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Sample records for functional delivery vehicle

  1. 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.

  2. 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

  3. 30 CFR 56.6802 - Bulk delivery vehicles.

    Science.gov (United States)

    2010-07-01

    ... Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Explosives Maintenance § 56.6802 Bulk delivery vehicles. No welding or cutting shall be performed on a bulk delivery vehicle...

  4. Magnetotactic Bacterial Cages as Safe and Smart Gene Delivery Vehicles

    KAUST Repository

    Alsaiari, Shahad K.

    2016-07-27

    In spite of the huge advances in the area of synthetic carriers, their efficiency still poorly compares to natural vectors. Herein, we report the use of unmodified magnetotactic bacteria as a guidable delivery vehicle for DNA functionalized gold nanoparticles (AuNPs). High cargo loading is established under anaerobic conditions (bacteria is alive) through endocytosis where AuNPs are employed as transmembrane proteins mimics (facilitate endocytosis) as well as imaging agents to verify and quantify loading and release. The naturally bio-mineralized magnetosomes, within the bacteria, induce heat generation inside bacteria through magnetic hyperthermia. Most importantly after exposing the system to air (bacteria is dead) the cell wall stays intact providing an efficient bacterial vessel. Upon incubation with THP-1 cells, the magnetotactic bacterial cages (MBCs) adhere to the cell wall and are directly engulfed through the phagocytic activity of these cells. Applying magnetic hyperthermia leads to the dissociation of the bacterial microcarrier and eventual release of cargo.

  5. Delivery of Unmanned Aerial Vehicle Data

    Science.gov (United States)

    Ivancic, William D.; Sullivan, Donald V.

    2011-01-01

    To support much of NASA's Upper Atmosphere Research Program science, NASA has acquired two Global Hawk Unmanned Aerial Vehicles (UAVs). Two major missions are currently planned using the Global Hawk: the Global Hawk Pacific (GloPac) and the Genesis and Rapid Intensification Processes (GRIP) missions. This paper briefly describes GloPac and GRIP, the concept of operations and the resulting requirements and communication architectures. Also discussed are requirements for future missions that may use satellite systems and networks owned and operated by third parties.

  6. 30 CFR 57.6802 - Bulk delivery vehicles.

    Science.gov (United States)

    2010-07-01

    ... Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND HEALTH SAFETY AND HEALTH STANDARDS-UNDERGROUND METAL AND NONMETAL MINES Explosives Maintenance-Surface and Underground § 57.6802 Bulk delivery vehicles. No welding or cutting shall be performed on a...

  7. Preactivated thiomers for vaginal drug delivery vehicles.

    Science.gov (United States)

    Friedl, Heike E; Dünnhaupt, Sarah; Waldner, Claudia; Bernkop-Schnürch, Andreas

    2013-10-01

    It was the purpose of this study to design and evaluate a chitosan derivative as mucoadhesive excipient for vaginal drug delivery systems. The chemical modification of chitosan was achieved by conjugation of thioglycolic acid (TGA) resulting in 1594 μmol thiol groups per gram of polymer followed by the linkage of mercaptonicotinic acid (MNA) to the immobilized thiol groups via disulfide bonding leading to 702 μmol ligand per gram of preactivated polymer. The mucoadhesive properties of these polymers within newly designed vaginal formulations (Chitosan-TGA and Chitosan-TGA-MNA) and commercially available vaginal formulations (Candibene®, Daktarin®, Dalacin®, GynoPevaryl®) were tested over a time period of 24 h via a mucoadhesion test system simulating vaginal conditions, tensile studies and mucus polymer interaction studies via viscosity measurements. Within the vaginal test system simulating vaginal in situ conditions, a 1.5-fold increase in mucoadhesion could be observed for preactivated thiomer formulations after 24 h in comparison to commercially available formulations. Similar results were achieved for tensile studies, as the chitosan-TGA-MNA containing formulation resulted in a 4.9-fold increase in total work of adhesion (TWA) in comparison to Candibene which showed the highest TWA value of all tested commercial formulations. Also in terms of rheology investigations of mucus/formulation mixtures, a 5.8-fold increase in dynamic viscosity for chitosan-TGA-MNA containing mixtures could be observed in comparison to the mucus-free control. In contrast, commercially available formulations achieved a maximum enhancement of 1.9-fold. These outcomes confirm that the newly developed polymer is a promising tool for vaginal drug delivery likely providing a prolonged vaginal residence time due to its comparatively high mucoadhesive properties. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges.

    Science.gov (United States)

    Ha, Dinh; Yang, Ningning; Nadithe, Venkatareddy

    2016-07-01

    Exosomes are small intracellular membrane-based vesicles with different compositions that are involved in several biological and pathological processes. The exploitation of exosomes as drug delivery vehicles offers important advantages compared to other nanoparticulate drug delivery systems such as liposomes and polymeric nanoparticles; exosomes are non-immunogenic in nature due to similar composition as body׳s own cells. In this article, the origin and structure of exosomes as well as their biological functions are outlined. We will then focus on specific applications of exosomes as drug delivery systems in pharmaceutical drug development. An overview of the advantages and challenges faced when using exosomes as a pharmaceutical drug delivery vehicles will also be discussed.

  9. A new memetic algorithm for solving split delivery vehicle routing problem

    Directory of Open Access Journals (Sweden)

    Ali Bozorgi-Amiri

    2015-11-01

    Full Text Available Split delivery vehicle routing problem is one of the traditional types of routing problems in which the demand of different points can be divided among vehicles and the objective is to minimize the path length, which vehicles travel. In this paper, fuel cost of vehicles which is assumed to be dependent on their traveled path and load is considered as the objective functions. Namely, the cost of the consumed fuel is proportionate to the unit of load carried per unit of distance. In order to solve the proposed model a new memetic algorithm is developed which has two rows. The performance of the proposed algorithm for 21 standard problems is compared with the optimum solutions obtained from mathematical programming standard solver and the solutions of the same algorithm with single row solution representation. The results express the efficiency of developed algorithm.

  10. Carbon nanotubes part I: preparation of a novel and versatile drug-delivery vehicle

    Science.gov (United States)

    Karimi, Mahdi; Solati, Navid; Amiri, Mohammad; Mirshekari, Hamed; Mohamed, Elmira; Taheri, Mahdiar; Hashemkhani, Mahshid; Saeidi, Ahad; Estiar, Mehrdad Asghari; Kiani, Parnian; Ghasemi, Amir; Basri, Seyed Masoud Moosavi; Aref, Amir R

    2015-01-01

    Introduction It is 23 years since carbon allotrope known as carbon nanotubes (CNT) was discovered by Iijima, who described them as “rolled graphite sheets inserted into each other”. Since then, CNTs have been studied in nanoelectronic devices. However, CNTs also possess the versatility to act as drug- and gene-delivery vehicles. Areas covered This review covers the synthesis, purification and functionalization of CNTs. Arc discharge, laser ablation and chemical vapor deposition are the principle synthesis methods. Non-covalent functionalization relies on attachment of biomolecules by coating the CNT with surfactants, synthetic polymers and biopolymers. Covalent functionalization often involves the initial introduction of carboxylic acids or amine groups, diazonium addition, 1,3-dipolar cycloaddition or reductive alkylation. The aim is to produce functional groups to attach the active cargo. Expert opinion In this review, the feasibility of CNT being used as a drug-delivery vehicle is explored. The molecular composition of CNT is extremely hydrophobic and highly aggregation-prone. Therefore, most of the efforts towards drug delivery has centered on chemical functionalization, which is usually divided in two categories; non-covalent and covalent. The biomedical applications of CNT are growing apace, and new drug-delivery technologies play a major role in these efforts. PMID:25601356

  11. METHOD OF CHOOSING THE TECHNOLOGY OF VEHICLE OPERATION ON DELIVERY ROUTES

    Directory of Open Access Journals (Sweden)

    Ye. Nagornyi

    2014-10-01

    Full Text Available A method for determining the technology of vehicles operation on delivery (team routes, which allows to determine the optimal sequence of cargo delivery to customers by vehicles of certain capacity in order to meet the requirements of cargo owners regarding the conditions of service is offered. Recommendations for creation of an automated system of forming the technology of vehicles operation on delivery routes are developed.

  12. Vehicle Motion Planning Using Stream Functions

    National Research Council Canada - National Science Library

    Waydo, Stephen

    2003-01-01

    ...) than previous methods. A method is developed for constructing analytic stream functions to produce arbitrary vehicle behaviors while avoiding obstacles, and an exact solution for the case of a single uniformly moving obstacle is presented...

  13. Silica nanoparticles as vehicles for therapy delivery in neurological injury

    Science.gov (United States)

    Schenk, Desiree

    Acrolein, a very reactive aldehyde, is a culprit in the biochemical cascade after primary, mechanical spinal cord injury (SCI), which leads to the destruction of tissue initially unharmed, referred to as "secondary injury". Additionally, in models of multiple sclerosis (MS) and some clinical research, acrolein levels are significantly increased. This aldehyde overwhelms the natural anti-oxidant system, reacts freely with proteins, and releases during lipid peroxidation (LPO), effectively regenerating its self. Due to its ability to make more copies of itself in the presence of tissue via lipid peroxidation, researchers believe that acrolein plays a role in the increased destruction of the central nervous system in both SCI and MS. Hydralazine, an FDA-approved hypertension drug, has been shown to scavenge acrolein, but its side effects and short half life at the appropriate dose for acrolein scavenging must be improved for beneficial clinical translation. Due to the inefficient delivery of therapeutic drugs, nanoparticles have become a major field of exploration for medical applications. Based on their material properties, they can help treat disease by delivering drugs to specific tissues, enhancing detection methods, or a mixture of both. Nanoparticles made from silica provide distinct advantages. They form porous networks that can carry therapeutic molecules throughout the body. Therefore, a nanomedical approach has been designed using silica nanoparticles as a porous delivery vehicle hydralazine. The silica nanoparticles are formed in a one-step method that incorporates poly(ethylene) glycol (PEG), a stealth molecule, directly onto the nanoparticles. As an additional avenue for study, a natural product in green tea, epigallocatechin gallate (EGCG), has been explored for its ability to react with acrolein, disabling its reactive capabilities. Upon demonstration of attenuating acrolein, EGCG's delivery may also be improved using the nanomedical approach. The

  14. HDL as a drug and nucleic acid delivery vehicle

    Directory of Open Access Journals (Sweden)

    Andras G Lacko

    2015-10-01

    Full Text Available This review is intended to evaluate the research findings and potential clinical applications of drug transport systems, developed based on the concepts of the structure/function and physiological role(s of high density lipoprotein=type nanoparticles. These macromolecules provide targeted transport of cholesteryl esters (a highly lipophilic payload in their natural/physiological environment. The property of accommodating highly water insoluble constituents in their core region enables HDL type nanoparticles to effectively transport hydrophobic drugs upon intravenous administration. Even though the application of reconstituted HDL in the treatment of a number of diseases is reviewed, the primary focus is on the application of HDL type drug delivery agents in cancer chemotherapy. The use of both native and synthetic HDL as drug delivery agents are compared to evaluate their respective potentials for commercial and clinical development. The current status and future perspectives for HDL type nanoparticles are discussed, including current obstacles and future applications in therapeutics.

