at discharge was associated with a good long-term prognosis irrespective of indication for PCI. © 2013.

  6. 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.

  7. 6. Home deliveries

    African Journals Online (AJOL)

    Sitwala

    determine factors associated with home deliveries. Main outcome ... deliver at home than a health facility compared to those who .... regression analysis, women who had four years of schooling or .... by report bias, the burden of home deliveries is a real challenge .... Journal of Econometrics 1987; 36: 185-204. 14. Michelo ...

  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...

  9. Health care delivery systems.

    NARCIS (Netherlands)

    Stevens, F.; Zee, J. van der

    2007-01-01

    A health care delivery system is the organized response of a society to the health problems of its inhabitants. Societies choose from alternative health care delivery models and, in doing so, they organize and set goals and priorities in such a way that the actions of different actors are effective,

  10. Global Delivery Models

    DEFF Research Database (Denmark)

    Manning, Stephan; Møller Larsen, Marcus; Bharati, Pratyush

    -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...

  11. Lysine-functionalized nanodiamonds as gene carriers: development of stable colloidal dispersion for in vitro cellular uptake studies and siRNA delivery application

    Science.gov (United States)

    Alwani, Saniya; Kaur, Randeep; Michel, Deborah; Chitanda, Jackson M; Verrall, Ronald E; Karunakaran, Chithra; Badea, Ildiko

    2016-01-01

    Purpose Nanodiamonds (NDs) are emerging as an attractive tool for gene therapeutics. To reach their full potential for biological application, NDs should maintain their colloidal stability in biological milieu. This study describes the behavior of lysine-functionalized ND (lys-ND) in various dispersion media, with an aim to limit aggregation and improve the colloidal stability of ND-gene complexes called diamoplexes. Furthermore, cellular and macromolecular interactions of lys-NDs are also analyzed in vitro to establish the understanding of ND-mediated gene transfer in cells. Methods lys-NDs were synthesized earlier through covalent conjugation of lysine amino acid to carboxylated NDs surface generated through re-oxidation in strong oxidizing acids. In this study, dispersions of lys-NDs were prepared in various media, and the degree of sedimentation was monitored for 72 hours. Particle size distributions and zeta potential measurements were performed for a period of 25 days to characterize the physicochemical stability of lys-NDs in the medium. The interaction profile of lys-NDs with fetal bovine serum showed formation of a protein corona, which was evaluated by size and charge distribution measurements. Uptake of lys-NDs in cervical cancer cells was analyzed by scanning transmission X-ray microscopy, flow cytometry, and confocal microscopy. Cellular uptake of diamoplexes (complex of lys-NDs with small interfering RNA) was also analyzed using flow cytometry. Results Aqueous dispersion of lys-NDs showed minimum sedimentation and remained stable over a period of 25 days. Size distributions showed good stability, remaining under 100 nm throughout the testing period. A positive zeta potential of >+20 mV indicated a preservation of surface charges. Size distribution and zeta potential changed for lys-NDs after incubation with blood serum, suggesting an interaction with biomolecules, mainly proteins, and a possible formation of a protein corona. Cellular internalization

  12. Lysine-functionalized nanodiamonds as gene carriers: development of stable colloidal dispersion for in vitro cellular uptake studies and siRNA delivery application.

    Science.gov (United States)

    Alwani, Saniya; Kaur, Randeep; Michel, Deborah; Chitanda, Jackson M; Verrall, Ronald E; Karunakaran, Chithra; Badea, Ildiko

    2016-01-01

    Nanodiamonds (NDs) are emerging as an attractive tool for gene therapeutics. To reach their full potential for biological application, NDs should maintain their colloidal stability in biological milieu. This study describes the behavior of lysine-functionalized ND (lys-ND) in various dispersion media, with an aim to limit aggregation and improve the colloidal stability of ND-gene complexes called diamoplexes. Furthermore, cellular and macromolecular interactions of lys-NDs are also analyzed in vitro to establish the understanding of ND-mediated gene transfer in cells. lys-NDs were synthesized earlier through covalent conjugation of lysine amino acid to carboxylated NDs surface generated through re-oxidation in strong oxidizing acids. In this study, dispersions of lys-NDs were prepared in various media, and the degree of sedimentation was monitored for 72 hours. Particle size distributions and zeta potential measurements were performed for a period of 25 days to characterize the physicochemical stability of lys-NDs in the medium. The interaction profile of lys-NDs with fetal bovine serum showed formation of a protein corona, which was evaluated by size and charge distribution measurements. Uptake of lys-NDs in cervical cancer cells was analyzed by scanning transmission X-ray microscopy, flow cytometry, and confocal microscopy. Cellular uptake of diamoplexes (complex of lys-NDs with small interfering RNA) was also analyzed using flow cytometry. Aqueous dispersion of lys-NDs showed minimum sedimentation and remained stable over a period of 25 days. Size distributions showed good stability, remaining under 100 nm throughout the testing period. A positive zeta potential of >+20 mV indicated a preservation of surface charges. Size distribution and zeta potential changed for lys-NDs after incubation with blood serum, suggesting an interaction with biomolecules, mainly proteins, and a possible formation of a protein corona. Cellular internalization of lys-NDs was confirmed

  13. Optimal construction and delivery of dual-functioning lentiviral vectors for type I collagen-suppressed chondrogenesis in synovium-derived mesenchymal stem cells.

    Science.gov (United States)

    Zhang, Feng; Yao, Yongchang; Zhou, Ruijie; Su, Kai; Citra, Fudiman; Wang, Dong-An

    2011-06-01

    This study aims to deliver both transforming growth factor β3 (TGF-β3) and shRNA targeting type I collagen (Col I) by optimal construction and application of various dual-functioning lentiviral vectors to induce Col I-suppressed chondrogenesis in synovium-derived mesenchymal stem cells (SMSCs). We constructed four lentiviral vectors (LV-1, LV-2, LV-3 and LV-4) with various arrangements of the two expression cassettes in different positions and orientations. Col I inhibition efficiency and chondrogenic markers were assessed with qPCR, ELISA and staining techniques. Among the four vectors, LV-1 has two distant and reversely oriented cassettes, LV-2 has two distant and same-oriented cassettes, LV-3 has two proximal and reversely oriented cassettes, and LV-4 has two proximal and same-oriented cassettes. Col I and chondrogenic markers, including type II collagen (Col II), aggrecan and glycosaminoglycan (GAG), were examined in SMSCs cultured in 3-D alginate hydrogel. All of the four vectors showed distinct effects in Col I level as well as diverse inductive efficiencies in upregulation of the cartilaginous markers. Based on real-time PCR results, LV-1 was optimal towards Col I-suppressed chondrogenesis. LV-1 vector is competent to promote Col I-suppressed chondrogenesis in SMSCs.

  14. 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.

  15. Functionalization of Strongly Interacting Magnetic Nanocubes with (Thermo)responsive Coating and their Application in Hyperthermia and Heat-Triggered Drug Delivery

    KAUST Repository

    Kakwere, Hamilton; Pernia Leal, Manuel; Materia, Maria-Elena; Curcio, Alberto; Guardia, Pablo; Niculaes, Dina; Marotta, Roberto; Falqui, Andrea; Pellegrino, Teresa

    2015-01-01

    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.

  16. A simple approach to design chitosan functionalized Fe3O4 nanoparticles for pH responsive delivery of doxorubicin for cancer therapy

    Science.gov (United States)

    Adimoolam, Mahesh G.; Amreddy, Narsireddy; Nalam, Madhusudana Rao; Sunkara, Manorama V.

    2018-02-01

    The use of magnetic nanoparticles (MNPs) in cancer therapy offer many advantages due to their unique size, physical and biocompatible properties. In this study we have developed a formulation, comprising of anti-cancer drug doxorubicin (Dox) conjugated to iron oxide nanoparticles via a pH sensitive imine linker. Different amounts of chitosan functionalized superparamagnetic iron oxide nanoparticles (Fe3O4-CHI) were synthesized in-situ by a simple hydrolysis method at room temperature. The synthesized nanoparticles were well characterized by TEM, Zeta Potential, TOC, XPS, TGA and VSM for their physicochemical properties. Dox was conjugated to the Fe3O4-CHI nanoparticles via a glutaraldehyde cross linker with the imine (sbnd Cdbnd Nsbnd) bond, which is sensitive to cleavage in the pH range of 4.4-6.4. The synthesized Fe3O4-Dox nanoparticles exhibited enhanced drug release in lower pH conditions which mimics the tumor microenvironment or intracellular organelles such as endosomes/lysosomes. The cell uptake and therapeutic efficacy of Fe3O4-Dox nanoparticles carried out in ovarian cancer cell (SK-OV-3) and breast cancer cell line (MCF7) showed improved therapeutic efficacy of Dox by nearly four-fold with Fe3O4-Dox nanoparticles.

  17. 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

  18. Lysine-functionalized nanodiamonds as gene carriers: development of stable colloidal dispersion for in vitro cellular uptake studies and siRNA delivery application

    Directory of Open Access Journals (Sweden)

    Alwani S

    2016-02-01

    Full Text Available Saniya Alwani,1 Randeep Kaur,1 Deborah Michel,1 Jackson M Chitanda,2 Ronald E Verrall,3 Chithra Karunakaran,4 Ildiko Badea1 1Drug Design and Discovery Research Group, College of Pharmacy and Nutrition, 2Department of Chemical & Biological Engineering, 3Department of Chemistry, University of Saskatchewan, 4Canadian Light Source, Saskatoon, SK, Canada Purpose: Nanodiamonds (NDs are emerging as an attractive tool for gene therapeutics. To reach their full potential for biological application, NDs should maintain their colloidal stability in biological milieu. This study describes the behavior of lysine-functionalized ND (lys-ND in various dispersion media, with an aim to limit aggregation and improve the colloidal stability of ND-gene complexes called diamoplexes. Furthermore, cellular and macromolecular interactions of lys-NDs are also analyzed in vitro to establish the understanding of ND-mediated gene transfer in cells. Methods: lys-NDs were synthesized earlier through covalent conjugation of lysine amino acid to carboxylated NDs surface generated through re-oxidation in strong oxidizing acids. In this study, dispersions of lys-NDs were prepared in various media, and the degree of sedimentation was monitored for 72 hours. Particle size distributions and zeta potential measurements were performed for a period of 25 days to characterize the physicochemical stability of lys-NDs in the medium. The interaction profile of lys-NDs with fetal bovine serum showed formation of a protein corona, which was evaluated by size and charge distribution measurements. Uptake of lys-NDs in cervical cancer cells was analyzed by scanning transmission X-ray microscopy, flow cytometry, and confocal microscopy. Cellular uptake of diamoplexes (complex of lys-NDs with small interfering RNA was also analyzed using flow cytometry. Results: Aqueous dispersion of lys-NDs showed minimum sedimentation and remained stable over a period of 25 days. Size distributions showed

  19. Hydroxypropyl-β-cyclodextrin functionalized calcium carbonate microparticles as a potential carrier for enhancing oral delivery of water-insoluble drugs.

    Science.gov (United States)

    Zhang, Lihua; Zhu, Wufu; Lin, Qisi; Han, Jin; Jiang, Liqun; Zhang, Yanzhuo

    2015-01-01

    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 (C max) 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 demonstrate that HP-β-CD/CC based porous ASD is a promising formulation approach to improve the aqueous solubility and the in vivo absorption performance of a water-insoluble compound like IRB.

  20. What Is a Cesarean Delivery?

    Science.gov (United States)

    ... Twitter Pinterest Email Print What is a cesarean delivery? A cesarean delivery is a surgical procedure in which a fetus ... 32.2% of U.S. births were by cesarean delivery. 2 The CDC also found that the number ...

  1. 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

  2. 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

  3. TRANSDERMAL DRUG DELIVERY SYSTEM: REVIEW

    OpenAIRE

    Vishvakarama Prabhakar; Agarwal Shivendra; Sharma Ritika; Saurabh Sharma

    2012-01-01

    Various new technologies have been developed for the transdermal delivery of some important drugs. Today about 74% of drugs are taken orally and are found not to be as effective as desired. To improve such characters transdermal drug delivery system was emerged. Drug delivery through the skin to achieve a systemic effect of a drug is commonly known as transdermal drug delivery and differs from traditional topical drug delivery. Transdermal drug delivery systems (TDDS) are dosage forms involve...

  4. Do low-income Cypriots experience food stress? The cost of a healthy food basket relative to guaranteed minimum income in Nicosia, Cyprus.

    Science.gov (United States)

    Chrysostomou, Stavri; Andreou, Sofia

    2017-04-01

    The aim of the present study was to assess the cost, acceptability and affordability of the healthy food basket (HFB) among low-income families in Cyprus. HFBs were constructed based on the National Guidelines for Nutrition and Exercise for six different types of households. Acceptability was tested through focus groups. Affordability was defined as the cost of the HFB as a percentage of the guaranteed minimum income (GMI). The value of the GMI is set to be equal to €480 for a single individual and increases with the size of the recipient unit in accordance with the Organization for Economic Co-operation and Development equivalence scales. The Ministry of Labour estimates that, on average, nearly 50% of the GMI is required for food. The total monthly budget for HFB is 0.80, 1.11, 1.27, 1.28, 1.44 and 1.48 times higher than the GMI budget for food among different types of households in Cyprus (a single woman, a single man, a couple, a single woman with two children, a single man with two children and a couple with two children, respectively). In particular, a family with two children on GMI would need to spend a large proportion of their income on the HFB (71.68%). The GMI scheme appears not to consider the cost of healthy food, and thus, families on welfare payments in Cyprus are at a high risk of experiencing food stress. Therefore, additional research is required to measure the cost of the six HFBs in various settings. © 2016 Dietitians Association of Australia.

  5. Total Diet Study. Mg and Mn content estimation of a Market Basket of Sao Paulo state (Brazil) by Instrumental Neutron Activation

    International Nuclear Information System (INIS)

    Roseane Pagliaro Avegliano; Vera Akiko Maihara

    2014-01-01

    Total Diet Studies (TDS) have been carried out to estimate dietary intakes of the essential and toxic elements for a large-scale population over a specific period of time. In this study, the TDS was based on the evaluation of food representing a Market Basket (MB), which reflected the dietary habits of the Sao Paulo State population, corresponding to 72 % of the average food consumption for the state of Sao Paulo. In the present Total Diet Study, magnesium and manganese concentrations were determined in 30 of the most consumed food groups of a MB of Sao Paulo State, Brazil. Instrumental Neutron Activation Analysis (INAA) has been successfully used on a regularly basis in several areas of nutrition and foodstuffs. Element concentrations were determined by INAA in freeze-dried samples and ranged in mg kg -1 . Mg 41.4 (fats)-5287 (coffee) and Mn 0.12 (prime grade beef)-32.9 (coffee). The average daily Mg and Mn intake was calculated by multiplying the concentration of each element in each table-ready food group by the respective weight (g day -1 ) of the food group in the MB and adding the products from all food groups. The results of daily dietary intakes in this study were: Mg 174.8 and Mn 1.34 mg day -1 . Theses values were lower than the adequate intake (AI) proposed by the Food and Nutrition Board of the Institute of Medicine (USA National Academy) for adults. The low levels of Mg and Mn intakes presented in this TDS are probably due to the fact that MB of this study represented only 72 % of the weight of the most consumed household foods of Sao Paulo State. (author)

  6. 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.

  7. Vaginal delivery - discharge

    Science.gov (United States)

    Pregnancy - discharge after vaginal delivery ... You may have bleeding from your vagina for up to 6 weeks. Early on, you may pass some small clots when you first get up. Bleeding will slowly become ...

  8. Bribes for Faster Delivery

    OpenAIRE

    Sanyal, Amal

    2000-01-01

    The paper models the practice of charging bribes for faster delivery of essential services in third world countries. It then examines the possibility of curbing corruption by supervision, and secondly, by introducing competition among delivery agents. It is argued that a supervisory solution eludes the problem because no hard evidence of the reduction of corruption can be established for this type of offenses. It is also shown that using more than one supplier cannot eliminate the practice, a...

  9. Seeking optimal renal replacement therapy delivery in intensive care units.

    Science.gov (United States)

    Kocjan, Marinka; Brunet, Fabrice P

    2010-01-01

    Globally, critical care environments within health care organizations strive to provide optimal quality renal replacement therapy (RRT), an artificial replacement for lost kidney function. Examination of RRT delivery model literature and a case study review of the multidisciplinary-mixed RRT delivery model utilized within a closed medical surgical intensive care unit illustrates the organizational and clinical management of specialized resource and multidisciplinary roles. The successful utilization of a specific RRT delivery model is dependent upon resource availability.

  10. Microfabrication for Drug Delivery

    Science.gov (United States)

    Koch, Brendan; Rubino, Ilaria; Quan, Fu-Shi; Yoo, Bongyoung; Choi, Hyo-Jick

    2016-01-01

    This review is devoted to discussing the application of microfabrication technologies to target challenges encountered in life processes by the development of drug delivery systems. Recently, microfabrication has been largely applied to solve health and pharmaceutical science issues. In particular, fabrication methods along with compatible materials have been successfully designed to produce multifunctional, highly effective drug delivery systems. Microfabrication offers unique tools that can tackle problems in this field, such as ease of mass production with high quality control and low cost, complexity of architecture design and a broad range of materials. Presented is an overview of silicon- and polymer-based fabrication methods that are key in the production of microfabricated drug delivery systems. Moreover, the efforts focused on studying the biocompatibility of materials used in microfabrication are analyzed. Finally, this review discusses representative ways microfabrication has been employed to develop systems delivering drugs through the transdermal and oral route, and to improve drug eluting implants. Additionally, microfabricated vaccine delivery systems are presented due to the great impact they can have in obtaining a cold chain-free vaccine, with long-term stability. Microfabrication will continue to offer new, alternative solutions for the development of smart, advanced drug delivery systems. PMID:28773770

  11. Advanced SLARette delivery machine

    International Nuclear Information System (INIS)

    Bodner, R.R.

    1995-01-01

    SLARette 1 equipment, comprising of a SLARette Delivery Machine, SLAR Tools, SLAR power supplies and SLAR Inspection Systems was designed, developed and manufactured to service fuel channels of CANDU 6 stations during the regular yearly station outages. The Mark 2 SLARette Delivery Machine uses a Push Tube system to provide the axial and rotary movements of the SLAR Tool. The Push Tubes are operated remotely but must be attached and removed manually. Since this operation is performed at the Reactor face, there is radiation dose involved for the workers. An Advanced SLARette Delivery Machine which incorporates a computer controlled telescoping Ram in the place of the Push Tubes has been recently designed and manufactured. Utilization of the Advanced SLARette Delivery Machine significantly reduces the amount of radiation dose picked up by the workers because the need to have workers at the face of the Reactor during the SLARette operation is greatly reduced. This paper describes the design, development and manufacturing process utilized to produce the Advanced SLARette Delivery Machine and the experience gained during the Gentilly-2 NGS Spring outage. (author)

  12. MRI in ocular drug delivery

    OpenAIRE

    Li, S. Kevin; Lizak, Martin J.; Jeong, Eun-Kee

    2008-01-01

    Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery de...

  13. Contents and daily intakes of gamma-ray emitting nuclides, 90Sr, and 238U using market-basket studies in japan

    International Nuclear Information System (INIS)

    Sugiyama, Hideo; Terada, Hiroshi; Takahashi, Mitsuko; Iijima, Ikuyo; Isomura, Kimio

    2007-01-01

    To investigate the contents of radionuclides in foods marketed in Japan and their daily intakes and exposure doses in adults, we performed market-basket studies concerning radionuclide intakes. The study period was 2003-2005, and the studies were performed in 13 cities in Japan. Foods including drinking water were divided into 14 food groups, and samples were prepared by common cooking procedures. γ-ray emitting nuclides (an artificial radionuclide, radioactive Cs, and natural radionuclides, 40 K and U series such as 214 Bi, and 212 Pb, and Th series) were measured in each food group, and artificial radionuclides, 90 Sr and 238 U, were measured in a mixed sample of 13 food groups excluding drinking water. The daily intakes in adults were calculated from the concentrations of the radionuclides and mean daily consumption of foods and drinking water. The daily 137 Cs and 40 K intakes (mBq/person · day) in the 13 cities were 12.5- 90 Sr intake from the food groups excluding drinking water was 20.8-53.6, with a mean of 39.2 (mBq/person · day) (deviation of the mean: 23%). Similarly, the daily 238 U intake was 5.9-31.1, with a mean of 12.6 (mBq/person · day) (deviation: 60%), showing a more than 5-fold difference between the minimum and maximum values, and there were regional differences. Since the contents of the U series, such as 214 Bi and 212 Pb, and Th series were lower than the lower detection limits in many samples, their daily intakes were not calculated. Regarding the daily intake of 137 Cs from each food group, the intakes from fish and shellfish, milk, meat/eggs, and mushrooms/seaweed tended to be higher. The daily 40 K intake from each food group varied among the areas, but the total intake from the 14 food groups was similar in all 13 cities. 40 K from these foods accounted for most of the annual effective dose (μSv/person · year) of γ-ray emitting nuclides, and the doses of 40 K, 90 Sr, and 238 U were 130-217, 0.21-0.55, and 0.10-0.51, respectively

  14. 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...... and governmental organizations that conceptualize mobility as involuntary and associated with social rupture. Challenging this understanding, we argue that mobility can be an important strategy for mobilizing resources through social relations, what we call ``social weaving.'' Analyzing young northern Ghanaian...... demonstrate how the development field can be seen to be largely based on, as well as generating, social relations. Indeed, while there has been a tendency towards anti-mobility sentiments among development organizations, NGOs themselves often become woven into the local artisans' fabric of relations...

  15. 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.

  16. Redefining continuing education delivery.

    Science.gov (United States)

    Carlton, K H

    1997-01-01

    Just as technology is transforming the delivery of education, the Internet and advanced telecommunication applications are changing the "face" of CE and the connotation of "lifelong learning." As late as the mid-1980s, a discussion of computer applications in nursing CE focused on the "timely" transition to microcomputers as tools for the enhancement of managerial tasks for increased productivity. Even as recently as 1990, there seemed to be "time" for those providers who were "slower to adopt innovation" to "catch up." Now, the CE provider who does not integrate the microcomputer and advanced telecommunications as an integral component of their delivery modalities may be outsourced rapidly by an educational or commercial competitive unit that is able to utilize the communication medium, mergers and partnerships, enterprise, and individual lifestyle and learning patterns that will epitomize the CE unit of the 21st century. As with the "re-engineering" of nursing education, the "re-engineered" delivery modalities of evolving CE entity might now best be conceptualized on a continuum from the traditional mode that time and place dependent to a mode of synchronous and asynchronous data and advanced telecommunication. Delivery methods will need to be selected according to the target populations, content, and situation. The health-care educational provider may discover, as in other industries, that a combination of distance and residential offerings will be the most successful medium for the delivery of CE to the progressively more "information and technologically savvy" lifelong learner of the 21st century. In addressing the dramatic effects of the information technology era on the refocused multimedia/interactive delivery method for student education, educators amply quoted Bob Dylan's phrase of the 1960s, "The times, they are a-changing." And so, we see that the times are also changing at an astronomical rate for the health-care educational provider as well as the

  17. Oral delivery of Bacillus subtilis spore expressing enolase of Clonorchis sinensis in rat model: induce systemic and local mucosal immune responses and has no side effect on liver function.

    Science.gov (United States)

    Yu, Jinyun; Chen, Tingjin; Xie, Zhizhi; Liang, Pei; Qu, Honglin; Shang, Mei; Mao, Qiang; Ning, Dan; Tang, Zeli; Shi, Mengchen; Zhou, Lina; Huang, Yan; Yu, Xinbing

    2015-07-01

    Caused by the consumption of raw or undercooked freshwater fish containing infective metacercariae of Clonorchis sinensis, human clonorchiasis remains a major public health problem in China. In previous study, we had expressed enolase from C. sinensis (CsENO) on the surface of Bacillus subtilis spore and the recombinant spore induced a pronounced protection in terms of reduced worm burden and eggs per gram feces, suggesting B. subtilis spore as an ideal vehicle for antigen delivery by oral treatment and CsENO as a promising vaccine candidate against clonorchiasis. In the current study, we detected CsENO-specific IgG and IgA levels both in serum and in intestinal mucus from rats orally administrated with B. subtilis spore surface expressing CsENO by ELISA. Lysozyme levels in serum and in intestinal mucus were analyzed too. In addition, IgA-secreting cells in intestine epithelium of the rats were detected by immunohistochemistry assay. The intestinal villi lengths of duodenum, jejunum, and ileum were also measured. Rats orally treated with B. subtilis spore or normal saline were used as controls. Our results showed that, compared with the control groups, oral administration of B. subtilis spore expressing CsENO induced both systemic and local mucosal immune response. The recombinant spores also enhanced non-specific immune response in rats. The spores had no side effect on liver function. Moreover, it might facilitate food utilization and digestion of the rats. Our work will pave the way to clarify the involved mechanisms of protective efficacy elicited by B. subtilis spore expressing CsENO and encourage us to carry out more assessment trails of the oral treated spore to develop vaccine against clonorchiasis.

  18. 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.

  19. 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.

  20. 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.

  1. Health Care Delivery.

    Science.gov (United States)

    Starfield, Barbara

    1987-01-01

    The article reviews emerging health care delivery options for handicapped children. Cost structures, quality of care, and future prospects are considered for Health Maintenance Organizations, Preferred Provider Organizations, Tax Supported Direct Service Programs, Hospital-Based Services, and Ambulatory Care Organizations. (Author/DB)

  2. Drug delivery and formulations.

    Science.gov (United States)

    Breitkreutz, Jörg; Boos, Joachim

    2011-01-01

    Paediatric drug delivery is a major challenge in drug development. Because of the heterogeneous nature of the patient group, ranging from newborns to adolescents, there is a need to use appropriate excipients, drug dosage forms and delivery devices for different age groups. So far, there is a lack of suitable and safe drug formulations for children, especially for the very young and seriously ill patients. The new EU legislation will enforce paediatric clinical trials and drug development. Current advances in paediatric drug delivery include interesting new concepts such as fast-dissolving drug formulations, including orodispersible tablets and oral thin strips (buccal wafers), and multiparticulate dosage forms based on mini-tabletting or pelletization technologies. Parenteral administration is likely to remain the first choice for children in the neonatal period and for emergency cases. Alternative routes of administration include transdermal, pulmonary and nasal drug delivery systems. A few products are already available on the market, but others still need further investigations and clinical proof of concept.

  3. Drug delivery through microneedles

    NARCIS (Netherlands)

    Luttge, R.; Dietzel, A.

    2016-01-01

    Drug delivery through microneedles is a new form of a pharmaceutical dosage system. While single microneedles have been clinically applied already, the out-of-plane integration of a multitude of microneedles in a pharmaceutical patch is a disruptive technology. To take advantage of micro- and

  4. 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...

  5. Global Delivery Models

    DEFF Research Database (Denmark)

    Manning, Stephan; Møller Larsen, Marcus; Bharati, Pratyush M.

    2015-01-01

    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...

  6. Food, physiology and drug delivery.

    Science.gov (United States)

    Varum, F J O; Hatton, G B; Basit, A W

    2013-12-05

    Gastrointestinal physiology is dynamic and complex at the best of times, and a multitude of known variables can affect the overall bioavailability of drugs delivered via the oral route. Yet while the influences of food and beverage intake as just two of these variables on oral drug delivery have been extensively documented in the wider literature, specific information on their effects remains sporadic, and is not so much contextually reviewed. Food co-ingestion with oral dosage forms can mediate several changes to drug bioavailability, yet the precise mechanisms underlying this have yet to be fully elucidated. Likewise, the often detrimental effects of alcohol (ethanol) on dosage form performance have been widely observed experimentally, but knowledge of which has only moderately impacted on clinical practice. Here, we attempt to piece together the available subject matter relating to the influences of both solid and liquid foodstuffs on the gastrointestinal milieu and the implications for oral drug delivery, with particular emphasis on the behaviour of modified-release dosage forms, formulation robustness and drug absorption. Providing better insight into these influences, and exemplifying cases where formulations have been developed or modified to circumvent their associated problems, can help to appropriately direct the design of future in vitro digestive modelling systems as well as oral dosage forms resilient to these effects. Moreover, this will help to better our understanding of the impact of food and alcohol intake on normal gut behaviour and function. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Plasmid DNA Delivery: Nanotopography Matters.

    Science.gov (United States)

    Song, Hao; Yu, Meihua; Lu, Yao; Gu, Zhengying; Yang, Yannan; Zhang, Min; Fu, Jianye; Yu, Chengzhong

    2017-12-20

    Plasmid DNA molecules with unique loop structures have widespread bioapplications, in many cases relying heavily on delivery vehicles to introduce them into cells and achieve their functions. Herein, we demonstrate that control over delicate nanotopography of silica nanoparticles as plasmid DNA vectors has significant impact on the transfection efficacy. For silica nanoparticles with rambutan-, raspberry-, and flower-like morphologies composed of spike-, hemisphere-, and bowl-type subunit nanotopographies, respectively, the rambutan-like nanoparticles with spiky surfaces demonstrate the highest plasmid DNA binding capability and transfection efficacy of 88%, higher than those reported for silica-based nanovectors. Moreover, it is shown that the surface spikes of rambutan nanoparticles provide a continuous open space to bind DNA chains via multivalent interactions and protect the gene molecules sheltered in the spiky layer against nuclease degradation, exhibiting no significant transfection decay. This unique protection feature is in great contrast to a commercial transfection agent with similar transfection performance but poor protection capability against enzymatic cleavage. Our study provides new understandings in the rational design of nonviral vectors for efficient gene delivery.

  8. 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.

  9. 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...

  10. Microneedles for intradermal and transdermal delivery

    Science.gov (United States)

    Tuan-Mahmood, Tuan-Mazlelaa; McCrudden, Maeliosa T.C.; Torrisi, Barbara M.; McAlister, Emma; Garland, Martin J; Singh, Thakur Raghu Raj; Donnelly, Ryan F

    2014-01-01

    The formidable barrier properties of the uppermost layer of the skin, the stratum corneum impose significant limitations for successful systemic delivery of a broad range of therapeutic molecules, particularly macromolecules and genetic material. Microneedle delivery has been proposed as a strategy to breach the SC barrier function in order to facilitate effective transport of molecules across the skin. This strategy involves the use of micron sized needles fabricated from different materials and using different geometries to create transient aqueous conduits across the skin. Microneedles in isolation, or in combination with other enhancing strategies, have been shown to dramatically enhance the skin permeability of numerous therapeutic molecules including biopharmaceuticals either in vitro, ex vivo or in vivo. Progress in the areas of microneedle design, development and manufacture have proven promising in terms of the potential use of this emerging delivery method in clinical applications such as insulin delivery, transcutaneous immunisations and cutaneous gene delivery. This review article focuses on recent and potential future developments in microneedle technologies. This will include the detailing of progress made in microneedle design, an exploration of the challenges faced in this field and potential forward strategies to embrace the exploitation of microneedle methodologies, while considering the inherent safety aspects of such therapeutic tools. PMID:23680534

  11. Seizure-induced alterations in fast-spiking basket cell GABA currents modulate frequency and coherence of gamma oscillation in network simulations

    Energy Technology Data Exchange (ETDEWEB)

    Proddutur, Archana; Yu, Jiandong; Elgammal, Fatima S. [Department of Neurology and Neurosciences, New Jersey Medical School, Rutgers, Newark, New Jersey 07103 (United States); Santhakumar, Vijayalakshmi, E-mail: santhavi@njms.rutgers.edu [Department of Neurology and Neurosciences, New Jersey Medical School, Rutgers, Newark, New Jersey 07103 (United States); Department of Pharmacology and Physiology, New Jersey Medical School, Rutgers, Newark, New Jersey 07103 (United States)

    2013-12-15

    Gamma frequency oscillations have been proposed to contribute to memory formation and retrieval. Fast-spiking basket cells (FS-BCs) are known to underlie development of gamma oscillations. Fast, high amplitude GABA synapses and gap junctions have been suggested to contribute to gamma oscillations in FS-BC networks. Recently, we identified that, apart from GABAergic synapses, FS-BCs in the hippocampal dentate gyrus have GABAergic currents mediated by extrasynaptic receptors. Our experimental studies demonstrated two specific changes in FS-BC GABA currents following experimental seizures [Yu et al., J. Neurophysiol. 109, 1746 (2013)]: increase in the magnitude of extrasynaptic (tonic) GABA currents and a depolarizing shift in GABA reversal potential (E{sub GABA}). Here, we use homogeneous networks of a biophysically based model of FS-BCs to examine how the presence of extrasynaptic GABA conductance (g{sub GABA-extra}) and experimentally identified, seizure-induced changes in g{sub GABA-extra} and E{sub GABA} influence network activity. Networks of FS-BCs interconnected by fast GABAergic synapses developed synchronous firing in the dentate gamma frequency range (40–100 Hz). Systematic investigation revealed that the biologically realistic range of 30 to 40 connections between FS-BCs resulted in greater coherence in the gamma frequency range when networks were activated by Poisson-distributed dendritic synaptic inputs rather than by homogeneous somatic current injections, which were balanced for FS-BC firing frequency in unconnected networks. Distance-dependent conduction delay enhanced coherence in networks with 30–40 FS-BC interconnections while inclusion of gap junctional conductance had a modest effect on coherence. In networks activated by somatic current injections resulting in heterogeneous FS-BC firing, increasing g{sub GABA-extra} reduced the frequency and coherence of FS-BC firing when E{sub GABA} was shunting (−74 mV), but failed to alter average

  12. Seizure-induced alterations in fast-spiking basket cell GABA currents modulate frequency and coherence of gamma oscillation in network simulations

    International Nuclear Information System (INIS)

    Proddutur, Archana; Yu, Jiandong; Elgammal, Fatima S.; Santhakumar, Vijayalakshmi

    2013-01-01

    Gamma frequency oscillations have been proposed to contribute to memory formation and retrieval. Fast-spiking basket cells (FS-BCs) are known to underlie development of gamma oscillations. Fast, high amplitude GABA synapses and gap junctions have been suggested to contribute to gamma oscillations in FS-BC networks. Recently, we identified that, apart from GABAergic synapses, FS-BCs in the hippocampal dentate gyrus have GABAergic currents mediated by extrasynaptic receptors. Our experimental studies demonstrated two specific changes in FS-BC GABA currents following experimental seizures [Yu et al., J. Neurophysiol. 109, 1746 (2013)]: increase in the magnitude of extrasynaptic (tonic) GABA currents and a depolarizing shift in GABA reversal potential (E GABA ). Here, we use homogeneous networks of a biophysically based model of FS-BCs to examine how the presence of extrasynaptic GABA conductance (g GABA-extra ) and experimentally identified, seizure-induced changes in g GABA-extra and E GABA influence network activity. Networks of FS-BCs interconnected by fast GABAergic synapses developed synchronous firing in the dentate gamma frequency range (40–100 Hz). Systematic investigation revealed that the biologically realistic range of 30 to 40 connections between FS-BCs resulted in greater coherence in the gamma frequency range when networks were activated by Poisson-distributed dendritic synaptic inputs rather than by homogeneous somatic current injections, which were balanced for FS-BC firing frequency in unconnected networks. Distance-dependent conduction delay enhanced coherence in networks with 30–40 FS-BC interconnections while inclusion of gap junctional conductance had a modest effect on coherence. In networks activated by somatic current injections resulting in heterogeneous FS-BC firing, increasing g GABA-extra reduced the frequency and coherence of FS-BC firing when E GABA was shunting (−74 mV), but failed to alter average FS-BC frequency when E GABA

  13. Supplier Cooperation in Drone Delivery

    OpenAIRE

    Sawadsitang, Suttinee; Niyato, Dusit; Siew, Tan Puay; Wang, Ping

    2018-01-01

    Recently, unmanned aerial vehicles (UAVs), also known as drones, has emerged as an efficient and cost-effective solution for package delivery. Especially, drones are expected to incur lower cost, and achieve fast and environment friendly delivery. While most of existing drone research concentrates on surveillance applications, few works studied the drone package delivery planning problem. Even so, the previous works only focus on the drone delivery planning of a single supplier. In this paper...

  14. Floating Microparticulate Oral Diltiazem Hydrochloride Delivery ...

    African Journals Online (AJOL)

    Delivery System for Improved Delivery to Heart ... Conclusion: Microparticulate floating (gastroretentive) oral drug delivery system of diltiazem prepared ..... treatment of cardiac disease. ... hydrochloride-loaded mucoadhesive microspheres.