  15. Cyclic delivery-scheduling problem with synchronization of vehicles\\' arrivals at logistic centers

    Directory of Open Access Journals (Sweden)

    Katarzyna Zofia Gdowska

    2015-12-01

    Full Text Available Background: In this paper a cyclic delivery-scheduling problem with vehicles serving fixed routes is presented. Each vehicle is assigned to one route to which some manufacturers' warehouses and logistics centers belong. A vehicle is to be loaded at a manufacturer's warehouse, then to deliver goods to a logistics center and may be also loaded there with other goods and to transport them to the next node along the route. One logistic center belongs to several routes, so the goods delivered by one vehicle may continue their journey by another truck. For every route the frequency of the vehicle is fixed and known. The objective here is to obtain such synchronization of vehicles arrivals in logistics centers, so that it is possible to organize their arrivals in repeatable blocks. Methods: In the paper the cyclic delivery-scheduling problem with vehicles serving fixed routes is formulated as a MIP model. Due to the fixed routes and desirable synchronization of vehicles arrivals in shared points this problem seems to be similar to the public transit network timetabling problem. Because of that the model presented here was based on a model dedicated to the public transit network timetabling problem, where optimization criterion was to maximize synchronization of vehicles' arrivals at the shared nodes. Results: Mixed integer programming model was employed for solving several cases of cyclic delivery-scheduling problem with vehicles serving fixed routes. Computational experiments are reported and obtained results are presented. Conclusions: The mixed integer programming model for the cyclic delivery-scheduling problem with synchronization of vehicles arrivals at logistic centers presented in this paper can be utilized for generating schedules for a group of vehicles serving fixed long routes. It may result in reducing total operational cost related to this group of vehicles as well as in reducing the goods travel time from the place of origin to their

  16. Nanoemulsions as vehicles for transdermal delivery of glycyrrhizin

    Directory of Open Access Journals (Sweden)

    Ranjit Kumar Harwansh

    2011-12-01

    Full Text Available The present investigation aims to evaluate an isotropic and thermodynamically stable nanoemulsion formulation for transdermal delivery of glycyrrhizin (GZ, with minimum surfactant and cosurfactant (Smix concentrations that could improve its solubility, permeation enhancement, and stability. Pseudo-ternary phase diagrams were developed and various nanoemulsion formulations were prepared using soyabean oil as oil, Span 80, Brij 35 as a surfactant and isopropyl alcohol as a cosurfactant. Nanoemulsion formulations that passed the thermodynamic stability tests were characterized for pH, viscosity and droplet size using a transmission electron microscopy. The transdermal ability of glycyrrhizin through human cadaver skin was determined using Franz diffusion cells. The in vitro skin permeation profile of the optimized nanoemulsion formulation (NE2 was compared to that of conventional gel. A significant increase in permeability parameters such as steady-state flux (Jss and permeability coefficient (Kp was observed in the optimized nanoemulsion formulation (NE2, which consisted of 1% wt/wt of mono ammonium glycyrrhizinate (MAG, 32.4% Span 80, 3.7% Brij 35, 10% isopropyl alcohol, 46.5% soyabean oil and 6.4% distilled water. No obvious skin irritation was observed for the studied nanoemulsion formulation (NE2 or the gel. The results indicated that nanoemulsions are promising vehicles for transdermal delivery of glycyrrhizin through human cadaver skin, without the use of additional permeation enhancers, because excipients of nanoemulsions act as permeation enhancers themselves.O objetivo da investigação é avaliar uma nanoemulsão isotrópica termodinamicamente estável para a administração transdérmica da glicirrizina (GZ, com concentrações mínimas de tensoativo e co-tensoativo (Smix, que poderiam melhorar a sua solubilidade, a permeação e a estabilidade. Os diagramas pseudo-ternários de fase foram desenvolvidos e diversas nanoemulsões foram

  17. 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.

  18. Single-Commodity Vehicle Routing Problem with Pickup and Delivery Service

    Directory of Open Access Journals (Sweden)

    Goran Martinovic

    2008-01-01

    Full Text Available We present a novel variation of the vehicle routing problem (VRP. Single commodity cargo with pickup and delivery service is considered. Customers are labeled as either cargo sink or cargo source, depending on their pickup or delivery demand. This problem is called a single commodity vehicle routing problem with pickup and delivery service (1-VRPPD. 1-VRPPD deals with multiple vehicles and is the same as the single-commodity traveling salesman problem (1-PDTSP when the number of vehicles is equal to 1. Since 1-VRPPD specializes VRP, it is hard in the strong sense. Iterative modified simulated annealing (IMSA is presented along with greedy random-based initial solution algorithm. IMSA provides a good approximation to the global optimum in a large search space. Experiment is done for the instances with different number of customers and their demands. With respect to average values of IMSA execution times, proposed method is appropriate for practical applications.

  19. Construction of a Nanodiamond–Tamoxifen Complex as a Breast Cancer Drug Delivery Vehicle

    Directory of Open Access Journals (Sweden)

    Linda-Lucila Landeros-Martínez

    2016-01-01

    Full Text Available According to the World Health Organization, breast cancer represents 16% of all cancer cases in women and is the second most common cancer. In the past decades, the mortality among patients with metastasis breast cancer has been reduced significantly via drug delivery by means of nanodiamond therapies, which are both biocompatible and scalable. In this study, we determined a theoretical pathway for the construction of a nanodiamond–tamoxifen complex that will act as a drug delivery vehicle for targeting tumor tissues of breast cancer. The tamoxifen pharmacophore was defined and the binding zone was identified for the electrostatic interaction between tamoxifen and a functionalized site of a nanodiamond particle allowing for attachment of the payload (this drug to the surface of the nanodiamond particle. In addition, an analysis of the intermolecular interaction between the nanodiamond and tamoxifen was conducted, showing three hydrogen bonds complying fully with Lipinski’s rule of five, which states that a compound should have five or fewer hydrogen bonds to be permeating and easily absorbed by the body (qualitative prediction. All calculations were performed using the conceptual Density Functional Theory with the M06 functional and the basis set 6-31G(d. The solvent effect has been taken into account by an implicit model, the conductor like polarizable continuum model.

  20. Effects of vehicles and enhancers on transdermal delivery of clebopride.

    Science.gov (United States)

    Rhee, Yun-Seok; Huh, Jai-Yong; Park, Chun-Woong; Nam, Tae-Young; Yoon, Koog-Ryul; Chi, Sang-Cheol; Park, Eun-Seok

    2007-09-01

    The effects of vehicles and penetration enhancers on the skin permeation of clebopride were evaluated using Franz type diffusion cells fitted with excised rat dorsal skins. The binary vehicle system, diethylene glycol monoethyl ether/isopropyl myristate (40/60, w/w), significantly enhanced the skin permeation rate of clebopride. The skin permeation enhancers, oleic acid and ethanol when used in the binary vehicle system, resulted in relatively high clebopride skin permeation rates. A gel formulation consisting of 1.5% (w/w) clebopride, 5% (w/w) oleic acid, and 7% (w/w) gelling agent with the binary vehicle system resulted in a permeation rate of 28.90 microg/cm2/h. Overall, these results highlight the potential of clebopride formulation for the transdermal route.

  1. Food Delivery System with the Utilization of Vehicle Using Geographical Information System (GIS) and A Star Algorithm

    Science.gov (United States)

    Siregar, B.; Gunawan, D.; Andayani, U.; Sari Lubis, Elita; Fahmi, F.

    2017-01-01

    Food delivery system is one kind of geographical information systems (GIS) that can be applied through digitation process. The main case in food delivery system is the way to determine the shortest path and food delivery vehicle movement tracking. Therefore, to make sure that the digitation process of food delivery system can be applied efficiently, it is needed to add shortest path determination facility and food delivery vehicle tracking. This research uses A Star (A*) algorithm for determining shortest path and location-based system (LBS) programming for moving food delivery vehicle object tracking. According to this research, it is generated the integrated system that can be used by food delivery driver, customer, and administrator in terms of simplifying the food delivery system. Through the application of shortest path and the tracking of moving vehicle, thus the application of food delivery system in the scope of geographical information system (GIS) can be executed.

  2. In-vehicle information system functions

    Energy Technology Data Exchange (ETDEWEB)

    Tufano, D.R.; Spelt, P.F.; Knee, H.E.

    1997-04-01

    This paper describes the functional requirement for an In-Vehicle Information System (IVIS), which will manage and display all driving-related information from many sources. There are numerous information systems currently being fielded or developed (e.g., routing and navigation, collision avoidance). However, without a logical integration of all of the possible on-board information, there is a potential for overwhelming the driver. The system described in this paper will filter and prioritize information across all sources, and present it to the driver in a timely manner, within a unified interface. To do this, IVIS will perform three general functions: (1) interact with other, on-board information subsystems and the vehicle; (2) manage the information by filtering, prioritizing, and integrating it; and (3) interact with the driver, both in terms of displaying information to the driver and allowing the driver to input requests, goals and preferences. The functional requirements described in this paper have either been derived from these three high-level functions or are directly mandated by the overriding requirements for modularity and flexibility. IVIS will have to be able to accommodate different types of information subsystems, of varying level of sophistication. The system will also have to meet the diverse needs of different types of drivers (private, commercial, transit), who may have very different levels of expertise in using information systems.

  3. Estimating Vehicle Stability Region Based on Energy Function

    Directory of Open Access Journals (Sweden)

    Yu-guang Yan

    2015-01-01

    Full Text Available In order to improve the deficiency of vehicle stability region, according to vehicle nonlinear dynamic model, method of estimating vehicle spatial stability region was proposed. With Pacejka magic formula tire model, nonlinear 3DOF vehicle model was deduced and verified though vehicle test. Detailed detecting system and data processing were introduced. In addition, stability of the vehicle system was discussed using Hurwitz criterion. By establishing energy function for vehicle system, the vehicle’s stability region in 20 m/s was estimated based on Lyapunov theorem and vehicle system characteristics. Vehicle test in the same condition shows that the calculated stability region defined by Lyapunov and system stability theorem has good effect on characterized vehicle stability and it could be a valuable reference for vehicle stability evaluation.

  4. Peptide-based soft materials as potential drug delivery vehicles.

    Science.gov (United States)

    Verma, Sandeep; Joshi, K B; Ghosh, Surajit

    2007-11-01

    Emerging concepts in the construction of nanostructures hold immense potential in the areas of drug delivery and targeting. Such nanoscopic assemblies/structures, similar to natural proteins and self-associating systems, may lead to the formation of programmable soft structures with expanded drug delivery options and the capability to circumvent first-pass metabolism. This article aims to illustrate key recent developments and innovative bioinspired design paradigms pertaining to peptide-containing self-assembled tubular and vesicular soft structures. Soft structures are composed of components that self-assemble to reveal diverse morphologies stabilized by weak, noncovalent interactions. Morphological properties of such structures and their ability to encapsulate drugs, biologicals and bioactive small molecules, with the promise of targeted delivery, are discussed.

  5. Systems Analysis and Structural Design of an Unpressurized Cargo Delivery Vehicle

    Science.gov (United States)

    Wu, K. Chauncey; Cruz, Jonathan N.; Antol, Jeffrey; Sasamoto, Washito A.

    2007-01-01

    The International Space Station will require a continuous supply of replacement parts for ongoing maintenance and repair after the planned retirement of the Space Shuttle in 2010. These parts are existing line-replaceable items collectively called Orbital Replacement Units, and include heavy and oversized items such as Control Moment Gyroscopes and stowed radiator arrays originally intended for delivery aboard the Space Shuttle. Current resupply spacecraft have limited to no capability to deliver these external logistics. In support of NASA's Exploration Systems Architecture Study, a team at Langley Research Center designed an Unpressurized Cargo Delivery Vehicle to deliver bulk cargo to the Space Station. The Unpressurized Cargo Delivery Vehicle was required to deliver at least 13,200 lbs of cargo mounted on at least 18 Flight Releasable Attachment Mechanisms. The Crew Launch Vehicle design recommended in the Exploration Systems Architecture Study would be used to launch one annual resupply flight to the International Space Station. The baseline vehicle design developed here has a cargo capacity of 16,000 lbs mounted on up to 20 Flight Releasable Attachment Mechanisms. Major vehicle components are a 5.5m-diameter cargo module containing two detachable cargo pallets with the payload, a Service Module to provide propulsion and power, and an aerodynamic nose cone. To reduce cost and risk, the Service Module is identical to the one used for the Crew Exploration Vehicle design.