  15. Supersaturating drug delivery systems

    DEFF Research Database (Denmark)

    Laitinen, Riikka; Löbmann, Korbinian; Grohganz, Holger

    2017-01-01

    of the bioavailability of poorly water-soluble drugs by increasing the driving force for drug absorption. However, ASDs often require a high weight percentage of carrier (usually a hydrophilic polymer) to ensure molecular mixing of the drug in the carrier and stabilization of the supersaturated state, often leading......Amorphous solid dispersions (ASDs) are probably the most common and important supersaturating drug delivery systems for the formulation of poorly water-soluble compounds. These delivery systems are able to achieve and maintain a sustained drug supersaturation which enables improvement...... strategy for poorly-soluble drugs. While the current research on co-amorphous formulations is focused on preparation and characterization of these systems, more detailed research on their supersaturation and precipitation behavior and the effect of co-formers on nucleation and crystal growth inhibition...

  16. Pyomyositis after vaginal delivery.

    LENUS (Irish Health Repository)

    Gaughan, Eve

    2011-01-01

    Pyomyositis is a purulent infection of skeletal muscle that arises from haematogenous spread, usually with abscess formation. It can develop after a transient bacteraemia of any cause. This type of infection has never been reported before in the literature after vaginal delivery. A 34-year-old woman had progressive severe pain in the left buttock and thigh and weakness in the left lower limb day 1 post spontaneous vaginal delivery. MRI showed severe oedema of the left gluteus, iliacus, piriformis and adductor muscles of the left thigh and a small fluid collection at the left hip joint. She was diagnosed with pyomyositis. She had fever of 37.9°C immediately postpartum and her risk factors for bacteraemia were a mild IV cannula-associated cellulitis and labour itself. She required prolonged treatment with antibiotics before significant clinical improvement was noted.

  17. Social video content delivery

    CERN Document Server

    Wang, Zhi; Zhu, Wenwu

    2016-01-01

    This brief presents new architecture and strategies for distribution of social video content. A primary framework for socially-aware video delivery and a thorough overview of the possible approaches is provided. The book identifies the unique characteristics of socially-aware video access and social content propagation, revealing the design and integration of individual modules that are aimed at enhancing user experience in the social network context. The change in video content generation, propagation, and consumption for online social networks, has significantly challenged the traditional video delivery paradigm. Given the massive amount of user-generated content shared in online social networks, users are now engaged as active participants in the social ecosystem rather than as passive receivers of media content. This revolution is being driven further by the deep penetration of 3G/4G wireless networks and smart mobile devices that are seamlessly integrated with online social networking and media-sharing s...

  18. Mucoadhesive drug delivery systems

    Directory of Open Access Journals (Sweden)

    Rahamatullah Shaikh

    2011-01-01

    Full Text Available Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Over the past few decades, mucosal drug delivery has received a great deal of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal.

  19. Peptide and protein delivery using new drug delivery systems.

    Science.gov (United States)

    Jain, Ashish; Jain, Aviral; Gulbake, Arvind; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K

    2013-01-01

    Pharmaceutical and biotechnological research sorts protein drug delivery systems by importance based on their various therapeutic applications. The effective and potent action of the proteins/peptides makes them the drugs of choice for the treatment of numerous diseases. Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate target-specific protein carriers. Many efforts have been made for effective delivery of proteins/peptidal drugs through various routes of administrations for successful therapeutic effects. Nanoparticles made of biodegradable polymers such as poly lactic acid, polycaprolactone, poly(lactic-co-glycolic acid), the poly(fumaric-co-sebacic) anhydride chitosan, and modified chitosan, as well as solid lipids, have shown great potential in the delivery of proteins/peptidal drugs. Moreover, scientists also have used liposomes, PEGylated liposomes, niosomes, and aquasomes, among others, for peptidal drug delivery. They also have developed hydrogels and transdermal drug delivery systems for peptidal drug delivery. A receptor-mediated delivery system is another attractive strategy to overcome the limitation in drug absorption that enables the transcytosis of the protein across the epithelial barrier. Modification such as PEGnology is applied to various proteins and peptides of the desired protein and peptides also increases the circulating life, solubility and stability, pharmacokinetic properties, and antigenicity of protein. This review focuses on various approaches for effective protein/peptidal drug delivery, with special emphasis on insulin delivery.

  20. A spatial model to quantify the mortality impact of service delivery in Sub-Saharan Africa: an ecological design utilizing data from South Africa.

    Science.gov (United States)

    Sartorius, Kurt; Sartorius, Benn K D

    2013-02-20

    Sub Saharan Africa is confronted with a wide range of interlinked health and economic problems that include high levels of mortality and poor service delivery. The objective of the paper is to develop a spatial model for Sub-Saharan Africa that can quantify the mortality impact of (poor) service delivery at sub-district level in order to integrate related health and local level policy interventions. In this regard, an expanded composite service delivery index was developed, and the data were analysed using a Bayesian Poisson spatial model. The results indicate significant differences in the risk of mortality and poor service delivery at sub-district level. In particular, the results indicate clusters of high mortality and poor service delivery in two of the bigger, poorer provinces with large rural communities. Conversely, two of the wealthier provinces have lower levels of mortality and higher levels of service delivery, but income inequality is more widespread. The bivariate and multivariate models, moreover, reflect significant positive linkages (p service delivery after adjusting for HIV/AIDS, income inequality, population density and the protective influence of metropolitan areas. Finally, the hypothesized provision of a basket of services reduced the mortality rate in South Africa's 248 sub-districts by an average of 5.3 (0.3-15.4) deaths per 1000. The results indicate that the model can accurately plot mortality and service delivery "hotspots' at sub-district level, as well as explain their associations and causality. A mortality reduction index shows that mortality in the highest risk sub-districts can be reduced by as much as 15.4 deaths per 1000 by providing a range of basic services. The ability to use the model in a wider SSA context and elsewhere is also feasible given the innovative use of available databases. Finally, the paper illustrates the importance of developing policy in SSA that can simultaneously solve both economic and health problems.

  1. Multifunctional quantum dots and liposome complexes in drug delivery

    Science.gov (United States)

    Wang, Qi; Chao, Yimin

    2018-01-01

    Incorporating both diagnostic and therapeutic functions into a single nanoscale system is an effective modern drug delivery strategy. Combining liposomes with semiconductor quantum dots (QDs) has great potential to achieve such dual functions, referred to in this review as a liposomal QD hybrid system (L-QD). Here we review the recent literature dealing with the design and application of L-QD for advances in bio-imaging and drug delivery. After a summary of L-QD synthesis processes and evaluation of their properties, we will focus on their multifunctional applications, ranging from in vitro cell imaging to theranostic drug delivery approaches. PMID:28866655

  2. Multifunctional quantum dots and liposome complexes in drug delivery.

    Science.gov (United States)

    Wang, Qi; Chao, Yi-Min

    2017-09-03

    Incorporating both diagnostic and therapeutic functions into a single nanoscale system is an effective modern drug delivery strategy. Combining liposomes with semiconductor quantum dots (QDs) has great potential to achieve such dual functions, referred to in this review as a liposomal QD hybrid system (L-QD). Here we review the recent literature dealing with the design and application of L-QD for advances in bio-imaging and drug delivery. After a summary of L-QD synthesis processes and evaluation of their properties, we will focus on their multifunctional applications, ranging from in vitro cell imaging to theranostic drug delivery approaches.

  3. Advanced materials and processing for drug delivery: the past and the future.

    Science.gov (United States)

    Zhang, Ying; Chan, Hon Fai; Leong, Kam W

    2013-01-01

    Design and synthesis of efficient drug delivery systems are of vital importance for medicine and healthcare. Materials innovation and nanotechnology have synergistically fueled the advancement of drug delivery. Innovation in material chemistry allows the generation of biodegradable, biocompatible, environment-responsive, and targeted delivery systems. Nanotechnology enables control over size, shape and multi-functionality of particulate drug delivery systems. In this review, we focus on the materials innovation and processing of drug delivery systems and how these advances have shaped the past and may influence the future of drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Ion-Responsive Drug Delivery Systems.

    Science.gov (United States)

    Yoshida, Takayuki; Shakushiro, Kohsuke; Sako, Kazuhiro

    2018-02-08

    Some kinds of cations and anions are contained in body fluids such as blood, interstitial fluid, gastrointestinal juice, and tears at relatively high concentration. Ionresponsive drug delivery is available to design the unique dosage formulations which provide optimized drug therapy with effective, safe and convenient dosing of drugs. The objective of the present review was to collect, summarize, and categorize recent research findings on ion-responsive drug delivery systems. Ions in body fluid/formulations caused structural changes of polymers/molecules contained in the formulations, allow formulations exhibit functions. The polymers/molecules responding to ions were ion-exchange resins/fibers, anionic or cationic polymers, polymers exhibiting transition at lower critical solution temperature, self-assemble supramolecular systems, peptides, and metalorganic frameworks. The functions of ion-responsive drug delivery systems were categorized to controlled drug release, site-specific drug release, in situ gelation, prolonged retention at the target sites, and enhancement of drug permeation. Administration of the formulations via oral, ophthalmic, transdermal, and nasal routes has showed significant advantages in the recent literatures. Many kinds of drug delivery systems responding to ions have been reported recently for several administration routes. Improvement and advancement of these systems can maximize drugs potential and contribute to patients in the world. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Cell and biomolecule delivery for regenerative medicine

    Science.gov (United States)

    Smith, Ian O; Ma, Peter X

    2010-01-01

    Regenerative medicine is an exciting field that aims to create regenerative alternatives to harvest tissues for transplantation. In this approach, the delivery of cells and biological molecules plays a central role. The scaffold (synthetic temporary extracellular matrix) delivers cells to the regenerative site and provides three-dimensional environments for the cells. To fulfil these functions, we design biodegradable polymer scaffolds with structural features on multiple size scales. To enhance positive cell–material interactions, we design nano-sized structural features in the scaffolds to mimic the natural extracellular matrix. We also integrate micro-sized pore networks to facilitate mass transport and neo tissue regeneration. We also design novel polymer devices and self-assembled nanospheres for biomolecule delivery to recapitulate key events in developmental and wound healing processes. Herein, we present recent work in biomedical polymer synthesis, novel processing techniques, surface engineering and biologic delivery. Examples of enhanced cellular/tissue function and regenerative outcomes of these approaches are discussed to demonstrate the excitement of the biomimetic scaffold design and biologic delivery in regenerative medicine. PMID:27877317

  6. Model for determining and optimizing delivery performance in industrial systems

    Directory of Open Access Journals (Sweden)

    Fechete Flavia

    2017-01-01

    Full Text Available Performance means achieving organizational objectives regardless of their nature and variety, and even overcoming them. Improving performance is one of the major goals of any company. Achieving the global performance means not only obtaining the economic performance, it is a must to take into account other functions like: function of quality, delivery, costs and even the employees satisfaction. This paper aims to improve the delivery performance of an industrial system due to their very low results. The delivery performance took into account all categories of performance indicators, such as on time delivery, backlog efficiency or transport efficiency. The research was focused on optimizing the delivery performance of the industrial system, using linear programming. Modeling the delivery function using linear programming led to obtaining precise quantities to be produced and delivered each month by the industrial system in order to minimize their transport cost, satisfying their customers orders and to control their stock. The optimization led to a substantial improvement in all four performance indicators that concern deliveries.

  7. Chitosan magnetic nanoparticles for drug delivery systems.

    Science.gov (United States)

    Assa, Farnaz; Jafarizadeh-Malmiri, Hoda; Ajamein, Hossein; Vaghari, Hamideh; Anarjan, Navideh; Ahmadi, Omid; Berenjian, Aydin

    2017-06-01

    The potential of magnetic nanoparticles (MNPs) in drug delivery systems (DDSs) is mainly related to its magnetic core and surface coating. These coatings can eliminate or minimize their aggregation under physiological conditions. Also, they can provide functional groups for bioconjugation to anticancer drugs and/or targeted ligands. Chitosan, as a derivative of chitin, is an attractive natural biopolymer from renewable resources with the presence of reactive amino and hydroxyl functional groups in its structure. Chitosan nanoparticles (NPs), due to their huge surface to volume ratio as compared to the chitosan in its bulk form, have outstanding physico-chemical, antimicrobial and biological properties. These unique properties make chitosan NPs a promising biopolymer for the application of DDSs. In this review, the current state and challenges for the application magnetic chitosan NPs in drug delivery systems were investigated. The present review also revisits the limitations and commercial impediments to provide insight for future works.

  8. Investigation of a thiolated polymer in gene delivery

    Science.gov (United States)

    Bacalocostantis, Irene

    Thiol-containing bioreducible polymers show significant potential as delivery vectors in gene therapy, a rapidly growing field which seeks to treat genetic-based disorders by delivering functional synthetic genes to diseased cells. Studies have shown that thiolated polymers exhibit improved biodegradability and prolonged in vivo circulation times over non-thiolated polymers. However, the extent to which thiol concentrations impact the carrier's delivery potential has not been well explored. The aim of this dissertation is to investigate how relative concentrations of free thiols and disulfide crosslinks impact a polymeric carriers delivery performance with respect to DNA packaging, complex stability, cargo protection, gene release, internalization efficiency and cytotoxicity. To accomplish this goal, several fluorescent polymers containing varying concentrations of thiol groups were synthesized by conjugating thiol-pendant chains onto the primary amines of cationic poly(allylamine). In vitro delivery assays and characterization techniques were employed to assess the effect of thiols in gene delivery.

  9. Multifunctional Nanoparticles for Drug Delivery Applications Imaging, Targeting, and Delivery

    CERN Document Server

    Prud'homme, Robert

    2012-01-01

    This book clearly demonstrates the progression of nanoparticle therapeutics from basic research to applications. Unlike other books covering nanoparticles used in medical applications, Multifunctional Nanoparticles for Drug Delivery Applications presents the medical challenges that can be reduced or even overcome by recent advances in nanoscale drug delivery. Each chapter highlights recent progress in the design and engineering of select multifunctional nanoparticles with topics covering targeting, imaging, delivery, diagnostics, and therapy.

  10. Dendrimers for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Abhay Singh Chauhan

    2018-04-01

    Full Text Available Dendrimers have come a long way in the last 25 years since their inception. Originally created as a wonder molecule of chemistry, dendrimer is now in the fourth class of polymers. Dr. Donald Tomalia first published his seminal work on Poly(amidoamine (PAMAM dendrimers in 1985. Application of dendrimers as a drug delivery system started in late 1990s. Dendrimers for drug delivery are employed using two approaches: (i formulation and (ii nanoconstruct. In the formulation approach, drugs are physically entrapped in a dendrimer using non-covalent interactions, whereas drugs are covalently coupled on dendrimers in the nanoconstruct approach. We have demonstrated the utility of PAMAM dendrimers for enhancing solubility, stability and oral bioavailability of various drugs. Drug entrapment and drug release from dendrimers can be controlled by modifying dendrimer surfaces and generations. PAMAM dendrimers are also shown to increase transdermal permeation and specific drug targeting. Dendrimer platforms can be engineered to attach targeting ligands and imaging molecules to create a nanodevice. Dendrimer nanotechnology, due to its multifunctional ability, has the potential to create next generation nanodevices.

  11. [Operative vaginal deliveries training].

    Science.gov (United States)

    Dupuis, O

    2008-12-01

    The appropriate use of forceps, vacuums or spatulas facilitates the rapid delivery of foetuses faced with life-threatening situations. It also makes possible the relief of certain cases of prolonged second-stage labor. In France, operative vaginal delivery (OVD) accounts for approximately 10% of all births. OVD training aims to optimize maternal, as well as neonatal safety. It should enable trainees to indicate or contraindicate an OVD safely, as well as to choose the appropriate instrument, use it correctly, and master quality control principles. Traditional OVD training is confronted with both spatial and time-related limitations. Spatial constraints involve both the teacher and trainee who only have limited visual access to the pelvic canal, and the head of the foetus; the time constraint occurs whenever the OVD occurs in an emergency setting. These limitations have been further aggravated by new constraints: decreasing time dedicated to training (European safety rules prohibit work the day after night duty), increasing litigation, and constraints imposed by society. Training by means of simulation removes such limitations making it possible to both avoid exposing pregnant women to the hazards of traditional training, and adapt the training to the skills of each trainee. OVD training should include forceps, vacuums and the use of spatulas. The OVD skills of obstetricians should be audited regularly on both a personal and a confidential level. Such audits could be based on a method using a simulator. Prospective studies comparing traditional and simulation-based training should be encouraged.

  12. Microneedles for drug and vaccine delivery

    Science.gov (United States)

    Kim, Yeu-Chun; Park, Jung-Hwan; Prausnitz, Mark R.

    2012-01-01

    Microneedles were first conceptualized for drug delivery many decades ago, but only became the subject of significant research starting in the mid-1990’s when microfabrication technology enabled their manufacture as (i) solid microneedles for skin pretreatment to increase skin permeability, (ii) microneedles coated with drug that dissolves off in the skin, (iii) polymer microneedles that encapsulate drug and fully dissolve in the skin and (iv) hollow microneedles for drug infusion into the skin. As shown in more than 350 papers now published in the field, microneedles have been used to deliver a broad range of different low molecular weight drugs, biotherapeutics and vaccines, including published human studies with a number of small-molecule and protein drugs and vaccines. Influenza vaccination using a hollow microneedle is in widespread clinical use and a number of solid microneedle products are sold for cosmetic purposes. In addition to applications in the skin, microneedles have also been adapted for delivery of bioactives into the eye and into cells. Successful application of microneedles depends on device function that facilitates microneedle insertion and possible infusion into skin, skin recovery after microneedle removal, and drug stability during manufacturing, storage and delivery, and on patient outcomes, including lack of pain, skin irritation and skin infection, in addition to drug efficacy and safety. Building off a strong technology base and multiple demonstrations of successful drug delivery, microneedles are poised to advance further into clinical practice to enable better pharmaceutical therapies, vaccination and other applications. PMID:22575858

  13. Role of Nanodiamonds in Drug Delivery and Stem Cell Therapy.

    Science.gov (United States)

    Ansari, Shakeel Ahmed; Satar, Rukhsana; Jafri, Mohammad Alam; Rasool, Mahmood; Ahmad, Waseem; Kashif Zaidi, Syed

    2016-09-01

    The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Nanodiamonds (NDs) have contributed significantly in the development of highly efficient and successful drug delivery systems, and in stem cell therapy. Drug delivery through NDs is an intricate and complex process that deserves special attention to unravel underlying molecular mechanisms in order to overcome certain bottlenecks associated with it. It has already been established that NDs based drug delivery systems have excellent biocompatibility, nontoxicity, photostability and facile surface functionalization properties. There is mounting evidence that suggests that such conjugated delivery systems well retain the properties of nanoparticles like small size, large surface area to volume ratio that provide greater biocatalytic activity to the attached drug in terms of selectivity, loading and stability. NDs based drug delivery systems may form the basis for the development of effective novel drug delivery vehicles with salient features that may facilitate their utility in fluorescence imaging, target specificity and sustainedrelease.

  14. Secondary fuel delivery system

    Science.gov (United States)

    Parker, David M.; Cai, Weidong; Garan, Daniel W.; Harris, Arthur J.

    2010-02-23

    A secondary fuel delivery system for delivering a secondary stream of fuel and/or diluent to a secondary combustion zone located in the transition piece of a combustion engine, downstream of the engine primary combustion region is disclosed. The system includes a manifold formed integral to, and surrounding a portion of, the transition piece, a manifold inlet port, and a collection of injection nozzles. A flowsleeve augments fuel/diluent flow velocity and improves the system cooling effectiveness. Passive cooling elements, including effusion cooling holes located within the transition boundary and thermal-stress-dissipating gaps that resist thermal stress accumulation, provide supplemental heat dissipation in key areas. The system delivers a secondary fuel/diluent mixture to a secondary combustion zone located along the length of the transition piece, while reducing the impact of elevated vibration levels found within the transition piece and avoiding the heat dissipation difficulties often associated with traditional vibration reduction methods.

  15. Focus on Delivery

    DEFF Research Database (Denmark)

    Hasman, Kirsten; Barfoed, Anne

    Background: Compared to other Nordic countries, Denmark has a high incidence of anal sphincter injury. Recent studies indicate that a strict focus on prevention of severe perineal trauma has decreased the incidence (1). This has resulted in changed clinical procedures in several Danish labour wards...... (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 the delivery, facilitated the midwife’s and the student’s structured reflection. Further, the project midwife held daily simulation workshops with midwives and students. Two focus group interviews with students and midwives were conducted and analyzed using content analysis. Results and conclusion...

  16. Amphiphilic block copolymers for drug delivery.

    Science.gov (United States)

    Adams, Monica L; Lavasanifar, Afsaneh; Kwon, Glen S

    2003-07-01

    Amphiphilic block copolymers (ABCs) have been used extensively in pharmaceutical applications ranging from sustained-release technologies to gene delivery. The utility of ABCs for delivery of therapeutic agents results from their unique chemical composition, which is characterized by a hydrophilic block that is chemically tethered to a hydrophobic block. In aqueous solution, polymeric micelles are formed via the association of ABCs into nanoscopic core/shell structures at or above the critical micelle concentration. Upon micellization, the hydrophobic core regions serve as reservoirs for hydrophobic drugs, which may be loaded by chemical, physical, or electrostatic means, depending on the specific functionalities of the core-forming block and the solubilizate. Although the Pluronics, composed of poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide), are the most widely studied ABC system, copolymers containing poly(L-amino acid) and poly(ester) hydrophobic blocks have also shown great promise in delivery applications. Because each ABC has unique advantages with respect to drug delivery, it may be possible to choose appropriate block copolymers for specific purposes, such as prolonging circulation time, introduction of targeting moieties, and modification of the drug-release profile. ABCs have been used for numerous pharmaceutical applications including drug solubilization/stabilization, alteration of the pharmacokinetic profile of encapsulated substances, and suppression of multidrug resistance. The purpose of this minireview is to provide a concise, yet detailed, introduction to the use of ABCs and polymeric micelles as delivery agents as well as to highlight current and past work in this area. Copyright 2003 Wiley-Liss, Inc. and the American Pharmacists Association

  17. Albumin and its application in drug delivery.

    Science.gov (United States)

    Sleep, Darrell

    2015-05-01

    Rapid clearance of drugs from the body results in short therapeutic half-life and is an integral property of many protein and peptide-based drugs. To maintain the desired therapeutic effect patients are required to administer higher doses more frequently, which is inconvenient and risks undesirable side effects. Drug delivery technologies aim to minimise the number of administrations and dose-related toxicity while maximising therapeutic efficacy. This review describes albumin's inherent biochemical and biophysical properties, which make it an attractive drug delivery platform and the developmental status of drugs that are associated, conjugated or genetically fused with albumin. Albumin interacts with a number of cell surface receptors including gp18, gp30, gp60, FcRn, cubilin and megalin. The importance of albumin's interaction with the FcRn receptor, the basis for albumin's long circulatory half-life, is described, as are engineered albumins with improved pharmacokinetics. Albumin naturally accumulates at tumours and sites of inflammation, a characteristic which can be augmented by the addition of targeting ligands. The development of albumin drug conjugates which reply upon this property is described. Albumin's inherent biochemical and biophysical properties make it an ideal drug delivery platform. Recent advances in our understanding of albumin physiology and the improvement in albumin-based therapies strongly suggest that albumin-based therapies have a significant advantage over alternative technologies in terms of half-life, stability, versatility, safety and ease of manufacture. Given the importance of the albumin:FcRn interaction, the interpretation of the pharmacokinetic and pharmacodynamic profiles of albumin-based therapeutics with disturbed albumin:FcRn interaction may have to be reassessed. The FcRn receptor has additional functionality, especially in relation to immunology, antigen presentation and delivery of proteins across mucosal membranes

  18. Hydrogen Delivery Technical Team Roadmap

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-06-01

    The mission of the Hydrogen Delivery Technical Team (HDTT) is to enable the development of hydrogen delivery technologies, which will allow for fuel cell competitiveness with gasoline and hybrid technologies by achieving an as-produced, delivered, and dispensed hydrogen cost of $2-$4 per gallon of gasoline equivalent of hydrogen.

  19. Emerging Frontiers in Drug Delivery.

    Science.gov (United States)

    Tibbitt, Mark W; Dahlman, James E; Langer, Robert

    2016-01-27

    Medicine relies on the use of pharmacologically active agents (drugs) to manage and treat disease. However, drugs are not inherently effective; the benefit of a drug is directly related to the manner by which it is administered or delivered. Drug delivery can affect drug pharmacokinetics, absorption, distribution, metabolism, duration of therapeutic effect, excretion, and toxicity. As new therapeutics (e.g., biologics) are being developed, there is an accompanying need for improved chemistries and materials to deliver them to the target site in the body, at a therapeutic concentration, and for the required period of time. In this Perspective, we provide an historical overview of drug delivery and controlled release followed by highlights of four emerging areas in the field of drug delivery: systemic RNA delivery, drug delivery for localized therapy, oral drug delivery systems, and biologic drug delivery systems. In each case, we present the barriers to effective drug delivery as well as chemical and materials advances that are enabling the field to overcome these hurdles for clinical impact.

  20. Synthetic sustained gene delivery systems.

    Science.gov (United States)

    Agarwal, Ankit; Mallapragada, Surya K

    2008-01-01

    Gene therapy today is hampered by the need of a safe and efficient gene delivery system that can provide a sustained therapeutic effect without cytotoxicity or unwanted immune responses. Bolus gene delivery in solution results in the loss of delivered factors via lymphatic system and may cause undesired effects by the escape of bioactive molecules to distant sites. Controlled gene delivery systems, acting as localized depot of genes, provide an extended sustained release of genes, giving prolonged maintenance of the therapeutic level of encoded proteins. They also limit the DNA degradation in the nuclease rich extra-cellular environment. While attempts have been made to adapt existing controlled drug delivery technologies, more novel approaches are being investigated for controlled gene delivery. DNA encapsulated in nano/micro spheres of polymers have been administered systemically/orally to be taken up by the targeted tissues and provide sustained release once internalized. Alternatively, DNA entrapped in hydrogels or scaffolds have been injected/implanted in tissues/cavities as platforms for gene delivery. The present review examines these different modalities for sustained delivery of viral and non-viral gene-delivery vectors. Design parameters and release mechanisms of different systems made with synthetic or natural polymers are presented along with their prospective applications and opportunities for continuous development.

  1. An intestinal Trojan horse for gene delivery.

    Science.gov (United States)

    Peng, Haisheng; Wang, Chao; Xu, Xiaoyang; Yu, Chenxu; Wang, Qun

    2015-03-14

    The intestinal epithelium forms an essential element of the mucosal barrier and plays a critical role in the pathophysiological response to different enteric disorders and diseases. As a major enteric dysfunction of the intestinal tract, inflammatory bowel disease is a genetic disease which results from the inappropriate and exaggerated mucosal immune response to the normal constituents in the mucosal microbiota environment. An intestine targeted drug delivery system has unique advantages in the treatment of inflammatory bowel disease. As a new concept in drug delivery, the Trojan horse system with the synergy of nanotechnology and host cells can achieve better therapeutic efficacy in specific diseases. Here, we demonstrated the feasibility of encapsulating DNA-functionalized gold nanoparticles into primary isolated intestinal stem cells to form an intestinal Trojan horse for gene regulation therapy of inflammatory bowel disease. This proof-of-concept intestinal Trojan horse will have a wide variety of applications in the diagnosis and therapy of enteric disorders and diseases.

  2. IMPROVEMENTS IN THE QUALITY OF COURIER DELIVERY

    Directory of Open Access Journals (Sweden)

    Jacek Karcz

    2016-06-01

    Full Text Available The functioning of courier companies is a vital component of modern trade. E-commerce services are changing the way of shopping. Along with them, also courier services change and become more advance. Customers of courier companies become more aware of quality, which they should expect from supplier of these services. The article presents the result of the research of the effectiveness and the timelines of deliveries realized by one of the terminals of a leading courier operator in Poland. The survey involved 55 courier routes over the course of 10 business days. The author analyses weak points of the supply chain and presents two solutions, which may improve quality of delivery processes.

  3. Diatomite silica nanoparticles for drug delivery

    Science.gov (United States)

    Ruggiero, Immacolata; Terracciano, Monica; Martucci, Nicola M.; De Stefano, Luca; Migliaccio, Nunzia; Tatè, Rosarita; Rendina, Ivo; Arcari, Paolo; Lamberti, Annalisa; Rea, Ilaria

    2014-07-01

    Diatomite is a natural fossil material of sedimentary origin, constituted by fragments of diatom siliceous skeletons. In this preliminary work, the properties of diatomite nanoparticles as potential system for the delivery of drugs in cancer cells were exploited. A purification procedure, based on thermal treatments in strong acid solutions, was used to remove inorganic and organic impurities from diatomite and to make them a safe material for medical applications. The micrometric diatomite powder was reduced in nanoparticles by mechanical crushing, sonication, and filtering. Morphological analysis performed by dynamic light scattering and transmission electron microscopy reveals a particles size included between 100 and 300 nm. Diatomite nanoparticles were functionalized by 3-aminopropyltriethoxysilane and labeled by tetramethylrhodamine isothiocyanate. Different concentrations of chemically modified nanoparticles were incubated with cancer cells and confocal microscopy was performed. Imaging analysis showed an efficient cellular uptake and homogeneous distribution of nanoparticles in cytoplasm and nucleus, thus suggesting their potentiality as nanocarriers for drug delivery.

  4. Cationic Bolaamphiphiles for Gene Delivery

    Science.gov (United States)

    Tan, Amelia Li Min; Lim, Alisa Xue Ling; Zhu, Yiting; Yang, Yi Yan; Khan, Majad

    2014-05-01

    Advances in medical research have shed light on the genetic cause of many human diseases. Gene therapy is a promising approach which can be used to deliver therapeutic genes to treat genetic diseases at its most fundamental level. In general, nonviral vectors are preferred due to reduced risk of immune response, but they are also commonly associated with low transfection efficiency and high cytotoxicity. In contrast to viral vectors, nonviral vectors do not have a natural mechanism to overcome extra- and intracellular barriers when delivering the therapeutic gene into cell. Hence, its design has been increasingly complex to meet challenges faced in targeting of, penetration of and expression in a specific host cell in achieving more satisfactory transfection efficiency. Flexibility in design of the vector is desirable, to enable a careful and controlled manipulation of its properties and functions. This can be met by the use of bolaamphiphile, a special class of lipid. Unlike conventional lipids, bolaamphiphiles can form asymmetric complexes with the therapeutic gene. The advantage of having an asymmetric complex lies in the different purposes served by the interior and exterior of the complex. More effective gene encapsulation within the interior of the complex can be achieved without triggering greater aggregation of serum proteins with the exterior, potentially overcoming one of the great hurdles faced by conventional single-head cationic lipids. In this review, we will look into the physiochemical considerations as well as the biological aspects of a bolaamphiphile-based gene delivery system.

  5. Electronic Nicotine Delivery Systems.

    Science.gov (United States)

    Walley, Susan C; Jenssen, Brian P

    2015-11-01

    Electronic nicotine delivery systems (ENDS) are rapidly growing in popularity among youth. ENDS are handheld devices that produce an aerosolized mixture from a solution typically containing concentrated nicotine, flavoring chemicals, and propylene glycol to be inhaled by the user. ENDS are marketed under a variety of names, most commonly electronic cigarettes and e-cigarettes. In 2014, more youth reported using ENDS than any other tobacco product. ENDS pose health risks to both users and nonusers. Nicotine, the major psychoactive ingredient in ENDS solutions, is both highly addictive and toxic. In addition to nicotine, other toxicants, carcinogens, and metal particles have been detected in solutions and aerosols of ENDS. Nonusers are involuntarily exposed to the emissions of these devices with secondhand and thirdhand aerosol. The concentrated and often flavored nicotine in ENDS solutions poses a poisoning risk for young children. Reports of acute nicotine toxicity from US poison control centers have been increasing, with at least 1 child death reported from unintentional exposure to a nicotine-containing ENDS solution. With flavors, design, and marketing that appeal to youth, ENDS threaten to renormalize and glamorize nicotine and tobacco product use. There is a critical need for ENDS regulation, legislative action, and counter promotion to protect youth. ENDS have the potential to addict a new generation of youth to nicotine and reverse more than 50 years of progress in tobacco control. Copyright © 2015 by the American Academy of Pediatrics.

  6. Ceramic drug-delivery devices.

    Science.gov (United States)

    Lasserre, A; Bajpai, P K

    1998-01-01

    A variety of ceramics and delivery systems have been used to deliver chemicals, biologicals, and drugs at various rates for desired periods of time from different sites of implantation. In vitro and in vivo studies have shown that ceramics can successfully be used as drug-delivery devices. Matrices, inserts, reservoirs, cements, and particles have been used to deliver a large variety of therapeutic agents such as antibiotics, anticancer drugs, anticoagulants, analgesics, growth factors, hormones, steroids, and vaccines. In this article, the advantages and disadvantages of conventional drug-delivery systems and the different approaches used to deliver chemical and biological agents by means of ceramic systems will be reviewed.

  7. Encapsulation systems for the delivery of hydrophilic nutraceuticals: Food application.

    Science.gov (United States)

    Aditya, N P; Espinosa, Yadira Gonzalez; Norton, Ian T

    2017-07-01

    Increased health risk associated with the sedentary life style is forcing the food manufacturers to look for food products with specific or general health benefits e.g. beverages enriched with nutraceuticals like catechin, curcumin rutin. Compounds like polyphenols, flavonoids, vitamins are the good choice of bioactive compounds that can be used to fortify the food products to enhance their functionality. However due to low stability and bioavailability of these bioactives (both hydrophobic and hydrophilic) within the heterogeneous food microstructure and in the Gastro Intestinal Tract (GIT), it becomes extremely difficult to pass on the real health benefits to the consumers. Recent developments in the application of nano-delivery systems for food product development is proving to be a game changer which has raised the expectations of the researchers, food manufacturers and consumers regarding possibility of enhancing the functionality of bioactives within the fortified food products. In this direction, nano/micro delivery systems using lipids, surfactants and other materials (carbohydrates, polymers, complexes, protein) have been fabricated to stabilize and enhance the biological activity of the bioactive compounds. In the present review, current status of the various delivery systems that are used for the delivery of hydrophilic bioactives and future prospects for using other delivery systems that have been not completely explored for the delivery of hydrophilic bioactives e.g. niosomes; bilosomes, cubosomes are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Efficient and gentle siRNA delivery by magnetofection

    Science.gov (United States)

    Ensenauer, R; Hartl, D; Vockley, J; Roscher, AA; Fuchs, U

    2015-01-01

    Magnetic force combined with magnetic nanoparticles recently has shown potential for enhancing nucleic acid delivery. Achieving effective siRNA delivery into primary cultured cells is challenging. We compared the utility of magnetofection with lipofection procedures for siRNA delivery to primary and immortalized mammalian fibroblasts. Transfection efficiency and cell viability were analyzed by flow cytometry and effects of gene knockdown were quantified by real-time PCR. Lipofectamine 2000 and magnetofection achieved high transfection efficiencies comparable to similar gene silencing effects of about 80%; the cytotoxic effect of magnetofection, however, was significantly less. Magnetofection is a reliable and gentle alternative method with low cytotoxicity for siRNA delivery into difficult to transfect cells such as mammalian fibroblasts. These features are especially advantageous for functional end point analyses of gene silencing, e.g., on the metabolite level. PMID:20297946

  9. DNA nanostructure-based drug delivery nanosystems in cancer therapy.

    Science.gov (United States)

    Wu, Dandan; Wang, Lei; Li, Wei; Xu, Xiaowen; Jiang, Wei

    2017-11-25

    DNA as a novel biomaterial can be used to fabricate different kinds of DNA nanostructures based on its principle of GC/AT complementary base pairing. Studies have shown that DNA nanostructure is a nice drug carrier to overcome big obstacles existing in cancer therapy such as systemic toxicity and unsatisfied drug efficacy. Thus, different types of DNA nanostructure-based drug delivery nanosystems have been designed in cancer therapy. To improve treating efficacy, they are also developed into more functional drug delivery nanosystems. In recent years, some important progresses have been made. The objective of this review is to make a retrospect and summary about these different kinds of DNA nanostructure-based drug delivery nanosystems and their latest progresses: (1) active targeting; (2) mutidrug co-delivery; (3) construction of stimuli-responsive/intelligent nanosystems. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Waste feed delivery planning at Hanford-13232

    International Nuclear Information System (INIS)

    Certa, Paul J.; West, Elizha B.; Rodriguez, Juissepp S.; Hohl, Ted M.; Larsen, Douglas C.; Ritari, Jaakob S.; Kelly, James W.