  6. Interaction between drug delivery vehicles and cells under the effect of shear stress

    DEFF Research Database (Denmark)

    Godoy-Gallardo, Maria; Ek, Pramod Kumar; Jansman, M. M. T.

    2015-01-01

    Over the last decades, researchers have developed an ever greater and more ingenious variety of drug delivery vehicles (DDVs). This has made it possible to encapsulate a wide selection of therapeutic agents, ranging from proteins, enzymes, and peptides to hydrophilic and hydrophobic small drugs...

  7. Evaluation of aftermarket fuel delivery systems for natural gas and LPG vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Willson, B. [Colorado State Univ., Fort Collins, CO (United States)

    1992-09-01

    This study was designed to evaluate the effectiveness of aftermarket fuel delivery systems for vehicles fueled by compressed natural gas (CNG) and liquefied petroleum gas (LPG). Most of the CNG and LPG vehicles studied were converted to the alternative fuel after purchase. There are wide variations in the quality of the conversion hardware and the installation. This leads to questions about the overall quality of the converted vehicles, in terms of emissions, safety, and performance. There is a considerable body of emissions data for converted light-duty vehicles, and a smaller amount for medium- and heavy-duty vehicles. However, very few of these data involve real world conditions, and there is growing concern about in-use emissions. This report also attempts to assess factors that could allow in-use emissions to vary from the ``best-case`` results normally reported. The study also addresses issues of fuel supply, fuel composition, performance, safety, and warranty waivers. The report is based on an extensive literature and product survey and on the author`s experience with fuel delivery systems for light-duty vehicles.

  8. Evaluation of aftermarket fuel delivery systems for natural gas and LPG vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Willson, B. (Colorado State Univ., Fort Collins, CO (United States))

    1992-09-01

    This study was designed to evaluate the effectiveness of aftermarket fuel delivery systems for vehicles fueled by compressed natural gas (CNG) and liquefied petroleum gas (LPG). Most of the CNG and LPG vehicles studied were converted to the alternative fuel after purchase. There are wide variations in the quality of the conversion hardware and the installation. This leads to questions about the overall quality of the converted vehicles, in terms of emissions, safety, and performance. There is a considerable body of emissions data for converted light-duty vehicles, and a smaller amount for medium- and heavy-duty vehicles. However, very few of these data involve real world conditions, and there is growing concern about in-use emissions. This report also attempts to assess factors that could allow in-use emissions to vary from the best-case'' results normally reported. The study also addresses issues of fuel supply, fuel composition, performance, safety, and warranty waivers. The report is based on an extensive literature and product survey and on the author's experience with fuel delivery systems for light-duty vehicles.

  9. Time Dependent Heterogeneous Vehicle Routing Problem for Catering Service Delivery Problem

    Science.gov (United States)

    Azis, Zainal; Mawengkang, Herman

    2017-09-01

    The heterogeneous vehicle routing problem (HVRP) is a variant of vehicle routing problem (VRP) which describes various types of vehicles with different capacity to serve a set of customers with known geographical locations. This paper considers the optimal service deliveries of meals of a catering company located in Medan City, Indonesia. Due to the road condition as well as traffic, it is necessary for the company to use different type of vehicle to fulfill customers demand in time. The HVRP incorporates time dependency of travel times on the particular time of the day. The objective is to minimize the sum of the costs of travelling and elapsed time over the planning horizon. The problem can be modeled as a linear mixed integer program and we address a feasible neighbourhood search approach to solve the problem.

  10. Mesoporous silica nanoparticles as a biomolecule delivery vehicle in plants

    Energy Technology Data Exchange (ETDEWEB)

    Hussain, Hashmath I., E-mail: hashmath.i@deakin.edu.au [Deakin University, Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences (Australia); Yi, Zhifeng [Deakin University, Institute for Frontier Materials (Australia); Rookes, James E. [Deakin University, Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences (Australia); Kong, Lingxue X. [Deakin University, Institute for Frontier Materials (Australia); Cahill, David M. [Deakin University, Centre for Chemistry and Biotechnology, School of Life and Environmental Sciences (Australia)

    2013-06-15

    We report the uptake by wheat, lupin and Arabidopsis of mesoporous silica nanoparticles functionalised with amine cross-linked fluorescein isothiocyanate (MSN-APTES-FITC). The preparation of these particles at room temperature enabled the synthesis of 20 nm particles that contained a network of interconnected pores around 2 nm in diameter. The uptake and distribution of these nanoparticles were examined during seed germination, in roots of plants grown in a hydroponic system and in whole leaves and roots of plants via vacuum infiltration. The nanoparticles did not affect seed germination in lupin and there was no phytotoxicity. Following germination of wheat and lupin grown in a nutrient solution containing nanoparticles, they were found within cells and cell walls of the emerging root and in the vascular transport elements, the xylem, and in other associated cells. In leaves and roots of Arabidopsis the nanoparticles were found, following vacuum infiltration of whole seedlings, to be taken up by the entire leaf and they were principally found in the intercellular spaces of the mesophyll but also throughout much of the root system. We propose that MSNs could be used as a novel delivery system for small molecules in plants.

  11. PEGylated Dendrimers as Drug Delivery Vehicles for the Photosensitizer Silicon Phthalocyanine Pc 4 for Candidal Infections.

    Science.gov (United States)

    Hutnick, Melanie A; Ahsanuddin, Sayeeda; Guan, Linna; Lam, Minh; Baron, Elma D; Pokorski, Jonathan K

    2017-02-13

    Fungi account for billions of infections worldwide. The second most prominent causative agent for fungal infections is Candida albicans (C. albicans). As strains of fungi become resistant to antifungal medications, new treatment modalities must be investigated to combat these infections. One approach is to employ photodynamic therapy (PDT). PDT utilizes a photosensitizer, light, and cellular O 2 to produce reactive oxygen species (ROS), which then induce oxidative stress resulting in apoptosis. Silicon phthalocyanine Pc 4 is a photosensitizer that has exhibited success in clinical trials for a myriad of skin diseases. The hydrophobic nature of Pc 4, however, poses significant formulation and delivery challenges in the use of this therapy. To mitigate these concerns, a drug delivery vehicle was synthesized to better formulate Pc 4 into a viable PDT agent for treating fungal infections. Utilizing poly(amidoamine) dendrimers as the framework for the vehicle, ∼13% of the amine chain ends were PEGylated to promote water solubility and deter nonspecific adsorption. In vitro studies with C. albicans demonstrate that the potency of Pc 4 was not hindered by the dendrimer vehicle. Encapsulated Pc 4 was able to effectively generate ROS and obliterate fungal pathogens upon photoactivation. The results presented within describe a nanoparticulate delivery vehicle for Pc 4 that readily kills drug-resistant C. albicans and eliminates solvent toxicity, thus, improving formulation characteristics for the hydrophobic photosensitizer.

  12. Molecular Imaging of Biological Gene Delivery Vehicles for Targeted Cancer Therapy: Beyond Viral Vectors

    Energy Technology Data Exchange (ETDEWEB)

    Min, Jung Joon; Nguyen, Vu H. [Chonnam National University Medical School, Gwangju (Korea, Republic of); Gambhir, Sanjiv S. [Stanford University, California(United States)

    2010-04-15

    Cancer persists as one of the most devastating diseases in the world. Problems including metastasis and tumor resistance to chemotherapy and radiotherapy have seriously limited the therapeutic effects of present clinical treatments. To overcome these limitations, cancer gene therapy has been developed over the last two decades for a broad spectrum of applications, from gene replacement and knockdown to vaccination, each with different requirements for gene delivery. So far, a number of genes and delivery vectors have been investigated, and significant progress has been made with several gene therapy modalities in clinical trials. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications. However, both have limitations and risks that restrict gene therapy applications, including the complexity of production, limited packaging capacity, and unfavorable immunological features. While continuing to improve these vectors, it is important to investigate other options, particularly nonarrival biological agents such as bacteria, bacteriophages, and bacteria-like particles. Recently, many molecular imaging techniques for safe, repeated, and high-resolution in vivo imaging of gene expression have been employed to assess vector-mediated gene expression in living subjects. In this review, molecular imaging techniques for monitoring biological gene delivery vehicles are described, and the specific use of these methods at different steps is illustrated. Linking molecular imaging to gene therapy will eventually help to develop novel gene delivery vehicles for preclinical study and support the development of future human applications.

  13. Aptamer-Mediated Polymeric Vehicles for Enhanced Cell-Targeted Drug Delivery.

    Science.gov (United States)

    Tan, Kei X; Danquah, Michael K; Sidhu, Amandeep; Yon, Lau Sie; Ongkudon, Clarence M

    2018-02-08

    The search for smart delivery systems for enhanced pre-clinical and clinical pharmaceutical delivery and cell targeting continues to be a major biomedical research endeavor owing to differences in the physicochemical characteristics and physiological effects of drug molecules, and this affects the delivery mechanisms to elicit maximum therapeutic effects. Targeted drug delivery is a smart evolution essential to address major challenges associated with conventional drug delivery systems. These challenges mostly result in poor pharmacokinetics due to the inability of the active pharmaceutical ingredients to specifically act on malignant cells thus, causing poor therapeutic index and toxicity to surrounding normal cells. Aptamers are oligonucleotides with engineered affinities to bind specifically to their cognate targets. Aptamers have gained significant interests as effective targeting elements for enhanced therapeutic delivery as they can be generated to specifically bind to wide range of targets including proteins, peptides, ions, cells and tissues. Notwithstanding, effective delivery of aptamers as therapeutic vehicles is challenged by cell membrane electrostatic repulsion, endonuclease degradation, low pH cleavage, and binding conformation stability. The application of molecularly engineered biodegradable and biocompatible polymeric particles with tunable features such as surface area and chemistry, particulate size distribution and toxicity creates opportunities to develop smart aptamer-mediated delivery systems for controlled drug release. This article discusses opportunities for particulate aptamer-drug formulations to advance current drug delivery modalities by navigating active ingredients through cellular and biomolecular traffic to target sites for sustained and controlled release at effective therapeutic dosages while minimizing systemic cytotoxic effects. A proposal for a novel drug-polymer-aptamer-polymer (DPAP) design of aptamer-drug formulation with

  14. Extracellular Vesicles as Drug Delivery Vehicles for Rheumatoid Arthritis.

    Science.gov (United States)

    Kim, Il-Kwon; Kim, Sun-Hyun; Choi, Seong-Mi; Youn, Byung-Soo; Kim, Han-Soo

    2016-01-01

    Rheumatoid arthritis (RA) is a chronic, systemic and progressive autoimmune disease of connective tissues common in middle age. Dysregulation of the tissue homeostasis involving inflammation is the hallmark of disease pathogenesis, inducing autoimmune insults that frequently lead to permanent disability. Although the advent of immunosuppressive and anti-inflammatory drugs and, more recently, pathogenic TNF-TNF-R axis-targeting biologics significantly delayed progressive joint destruction with significant reduction of disability and physical improvement, a large proportion of RA patients failed to respond to the treatment. In this regard, mesenchymal stem/stromal cells (MSC) are particularly attractive to the refractory patients to the pharmacologic intervention for their immunosuppressive/anti-inflammatory capacity as well as tissue reparative and/or regenerative potential. Local or systemic delivery of MSCs led to promising results in preclinical as well as in clinical studies of RA and thus proposing that these cells can be further exploited for their therapeutic application in RA and other degenerative connective tissue diseases. Mechanistically, paracrine factors appear to be the main contributors of MSC-mediated tissue regeneration in a number of preclinical and clinical studies rather than direct tissue cell replacement. More recently, extracellular vesicles (EVs) released from MSCs emerged as key paracrine messengers that can also participate in the healing process through influencing the local microenvironment with anti-inflammatory effects. It is highly likely that the use of these EVs becomes beneficial in the treatment of RA. Yet, identification of key components involved in the regenerative process needs to be assessed for developing efficient MSC-based strategy of RA treatment.

  15. Fibrin nanoparticles as Possible vehicles for drug delivery.

    Science.gov (United States)

    Vedakumari, Weslen S; Prabu, Periyathambi; Babu, Saravana C; Sastry, Thotapalli P

    2013-08-01

    Several issues have been raised emphasizing the harmful toxic effects of metal nanoparticles towards biological systems. Search of biological nanoparticles with excellent biocompatibility and bioavailability could address this problem. Fibrin nanoparticles (FNP) were prepared using a novel technique and characterized for their physico-chemical properties. In vitro studies were performed to examine cytotoxicity and cellular uptake of FNP. Innate immune response to FNP was studied by (i) estimating in vitro generation of complement split products, C3a and C4d and (ii) in vivo expression of pro-inflammatory cytokines, TNF-α, IL-1 and IL-6. In vivo biodistribution study was carried out by intravenous administration of FITC-labelled FNP in mice. FNP were spherical with size ranging from 25 to 28nm. In vitro studies proved the biocompatibility of the nanoparticles, with their distribution across the cytoplasm and nucleus of treated cells. Complement activation studies showed insignificant increase in the level of C3a when compared with positive control. RT-PCR results revealed significant upregulation of TNF-α and downregulation of IL-6 cytokines after 6h of FNP administration. In vivo biodistribution studies showed moderate blood circulation time, with predominant distribution of nanoparticles in the liver followed by the lungs, kidney and spleen. Haematology, serum biochemistry, and histopathology analyses demonstrated that FNP were non-toxic. Owing to their small size, low cost, ease of preparation and excellent biocompatibility, FNP might be a promising novel material for drug delivery applications. Our results demonstrate the safe and promising use of FNP for biomedical applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. 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......-mediated drug transport across the BBB, where nanoparticles take advantage of physiological receptor-mediated transport processes....

  17. Injury severity in delivery-motorcycle to vehicle crashes in the Seoul metropolitan area.

    Science.gov (United States)

    Chung, Younshik; Song, Tai-Jin; Yoon, Byoung-Jo

    2014-01-01

    More than 56% of motorcycles in Korea are used for the purpose of delivering parcels and food. Since such delivery requires quick service, most motorcyclists commit traffic violations while delivering, such as crossing the centerline, speeding, running a red light, and driving in the opposite direction down one-way streets. In addition, the fatality rate for motorcycle crashes is about 12% of the fatality rate for road traffic crashes, which is considered to be high, although motorcycle crashes account for only 5% of road traffic crashes in South Korea. Therefore, the objective of this study is to analyze the injury severity of vehicle-to-motorcycle crashes that have occurred during delivery. To examine the risk of different injury levels sustained under all crash types of vehicle-to-motorcycle, this study applied an ordered probit model. Based on the results, this study proposes policy implications to reduce the injury severity of vehicle-to-motorcycle crashes during delivery. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Hydraulic Hybrid and Conventional Parcel Delivery Vehicles' Measured Laboratory Fuel Economy on Targeted Drive Cycles

    Energy Technology Data Exchange (ETDEWEB)

    Lammert, M. P.; Burton, J.; Sindler, P.; Duran, A.

    2014-10-01

    This research project compares laboratory-measured fuel economy of a medium-duty diesel powered hydraulic hybrid vehicle drivetrain to both a conventional diesel drivetrain and a conventional gasoline drivetrain in a typical commercial parcel delivery application. Vehicles in this study included a model year 2012 Freightliner P100H hybrid compared to a 2012 conventional gasoline P100 and a 2012 conventional diesel parcel delivery van of similar specifications. Drive cycle analysis of 484 days of hybrid parcel delivery van commercial operation from multiple vehicles was used to select three standard laboratory drive cycles as well as to create a custom representative cycle. These four cycles encompass and bracket the range of real world in-use data observed in Baltimore United Parcel Service operations. The NY Composite cycle, the City Suburban Heavy Vehicle Cycle cycle, and the California Air Resources Board Heavy Heavy-Duty Diesel Truck (HHDDT) cycle as well as a custom Baltimore parcel delivery cycle were tested at the National Renewable Energy Laboratory's Renewable Fuels and Lubricants Laboratory. Fuel consumption was measured and analyzed for all three vehicles. Vehicle laboratory results are compared on the basis of fuel economy. The hydraulic hybrid parcel delivery van demonstrated 19%-52% better fuel economy than the conventional diesel parcel delivery van and 30%-56% better fuel economy than the conventional gasoline parcel delivery van on cycles other than the highway-oriented HHDDT cycle.

  19. Autonomous self-navigating drug-delivery vehicles: from science fiction to reality.

    Science.gov (United States)

    Petrenko, Valery A

    2017-12-01

    Low efficacy of targeted nanomedicines in biological experiments enforced us to challenge the traditional concept of drug targeting and suggest a paradigm of 'addressed self-navigating drug-delivery vehicles,' in which affinity selection of targeting peptides and vasculature-directed in vivo phage screening is replaced by the migration selection, which explores ability of 'promiscuous' phages and their proteins to migrate through the tumor-surrounding cellular barriers, using a 'hub and spoke' delivery strategy, and penetrate into the tumor affecting the diverse tumor cell population. The 'self-navigating' drug-delivery paradigm can be used as a theoretical and technical platform in design of a novel generation of molecular medications and imaging probes for precise and personal medicine. [Formula: see text].

  20. Highly stable, protein capped gold nanoparticles as effective drug delivery vehicles for amino-glycosidic antibiotics

    International Nuclear Information System (INIS)

    Rastogi, Lori; Kora, Aruna Jyothi; Arunachalam, J.

    2012-01-01

    A method for the production of highly stable gold nanoparticles (Au NP) was optimized using sodium borohydride as reducing agent and bovine serum albumin as capping agent. The synthesized nanoparticles were characterized using UV–visible spectroscopy, transmission electron microscopy, X‐ray diffraction (XRD) and dynamic light scattering techniques. The formation of gold nanoparticles was confirmed from the appearance of pink colour and an absorption maximum at 532 nm. These protein capped nanoparticles exhibited excellent stability towards pH modification and electrolyte addition. The produced nanoparticles were found to be spherical in shape, nearly monodispersed and with an average particle size of 7.8 ± 1.7 nm. Crystalline nature of the nanoparticles in face centered cubic structure is confirmed from the selected‐area electron diffraction and XRD patterns. The nanoparticles were functionalized with various amino-glycosidic antibiotics for utilizing them as drug delivery vehicles. Using Fourier transform infrared spectroscopy, the possible functional groups of antibiotics bound to the nanoparticle surface have been examined. These drug loaded nanoparticle solutions were tested for their antibacterial activity against Gram-negative and Gram-positive bacterial strains, by well diffusion assay. The antibiotic conjugated Au NP exhibited enhanced antibacterial activity, compared to pure antibiotic at the same concentration. Being protein capped and highly stable, these gold nanoparticles can act as effective carriers for drugs and might have considerable applications in the field of infection prevention and therapeutics. - Highlights: ► Method for NaBH 4 reduced and BSA capped gold nanoparticle was standardized. ► Nanoparticles were spherical and nearly monodispersed with a size of 7.8 nm. ► Nanoparticles are extremely stable towards pH modification and electrolyte addition. ► Antibiotic conjugated nanoparticles exhibited enhanced antibacterial activity

  1. Highly stable, protein capped gold nanoparticles as effective drug delivery vehicles for amino-glycosidic antibiotics

    Energy Technology Data Exchange (ETDEWEB)

    Rastogi, Lori; Kora, Aruna Jyothi; Arunachalam, J., E-mail: aruncccm@gmail.com

    2012-08-01

    A method for the production of highly stable gold nanoparticles (Au NP) was optimized using sodium borohydride as reducing agent and bovine serum albumin as capping agent. The synthesized nanoparticles were characterized using UV-visible spectroscopy, transmission electron microscopy, X-ray diffraction (XRD) and dynamic light scattering techniques. The formation of gold nanoparticles was confirmed from the appearance of pink colour and an absorption maximum at 532 nm. These protein capped nanoparticles exhibited excellent stability towards pH modification and electrolyte addition. The produced nanoparticles were found to be spherical in shape, nearly monodispersed and with an average particle size of 7.8 {+-} 1.7 nm. Crystalline nature of the nanoparticles in face centered cubic structure is confirmed from the selected-area electron diffraction and XRD patterns. The nanoparticles were functionalized with various amino-glycosidic antibiotics for utilizing them as drug delivery vehicles. Using Fourier transform infrared spectroscopy, the possible functional groups of antibiotics bound to the nanoparticle surface have been examined. These drug loaded nanoparticle solutions were tested for their antibacterial activity against Gram-negative and Gram-positive bacterial strains, by well diffusion assay. The antibiotic conjugated Au NP exhibited enhanced antibacterial activity, compared to pure antibiotic at the same concentration. Being protein capped and highly stable, these gold nanoparticles can act as effective carriers for drugs and might have considerable applications in the field of infection prevention and therapeutics. - Highlights: Black-Right-Pointing-Pointer Method for NaBH{sub 4} reduced and BSA capped gold nanoparticle was standardized. Black-Right-Pointing-Pointer Nanoparticles were spherical and nearly monodispersed with a size of 7.8 nm. Black-Right-Pointing-Pointer Nanoparticles are extremely stable towards pH modification and electrolyte addition. Black

  2. 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.

  3. Next Generation Car — Example of Function Integration at the Light Urban Vehicle (LUV) Vehicle Concept

    Science.gov (United States)

    Kopp, G.; Brückmann, S.; Kriescher, M.; Friedrich, H. E.

    In times of climate change vehicle emissions have to be reduced clearly. One possibility is to reduce the mass of the body in white using lightweight sandwich structures. The department `Lightweight and Hybrid Design Methods' of the Institute of Vehicle Concepts develops a vehicle body structure by using sandwiches with aluminum top layers and polyurethane foam as core material. For that the foam and the sandwiches were investigated under different load cases, e.g. pressure loading and in-plane tests. In tests with components the high potential of the sandwich materials were shown. On the dynamic component test facility of the institute, vehicle front structures were tested successfully. The results of all investigations regarding sandwich materials, integration of functions (e.g. crash, thermal) in vehicle structures and the concept LUV are developed under the research program of Next Generation Car of the DLR. We will show the development and results of the LUV.

  4. Effects of Fuel Type and Fuel Delivery System on Pollutant Emissions of Pride and Samand Vehicles

    Directory of Open Access Journals (Sweden)

    Akbar Sarhadi

    2017-04-01

    Full Text Available This research was aimed to study the effect of the type of fuel delivery system (petrol, dedicated or bifuel, the type of consumed fuel (petrol or gas, the portion of consumed fuel and also the duration of dual-fuelling in producing carbon monoxide, carbon dioxide and unburned hydrocarbons from Pride and Samand. According to research objectives, data gathering from 2000 vehicles has been done by visiting Hafiz Vehicle Inspection Center every day for 2 months. The results of this survey indicated that although there is no significant difference between various fuel delivery systems in terms of producing the carbon monoxide, carbon dioxide and unburned hydrocarbons by Samand, considering the emission amount of carbon dioxide, the engine performance of Pride in bifuel and dedicated state in GTXI and 132 types is more unsatisfactory than that of petrol state by 0.3 and 0.4%, respectively. On the other hand, consuming natural gas increases the amount of carbon monoxide emission in dual- fuel Pride by 0.18% and decreases that in dual-fuel Samand by 1.2%, which signifies the better design of Samand in terms of fuel pumps, used kit type and other engine parts to use this alternative fuel compared to Pride. Since the portion of consumed fuel and also duration of dual-fuelling does not have a significant effect on the amount of output pollutants from the studied vehicles, it can be claimed that the output substances from the vehicle exhaust are more related to the vehicle’s condition than the fuel type.