    2013-01-01

    The Integrated Waste Feed Delivery Plan (IWFDP) describes how waste feed will be delivered to the Waste Treatment and Immobilization Plant (WTP) to safely and efficiently accomplish the River Protection Project (RPP) mission. The IWFDP, which is integrated with the Baseline Case operating scenario, is comprised of three volumes. Volume 1 - Process Strategy provides an overview of waste feed delivery (WFD) and describes how the WFD system will be used to prepare and deliver feed to the WTP based on the equipment configuration and functional capabilities of the WFD system. Volume 2 - Campaign Plan describes the plans for the first eight campaigns for delivery to the WTP, evaluates projected feed for systematic issues, projects 242-A Evaporator campaigns, and evaluates double-shell tank (DST) space and availability of contingency feed. Volume 3 - Project Plan identifies the scope and timing of the DST and infrastructure upgrade projects necessary to feed the WTP, and coordinates over 30 projectized projects and operational activities that comprise the needed WFD upgrades

  11. Waste Feed Delivery Planning at Hanford - 13232

    International Nuclear Information System (INIS)

    Certa, Paul J.; Hohl, Ted M.; Kelly, James W.; Larsen, Douglas C.; West, Elizha B.; Ritari, Jaakob S.; Rodriguez, Juissepp S.

    2013-01-01

    The Integrated Waste Feed Delivery Plan (IWFDP) describes how waste feed will be delivered to the Waste Treatment and Immobilization Plant (WTP) to safely and efficiently accomplish the River Protection Project (RPP) mission. The IWFDP, which is integrated with the Baseline Case operating scenario, is comprised of three volumes. Volume 1 - Process Strategy provides an overview of waste feed delivery (WFD) and describes how the WFD system will be used to prepare and deliver feed to the WTP based on the equipment configuration and functional capabilities of the WFD system. Volume 2 - Campaign Plan describes the plans for the first eight campaigns for delivery to the WTP, evaluates projected feed for systematic issues, projects 242-A Evaporator campaigns, and evaluates double-shell tank (DST) space and availability of contingency feed. Volume 3 - Project Plan identifies the scope and timing of the DST and infrastructure upgrade projects necessary to feed the WTP, and coordinates over 30 projectized projects and operational activities that comprise the needed WFD upgrades. (authors)

  12. Waste Feed Delivery Planning at Hanford - 13232

    Energy Technology Data Exchange (ETDEWEB)

    Certa, Paul J.; Hohl, Ted M.; Kelly, James W.; Larsen, Douglas C.; West, Elizha B.; Ritari, Jaakob S.; Rodriguez, Juissepp S. [Washington River Protection Solutions, LLC, P.O. 850, Richland, WA 99352 (United States)

    2013-07-01

    The Integrated Waste Feed Delivery Plan (IWFDP) describes how waste feed will be delivered to the Waste Treatment and Immobilization Plant (WTP) to safely and efficiently accomplish the River Protection Project (RPP) mission. The IWFDP, which is integrated with the Baseline Case operating scenario, is comprised of three volumes. Volume 1 - Process Strategy provides an overview of waste feed delivery (WFD) and describes how the WFD system will be used to prepare and deliver feed to the WTP based on the equipment configuration and functional capabilities of the WFD system. Volume 2 - Campaign Plan describes the plans for the first eight campaigns for delivery to the WTP, evaluates projected feed for systematic issues, projects 242-A Evaporator campaigns, and evaluates double-shell tank (DST) space and availability of contingency feed. Volume 3 - Project Plan identifies the scope and timing of the DST and infrastructure upgrade projects necessary to feed the WTP, and coordinates over 30 projectized projects and operational activities that comprise the needed WFD upgrades. (authors)

  13. Oxygen delivery in irradiated normal tissue

    Energy Technology Data Exchange (ETDEWEB)

    Kiani, M.F.; Ansari, R. [Univ. of Tennessee Health Science Center, Memphis, TN (United States). School of Biomedical Engineering; Gaber, M.W. [St. Jude Children' s Research Hospital, Memphis, TN (United States)

    2003-03-01

    Ionizing radiation exposure significantly alters the structure and function of microvascular networks, which regulate delivery of oxygen to tissue. In this study we use a hamster cremaster muscle model to study changes in microvascular network parameters and use a mathematical model to study the effects of these observed structural and microhemodynamic changes in microvascular networks on oxygen delivery to the tissue. Our experimental observations indicate that in microvascular networks while some parameters are significantly affected by irradiation (e.g. red blood cell (RBC) transit time), others remain at the control level (e.g. RBC path length) up to 180 days post-irradiation. The results from our mathematical model indicate that tissue oxygenation patterns are significantly different in irradiated normal tissue as compared to age-matched controls and the differences are apparent as early as 3 days post irradiation. However, oxygen delivery to irradiated tissue was not found to be significantly different from age matched controls at any time between 7 days to 6 months post-irradiation. These findings indicate that microvascular late effects in irradiated normal tissue may be due to factors other than compromised tissue oxygenation. (author)

  14. Matrix Metalloproteinase Responsive Delivery of Myostatin Inhibitors.

    Science.gov (United States)

    Braun, Alexandra C; Gutmann, Marcus; Ebert, Regina; Jakob, Franz; Gieseler, Henning; Lühmann, Tessa; Meinel, Lorenz

    2017-01-01

    The inhibition of myostatin - a member of the transforming growth factor (TGF-β) family - drives regeneration of functional skeletal muscle tissue. We developed a bioresponsive drug delivery system (DDS) linking release of a myostatin inhibitor (MI) to inflammatory flares of myositis to provide self-regulated MI concentration gradients within tissues of need. A protease cleavable linker (PCL) - responding to MMP upregulation - is attached to the MI and site-specifically immobilized on microparticle surfaces. The PCL disintegrated in a matrix metalloproteinase (MMP) 1, 8, and particularly MMP-9 concentration dependent manner, with MMP-9 being an effective surrogate biomarker correlating with the activity of myositis. The bioactivity of particle-surface bound as well as released MI was confirmed by luciferase suppression in stably transfected HEK293 cells responding to myostatin induced SMAD phosphorylation. We developed a MMP-responsive DDS for MI delivery responding to inflammatory flare of a diseased muscle matching the kinetics of MMP-9 upregulation, with MMP-9 kinetics matching (patho-) physiological myostatin levels. ᅟ: Graphical Abstract Schematic illustration of the matrix metalloproteinase responsive delivery system responding to inflammatory flares of muscle disease. The protease cleavable linker readily disintegrates upon entry into the diseased tissue, therby releasing the mystatin inhibitor.

  15. Mode of delivery after obstetric anal sphincter injury.

    Science.gov (United States)

    Karmarkar, Roopali; Bhide, Alka; Digesu, Alex; Khullar, Vik; Fernando, Ruwan

    2015-11-01

    To assess the effect of vaginal delivery and caesarean section on faecal symptoms and structure and function of anal sphincter in women who sustained obstetric anal sphincter injuries (OASIS) in their previous pregnancy and were advised about the mode of delivery based on faecal incontinence symptoms, anal manometry and endoanal ultrasound. It is a descriptive study on a cohort of women who had OASIS from 2006 to 2013. They were assessed after OASIS and during subsequent pregnancy with a questionnaire, endoanal ultrasound and anal manometry. Vaginal delivery was recommended to asymptomatic women with normal investigations. Elective caesarean section was recommended to women with faecal symptoms, anal sphincter defects of more than 30° or low resting or incremental anal pressures. All women were reassessed after subsequent delivery. Fifty women who had pregnancies after OASIS, were seen after OASIS, during subsequent pregnancy and after the second delivery. 15 women had faecal symptoms after OASIS. The external, internal and combined anal sphincter defects were seen in 13, 11 and 9 women respectively. Low resting and incremental pressure were seen in 15 and 11 women respectively. Caesarean section was done in 22 women and 28 women delivered vaginally. Worsening of faecal symptoms and reduction in anal pressures were not observed in planned vaginal delivery or elective caesarean section groups. Faecal symptoms were worse with reduced anal pressures in three women from the planned caesarean section group. One of the women had a vaginal delivery and two women had emergency caesarean section at 7cm and 10cm dilatation. There were no new sphincter defects or recurrent OASIS in any of the women in the study group. Decision about the mode of delivery of pregnancy after OASIS based on symptoms, anal manometry and endoanal ultrasound helps in preserving the anal sphincter function and avoiding unnecessary caesarean sections. Further follow-up of these patients is essential

  16. Drug delivery across length scales.

    Science.gov (United States)

    Delcassian, Derfogail; Patel, Asha K; Cortinas, Abel B; Langer, Robert

    2018-02-20

    Over the last century, there has been a dramatic change in the nature of therapeutic, biologically active molecules available to treat disease. Therapies have evolved from extracted natural products towards rationally designed biomolecules, including small molecules, engineered proteins and nucleic acids. The use of potent drugs which target specific organs, cells or biochemical pathways, necessitates new tools which can enable controlled delivery and dosing of these therapeutics to their biological targets. Here, we review the miniaturisation of drug delivery systems from the macro to nano-scale, focussing on controlled dosing and controlled targeting as two key parameters in drug delivery device design. We describe how the miniaturisation of these devices enables the move from repeated, systemic dosing, to on-demand, targeted delivery of therapeutic drugs and highlight areas of focus for the future.

  17. Bioresponsive matrices in drug delivery

    Directory of Open Access Journals (Sweden)

    Ye George JC

    2010-11-01

    Full Text Available Abstract For years, the field of drug delivery has focused on (1 controlling the release of a therapeutic and (2 targeting the therapeutic to a specific cell type. These research endeavors have concentrated mainly on the development of new degradable polymers and molecule-labeled drug delivery vehicles. Recent interest in biomaterials that respond to their environment have opened new methods to trigger the release of drugs and localize the therapeutic within a particular site. These novel biomaterials, usually termed "smart" or "intelligent", are able to deliver a therapeutic agent based on either environmental cues or a remote stimulus. Stimuli-responsive materials could potentially elicit a therapeutically effective dose without adverse side effects. Polymers responding to different stimuli, such as pH, light, temperature, ultrasound, magnetism, or biomolecules have been investigated as potential drug delivery vehicles. This review describes the most recent advances in "smart" drug delivery systems that respond to one or multiple stimuli.

  18. Continuous Delivery and Quality Monitoring

    CERN Multimedia

    CERN. Geneva

    2016-01-01

    After introducing Continuous Delivery, I will switch the topic and try to answer the question how much should we invest in quality and how to do it efficiently. My observations reveal that software quality is often considered as the slo...

  19. Selenium nanoparticles: potential in cancer gene and drug delivery.

    Science.gov (United States)

    Maiyo, Fiona; Singh, Moganavelli

    2017-05-01

    In recent decades, colloidal selenium nanoparticles have emerged as exceptional selenium species with reported chemopreventative and therapeutic properties. This has sparked widespread interest in their use as a carrier of therapeutic agents with results displaying synergistic effects of selenium with its therapeutic cargo and improved anticancer activity. Functionalization remains a critical step in selenium nanoparticles' development for application in gene or drug delivery. In this review, we highlight recent developments in the synthesis and functionalization strategies of selenium nanoparticles used in cancer drug and gene delivery systems. We also provide an update of recent preclinical studies utilizing selenium nanoparticles in cancer therapeutics.

  20. Organoclays for drug delivery Systems

    OpenAIRE

    Canovas Creus, Alba

    2008-01-01

    Modified clays can be used as carriers of drugs due to their suitable properties and structure in order to achieve improvements in drug delivery. The study of this thesis starts with an introduction to mineral clays and its classification, properties and characterization, then deepens into modified clays (properties, comparison with mineral clays, applications and procedure of modification). Another chapter is focused in drug delivery: definition, its difficulties nowadays and the different w...

  1. Designing synthetic RNA for delivery by nanoparticles

    International Nuclear Information System (INIS)

    Jedrzejczyk, Dominika; Pawlowska, Roza; Chworos, Arkadiusz; Gendaszewska-Darmach, Edyta

    2017-01-01

    The rapid development of synthetic biology and nanobiotechnology has led to the construction of various synthetic RNA nanoparticles of different functionalities and potential applications. As they occur naturally, nucleic acids are an attractive construction material for biocompatible nanoscaffold and nanomachine design. In this review, we provide an overview of the types of RNA and nucleic acid’s nanoparticle design, with the focus on relevant nanostructures utilized for gene-expression regulation in cellular models. Structural analysis and modeling is addressed along with the tools available for RNA structural prediction. The functionalization of RNA-based nanoparticles leading to prospective applications of such constructs in potential therapies is shown. The route from the nanoparticle design and modeling through synthesis and functionalization to cellular application is also described. For a better understanding of the fate of targeted RNA after delivery, an overview of RNA processing inside the cell is also provided. (topical review)

  2. Characteristics of exogenous carbon monoxide deliveries

    Directory of Open Access Journals (Sweden)

    Hui-jun Hu

    2016-01-01

    Full Text Available Carbon monoxide (CO has long been considered an environmental pollutant and a poison. Exogenous exposure to amounts of CO beyond the physiologic level of the body can result in a protective or adaptive response. However, as a gasotransmitter, endogenous CO is important for multiple physiologic functions. To date, at least seven distinct methods of delivering CO have been utilized in animal and clinical studies. In this mini-review, we summarize the exogenous CO delivery methods and compare their advantages and disadvantages.

  3. Levodopa delivery systems: advancements in delivery of the gold standard.

    Science.gov (United States)

    Ngwuluka, Ndidi; Pillay, Viness; Du Toit, Lisa C; Ndesendo, Valence; Choonara, Yahya; Modi, Girish; Naidoo, Dinesh

    2010-02-01

    Despite the fact that Parkinson's disease (PD) was discovered almost 200 years ago, its treatment and management remain immense challenges because progressive loss of dopaminergic nigral neurons, motor complications experienced by the patients as the disease progresses and drawbacks of pharmacotherapeutic management still persist. Various therapeutic agents have been used in the management of PD, including levodopa (l-DOPA), selegiline, amantadine, bromocriptine, entacapone, pramipexole dihydrochloride and more recently istradefylline and rasagiline. Of all agents, l-DOPA although the oldest, remains the most effective. l-DOPA is easier to administer, better tolerated, less expensive and is required by almost all PD patients. However, l-DOPA's efficacy in advanced PD is significantly reduced due to metabolism, subsequent low bioavailability and irregular fluctuations in its plasma levels. Significant strides have been made to improve the delivery of l-DOPA in order to enhance its bioavailability and reduce plasma fluctuations as well as motor complications experienced by patients purportedly resulting from pulsatile stimulation of the striatal dopamine receptors. Drug delivery systems that have been instituted for the delivery of l-DOPA include immediate release formulations, liquid formulations, dispersible tablets, controlled release formulations, dual-release formulations, microspheres, infusion and transdermal delivery, among others. In this review, the l-DOPA-loaded drug delivery systems developed over the past three decades are elaborated. The ultimate aim was to assess critically the attempts made thus far directed at improving l-DOPA absorption, bioavailability and maintenance of constant plasma concentrations, including the drug delivery technologies implicated. This review highlights the fact that neuropharmaceutics is at a precipice, which is expected to spur investigators to take that leap to enable the generation of innovative delivery systems for the

  4. Inclusion Extraction of Alkali Metals by Emulsion Liquid Membranes and Nano-baskets of p-tert-Calix[4]arene Bearing Di-[N-(X)sulfonyl Carboxamide] and Di-(1-propoxy) in ortho-cone Conformation

    Energy Technology Data Exchange (ETDEWEB)

    Mokhtari, Bahram; Pourabdollah, Kobra [Islamic Azad University, Province (Iran, Islamic Republic of)

    2012-05-15

    Nano-assisted inclusion separation of alkali metals from basic solutions was reported by inclusion-facilitated emulsion liquid membrane process. The novelty of this study is application of nano-baskets of calixarene in the selective and efficient separation of alkali metals as both the carrier and the surfactant. For this aim, four derivatives of p-tert-calix[4]arene bearing different sulfonamide moieties were synthesized and their inclusionextraction parameters were optimized including the calixarene scaffold 3 (4 wt %) as the carrier/demulsifier, the commercial kerosene as diluent in membrane, sulphonic acid (0.2 M) and ammonium carbonate (0.4 M) as the strip and the feed phases, the phase and the treat ratios of 0.8 and 0.3, mixing speed (300 rpm), and initial solute concentration (100 mg/L). The selectivity of membrane over more than ten interfering cations was examined and the results reveled that under the optimized operating condition, the degree of inclusionextraction of alkali metals was as high as 98-99%.

  5. Inclusion Extraction of Alkali Metals by Emulsion Liquid Membranes and Nano-baskets of p-tert-Calix[4]arene Bearing Di-[N-(X)sulfonyl Carboxamide] and Di-(1-propoxy) in ortho-cone Conformation

    International Nuclear Information System (INIS)

    Mokhtari, Bahram; Pourabdollah, Kobra

    2012-01-01

    Nano-assisted inclusion separation of alkali metals from basic solutions was reported by inclusion-facilitated emulsion liquid membrane process. The novelty of this study is application of nano-baskets of calixarene in the selective and efficient separation of alkali metals as both the carrier and the surfactant. For this aim, four derivatives of p-tert-calix[4]arene bearing different sulfonamide moieties were synthesized and their inclusionextraction parameters were optimized including the calixarene scaffold 3 (4 wt %) as the carrier/demulsifier, the commercial kerosene as diluent in membrane, sulphonic acid (0.2 M) and ammonium carbonate (0.4 M) as the strip and the feed phases, the phase and the treat ratios of 0.8 and 0.3, mixing speed (300 rpm), and initial solute concentration (100 mg/L). The selectivity of membrane over more than ten interfering cations was examined and the results reveled that under the optimized operating condition, the degree of inclusionextraction of alkali metals was as high as 98-99%

  6. Colloidal drug delivery system: amplify the ocular delivery.

    Science.gov (United States)

    Ali, Javed; Fazil, Mohd; Qumbar, Mohd; Khan, Nazia; Ali, Asgar

    2016-01-01

    The ocular perceivers are the most voluntarily accessible organs in terms of location in the body, yet drug distribution to these tissues is one of the most intriguing and challenging endeavors and problematic to the pharmaceutical scientist. The most of ocular diseases are treated with topical application of conventional formulation, i.e. solutions, suspensions and ointment. Typically on installation of these conventional formulations, only <5% of the applied dose penetrates the cornea and reaches intraocular tissues, while a major fraction of the instilled dose is wastage due to the presence of many ocular barriers like external barriers, rapid loss of the instilled solution from the precorneal area and nasolacrimal drainage system. Systemic absorption caused systemic side effects varying from mild to life-threatening events. The main objective of this review is to explore the role of colloidal delivery of drug to minimize the drawbacks associated with them. This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings and applications of colloidal delivery systems, i.e. nanoparticles, nanosuspensions, liposomes, niosomes, dendrimers and contact lenses containing nanoparticles have the capacity to distribute ocular drugs to categorical target sites and hold promise to revolutionize the therapy of many ocular perceiver diseases and minimized the circumscription of conventional delivery. Form the basis of literature review, it has been found that the novel delivery system have greater impact to maximize ocular drug absorption, and minimize systemic absorption and side effects.