  5. Albumin–Polymer–Drug Conjugates: Long Circulating, High Payload Drug Delivery Vehicles

    DEFF Research Database (Denmark)

    Smith, Anton Allen Abbotsford; Zuwala, Kaja; Pilgram, Oliver

    2016-01-01

    a marginal increase in the circulation lifetime of the drugs. We combine the benefits of the two platforms and at the same time overcome their respective limitations. Specifically, we develop the synthesis of albumin–polymer–drug conjugates to obtain long circulating, high payload drug delivery vehicles......Albumin is an exquisite tool of nature used in biomedicine to achieve long blood residence time for drugs, but the payload it can carry is typically limited to one molecule per protein. In contrast, synthetic macromolecular prodrugs contain multiple copies of drugs per polymer chain but offer only...... the drug in terms of efficacy of treatment...

  6. Synthetic Nano-Low Density Lipoprotein as Targeted Drug DeliveryVehicle for Glioblastoma Multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Nikanjam, Mina; Blakely, Eleanor A.; Bjornstad, Kathleen A.; Shu,Xiao; Budinger, Thomas F.; Forte, Trudy M.

    2006-06-14

    This paper discribes a synthetic low density lipoprotein(LDL) made by complexing a 29 amino acid that consists of a lipid bindingdomain and the LDL receptor binding domain with a lipid microemulsion.The nano-LDL particles were intermdiate in size between LDL and HDL andbound to LDL receptors on GBM brain tumor cells. Synthetic nano-LDLuptake by GBM cells was LDL receptor specific and dependent on cellreceptor number. It is suggested that these synthetic particles can serveas a delivery vehicle for hydophobic anti-tumor drugs by targeting theLDL receptor.

  7. Vehicle to Grid regulation services of electric delivery trucks: Economic and environmental benefit analysis

    International Nuclear Information System (INIS)

    Zhao, Yang; Noori, Mehdi; Tatari, Omer

    2016-01-01

    Highlights: • Potential net present revenues of electric truck based V2G regulation services are investigated. • GHG emission mitigation of V2G regulation services provided by electric trucks are quantified. • The total cost of ownership and the life-cycle GHG emissions of electric trucks are also analyzed. • V2G regulation services for electric trucks could yield considerable revenues and GHG emission savings. - Abstract: Concerns regarding the fuel costs and climate change impacts associated with petroleum combustion are among the main driving factors for the adoption of electric vehicles. Future commercial delivery truck fleets may include Battery Electric Vehicles (BEVs) and Extended Range Electric Vehicles (EREVs); in addition to savings on fuel and maintenance costs, the introduction of these grid accessible electric vehicles will also provide fleet owners with possible Vehicle to Grid (V2G) opportunities. This study investigates the potential net present revenues and greenhouse gas (GHG) emission mitigation of V2G regulation services provided by electric trucks in a typical fleet. The total cost of ownership and the life-cycle GHG emissions of electric trucks are also analyzed and compared to those of traditional diesel trucks. To account for uncertainties, possible ranges for key parameters are considered instead of only considering fixed single data values for each parameter. The results of this research indicate that providing V2G regulation services for electric trucks could yield considerable additional revenues ($20,000–50,000) and significant GHG emission savings (approximately 300 ton CO 2 ) compared to conventional diesel trucks.

  8. Boswellia gum resin/chitosan polymer composites: Controlled delivery vehicles for aceclofenac.

    Science.gov (United States)

    Jana, Sougata; Laha, Bibek; Maiti, Sabyasachi

    2015-01-01

    This study was undertaken to evaluate the effect of Boswellia gum resin on the properties of glutaraldehyde (GA) crosslinked chitosan polymer composites and their potential as oral delivery vehicles for a non-steroidal anti-inflammatory drug, aceclofenac. The incorporation of resinous material caused a significant improvement in drug entrapment efficiency (∼40%) of the polymer composites. Fourier transform infrared (FTIR) spectroscopic analysis confirmed the formation of chitosan-gum resin composites and did not show any evidence of drug-polymer chemical interaction. Field emission scanning electron microscopy (FE-SEM) suggested the formation of particulate polymer composites up to chitosan:gum resin mass ratio of 1:3. Only 8-17% drug was released into HCl solution (pH 1.2) in 2h. The drug release rate of polymer composites was faster in phosphate buffer solution (pH 6.8). The composites released ∼60-68% drug load in 7h. In same duration, the drug release rate suddenly boosted up to 92% as the concentration of gum resin in the composites was raised to 80%. The drug release mechanism deviated from non-Fickian to case-II type with increasing resin concentration in the composites. Hence, GA-treated Boswellia resin-chitosan composites could be considered as alternative vehicles for oral delivery of aceclofenac. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Basic peptides as functional components of non-viral gene transfer vehicles.

    Science.gov (United States)

    Nakanishi, Mahito; Eguchi, Akiko; Akuta, Teruo; Nagoshi, Emi; Fujita, Shigeo; Okabe, Jun; Senda, Takao; Hasegawa, Mamoru

    2003-04-01

    Improving the performance of non-viral gene-delivery vehicles that consist of synthetic compounds and nucleic acids is a key to successful gene therapy. Supplementing synthetic vehicles with various biological functions by using natural or artificial peptides is a promising approach with which to achieve this goal. One of the obstacles hindering this effort is that some of the potentially useful peptides, especially those with many basic amino acid residues, interfere with the formation of the complex owing to strong electrostatic interactions with the nucleic acid. In this review, we describe our recent work in examining the potential of these peptides in gene delivery, using a recombinant lambda phage particle as the model for the gene-delivery complex. Lambda phage encapsulates large duplex DNA in a rigid polyplex-like shell with a diameter of 55 nm, and can display various peptides on this capsid, independently of particle formation. By examining the expression of marker genes encapsulated in the phage capsid, we have demonstrated that the protein transduction domain of HIV Tat protein and the nuclear localization signal derived from SV40 T antigen can remarkably facilitate the delivery of these marker genes across the two major barriers, the cell membrane and the nuclear membrane, respectively. Our results indicate that these basic peptides can constitute effective components of synthetic gene-transfer complexes, as long as sufficient copies are displayed on the outer surface of the complex.

  10. Molecular dynamics study on DNA nanotubes as drug delivery vehicle for anticancer drugs.

    Science.gov (United States)

    Liang, Lijun; Shen, Jia-Wei; Wang, Qi

    2017-05-01

    In recent years, self-assembled DNA nanotubes have emerged as a type of nano-biomaterials with great potential for biomedical applications. To develop universal nanocarriers for smart and targeted drug delivery from DNA nanotubes, the understanding of interaction mechanism between DNA nanotubes and drugs is essential. In this study, the interactions between anti-cancer drugs and DNA nanotubes were investigated via molecular dynamics simulation. Our simulation results demonstrated that the DNA nanotubes could serve as a good drug delivery material by absorption of anti-cancer drugs with π-π interactions. At high concentration of anti-cancer drugs, most of the drugs could be absorbed by DNA nanotubes. Therefore, it could greatly decrease the aggregation of anti-cancer drugs in aqueous solution. In addition, the stability of DNA nanotubes could be improved with the absorption of anti-cancer drugs. These findings greatly enhance the understanding of the interaction mechanism of DNA nanotubes and anti-cancer drugs. Our study suggests that DNA nanotubes are promising delivery vehicles by strong absorption of anti-cancer drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Chitosan/TPP-hyaluronic acid nanoparticles: a new vehicle for gene delivery to the spinal cord.

    Science.gov (United States)

    Gwak, So-Jung; Jung, Jong Kwon; An, Sung Su; Kim, Hyo Jin; Oh, Jin Soo; Pennant, William A; Lee, Hye Yeong; Kong, Min Ho; Kim, Keung Nyun; Yoon, Do Heum; Ha, Yoon

    2012-01-01

    Gene delivery offers therapeutic promise for the treatment of neurological diseases and spinal cord injury. Several studies have offered viral vectors as vehicles to deliver therapeutic agents, yet their toxicity and immunogenicity, along with the cost of their large-scale formulation, limits their clinical use. As such, non-viral vectors are attractive in that they offer improved safety profiles compared to viruses. Poly(ethylene imine) (PEI) is one of the most extensively studied non-viral vectors, but its clinical value is limited y its cytotoxicity. Recently, chitosan/DNA complex nanoparticles have een considered as a vector for gene delivery. Here, we demonstrate that DNA nanoparticles made of hyaluronic acid (HA) and chitosan have low cytotoxicity and induce high transgene expression in neural stem cells and organotypic spinal cord slice tissue. Chitosan-TPP/HA nanoparticles were significantly less cytotoxic than PEI at various concentrations. Additionally, chitosan-TPP/HA nanoparticles with pDNA induced higher transgene expression in vitro for a longer duration than PEI in neural stem cells. These results suggest chitosan-TPP/HA nanoparticles may have the potential to serve as an option for gene delivery to the spinal cord.

  12. Exosomes as Drug Delivery Vehicles for Parkinson’s Disease Therapy

    Science.gov (United States)

    Haney, Matthew J.; Klyachko, Natalia L.; Zhao, Yuling; Gupta, Richa; Plotnikova, Evgeniya G.; He, Zhijian; Patel, Tejash; Piroyan, Aleksandr; Sokolsky, Marina; Kabanov, Alexander V.; Batrakova, Elena V.

    2015-01-01

    Exosomes are naturally occurring nanosized vesicles that have attracted considerable attention as drug delivery vehicles in the past few years. Exosomes are comprised of natural lipid bilayers with the abundance of adhesive proteins that readily interact with cellular membranes. We posit that exosomes secreted by monocytes and macrophages can provide an unprecedented opportunity to avoid entrapment in mononuclear phagocytes (as a part of the host immune system), and at the same time enhance delivery of incorporated drugs to target cells ultimately increasing drug therapeutic efficacy. In light of this, we developed a new exosomal-based delivery system for a potent antioxidant, catalase, to treat Parkinson’s disease (PD). Catalase was loaded into exosomes ex vivo using different methods: the incubation at room temperature, permeabilization with saponin, freeze-thaw cycles, sonication, or extrusion. The size of the obtained catalase-loaded exosomes (exoCAT) was in the range of 100 - 200 nm. A reformation of exosomes upon sonication and extrusion, or permeabilization with saponin resulted in high loading efficiency, sustained release, and catalase preservation against proteases degradation. Exosomes were readily taken up by neuronal cells in vitro. A considerable amount of exosomes was detected in PD mouse brain following intranasal administration. ExoCAT provided significant neuroprotective effects in in vitro and in vivo models of PD. Overall, exosome-based catalase formulations have a potential to be a versatile strategy to treat inflammatory and neurodegenerative disorders. PMID:25836593

  13. Bacteriophages as vehicles for gene delivery into mammalian cells: prospects and problems.

    Science.gov (United States)

    Bakhshinejad, Babak; Sadeghizadeh, Majid

    2014-10-01

    The identification of more efficient gene delivery vehicles (GDVs) is essential to fulfill the expectations of clinical gene therapy. Bacteriophages, due to their excellent safety profile, extreme stability under a variety of harsh environmental conditions and the capability for being genetically manipulated, have drawn a flurry of interest to be applied as a newly arisen category of gene delivery platforms. The incessant evolutionary interaction of bacteriophages with human cells has turned them into a part of our body's natural ecosystem. However, these carriers represent several barriers to gene transduction of mammalian cells. The lack of evolvement of specialized machinery for targeted cellular internalization, endosomal, lysosomal and proteasomal escape, cytoplasmic entry, nuclear localization and intranuclear transcription poses major challenges to the expression of the phage-carried gene. In this review, we describe pros and cons of bacteriophages as GDVs, provide an insight into numerous barriers that bacteriophages face for entry into and subsequent trafficking inside mammalian cells and elaborate on the strategies used to bypass these barriers. Tremendous genetic flexibility of bacteriophages to undergo numerous surface modifications through phage display technology has proven to be a turning point in the uncompromising efforts to surmount the limitations of phage-mediated gene expression. The revelatory outcomes of the studies undertaken within the recent years have been promising for phage-mediated gene delivery to move from concept to reality.

  14. Cascade Storage and Delivery System for a Multi Mission Space Exploration Vehicle (MMSEV)

    Science.gov (United States)

    Yagoda, Evan; Swickrath, Michael; Stambaugh, Imelda

    2012-01-01

    NASA is developing a Multi Mission Space Exploration Vehicle (MMSEV) for missions beyond Low Earth Orbit (LEO). The MMSEV is a pressurized vehicle used to extend the human exploration envelope for Lunar, Near Earth Object (NEO), and Deep Space missions. The Johnson Space Center is developing the Environmental Control and Life Support System (ECLSS) for the MMSEV. The MMSEV s intended use is to support longer sortie lengths with multiple Extra Vehicular Activities (EVAs) on a higher magnitude than any previous vehicle. This paper presents an analysis of a high pressure oxygen cascade storage and delivery system that will accommodate the crew during long duration Intra Vehicular Activity (IVA) and capable of multiple high pressure oxygen fills to the Portable Life Support System (PLSS) worn by the crew during EVAs. A cascade is a high pressure gas cylinder system used for the refilling of smaller compressed gas cylinders. Each of the large cylinders are filled by a compressor, but the cascade system allows small cylinders to be filled without the need of a compressor. In addition, the cascade system is useful as a "reservoir" to accommodate low pressure needs. A regression model was developed to provide the mechanism to size the cascade systems subject to constraints such as number of crew, extravehicular activity duration and frequency, and ullage gas requirements under contingency scenarios. The sizing routine employed a numerical integration scheme to determine gas compressibility changes during depressurization and compressibility effects were captured using the Soave-Redlich-Kwong (SRK) equation of state. A multi-dimensional nonlinear optimization routine was used to find the minimum cascade tank system mass that meets the mission requirements. The sizing algorithms developed in this analysis provide a powerful framework to assess cascade filling, compressor, and hybrid systems to design long duration vehicle ECLSS architecture. 1

  15. 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

  16. NREL/Industry Range-Extended Electric Vehicle for Package Delivery

    Energy Technology Data Exchange (ETDEWEB)

    Farrell, John T [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Kelly, Kenneth J [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Duran, Adam W [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Lammert, Michael P [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Miller, Eric S [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2018-01-15

    Range-extended electric vehicle (EV) technology can be a viable option for reducing fuel consumption from medium-duty (MD) and heavy-duty (HD) engines by approximately 50 percent or more. Such engines have wide variations in use and duty cycles, however, and identifying the vocations/duty cycles most suitable for range-extended applications is vital for maximizing the potential benefits. This presentation provides information about NREL's research on range-extended EV technologies, with a focus on NREL's real-world data collection and analysis approach to identifying the vocations/duty cycles best suited for range-extender applications and to help guide related powertrain optimization and design requirements. The presentation also details NREL's drive cycle development process as it pertains to package delivery applications.

  17. Edible Nanoencapsulation Vehicles for Oral Delivery of Phytochemicals: A Perspective Paper.

    Science.gov (United States)

    Xiao, Jie; Cao, Yong; Huang, Qingrong

    2017-08-16

    Edible nanoencapsulation vehicles (ENVs) designed for the delivery of phytochemicals have gained increasing research interest. The major driving force for this trend is the potential bioavailability enhancement effect for phytochemicals when delivered via ENVs. ENVs affect the bioefficacy of phytochemicals by influencing their dispersion and gastrointestinal stability, rate and site of release, transportation efficiency across the endothelial layer, systemic circulation and biodistribution, and regulation of gut microflora. Enhanced bioefficacy can be achieved by rational design of the size, surface property, matrix materials, and compartment structure of ENVs according to properties of phytochemicals. Future investigations may lay particular emphasis on examining the relevance between results gained by in vitro digestion simulations and those obtained via in vivo digestion simulations, structural evolutions of ENVs during digestion and absorption, impacts of ENVs on the metabolism of phytochemicals, and using ENVs for deciphering the reciprocal interactions between phytochemicals and gut microbiota.

  18. Optimization of self-microemulsifying drug delivery systems (SMEDDS) using a D-optimal design and the desirability function.

    Science.gov (United States)

    Holm, R; Jensen, I H M; Sonnergaard, J

    2006-10-01

    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 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 was demonstrated to be a powerful tool to predict the optimal formulation for the explored system.

  19. 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

    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...... 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...

  20. Novel vehicle based on cubosomes for ophthalmic delivery of flurbiprofen with low irritancy and high bioavailability

    Science.gov (United States)

    Han, Shun; Shen, Jin-qiu; Gan, Yong; Geng, Hai-ming; Zhang, Xin-xin; Zhu, Chun-liu; Gan, Li

    2010-01-01

    Aim: To develop a novel vehicle based on cubosomes as an ophthalmic drug delivery system for flurbiprofen (FB) to reduce ocular irritancy and improve bioavailability. Methods: FB-loaded cubosomes were prepared using hot and high-pressure homogenization. Cubosomes were then characterized by particle size, zeta potential, encapsulation efficiency, particle morphology, inner cubic structure and in vitro release. Corneal permeation was evaluated using modified Franz-type cells. Ocular irritation was then evaluated using both the Draize method and histological examination. The ocular pharmacokinetics of FB was determined using microdialysis. Results: The particle size of each cubosome formulation was about 150 nm. A bicontinuous cubic phase of cubic P-type was determined using cryo-transmission electron microscopy (cryo-TEM) observation and small angle X-ray scattering (SAXS) analysis. In vitro corneal permeation study revealed that FB formulated in cubosomes exhibited 2.5-fold (F1) and 2.0-fold (F2) increase in Papp compared with FB PBS. In the ocular irritation test, irritation scores for each group were less than 2, indicating that all formulations exhibited excellent ocular tolerance. Histological examination revealed that neither the structure nor the integrity of the cornea was visibly affected after incubation with FB cubosomes. The AUC of FB administered as FB cubosome F2 was 486.36±38.93 ng·mL−1·min·μg−1, which was significantly higher than that of FB Na eye drops (P<0.01). Compared with FB Na eye drops, the Tmax of FB cubosome F2 was about 1.6-fold higher and the MRT was also significantly longer (P<0.001). Conclusion: This novel low-irritant vehicle based on cubosomes might be a promising system for effective ocular drug delivery. PMID:20686524

  1. In-vehicle signing functions of an in-vehicle information system

    Energy Technology Data Exchange (ETDEWEB)

    Tufano, D.R.; Knee, H.E.; Spelt, P.F.

    1996-04-01

    The definition of In-Vehicle Signing (IVS) functions was guided by the principles of traffic engineering as they apply to the design and placement of roadway signs. Because of the dynamic and active nature of computing, communications, and display technology, IVS can fulfill the signing principles of traffic engineering in ways that have been impossible with conventional signage. Current signing technology represents a series of compromises of these principles, especially the data and equations contributing to the calculation of required sight distance. A number of conditions relevant to sight distance are quite variable, e.g.: vehicle speed, visibility, weather, and driver reaction time. However, conventional signing requires that there are fixed values of each variable for the determination of (e.g.) legibility distance. IVS, on the other hand, will be able to tailor the timing of sign presentation to the dynamically diverse variable values of all of these conditions. A clear, in-vehicle sign display, adaptive to ambient and driver conditions, will in fact obviate the entire issue of sign legibility. These capabilities, together with information filtering functions, will truly enhance the presentation of sign information to drivers. The development of IVS is a critical step in the development of an integrated In-Vehicle Information System (IVIS).

  2. Engineering Botulinum Neurotoxin C1 as a Molecular Vehicle for Intra-Neuronal Drug Delivery.

    Science.gov (United States)

    Vazquez-Cintron, Edwin J; Beske, Phillip H; Tenezaca, Luis; Tran, Bao Q; Oyler, Jonathan M; Glotfelty, Elliot J; Angeles, Christopher A; Syngkon, Aurelia; Mukherjee, Jean; Kalb, Suzanne R; Band, Philip A; McNutt, Patrick M; Shoemaker, Charles B; Ichtchenko, Konstantin

    2017-02-21

    Botulinum neurotoxin (BoNT) binds to and internalizes its light chain into presynaptic compartments with exquisite specificity. While the native toxin is extremely lethal, bioengineering of BoNT has the potential to eliminate toxicity without disrupting neuron-specific targeting, thereby creating a molecular vehicle capable of delivering therapeutic cargo into the neuronal cytosol. Building upon previous work, we have developed an atoxic derivative (ad) of BoNT/C1 through rationally designed amino acid substitutions in the metalloprotease domain of wild type (wt) BoNT/C1. To test if BoNT/C1 ad retains neuron-specific targeting without concomitant toxic host responses, we evaluated the localization, activity, and toxicity of BoNT/C1 ad in vitro and in vivo. In neuronal cultures, BoNT/C1 ad light chain is rapidly internalized into presynaptic compartments, but does not cleave SNARE proteins nor impair spontaneous neurotransmitter release. In mice, systemic administration resulted in the specific co-localization of BoNT/C1 ad with diaphragmatic motor nerve terminals. The mouse LD 50 of BoNT/C1 ad is 5 mg/kg, with transient neurological symptoms emerging at sub-lethal doses. Given the low toxicity and highly specific neuron-targeting properties of BoNT/C1 ad, these data suggest that BoNT/C1 ad can be useful as a molecular vehicle for drug delivery to the neuronal cytoplasm.

  3. Priority-Based Content Delivery in the Internet of Vehicles through Named Data Networking

    Directory of Open Access Journals (Sweden)

    Marica Amadeo

    2016-11-01

    Full Text Available Named Data Networking (NDN has been recently proposed as a prominent solution for content delivery in the Internet of Vehicles (IoV, where cars equipped with a variety of wireless communication technologies exchange information aimed to support safety, traffic efficiency, monitoring and infotainment applications. The main NDN tenets, i.e., name-based communication and in-network caching, perfectly fit the demands of time- and spatially-relevant content requested by vehicles regardless of their provenance. However, existing vehicular NDN solutions have not been targeted to wisely ensure prioritized traffic treatment based on the specific needs of heterogeneous IoV content types. In this work, we propose a holistic NDN solution that, according to the demands of data traffic codified in NDN content names, dynamically shapes the NDN forwarding decisions to ensure the appropriate prioritization. Specifically, our proposal first selects the outgoing interface(s (i.e., 802.11, LTE for NDN packets and then properly tunes the timing of the actual transmissions. Simulation results show that the proposed enhancements succeed in achieving differentiated traffic treatment, while keeping traffic load under control.

  4. The effect of diethylene glycol monoethyl ether as a vehicle for topical delivery of ivermectin.

    Science.gov (United States)

    Yazdanian, M; Chen, E

    1995-01-01

    The effect of diethylene glycol monoethyl ether (DGME; Transcutol) on the permeation of ivermectin, a broad-spectrum antiparasitic agent, through bovine skin was evaluated by in vitro permeation experiments followed by serial sectioning of the skin to assess the amount of ivermectin retained in the skin. Ivermectin permeation through bovine skin was enhanced by DGME and this enhancement was DGME-concentration-dependent. Permeation of ivermectin was effectively enhanced in vehicles with low proportions of DGME, but the magnitude of permeation enhancement decreased as the proportion of DGME increased. The permeation was accompanied by the formation of cutaneous depots of ivermectin. Furthermore, the data indicated that the flux and the cutaneous accumulation of ivermectin were sensitive to the concentration gradient of DGME across the skin. This suggested that ivermectin was permeating with DGME, in which it is very soluble. Hence, the enhancing mechanism involves solubilization of the ivermectin by DGME and the transport of DGME itself across the skin. Based on these results, DGME appears to be a potential vehicle for topical delivery of ivermectin by transport through the skin and through formation of cutaneous depots of ivermectin.