  7. Neonatal outcomes and operative vaginal delivery versus cesarean delivery.

    LENUS (Irish Health Repository)

    Contag, Stephen A

    2010-06-01

    We compared outcomes for neonates with forceps-assisted, vacuum-assisted, or cesarean delivery in the second stage of labor. This is a secondary analysis of a randomized trial in laboring, low-risk, nulliparous women at >or=36 weeks\\' gestation. Neonatal outcomes after use of forceps, vacuum, and cesarean were compared among women in the second stage of labor at station +1 or below (thirds scale) for failure of descent or nonreassuring fetal status. Nine hundred ninety women were included in this analysis: 549 (55%) with an indication for delivery of failure of descent and 441 (45%) for a nonreassuring fetal status. Umbilical cord gases were available for 87% of neonates. We found no differences in the base excess (P = 0.35 and 0.78 for failure of descent and nonreassuring fetal status) or frequencies of pH below 7.0 (P = 0.73 and 0.34 for failure of descent and nonreassuring fetal status) among the three delivery methods. Birth outcomes and umbilical cord blood gas values were similar for those neonates with a forceps-assisted, vacuum-assisted, or cesarean delivery in the second stage of labor. The occurrence of significant fetal acidemia was not different among the three delivery methods regardless of the indication.

  8. SU-F-T-660: Evaluating the Benefit of Using Dual-Function Fiducial Markers for In-Situ Delivery of Radiosenistizing Gold Nanoparticles During Image-Guided Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    AlMansour, S; Chin, J; Sajo, E; Ngwa, W [University Massachusetts Lowell, Lowell, MA (United States)

    2016-06-15

    Purpose: Dual-function fiducials loaded with radiosensitizers, like gold nanoparticles (GNP), offer an innovative approach for ensuring geometric accuracy during image-guided radiotherapy (IGRT) and significantly increasing therapeutic efficacy due to controlled in-situ release of the radiosensitizers. This study retrospectively investigates the dosimetric benefit of using up to two such dual-function fiducial markers instead of traditional single function fiducials during IGRT. Methods: A computational code was developed to investigate the dosimetric benefit for 10 real patient tumor volumes of up to 6.5 cm diameter. The intra-tumoral space-time biodistribution of the GNP was modeled as in previous studies based on Fick’s second law. The corresponding dose-enhancement for each tumor voxel due to the GNP was also calculated for clinical 6MV beam configurations. Various loading concentrations (25–50 mg/g) were studied, as a function of GNP size, to determine potential for clinically significant dose enhancement. The time between initial implantation of dual-function fiducials to the beginning of radiotherapy was assumed to be 14 days as typical for many clinics. Results: A single dual-function fiducial could achieve at least a DEF of 1.2 for patients with tumors less than 1.4 cm diameter after 14 days. Replacing two single function fiducials with dual-function ones at the same locations achieved at least the required minimal DEF for tumors that are 2 cm diameter in 3 patients. The results also revealed dosimetrically better fiducial locations which could enable significant DEF when using one or two dual function fiducials. 2 nm sizes showed the most feasibility. Conclusion: The results highlight the potential of tumor sub-volume radiation boosting using GNP released from fiducials, and the ability to customize the DEF throughout the tumor by using two dual-function fiducials, varying the initial concentration and nanoparticle size. The results demonstrate

  9. SU-F-T-660: Evaluating the Benefit of Using Dual-Function Fiducial Markers for In-Situ Delivery of Radiosenistizing Gold Nanoparticles During Image-Guided Radiotherapy

    International Nuclear Information System (INIS)

    AlMansour, S; Chin, J; Sajo, E; Ngwa, W

    2016-01-01

    Purpose: Dual-function fiducials loaded with radiosensitizers, like gold nanoparticles (GNP), offer an innovative approach for ensuring geometric accuracy during image-guided radiotherapy (IGRT) and significantly increasing therapeutic efficacy due to controlled in-situ release of the radiosensitizers. This study retrospectively investigates the dosimetric benefit of using up to two such dual-function fiducial markers instead of traditional single function fiducials during IGRT. Methods: A computational code was developed to investigate the dosimetric benefit for 10 real patient tumor volumes of up to 6.5 cm diameter. The intra-tumoral space-time biodistribution of the GNP was modeled as in previous studies based on Fick’s second law. The corresponding dose-enhancement for each tumor voxel due to the GNP was also calculated for clinical 6MV beam configurations. Various loading concentrations (25–50 mg/g) were studied, as a function of GNP size, to determine potential for clinically significant dose enhancement. The time between initial implantation of dual-function fiducials to the beginning of radiotherapy was assumed to be 14 days as typical for many clinics. Results: A single dual-function fiducial could achieve at least a DEF of 1.2 for patients with tumors less than 1.4 cm diameter after 14 days. Replacing two single function fiducials with dual-function ones at the same locations achieved at least the required minimal DEF for tumors that are 2 cm diameter in 3 patients. The results also revealed dosimetrically better fiducial locations which could enable significant DEF when using one or two dual function fiducials. 2 nm sizes showed the most feasibility. Conclusion: The results highlight the potential of tumor sub-volume radiation boosting using GNP released from fiducials, and the ability to customize the DEF throughout the tumor by using two dual-function fiducials, varying the initial concentration and nanoparticle size. The results demonstrate

  10. On the concavity of delivery games

    NARCIS (Netherlands)

    Hamers, H.J.M.

    1995-01-01

    Delivery games, introduced by Hamers, Borm, van de Leensel and Tijs (1994), are combinatorial optimization games that arise from delivery problems closely related to the Chinese postman problem (CPP). They showed that delivery games are not necessarily balanced. For delivery problems corresponding

  11. 38 CFR 21.4505 - Check delivery.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Check delivery. 21.4505...) VOCATIONAL REHABILITATION AND EDUCATION Education Loans § 21.4505 Check delivery. (a) General. Education... surviving spouse is enrolled for delivery by the educational institution. (b) Delivery and certification. (1...

  12. 18 CFR 157.211 - Delivery points.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Delivery points. 157... for Certain Transactions and Abandonment § 157.211 Delivery points. (a) Construction and operation—(1... delivery point, excluding the construction of certain delivery points subject to the prior notice...

  13. 19 CFR 10.101 - Immediate delivery.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Immediate delivery. 10.101 Section 10.101 Customs... Importations § 10.101 Immediate delivery. (a) Shipments entitled to immediate delivery. Shipments consigned to... as shipments the immediate delivery of which is necessary within the purview of section 448(b...

  14. Mucosal delivery of liposome-chitosan nanoparticle complexes.

    Science.gov (United States)

    Carvalho, Edison L S; Grenha, Ana; Remuñán-López, Carmen; Alonso, Maria José; Seijo, Begoña

    2009-01-01

    Designing adequate drug carriers has long been a major challenge for those working in drug delivery. Since drug delivery strategies have evolved for mucosal delivery as the outstanding alternative to parenteral administration, many new drug delivery systems have been developed which evidence promising properties to address specific issues. Colloidal carriers, such as nanoparticles and liposomes, have been referred to as the most valuable approaches, but still have some limitations that can become more inconvenient as a function of the specific characteristics of administration routes. To overcome these limitations, we developed a new drug delivery system that results from the combination of chitosan nanoparticles and liposomes, in an approach of combining their advantages, while avoiding their individual limitations. These lipid/chitosan nanoparticle complexes are, thus, expected to protect the encapsulated drug from harsh environmental conditions, while concomitantly providing its controlled release. To prepare these assemblies, two different strategies have been applied: one focusing on the simple hydration of a previously formed dry lipid film with a suspension of chitosan nanoparticles, and the other relying on the lyophilization of both basic structures (nanoparticles and liposomes) with a subsequent step of hydration with water. The developed systems are able to provide a controlled release of the encapsulated model peptide, insulin, evidencing release profiles that are dependent on their lipid composition. Moreover, satisfactory in vivo results have been obtained, confirming the potential of these newly developed drug delivery systems as drug carriers through distinct mucosal routes.

  15. Au nanoinjectors for electrotriggered gene delivery into the cell nucleus.

    Science.gov (United States)

    Kang, Mijeong; Kim, Bongsoo

    2015-01-01

    Intracellular delivery of exogenous materials is an essential technique required for many fundamental biological researches and medical treatments. As our understanding of cell structure and function has been improved and diverse therapeutic agents with a subcellular site of action have been continuously developed, there is a demand to enhance the performance of delivering devices. Ideal intracellular delivery devices should convey various kinds of exogenous materials without deteriorating cell viability regardless of cell type and, furthermore, precisely control the location and the timing of delivery as well as the amount of delivered materials for advanced researches.In this chapter the development of a new intracellular delivery device, a nanoinjector made of a Au (gold) nanowire (a Au nanoinjector) is described in which delivery is triggered by external application of an electric pulse. As a model study, a gene was delivered directly into the nucleus of a neuroblastoma cell, and successful delivery without cell damage was confirmed by the expression of the delivered gene. The insertion of a Au nanoinjector directly into a cell can be generally applied to any kind of cell, and a high degree of surface modification of Au allows attachment of diverse materials such as proteins, small molecules, or nanoparticles as well as genes on Au nanoinjectors. This expands their applicability, and it is expected that they will provide important information on the effects of delivered exogenous materials and consequently contribute to the development of related therapeutic or clinical technologies.

  16. Oral delivery of Bacillus subtilis spores expressing cysteine protease of Clonorchis sinensis to grass carp (Ctenopharyngodon idellus): Induces immune responses and has no damage on liver and intestine function.

    Science.gov (United States)

    Tang, Zeli; Sun, Hengchang; Chen, TingJin; Lin, Zhipeng; Jiang, Hongye; Zhou, Xinyi; Shi, Cunbin; Pan, Houjun; Chang, Ouqin; Ren, Pengli; Yu, Jinyun; Li, Xuerong; Xu, Jin; Huang, Yan; Yu, Xinbing

    2017-05-01

    Clonorchis sinensis (C. sinensis) is a fish-borne trematode. Human can be infected by ingestion of C. sinensis metacercariae parasitized in grass carp (Ctenopharyngodon idella). For induction of effective oral immune responses, spores of Bacillus subtilis (B. subtilis) WB600 were utilized as vehicle to delivery CsCP (cysteine protease of C. sinensis) cooperated with CotC (B.s-CotC-CP), one of coat proteins, to the gastrointestinal tract. After routine culture of 8-12 h in LB medium, B. subtilis containing CotC-CsCP was transferred into the sporulation culture medium. SDS-PAGE, western blotting and the growth curve indicated that the best sporulation time of recombinant WB600 was 24-30 h at 37 °C with continuous shaking (250 rpm). Grass carp were fed with three levels of B.s-CotC-CP (1 × 10 6 , 1 × 10 7 , and 1 × 10 8  CFU g -1 ) incorporated in the basal pellets diet. The commercial pellets or supplemented with spores just expressing CotC (1 × 10 7  CFU g -1 ) were served as control diet. Our results showed that grass carp orally immunized with the feed-based B.s-CotC-CP developed a strong specific immune response with significantly (P sinensis in fish body. Therefore, this study demonstrated that the feed-based recombinant spores could trigger high levels of mucosal and humoral immunity, and would be a promising candidate vaccine against C. sinensis metacercariae formation in freshwater fish. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. [Delivery of the IUGR fetus].

    Science.gov (United States)

    Perrotin, F; Simon, E G; Potin, J; Laffon, M

    2013-12-01

    The purpose of this paper is to review available data regarding the management of delivery in intra uterine growth retarded fetuses and try to get recommendations for clinical obstetrical practice. Bibliographic research performed by consulting PubMed database and recommendations from scientific societies with the following words: small for gestational age, intra-uterine growth restriction, fetal growth restriction, very low birth weight infants, as well as mode of delivery, induction of labor, cesarean section and operative delivery. The diagnosis of severe IUGR justifies the orientation of the patient to a referral centre with all necessary resources for very low birth weight or premature infants Administration of corticosteroids for fetal maturation (before 34 WG) and a possible neuroprotective treatment by with magnesium sulphate (before 32-33 WG) should be discussed. Although elective caesarean section is common, there is no current evidence supporting the use of systematic cesarean section, especially when the woman is in labor. Induction of labor, even with unfavorable cervix is possible under continuous FHR monitoring, in favorable obstetric situations and in the absence of severe fetal hemodynamic disturbances. Instrumental delivery and routine episiotomy are not recommended. For caesarean section under spinal anesthesia, an adequate anesthetic management must ensure the maintenance of basal blood pressure. Compared with appropriate for gestational age fetus, IUGR fetus is at increased risk of metabolic acidosis or perinatal asphyxia during delivery. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  18. Buccal and sublingual vaccine delivery.

    Science.gov (United States)

    Kraan, Heleen; Vrieling, Hilde; Czerkinsky, Cecil; Jiskoot, Wim; Kersten, Gideon; Amorij, Jean-Pierre

    2014-09-28

    Because of their large surface area and immunological competence, mucosal tissues are attractive administration and target sites for vaccination. An important characteristic of mucosal vaccination is its ability to elicit local immune responses, which act against infection at the site of pathogen entry. However, mucosal surfaces are endowed with potent and sophisticated tolerance mechanisms to prevent the immune system from overreacting to the many environmental antigens. Hence, mucosal vaccination may suppress the immune system instead of induce a protective immune response. Therefore, mucosal adjuvants and/or special antigen delivery systems as well as appropriate dosage forms are required in order to develop potent mucosal vaccines. Whereas oral, nasal and pulmonary vaccine delivery strategies have been described extensively, the sublingual and buccal routes have received considerably less attention. In this review, the characteristics of and approaches for sublingual and buccal vaccine delivery are described and compared with other mucosal vaccine delivery sites. We discuss recent progress and highlight promising developments in the search for vaccine formulations, including adjuvants and suitable dosage forms, which are likely critical for designing a successful sublingual or buccal vaccine. Finally, we outline the challenges, hurdles to overcome and formulation issues relevant for sublingual or buccal vaccine delivery. Copyright © 2014. Published by Elsevier B.V.

  19. Aerosol delivery in intubated, mechanically ventilated patients

    International Nuclear Information System (INIS)

    MacIntyre, N.R.; Silver, R.M.; Miller, C.W.; Schuler, F.; Coleman, R.E.

    1985-01-01

    To study the effects of respiratory failure and mechanical ventilation on aerosol delivery to the lungs, nuclear scans were performed after aerosolization of 5 to 9 mCi of Tc-99m diethylenetriamine pentaacetic acid in seven stable, intubated, and mechanically ventilated patients. The radioactivity reaching the lungs was 2.9 +/- .7% (mean +/- SD) of the administered dose, an amount significantly less than that in three healthy nonintubated subjects and also less than what would be expected in nonintubated subjects from other published reports. A subsequent study was performed in 15 additional mechanically ventilated patients who were receiving aerosolized bronchodilators through their endotracheal tube. In these patients, heart rate and lung mechanical function values before and after treatment were not significantly different. It is concluded from these studies that aerosol delivery in mechanically ventilated patients is significantly reduced and that this is probably due to a combination of suboptimal breathing pattern, intrinsic airway disease, and the endotracheal tube functioning as both a site for aerosol deposition through impaction as well as a barrier to gastrointestinal absorption

  20. Oral Drug Delivery Systems Comprising Altered Geometric Configurations for Controlled Drug Delivery

    Directory of Open Access Journals (Sweden)

    Priya Bawa

    2011-12-01

    Full Text Available Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments.

  1. Albumin-based drug delivery

    DEFF Research Database (Denmark)

    Larsen, Maja Thim; Kuhlmann, Matthias; Hvam, Michael Lykke

    2016-01-01

    The effectiveness of a drug is dependent on accumulation at the site of action at therapeutic levels, however, challenges such as rapid renal clearance, degradation or non-specific accumulation requires drug delivery enabling technologies. Albumin is a natural transport protein with multiple ligand...... binding sites, cellular receptor engagement, and a long circulatory half-life due to interaction with the recycling neonatal Fc receptor. Exploitation of these properties promotes albumin as an attractive candidate for half-life extension and targeted intracellular delivery of drugs attached by covalent...... conjugation, genetic fusions, association or ligand-mediated association. This review will give an overview of albumin-based products with focus on the natural biological properties and molecular interactions that can be harnessed for the design of a next-generation drug delivery platform....

  2. Polymer architecture and drug delivery.

    Science.gov (United States)

    Qiu, Li Yan; Bae, You Han

    2006-01-01

    Polymers occupy a major portion of materials used for controlled release formulations and drug-targeting systems because this class of materials presents seemingly endless diversity in topology and chemistry. This is a crucial advantage over other classes of materials to meet the ever-increasing requirements of new designs of drug delivery formulations. The polymer architecture (topology) describes the shape of a single polymer molecule. Every natural, seminatural, and synthetic polymer falls into one of categorized architectures: linear, graft, branched, cross-linked, block, star-shaped, and dendron/dendrimer topology. Although this topic spans a truly broad area in polymer science, this review introduces polymer architectures along with brief synthetic approaches for pharmaceutical scientists who are not familiar with polymer science, summarizes the characteristic properties of each architecture useful for drug delivery applications, and covers recent advances in drug delivery relevant to polymer architecture.