  5. Red blood cells and polyelectrolyte multilayer capsules: natural carriers versus polymer-based drug delivery vehicles.

    Science.gov (United States)

    Kolesnikova, Tatiana A; Skirtach, Andre G; Möhwald, Helmuth

    2013-01-01

    Red blood cells (RBCs) and lipid-based carriers on the one hand and polymeric capsules on the other hand represent two of the most widely used carriers in drug delivery. Each class of these carriers has its own set of properties, specificity and advantages. Thorough comparative studies of such systems are reported here for the first time. In this review, RBCs are described in comparison with synthetic polymeric drug delivery vehicles using polyelectrolyte multilayer capsules as an example. Lipid-based composition of the shell in the former case is particularly attractive due to their inherent biocompatibility and flexibility of the carriers. On the other hand, synthetic approaches to fabrication of polyelectrolyte multilayer capsules permit manipulation of the permeability of their shell as well as tuning their composition, mechanical properties, release methods and targeting. In conclusion, properties of RBCs and polyelectrolyte multilayer capsules are reported here highlighting similarities and differences in their preparation and applications. In addition, their advantages and disadvantages are discussed.

  6. In-vehicle signing functions and systems concepts

    Energy Technology Data Exchange (ETDEWEB)

    Tufano, D.R.; Spelt, P.F.; Knee, H.E.

    1996-03-01

    This paper describes functional requirements and system concepts for an In-Vehicle Signing (IVS) system, which will bring information from roadway signs, signals, and pavement markings into the vehicle for presentation to the driver. Information filter functions will assure that the only messages displayed are those which are important to the driver and which apply. Display functions will optimize the presentation of the message to ambient conditions, driver preferences, the number of simultaneous messages, and the urgency of the message. Timing functions will display a sign as soon as it is needed, for the entire time that it applies, and only while it applies. IVS is one of the core components of an integrated In-Vehicle Information System, which will manage and fuse all driving-related information. Two different IVS system concepts have been investigated: one based on a map database, the other on beacon technology. This work is being conducted by the Oak Ridge National Laboratory for the US Federal Highway Administration as part of the Intelligent Transportation System Program.

  7. Functionalized mesoporous silica materials for controlled drug delivery.

    Science.gov (United States)

    Yang, Piaoping; Gai, Shili; Lin, Jun

    2012-05-07

    In the past decade, non-invasive and biocompatible mesoporous silica materials as efficient drug delivery systems have attracted special attention. Great progress in structure control and functionalization (magnetism and luminescence) design has been achieved for biotechnological and biomedical applications. This review highlights the most recent research progress on silica-based controlled drug delivery systems, including: (i) pure mesoporous silica sustained-release systems, (ii) magnetism and/or luminescence functionalized mesoporous silica systems which integrate targeting and tracking abilities of drug molecules, and (iii) stimuli-responsive controlled release systems which are able to respond to environmental changes, such as pH, redox potential, temperature, photoirradiation, and biomolecules. Although encouraging and potential developments have been achieved, design and mass production of novel multifunctional carriers, some practical biological application, such as biodistribution, the acute and chronic toxicities, long-term stability, circulation properties and targeting efficacy in vivo are still challenging. This journal is © The Royal Society of Chemistry 2012

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

    Science.gov (United States)

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

    2015-09-28

    The ever-growing interest for finding efficient and reliable methods for treatment of diseases has set a precedent for the design and synthesis of new functional hybrid materials, namely porous nanoparticles, for controlled drug delivery. Mesoporous silica nanoparticles (MSNPs) represent one of the most promising nanocarriers for drug delivery as they possess interesting chemical and physical properties, thermal and mechanical stabilities, and are biocompatibile. In particular, their easily functionalizable surface allows a large number of property modifications further improving their efficiency in this field. This Concept article deals with the advances on the novel methods of functionalizing MSNPs, inside or outside the pores, as well as within the walls, to produce efficient and smart drug carriers for therapy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. 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

  10. Bacteriomimetic invasin-functionalized nanocarriers for intracellular delivery.

    Science.gov (United States)

    Labouta, Hagar Ibrahim; Menina, Sara; Kochut, Annika; Gordon, Sarah; Geyer, Rebecca; Dersch, Petra; Lehr, Claus-Michael

    2015-12-28

    Intracellular bacteria invade mammalian cells to establish an infectious niche. The current work models adhesion and subsequent internalization strategy of pathogenic bacteria into mammalian cells to design a bacteriomimetic bioinvasive delivery system. We report on the surface functionalization of liposomes with a C-terminal fragment of invasin (InvA497), an invasion factor in the outer membrane of Yersinia pseudotuberculosis. InvA497-functionalized liposomes adhere to mammalian epithelial HEp-2 cell line at different infection stages with a significantly higher efficiency than liposomes functionalized with bovine serum albumin. Covalent attachment of InvA497 results in higher cellular adhesion than liposomes with physically adsorbed InvA497 with non-specific surface protein alignment. Uptake studies in HEp-2 cells indicate active internalization of InvA497-functionalized liposomes via β1-integrin receptor-mediated uptake mechanism mimicking the natural invasion strategy of Y. pseudotuberculosis. Uptake studies in Caco-2 cells at different polarization states demonstrate specific targeting of the InvA497-functionalized liposomes to less polarized cells reflecting the status of inflamed cells. Moreover, when loaded with the anti-infective agent gentamicin and applied to HEp-2 cells infected with Y. pseudotuberculosis, InvA497-functionalized liposomes are able to significantly reduce the infection load relative to non-functionalized drug-loaded liposomes. This indicates a promising application of such a bacteriomimetic system for drug delivery to intracellular compartments. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Cell mediated therapeutics for cancer treatment: Tumor homing cells as therapeutic delivery vehicles

    Science.gov (United States)

    Balivada, Sivasai

    Many cell types were known to have migratory properties towards tumors and different research groups have shown reliable results regarding cells as delivery vehicles of therapeutics for targeted cancer treatment. Present report discusses proof of concept for 1. Cell mediated delivery of Magnetic nanoparticles (MNPs) and targeted Magnetic hyperthermia (MHT) as a cancer treatment by using in vivo mouse cancer models, 2. Cells surface engineering with chimeric proteins for targeted cancer treatment by using in vitro models. 1. Tumor homing cells can carry MNPs specifically to the tumor site and tumor burden will decrease after alternating magnetic field (AMF) exposure. To test this hypothesis, first we loaded Fe/Fe3O4 bi-magnetic NPs into neural progenitor cells (NPCs), which were previously shown to migrate towards melanoma tumors. We observed that NPCs loaded with MNPs travel to subcutaneous melanoma tumors. After alternating magnetic field (AMF) exposure, the targeted delivery of MNPs by the NPCs resulted in a mild decrease in tumor size (Chapter-2). Monocytes/macrophages (Mo/Ma) are known to infiltrate tumor sites, and also have phagocytic activity which can increase their uptake of MNPs. To test Mo/Ma-mediated MHT we transplanted Mo/Ma loaded with MNPs into a mouse model of pancreatic peritoneal carcinomatosis. We observed that MNP-loaded Mo/Ma infiltrated pancreatic tumors and, after AMF treatment, significantly prolonged the lives of mice bearing disseminated intraperitoneal pancreatic tumors (Chapter-3). 2. Targeted cancer treatment could be achieved by engineering tumor homing cell surfaces with tumor proteases cleavable, cancer cell specific recombinant therapeutic proteins. To test this, Urokinase and Calpain (tumor specific proteases) cleavable; prostate cancer cell (CaP) specific (CaP1 targeting peptide); apoptosis inducible (Caspase3 V266ED3)- rCasp3V266ED3 chimeric protein was designed in silico. Hypothesized membrane anchored chimeric protein (rCasp3V

  12. Direct observation of key photoinduced dynamics in a potential nano-delivery vehicle of cancer drugs.

    Science.gov (United States)

    Sardar, Samim; Chaudhuri, Siddhi; Kar, Prasenjit; Sarkar, Soumik; Lemmens, Peter; Pal, Samir Kumar

    2015-01-07

    In recent times, significant achievements in the use of zinc oxide (ZnO) nanoparticles (NPs) as delivery vehicles of cancer drugs have been made. The present study is an attempt to explore the key photoinduced dynamics in ZnO NPs upon complexation with a model cancer drug protoporphyrin IX (PP). The nanohybrid has been characterized by FTIR, Raman scattering and UV-Vis absorption spectroscopy. Picosecond-resolved Förster resonance energy transfer (FRET) from the defect mediated emission of ZnO NPs to PP has been used to study the formation of the nanohybrid at the molecular level. Picosecond-resolved fluorescence studies of PP-ZnO nanohybrids reveal efficient electron migration from photoexcited PP to ZnO, eventually enhancing the ROS activity. The dichlorofluorescin (DCFH) oxidation and no oxidation of luminol in PP/PP-ZnO nanohybrids upon green light illumination unravel that the nature of ROS is essentially singlet oxygen rather than superoxide anions. Surface mediated photocatalysis of methylene blue (MB) in an aqueous solution of the nanohybrid has also been investigated. Direct evidence of the role of electron transfer as a key player in enhanced ROS generation from the nanohybrid is also clear from the photocurrent measurement studies. We have also used the nanohybrid in a model photodynamic therapy application in a light sensitized bacteriological culture experiment.

  13. Palm Olein Emulsion: a Novel Vehicle for Topical Drug Delivery of Betamethasone 17-Valerate.

    Science.gov (United States)

    Ahmad, Kausar; Win, Thazin; Jaffri, Juliana Md; Edueng, Khadijah; Taher, Muhammad

    2018-01-01

    This study aims to investigate the use of palm olein as the oil phase for betamethasone 17-valerate (BV) emulsions. The physicochemical properties of the formulations were characterized. In vitro drug release study was performed with the Hanson Vertical Diffusion Cell System; the samples were quantified with HPLC and the results were compared with commercial products. Optimized emulsion formulations were subjected to stability studies for 3 months at temperatures of 4, 25, and 40°C; the betamethasone 17-valerate content was analyzed using HPLC. The formulations produced mean particle size of 2-4 μm, viscosities of 50-250 mPa.s, and zeta potential between -45 and -68 mV. The rheological analyses showed that the emulsions exhibited pseudoplastic and viscoelastic behavior. The in vitro release of BV from palm olein emulsion through cellulose acetate was 4.5 times higher than that of commercial products and more BV molecules deposited in rat skin. Less than 4% of the drug was degraded in the formulations during the 3-month period when they were subjected to the three different temperatures. These findings indicate that palm olein-in-water emulsion can be an alternative vehicle for topical drug delivery system with superior permeability.

  14. Cinnamate of inulin as a vehicle for delivery of colonic drugs.

    Science.gov (United States)

    López-Molina, Dorotea; Chazarra, Soledad; How, Chee Wun; Pruidze, Nikolov; Navarro-Perán, Enma; García-Cánovas, Francisco; García-Ruiz, Pedro Antonio; Rojas-Melgarejo, Francisco; Rodríguez-López, José Neptuno

    2015-02-01

    Colon diseases are difficult to treat because oral administrated drugs are absorbed at the stomach and intestine levels and they do not reach colon; in addition, intravenous administrated drugs are eliminated from the body before reaching colon. Inulin is a naturally occurring polysaccharide found in many plants. It consists of β 2-1 linked D-fructose molecules having a glucosyl unit at the reducing end. Various inulin and dextran hydrogels have been developed that serve as potential carrier for introduction of drugs into the colon. Because inulin is not absorbed in the stomach or in the small intestine, and inulin is degraded by colonic bacteria, drugs encapsulated in inulin-coated vesicles could be specifically liberated in the colon. Therefore, the use of inulin-coated vesicles could represent an advance for the treatment of colon diseases. Here, we study the use of a cinnamoylated derivative of chicory inulin as a vehicle for the controlled delivery of colonic drugs. The encapsulation of methotrexate in inulin vesicles and its release and activity was studied in colon cancer cells in cultures. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Metallothionein bioconjugates as delivery vehicles for bismuth-212 alpha particle therapy

    International Nuclear Information System (INIS)

    Macklis, R.M.; Morris, C.; Humm, J.; Hines, J.; Atcher, R.