  3. Assistive Technology Service Delivery in Rural School Districts

    Science.gov (United States)

    Ault, Melinda Jones; Bausch, Margaret E.; Mclaren, Elizabeth M.

    2013-01-01

    Little is known about the implementation of assistive technology (AT) services for students in rural areas. This study investigated the AT service delivery in 10 rural districts across six states. The results indicated that students use AT across functional areas, but considerably fewer number of devices than do those not living in rural areas. AT…

  4. Atom sharp needles, the missing link in microneedle drug delivery

    NARCIS (Netherlands)

    Wissink, J.; Berenschot, Johan W.; Tas, Niels Roelof

    2008-01-01

    The skin barrier function is a major challenge for delivery of drugs via the skin. Located in the outermost layer of the skin, the stratum corneum (SC) consists of dead cells embedded in lipid regions, only 10-20 microm thick, tough but flexible and elastic. Hyperdermic needles penetrate the skin

  5. Cesarean delivery on maternal request.

    Science.gov (United States)

    Viswanathan, Meera; Visco, Anthony G; Hartmann, Katherine; Wechter, Mary Ellen; Gartlehner, Gerald; Wu, Jennifer M; Palmieri, Rachel; Funk, Michele Jonsson; Lux, Linda; Swinson, Tammeka; Lohr, Kathleen N

    2006-03-01

    The RTI International-University of North Carolina at Chapel Hill Evidence-based Practice Center (RTI-UNC EPC) systematically reviewed the evidence on the trend and incidence of cesarean delivery (CD) in the United States and in other developed countries, maternal and infant outcomes of cesarean delivery on maternal request (CDMR) compared with planned vaginal delivery (PVD), factors affecting the magnitude of the benefits and harms of CDMR, and future research directions. We searched MEDLINE, Cochrane Collaboration resources, and Embase and identified 1,406 articles to examine against a priori inclusion criteria. We included studies published from 1990 to the present, written in English. Studies had to include comparison between the key reference group (CDMR or proxies) and PVD. A primary reviewer abstracted detailed data on key variables from included articles; a second senior reviewer confirmed accuracy. We identified 13 articles for trends and incidence of CD, 54 for maternal and infant outcomes, and 5 on modifiers of CDMR. The incidence of CDMR appears to be increasing. However, accurately assessing either its true incidence or trends over time is difficult because currently CDMR is neither a well-recognized clinical entity nor an accurately reported indication for diagnostic coding or reimbursement. Virtually no studies exist on CDMR, so the knowledge base rests chiefly on indirect evidence from proxies possessing unique and significant limitations. Furthermore, most studies compared outcomes by actual routes of delivery, resulting in great uncertainty as to their relevance to planned routes of delivery. Primary CDMR and planned vaginal delivery likely do differ with respect to individual outcomes for either mothers or infants. However, our comprehensive assessment, across many different outcomes, suggests that no major differences exist between primary CDMR and planned vaginal delivery, but the evidence is too weak to conclude definitively that differences

  6. Influencia del tamaño del balón y la altura de la canasta en la eficacia del lanzamiento en categoría pre-infantil (11-12 años femenina.[Influence of ball size and basket height in the effectiveness of the shooting in femalepre-child level (11-12 years

    Directory of Open Access Journals (Sweden)

    María Teresa Gutiérrez Colón

    2010-03-01

    Full Text Available Resumen El objetivo de este estudio es conocer cuáles son las mejores condiciones de aprendizaje del lanzamiento a canasta en baloncesto en la etapa pre-infantil. En esta etapa existe un cambio brusco para el niño en función del tamaño del equipamiento, que exige realizar un proceso de adaptación progresivo de las dimensiones del balón y de la canasta, permitiendo que los jugadores tengan un aprendizaje más adecuado y adaptado a sus características. La muestra estuvo formada por 12 jugadoras pre-infantiles (11-12 años, pertenecientes a un equipo de baloncesto femenino. Se analizó la eficacia de los lanzamientos a canasta en función del tamaño del balón y la altura de la canasta, así como de la posición del lanzamiento, antes y después de un proceso de intervención. Los resultados mostraron que al inicio del proceso existían diferencias en la eficacia de los lanzamientos. Las jugadoras eran más eficaces lanzando con balón minibasket (numero 5 y canasta de minibasket que con los del juego adulto (numero 6. Finalmente, tras el proceso de intervención los resultados mostraron como las jugadoras aumentan su eficacia cuando lanzan con balón y canasta grande con respecto al inicio de la temporada. Además, en el pos-test obtuvieron mayores valores de eficacia con este material que con el balón y la canasta pequeña. Palabras clave: baloncesto, pre-infantil, eficacia, lanzamiento, tamaño de balón, altura de la canasta.Abstract The aim of this study is to know which are learning best conditions of the shooting basketball in the phase pre-child. In this phase is a sharp change for the boy depending on the size of the equipment, that demands to carry out a progressive adaptation process of dimensions of the ball and of the basket, allowing that players have a more suitable and adapted learning to his characteristics. The sample was formed by 12 players pre-child (11-12 years, belonging an equipment from feminine basketball. The

  7. Image-guided, targeted and triggered drug delivery to tumors using polymer-based microbubbles.

    NARCIS (Netherlands)

    Fokong, S.; Theek, B.; Koczera, P.; Appold, L.; Resch-Genger, U.; van Zandvoort, M.; Storm, Gerrit; Kiessling, F.; Lammers, Twan Gerardus Gertudis Maria

    2012-01-01

    Abstract Microbubbles (MB) are routinely used contrast agents for functional and molecular ultrasound (US) imaging. In addition, they have been attracting more and more attention for drug delivery purposes, enabling e.g. US-mediated drug delivery across biological barriers and US-induced triggered

  8. Aptamer-Gated Nanoparticles for Smart Drug Delivery

    Directory of Open Access Journals (Sweden)

    Huseyin Avni Oktem

    2011-08-01

    Full Text Available Aptamers are functional nucleic acid sequences which can bind specific targets. An artificial combinatorial methodology can identify aptamer sequences for any target molecule, from ions to whole cells. Drug delivery systems seek to increase efficacy and reduce side-effects by concentrating the therapeutic agents at specific disease sites in the body. This is generally achieved by specific targeting of inactivated drug molecules. Aptamers which can bind to various cancer cell types selectively and with high affinity have been exploited in a variety of drug delivery systems for therapeutic purposes. Recent progress in selection of cell-specific aptamers has provided new opportunities in targeted drug delivery. Especially functionalization of nanoparticles with such aptamers has drawn major attention in the biosensor and biomedical areas. Moreover, nucleic acids are recognized as an attractive building materials in nanomachines because of their unique molecular recognition properties and structural features. A active controlled delivery of drugs once targeted to a disease site is a major research challenge. Stimuli-responsive gating is one way of achieving controlled release of nanoparticle cargoes. Recent reports incorporate the structural properties of aptamers in controlled release systems of drug delivering nanoparticles. In this review, the strategies for using functional nucleic acids in creating smart drug delivery devices will be explained. The main focus will be on aptamer-incorporated nanoparticle systems for drug delivery purposes in order to assess the future potential of aptamers in the therapeutic area. Special emphasis will be given to the very recent progress in controlled drug release based on molecular gating achieved with aptamers.

  9. Vaginal Birth After Cesarean Delivery: Deciding on a Trial of Labor After a Cesarean Delivery (TOLAC)

    Science.gov (United States)

    f AQ FREQUENTLY ASKED QUESTIONS FAQ070 LABOR, DELIVERY, AND POSTPARTUM CARE Vaginal Birth After Cesarean Delivery • What is a vaginal birth after cesarean delivery (VBAC)? • What is a trial of labor ...

  10. Document Delivery: Evaluating the Options.

    Science.gov (United States)

    Ward, Suzanne M.

    1997-01-01

    Discusses options available to libraries for document delivery. Topics include users' needs; cost; copyright compliance; traditional interlibrary loan; types of suppliers; selection criteria, including customer service; new developments in interlibrary loan, including outsourcing arrangements; and the need to evaluate suppliers. (LRW)

  11. Advances in buccal drug delivery.

    Science.gov (United States)

    Birudaraj, Raj; Mahalingam, Ravichandran; Li, Xiaoling; Jasti, Bhaskara R

    2005-01-01

    The buccal route offers an attractive alternative for systemic drug delivery of drugs because of better patient compliance, ease of dosage form removal in emergencies, robustness, and good accessibility. Use of buccal mucosa for drug absorption was first attempted by Sobrero in 1847, and since then much research was done to deliver drugs through this route. Today, research is more focused on the development of suitable delivery devices, permeation enhancement, and buccal delivery of drugs that undergo a first-pass effect, such as cardiovascular drugs, analgesics, and peptides. In addition, studies have been conducted on the development of controlled or slow release delivery systems for systemic and local therapy of diseases in the oral cavity. In this review, the anatomy and physiology of buccal mucosa, followed by discussion of recent literature on the buccal permeation enhancement, and pathways of enhancement for various molecules are detailed. In addition, bioadhesion theories from historic perspective and current status are discussed. The various dosage forms on the market and in different stages of development are also reviewed.

  12. Transdermal Spray in Hormone Delivery

    African Journals Online (AJOL)

    market for the delivery system and ongoing development of transdermal sprays for hormone ... (DOAJ), African Journal Online, Bioline International, Open-J-Gate and Pharmacy Abstracts ... patches and gels have been very popular owing ... This product was developed for ... In a safety announcement, the US Food and.

  13. Biomaterials for drug delivery patches.

    Science.gov (United States)

    Santos, Lúcia F; Correia, Ilídio J; Silva, A Sofia; Mano, João F

    2018-06-15

    The limited efficiency of conventional drugs has been instigated the development of new and more effective drug delivery systems (DDS). Transdermal DDS, are associated with numerous advantages such its painless application and less frequent replacement and greater flexibility of dosing, features that triggered the research and development of such devices. Such systems have been produced using either biopolymer; or synthetic polymers. Although the first ones are safer, biocompatible and present a controlled degradation by human enzymes or water, the second ones are the most currently available in the market due to their greater mechanical resistance and flexibility, and non-degradation over time. This review highlights the most recent advances (mainly in the last five years) of patches aimed for transdermal drug delivery, focusing on the different materials (natural, synthetic and blends) and latest designs for the development of such devices, emphasizing also their combination with drug carriers that enable enhanced drug solubility and a more controlled release of the drug over the time. The benefits and limitations of different patches formulations are considered with reference to their appliance to transdermal drug delivery. Furthermore, a record of the currently available patches on the market is given, featuring their most relevant characteristics. Finally, a list of most recent/ongoing clinical trials regarding the use of patches for skin disorders is detailed and critical insights on the current state of patches for transdermal drug delivery are also provided. Copyright © 2018. Published by Elsevier B.V.

  14. Software Build and Delivery Systems

    Energy Technology Data Exchange (ETDEWEB)

    Robey, Robert W. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-07-10

    This presentation deals with the hierarchy of software build and delivery systems. One of the goals is to maximize the success rate of new users and developers when first trying your software. First impressions are important. Early successes are important. This also reduces critical documentation costs. This is a presentation focused on computer science and goes into detail about code documentation.

  15. Microcontainers for Intestinal Drug Delivery

    DEFF Research Database (Denmark)

    Tentor, Fabio; Mazzoni, Chiara; Keller, Stephan Sylvest

    Among all the drug administration routes, the oral one is the most preferred by the patients being less invasive, faster and easier. Oral drug delivery systems designed to target the intestine are produced by powder technology and capsule formulations. Those systems including micro- and nano...

  16. Enabling Anticancer Therapeutics by Nanoparticle Carriers: The Delivery of Paclitaxel

    Directory of Open Access Journals (Sweden)

    Bing Yan

    2011-07-01

    Full Text Available Anticancer drugs, such as paclitaxel (PTX, are indispensable for the treatment of a variety of malignancies. However, the application of most drugs is greatly limited by the low water solubility, poor permeability, or high efflux from cells. Nanoparticles have been widely investigated to enable drug delivery due to their low toxicity, sustained drug release, molecular targeting, and additional therapeutic and imaging functions. This review takes paclitaxel as an example and compares different nanoparticle-based delivery systems for their effectiveness in cancer chemotherapy.

  17. Preparing and evaluating delivery systems for proteins

    DEFF Research Database (Denmark)

    Jorgensen, L; Moeller, E H; van de Weert, M

    2006-01-01

    From a formulation perspective proteins are complex and therefore challenging molecules to develop drug delivery systems for. The success of a formulation depends on the ability of the protein to maintain the native structure and activity during preparation and delivery as well as during shipping...... and long-term storage of the formulation. Therefore, the development and evaluation of successful and promising drug delivery systems is essential. In the present review, some of the particulate drug delivery systems for parenteral delivery of protein are presented and discussed. The challenge...... for incorporation of protein in particulate delivery systems is exemplified by water-in-oil emulsions....

  18. Oral transmucosal delivery of naratriptan.

    Science.gov (United States)

    Sattar, Mohammed; Lane, Majella E

    2016-11-30

    Naratriptan (NAR) is currently used as the hydrochloride salt (NAR.HCl) for the treatment of migraine and is available in tablet dosage forms for oral administration. Buccal drug delivery offers a number of advantages compared with conventional oral delivery including rapid absorption, avoidance of first pass metabolism and improved patient compliance. We have previously prepared and characterised the base form of NAR and shown that it has more favourable properties for buccal delivery compared with NAR.HCl. This study describes the design and evaluation of a range of formulations for oral transmucosal delivery of NAR base. Permeation studies were conducted using excised porcine buccal tissue mounted in Franz cells. Of the neat solvents examined, Transcutol ® P (TC) showed the greatest enhancement effects and was the vehicle in which NAR was most soluble. The mechanisms by which TC might promote permeation were further probed using binary systems containing TC with either buffer or Miglyol 812 ® (MG). Mass balance studies were also conducted for these systems. The permeation of TC as well as NAR was also monitored for TC:MG formulations. Overall, TC appears to promote enhanced membrane permeation of NAR because of its rapid uptake into the buccal tissue. Synergistic enhancement of buccal permeation was observed when TC was combined with MG and this is attributed to the increased thermodynamic activity of NAR in these formulations. Significantly enhanced permeation of NAR was achieved for TC:MG and this was also associated with less TC remaining on the tissue or in the tissue at the end of the experiment. To our knowledge this is the first report where both enhancer and active have been monitored in buccal permeation studies. The findings underline the importance of understanding the fate of vehicle components for rational formulation design of buccal delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Quality correction factors of composite IMRT beam deliveries: Theoretical considerations

    International Nuclear Information System (INIS)

    Bouchard, Hugo

    2012-01-01

    Purpose: In the scope of intensity modulated radiation therapy (IMRT) dosimetry using ionization chambers, quality correction factors of plan-class-specific reference (PCSR) fields are theoretically investigated. The symmetry of the problem is studied to provide recommendable criteria for composite beam deliveries where correction factors are minimal and also to establish a theoretical limit for PCSR delivery k Q factors. Methods: The concept of virtual symmetric collapsed (VSC) beam, being associated to a given modulated composite delivery, is defined in the scope of this investigation. Under symmetrical measurement conditions, any composite delivery has the property of having a k Q factor identical to its associated VSC beam. Using this concept of VSC, a fundamental property of IMRT k Q factors is demonstrated in the form of a theorem. The sensitivity to the conditions required by the theorem is thoroughly examined. Results: The theorem states that if a composite modulated beam delivery produces a uniform dose distribution in a volume V cyl which is symmetric with the cylindrical delivery and all beams fulfills two conditions in V cyl : (1) the dose modulation function is unchanged along the beam axis, and (2) the dose gradient in the beam direction is constant for a given lateral position; then its associated VSC beam produces no lateral dose gradient in V cyl , no matter what beam modulation or gantry angles are being used. The examination of the conditions required by the theorem lead to the following results. The effect of the depth-dose gradient not being perfectly constant with depth on the VSC beam lateral dose gradient is found negligible. The effect of the dose modulation function being degraded with depth on the VSC beam lateral dose gradient is found to be only related to scatter and beam hardening, as the theorem holds also for diverging beams. Conclusions: The use of the symmetry of the problem in the present paper leads to a valuable theorem showing

  20. Vector-free intracellular delivery by reversible permeabilization.

    Directory of Open Access Journals (Sweden)

    Shirley O'Dea

    Full Text Available Despite advances in intracellular delivery technologies, efficient methods are still required that are vector-free, can address a wide range of cargo types and can be applied to cells that are difficult to transfect whilst maintaining cell viability. We have developed a novel vector-free method that uses reversible permeabilization to achieve rapid intracellular delivery of cargos with varying composition, properties and size. A permeabilizing delivery solution was developed that contains a low level of ethanol as the permeabilizing agent. Reversal of cell permeabilization is achieved by temporally and volumetrically controlling the contact of the target cells with this solution. Cells are seeded in conventional multi-well plates. Following removal of the supernatant, the cargo is mixed with the delivery solution and applied directly to the cells using an atomizer. After a short incubation period, permeabilization is halted by incubating the cells in a phosphate buffer saline solution that dilutes the ethanol and is non-toxic to the permeabilized cells. Normal culture medium is then added. The procedure lasts less than 5 min. With this method, proteins, mRNA, plasmid DNA and other molecules have been delivered to a variety of cell types, including primary cells, with low toxicity and cargo functionality has been confirmed in proof-of-principle studies. Co-delivery of different cargo types has also been demonstrated. Importantly, delivery occurs by diffusion directly into the cytoplasm in an endocytic-independent manner. Unlike some other vector-free methods, adherent cells are addressed in situ without the need for detachment from their substratum. The method has also been adapted to address suspension cells. This delivery method is gentle yet highly reproducible, compatible with high throughput and automated cell-based assays and has the potential to enable a broad range of research, drug discovery and clinical applications.

  1. Silk Electrogel Based Gastroretentive Drug Delivery System

    Science.gov (United States)

    Wang, Qianrui

    Gastric cancer has become a global pandemic and there is imperative to develop efficient therapies. Oral dosing strategy is the preferred route to deliver drugs for treating the disease. Recent studies suggested silk electro hydrogel, which is pH sensitive and reversible, has potential as a vehicle to deliver the drug in the stomach environment. The aim of this study is to establish in vitro electrogelation e-gel based silk gel as a gastroretentive drug delivery system. We successfully extended the duration of silk e-gel in artificial gastric juice by mixing silk solution with glycerol at different ratios before the electrogelation. Structural analysis indicated the extended duration was due to the change of beta sheet content. The glycerol mixed silk e-gel had good doxorubicin loading capability and could release doxorubicin in a sustained-release profile. Doxorubicin loaded silk e-gels were applied to human gastric cancer cells. Significant cell viability decrease was observed. We believe that with further characterization as well as functional analysis, the silk e-gel system has the potential to become an effective vehicle for gastric drug delivery applications.

  2. Drug Delivery Nanoparticles in Skin Cancers

    Science.gov (United States)

    Dianzani, Chiara; Zara, Gian Paolo; Maina, Giovanni; Pettazzoni, Piergiorgio; Pizzimenti, Stefania; Rossi, Federica; Gigliotti, Casimiro Luca; Ciamporcero, Eric Stefano; Daga, Martina; Barrera, Giuseppina

    2014-01-01

    Nanotechnology involves the engineering of functional systems at nanoscale, thus being attractive for disciplines ranging from materials science to biomedicine. One of the most active research areas of the nanotechnology is nanomedicine, which applies nanotechnology to highly specific medical interventions for prevention, diagnosis, and treatment of diseases, including cancer disease. Over the past two decades, the rapid developments in nanotechnology have allowed the incorporation of multiple therapeutic, sensing, and targeting agents into nanoparticles, for detection, prevention, and treatment of cancer diseases. Nanoparticles offer many advantages as drug carrier systems since they can improve the solubility of poorly water-soluble drugs, modify pharmacokinetics, increase drug half-life by reducing immunogenicity, improve bioavailability, and diminish drug metabolism. They can also enable a tunable release of therapeutic compounds and the simultaneous delivery of two or more drugs for combination therapy. In this review, we discuss the recent advances in the use of different types of nanoparticles for systemic and topical drug delivery in the treatment of skin cancer. In particular, the progress in the treatment with nanocarriers of basal cell carcinoma, squamous cell carcinoma, and melanoma has been reported. PMID:25101298

  3. Fluorescence optical imaging in anticancer drug delivery.

    Science.gov (United States)

    Etrych, Tomáš; Lucas, Henrike; Janoušková, Olga; Chytil, Petr; Mueller, Thomas; Mäder, Karsten

    2016-03-28

    In the past several decades, nanosized drug delivery systems with various targeting functions and controlled drug release capabilities inside targeted tissues or cells have been intensively studied. Understanding their pharmacokinetic properties is crucial for the successful transition of this research into clinical practice. Among others, fluorescence imaging has become one of the most commonly used imaging tools in pre-clinical research. The development of increasing numbers of suitable fluorescent dyes excitable in the visible to near-infrared wavelengths of the spectrum has significantly expanded the applicability of fluorescence imaging. This paper focuses on the potential applications and limitations of non-invasive imaging techniques in the field of drug delivery, especially in anticancer therapy. Fluorescent imaging at both the cellular and systemic levels is discussed in detail. Additionally, we explore the possibility for simultaneous treatment and imaging using theranostics and combinations of different imaging techniques, e.g., fluorescence imaging with computed tomography. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Diatomite silica nanoparticles for drug delivery.

    Science.gov (United States)

    Ruggiero, Immacolata; Terracciano, Monica; Martucci, Nicola M; De Stefano, Luca; Migliaccio, Nunzia; Tatè, Rosarita; Rendina, Ivo; Arcari, Paolo; Lamberti, Annalisa; Rea, Ilaria

    2014-01-01

    Diatomite is a natural fossil material of sedimentary origin, constituted by fragments of diatom siliceous skeletons. In this preliminary work, the properties of diatomite nanoparticles as potential system for the delivery of drugs in cancer cells were exploited. A purification procedure, based on thermal treatments in strong acid solutions, was used to remove inorganic and organic impurities from diatomite and to make them a safe material for medical applications. The micrometric diatomite powder was reduced in nanoparticles by mechanical crushing, sonication, and filtering. Morphological analysis performed by dynamic light scattering and transmission electron microscopy reveals a particles size included between 100 and 300 nm. Diatomite nanoparticles were functionalized by 3-aminopropyltriethoxysilane and labeled by tetramethylrhodamine isothiocyanate. Different concentrations of chemically modified nanoparticles were incubated with cancer cells and confocal microscopy was performed. Imaging analysis showed an efficient cellular uptake and homogeneous distribution of nanoparticles in cytoplasm and nucleus, thus suggesting their potentiality as nanocarriers for drug delivery. 87.85.J81.05.Rm; 61.46. + w.

  5. Thiolated chitosans: useful excipients for oral drug delivery.

    Science.gov (United States)

    Werle, Martin; Bernkop-Schnürch, Andreas

    2008-03-01

    To improve the bioavailability of orally administered drugs, formulations based on polymers are of great interest for pharmaceutical technologists. Thiolated chitosans are multifunctional polymers that exhibit improved mucoadhesive, cohesive and permeation-enhancing as well as efflux-pump-inhibitory properties. They can be synthesized by derivatization of the primary amino groups of chitosan with coupling reagents bearing thiol functions. Various data gained in-vitro as well as in-vivo studies clearly demonstrate the potential of thiolated chitosans for oral drug delivery. Within the current review, the synthesis and characterization of thiolated chitosans so far developed is summarized. Features of thiolated chitosans important for oral drug delivery are discussed as well. Moreover, different formulation approaches, such as matrix tablets and micro-/nanoparticles, as well as the applicability of thiolated chitosans for the oral delivery of various substance classes including peptides and efflux pump substrates, are highlighted.

  6. A high-density lipoprotein-mediated drug delivery system.

    Science.gov (United States)

    Mo, Zhong-Cheng; Ren, Kun; Liu, Xing; Tang, Zhen-Li; Yi, Guang-Hui

    2016-11-15

    High-density lipoprotein (HDL) is a comparatively dense and small lipoprotein that can carry lipids as a multifunctional aggregate in plasma. Several studies have shown that increasing the levels or improving the functionality of HDL is a promising target for treating a wide variety of diseases. Among lipoproteins, HDL particles possess unique physicochemical properties, including naturally synthesized physiological components, amphipathic apolipoproteins, lipid-loading and hydrophobic agent-incorporating characteristics, specific protein-protein interactions, heterogeneity, nanoparticles, and smaller size. Recently, the feasibility and superiority of using HDL particles as drug delivery vehicles have been of great interest. In this review, we summarize the structure, constituents, biogenesis, remodeling, and reconstitution of HDL drug delivery systems, focusing on their delivery capability, characteristics, applications, manufacturing, and drug-loading and drug-targeting characteristics. Finally, the future prospects are presented regarding the clinical application and challenges of using HDL as a pharmacodelivery carrier. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Connecting drug delivery reality to smart materials design.

    Science.gov (United States)

    Grainger, David W

    2013-09-15

    Inflated claims to both design and mechanistic novelty in drug delivery and imaging systems, including most nanotechnologies, are not supported by the generally poor translation of these systems to clinical efficacy. The "form begets function" design paradigm is seductive but perhaps over-simplistic in translation to pharmaceutical efficacy. Most innovations show few clinically important distinctions in their therapeutic benefits in relevant preclinical disease and delivery models, despite frequent claims to the contrary. Long-standing challenges in drug delivery issues must enlist more realistic, back-to-basics approaches to address fundamental materials properties in complex biological systems, preclinical test beds, and analytical methods to more reliably determine fundamental pharmaceutical figures of merit, including drug carrier purity and batch-batch variability, agent biodistribution, therapeutic index (safety), and efficacy. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Significant role of cationic polymers in drug delivery systems.

    Science.gov (United States)

    Farshbaf, Masoud; Davaran, Soodabeh; Zarebkohan, Amir; Annabi, Nasim; Akbarzadeh, Abolfazl; Salehi, Roya

    2017-11-06

    Cationic polymers are characterized as the macromolecules that possess positive charges, which can be either inherently in the polymer side chains and/or its backbone. Based on their origins, cationic polymers are divided in two category including natural and synthetic, in which the possessed positive charges are as result of primary, secondary or tertiary amine functional groups that could be protonated in particular situations. Cationic polymers have been employed commonly as drug delivery agents due to their superior encapsulation efficacy, enhanced bioavailability, low toxicity and improved release profile. In this paper, we focus on the most prominent examples of cationic polymers which have been revealed to be applicable in drug delivery systems and we also discuss their general synthesis and surface modification methods as well as their controlled release profile in drug delivery.

  9. ANAL SPHINCTER INJURIES (OASIS AT DELIVERY

    Directory of Open Access Journals (Sweden)

    Katja Jakopič

    2018-02-01

    feel the pressure but cannot hold bowel contents for long. IAS injury leads to complete inability to control passing of bowel contents. Perineal tears are classified to four degrees depending on tear depth. With first degree tear only vaginal mucosa is torn, second degree perineal muscles are damaged, third degree describes any tearing of anal sphincter and fourth of rectal mucosa. New guidelines recom- mend further classification of 3rd degree tears: 3a = 50 % EAS ruptured 3c = IAS rupture Ultrasound with anal plug is nowadays considered to be the golden standard for diagnosis and follow-up of anal sphincter injuries. Entire length of anal sphincter muscle is shown from U shaped puborectalis muscle to anus. IAS appears as hypo-echoic homogenous circle around rectal mucosa, while EAS appears as outer hyper- echoic heterogenous circle. Dur- ing voluntary contraction distance between ruptured ends of EAS enlarges. 3D ultrasound shows promising results but is not yet standardized. Anal sphincter manometry, pudendal nerve latency and EMG of anal sphincter also contribute valuable information on anal sphincter function and injuries. Risk factors are: fetal weight over 3500g, forceps delivery (but not vacuum extraction occipito-posterior presentation, shoulder dystocia, prolonged second stage of delivery, median episiotomy, previous anorectal surgery and maternal age over 35 years at first delivery are described as risk factors. Caesarean section prevents anal sphincter injuries. Studies show that restrictive use of mediolateral episiotomy in comparison to spontaneous delivery prevents anal sphincter injuries. Rectal examination prior to suturing perineal tears is essential for timely recognition of anal sphincter injuries. EAS appears more read while IAS smooth muscle has a lighter colour (white meat. Sphincter continuity can be palpated between index finger and thumb (pill-rolling motion and voluntary contraction felt. Immediately after delivery voluntary contraction can

  10. Filled carbon nanotubes in biomedical imaging and drug delivery.

    Science.gov (United States)

    Martincic, Markus; Tobias, Gerard

    2015-04-01

    Carbon nanotubes have been advocated as promising candidates in the biomedical field in the areas of diagnosis and therapy. In terms of drug delivery, the use of carbon nanotubes can overcome some limitations of 'free' drugs by improving the formulation of poorly water-soluble drugs, allowing targeted delivery and even enabling the co-delivery of two or more drugs for combination therapy. Two different approaches are currently being explored for the delivery of diagnostic and therapeutic agents by carbon nanotubes, namely attachment of the payload to the external sidewalls or encapsulation into the inner cavities. Although less explored, the latter confers additional stability to the chosen diagnostic or therapeutic agents, and leaves the backbone structure of the nanotubes available for its functionalization with dispersing and targeting moieties. Several drug delivery systems and diagnostic agents have been developed in the last years employing the inner tubular cavities of carbon nanotubes. The research discussed in this review focuses on the use of carbon nanotubes that contain in their interior drug molecules and diagnosis-related compounds. The approaches employed for the development of such nanoscale vehicles along with targeting and releasing strategies are discussed. The encapsulation of both biomedical contrast agents and drugs inside carbon nanotubes is further expanding the possibilities to allow an early diagnosis and treatment of diseases.

  11. Design of an Implantable Device for Ocular Drug Delivery

    Directory of Open Access Journals (Sweden)

    Jae-Hwan Lee

    2012-01-01

    Full Text Available Ocular diseases, such as, glaucoma, age-related macular degeneration (AMD, diabetic retinopathy, and retinitis pigmentosa require drug management in order to prevent blindness and affecting million of adults in USA and worldwide. There is an increasing need to develop devices for drug delivery to address ocular diseases. This study focuses on the design, simulation, and development of an implantable ocular drug delivery device consisting of micro-/nanochannels embedded between top and bottom covers with a drug reservoir made from polydimethylsiloxane (PDMS which is silicon-based organic and biodegradable polymer. Several simulations were carried out with six different micro-channel configurations in order to see the feasibility for ocular drug delivery applications. Based on the results obtained, channel design of osmotic I and osmotic II satisfied the diffusion rates required for ocular drug delivery. Finally, a prototype illustrating the three components of the drug delivery design is presented. In the future, the device will be tested for its functionality and diffusion characteristics.

  12. Nature engineered diatom biosilica as drug delivery systems.

    Science.gov (United States)

    Uthappa, U T; Brahmkhatri, Varsha; Sriram, G; Jung, Ho-Young; Yu, Jingxian; Kurkuri, Nikita; Aminabhavi, Tejraj M; Altalhi, Tariq; Neelgund, Gururaj M; Kurkuri, Mahaveer D

    2018-05-14

    Diatoms, unicellular photosynthetic algae covered with siliceous cell wall, are also called frustule. These are the most potential naturally available materials for the development of cost-effective drug delivery systems because of their excellent biocompatibility, high surface area, low cost and ease of surface modification. Mesoporous silica materials such as MCM-41 and SBA-15 have been extensively used in drug delivery area. Their synthesis is challenging, time consuming, requires toxic chemicals and are energy intensive, making the entire process expensive and non-viable. Therefore, it is necessary to explore alternative materials. Surprisingly, nature has provided some exciting materials called diatoms; biosilica is one such a material that can be potentially used as a drug delivery vehicle. The present review focuses on different types of diatom species used in drug delivery with respect to their structural properties, morphology, purification process and surface functionalization. In this review, recent advances along with their limitations as well as the future scope to develop them as potential drug delivery vehicles are discussed. Copyright © 2018. Published by Elsevier B.V.

  13. Sterile Product Packaging and Delivery Systems.

    Science.gov (United States)

    Akers, Michael J

    2015-01-01

    Both conventional and more advanced product container and delivery systems are the focus of this brief article. Six different product container systems will be discussed, plus advances in primary packaging for special delivery systems and needle technology.

  14. After vaginal delivery - in the hospital

    Science.gov (United States)

    After vaginal birth; Pregnancy - after vaginal delivery; Postpartum care - after vaginal delivery ... blood pressure, heart rate, and the amount of vaginal bleeding Check to make sure your uterus is ...

  15. Waste feed delivery test and evaluation plan

    Energy Technology Data Exchange (ETDEWEB)

    O' TOOLE, S.M.

    1999-09-30

    This plan documents the Waste Feed Delivery Program test and evaluation planning and implementation approach. The purpose of this document is to define and communicate the Waste Feed Delivery Program Test and Evaluation scope, objectives, planning and implementation approach.

  16. Waste feed delivery test and evaluation plan

    International Nuclear Information System (INIS)

    O'TOOLE, S.M.

    1999-01-01

    This plan documents the Waste Feed Delivery Program test and evaluation planning and implementation approach. The purpose of this document is to define and communicate the Waste Feed Delivery Program Test and Evaluation scope, objectives, planning and implementation approach

  17. Electronic Nicotine Delivery Systems Key Facts Infographic

    Data.gov (United States)

    U.S. Department of Health & Human Services — Explore the Electronic Nicotine Delivery Systems Key Facts Infographic which outlines key facts related to electronic nicotine delivery systems (ENDS), including...

  18. Ultrasound mediated nanoparticle drug delivery

    Science.gov (United States)

    Mullin, Lee B.

    Ultrasound is not only a powerful diagnostic tool, but also a promising therapeutic technology that can be used to improve localized drug delivery. Microbubble contrast agents are micron sized encapsulated gas filled bubbles that are administered intravenously. Originally developed to enhance ultrasound images, microbubbles are highly echogenic due to the gas core that provides a detectable impedance difference from the surrounding medium. The core also allows for controlled response of the microbubbles to ultrasound pulses. Microbubbles can be pushed using acoustic radiation force and ruptured using high pressures. Destruction of microbubbles can increase permeability at the cellular and vascular level, which can be advantageous for drug delivery. Advances in drug delivery methods have been seen with the introduction of nanoparticles, nanometer sized objects often carrying a drug payload. In chemotherapy, nanoparticles can deliver drugs to tumors while limiting systemic exposure due to abnormalities in tumor vasculature such large gaps between endothelial cells that allow nanoparticles to enter into the interstitial space; this is referred to as the enhanced permeability and retention (EPR) effect. However, this effect may be overestimated in many tumors. Additionally, only a small percentage of the injected dose accumulates in the tumor, which most the nanoparticles accumulating in the liver and spleen. It is hypothesized that combining the acoustic activity of an ultrasound contrast agent with the high payload and extravasation ability of a nanoparticle, localized delivery to the tumor with reduced systemic toxicity can be achieved. This method can be accomplished by either loading nanoparticles onto the shell of the microbubble or through a coadministration method of both nanoparticles and microbubbles. The work presented in this dissertation utilizes novel and commercial nanoparticle formulations, combined with microbubbles and a variety of ultrasound systems

  19. Ultrasound-guided drug delivery in cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chowdhury, Sayan Mullick; Lee, Tae Hwa; Willmann, Jugen K. [Dept. of Radiology, Stanford University School of Medicine, Stanford (United States)

    2017-07-15

    Recent advancements in ultrasound and microbubble (USMB) mediated drug delivery technology has shown that this approach can improve spatially confined delivery of drugs and genes to target tissues while reducing systemic dose and toxicity. The mechanism behind enhanced delivery of therapeutics is sonoporation, the formation of openings in the vasculature, induced by ultrasound-triggered oscillations and destruction of microbubbles. In this review, progress and challenges of USMB mediated drug delivery are summarized, with special focus on cancer therapy.

  20. Ultrasound-guided drug delivery in cancer

    Directory of Open Access Journals (Sweden)

    Sayan Mullick Chowdhury

    2017-07-01

    Full Text Available Recent advancements in ultrasound and microbubble (USMB mediated drug delivery technology has shown that this approach can improve spatially confined delivery of drugs and genes to target tissues while reducing systemic dose and toxicity. The mechanism behind enhanced delivery of therapeutics is sonoporation, the formation of openings in the vasculature, induced by ultrasound-triggered oscillations and destruction of microbubbles. In this review, progress and challenges of USMB mediated drug delivery are summarized, with special focus on cancer therapy.