    1991-01-01

    Metallothioneins (MTHs) are small cysteine-rich polypeptides that binds cationic metals at physiologic pH ranges through noncovalent -SH ligand interactions. Some leucine-rich renal MTHs have a particular avidity for bismuth. The authors have examined the ability of MTHs to selectively incorporate Bi-212, a short-lived high-energy alpha particle emitter currently under exploration as a potential therapeutic radiolabel for use in molecularly targeted cancer therapy. They find that under physiologic conditions, MTH will selectively incorporate Bi-212 after incubation with an equilibrium mixture of its upstream and downstream parents. The MTH moieties may be linked to tumor-binding macromolecules such as antibodies via thiolation reactions using SPDP, and the resultant Bismuth-avid molecules may be used either as primary delivery vehicles for the Bi-212 or as part of a 2-step release-and-catch isotope localization system in which the MTH-antibody conjugate is pre-localized at the tumor site and the radiometal is then administered and chelated in situ. They present the chemistry, dosimetry and potential clinical applications of this system

  16. 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.

  17. Exact Solutions to the Symmetric and Asymmetric Vehicle Routing Problem with Simultaneous Delivery and Pick-Up

    Directory of Open Access Journals (Sweden)

    Julia Rieck

    2013-05-01

    Full Text Available In reverse logistics networks, products (e.g., bottles or containers have to be transported from a depot to customer locations and, after use, from customer locations back to the depot. In order to operate economically beneficial, companies prefer a simultaneous delivery and pick-up service. The resulting Vehicle Routing Problem with Simultaneous Delivery and Pick-up (VRPSDP is an operational problem, which has to be solved daily by many companies. We present two mixed-integer linear model formulations for the VRPSDP, namely a vehicle-flow and a commodity-flow model. In order to strengthen the models, domain-reducing preprocessing techniques, and effective cutting planes are outlined. Symmetric benchmark instances known from the literature as well as new asymmetric instances derived from real-world problems are solved to optimality using CPLEX 12.1.

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

    Science.gov (United States)

    Leonard, Ashley Dawn

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

  19. 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

  20. Decal bone matrix as a local antibiotic delivery vehicle in a MRSA-infected bone model: An experimental study

    Directory of Open Access Journals (Sweden)

    Saraf Shyam

    2010-01-01

    Full Text Available Background: Polymethyl methacrylate (PMMA antibiotic beads though have proved their utility as a local antibiotic delivery system, however, there are limitations. Decalcified bone matrix (DBM as a vehicle of antibiotics can serve the purpose, provided a minimum inhibitory concentration is sustained. Healing of the defect and avoiding the second surgery is another advantage. We studied the DBM as the delivery vehicle for vancomycin in controlling the methicillin-resistant Staphylococcus aureus (MRSA osteomyelitis as well as healing of the cavity simultaneously in an experimental study. Materials and Methods: An in vitro study was conducted to optimize vancomycin impregnation in the DBM. For the in vivo study, a unicortical defect was created in the metaphysis of the distal femur in 18 rabbits. After contaminating the defect with MRSA, rabbits were divided into three groups. Group I (eight limbs received no graft. Defects in group II (11 limbs were filled with plain DBM chips and in group III (14 limbs, cavities were implanted with vancomycin-impregnated decal bone chips. Rabbits were assessed by clinical, radiological, histological, gross examination and bacterial load assay. High Performance Liquid Chromatography HPLC analysis of vancomycin in group III was done to assess the concentration in DBM chips. Results: In group I, the infection persisted throughout the period of the study. Group II showed the fulminated infection at the grafted site with DBM chips sequestrating out. Vancomycin-impregnated decal chips in group III did not show any sign of infection and eventually incorporated. The bacterial load study showed a progressive load change and HPLC revealed an effective antibiotic concentration up to 3 weeks in both in vitro and in vivo. Conclusion: Decal bone chips were effective as the local antibiotic delivery vehicle in preventing the MRSA osteomyelitis model. It eluted vancomycin significantly and the graft uptake was also excellent

  1. 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.

  2. Inclusion bodies as potential vehicles for recombinant protein delivery into epithelial cells

    Science.gov (United States)

    2012-01-01

    Background We present the potential of inclusion bodies (IBs) as a protein delivery method for polymeric filamentous proteins. We used as cell factory a strain of E. coli, a conventional host organism, and keratin 14 (K14) as an example of a complex protein. Keratins build the intermediate filament cytoskeleton of all epithelial cells. In order to build filaments, monomeric K14 needs first to dimerize with its binding partner (keratin 5, K5), which is then followed by heterodimer assembly into filaments. Results K14 IBs were electroporated into SW13 cells grown in culture together with a “reporter” plasmid containing EYFP labeled keratin 5 (K5) cDNA. As SW13 cells do not normally express keratins, and keratin filaments are built exclusively of keratin heterodimers (i.e. K5/K14), the short filamentous structures we obtained in this study can only be the result of: a) if both IBs and plasmid DNA are transfected simultaneously into the cell(s); b) once inside the cells, K14 protein is being released from IBs; c) released K14 is functional, able to form heterodimers with EYFP-K5. Conclusions Soluble IBs may be also developed for complex cytoskeletal proteins and used as nanoparticles for their delivery into epithelial cells. PMID:22624805

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

    Science.gov (United States)

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

    2016-01-14

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

  4. Multitriggered Tumor-Responsive Drug Delivery Vehicles Based on Protein and Polypeptide Coassembly for Enhanced Photodynamic Tumor Ablation.

    Science.gov (United States)

    Zhang, Ning; Zhao, Fenfang; Zou, Qianli; Li, Yongxin; Ma, Guanghui; Yan, Xuehai

    2016-11-01

    Tumor-responsive nanocarriers are highly valuable and demanded for smart drug delivery particularly in the field of photodynamic therapy (PDT), where a quick release of photosensitizers in tumors is preferred. Herein, it is demonstrated that protein-based nanospheres, prepared by the electrostatic assembly of proteins and polypeptides with intermolecular disulfide cross-linking and surface polyethylene glycol coupling, can be used as versatile tumor-responsive drug delivery vehicles for effective PDT. These nanospheres are capable of encapsulation of various photosensitizers including Chlorin e6 (Ce6), protoporphyrin IX, and verteporfin. The Chlorin e6-encapsulated nanospheres (Ce6-Ns) are responsive to changes in pH, redox potential, and proteinase concentration, resulting in multitriggered rapid release of Ce6 in an environment mimicking tumor tissues. In vivo fluorescence imaging results indicate that Ce6-Ns selectively accumulate near tumors and the quick release of Ce6 from Ce6-Ns can be triggered by tumors. In tumors the fluorescence of released Ce6 from Ce6-Ns is observed at 0.5 h postinjection, while in normal tissues the fluorescence appeared at 12 h postinjection. Tumor ablation is demonstrated by in vivo PDT using Ce6-Ns and the biocompatibility of Ce6-Ns is evident from the histopathology imaging, confirming the enhanced in vivo PDT efficacy and the biocompatibility of the assembled drug delivery vehicles. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Extracellular vesicles for drug delivery

    NARCIS (Netherlands)

    Vader, Pieter; Mol, Emma A; Pasterkamp, Gerard; Schiffelers, Raymond M

    2016-01-01

    Extracellular vesicles (EVs) are cell-derived membrane vesicles, and represent an endogenous mechanism for intercellular communication. Since the discovery that EVs are capable of functionally transferring biological information, the potential use of EVs as drug delivery vehicles has gained

  6. 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.

  7. Nanoparticle-functionalized microcapsules for in vitro delivery and sensing

    Science.gov (United States)

    Carregal-Romero, Susana; Ochs, Markus; Parak, Wolfgang J.

    2012-11-01

    Inorganic nanoparticles such as magnetic nanoparticles, fluorescent quantum dots, and plasmonic nanoparticles can be used as building blocks for designing multifunctional systems based on polymeric capsules. The properties of the inorganic nanoparticles hereby are harnessed to provide additional functionality to the polymer capsules. Biological applications towards in vitro sensing and delivery are discussed. Examples will be given in which magnetic nanoparticles are used to direct capsules with magnetic field gradients, colloidal quantum dots are used to identify capsules via the formation of optical barcodes, and gold nanoparticles are used as light-controlled heat-sources for opening capsules and releasing macromolecules from their cavity upon optical excitation. This demonstrates that combination of inorganic nanoparticles and organic/polymeric molecules as carrier matrices allow for tailoring multifunctional hybrid particles for practical applications.

  8. Protein-engineered block-copolymers as stem cell delivery vehicles

    Science.gov (United States)

    Heilshorn, Sarah

    2015-03-01

    Stem cell transplantation is a promising therapy for a myriad of debilitating diseases and injuries; however, current delivery protocols are inadequate. Transplantation by direct injection, which is clinically preferred for its minimal invasiveness, commonly results in less than 5% cell viability, greatly inhibiting clinical outcomes. We demonstrate that mechanical membrane disruption results in significant acute loss of viability at clinically relevant injection rates. As a strategy to protect cells from these damaging forces, we show that cell encapsulation within hydrogels of specific mechanical properties will significantly improve viability. Building on these fundamental studies, we have designed a reproducible, bio-resorbable, customizable hydrogel using protein-engineering technology. In our Mixing-Induced Two-Component Hydrogel (MITCH), network assembly is driven by specific and stoichiometric peptide-peptide binding interactions. By integrating protein science methodologies with simple polymer physics models, we manipulate the polypeptide chain interactions and demonstrate the direct ability to tune the network crosslinking density, sol-gel phase behavior, and gel mechanics. This is in contrast to many other physical hydrogels, where predictable tuning of bulk mechanics from the molecular level remains elusive due to the reliance on non-specific and non-stoichiometric chain interactions for network formation. Furthermore, the hydrogel network can be easily modified to deliver a variety of bioactive payloads including growth factors, peptide drugs, and hydroxyapatite nanoparticles. Through a series of in vitro and in vivo studies, we demonstrate that these materials may significantly improve transplanted stem cell retention and function.

  9. A novel vehicle for local protein delivery to the inner ear: injectable and biodegradable thermosensitive hydrogel loaded with PLGA nanoparticles.

    Science.gov (United States)

    Dai, Juan; Long, Wei; Liang, Zhongping; Wen, Lu; Yang, Fan; Chen, Gang

    2018-01-01

    Delivery of biomacromolecular drugs into the inner ear is challenging, mainly because of their inherent instability as well as physiological and anatomical barriers. Therefore, protein-friendly, hydrogel-based delivery systems following local administration are being developed for inner ear therapy. Herein, biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing interferon α-2 b (IFN α-2 b) were loaded in chitosan/glycerophosphate (CS/GP)-based thermosensitive hydrogel for IFN delivery by intratympanic injection. The injectable hydrogel possessed a physiological pH and formed semi-solid gel at 37 °C, with good swelling and deswelling properties. The CS/GP hydrogel could slowly degrade as visualized by scanning electron microscopy (SEM). The presence of NPs in CS/GP gel largely influenced in vitro drug release. In the guinea pig cochlea, a 1.5- to 3-fold increase in the drug exposure time of NPs-CS/GP was found than those of the solution, NPs and IFN-loaded hydrogel. Most importantly, a prolonged residence time was attained without obvious histological changes in the inner ear. This biodegradable, injectable, and thermosensitive NPs-CS/GP system may allow longer delivery of protein drugs to the inner ear, thus may be a potential novel vehicle for inner ear therapy.

  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. Brain delivery of microencapsulated GDNF induces functional and structural recovery in parkinsonian monkeys.

    Science.gov (United States)

    Garbayo, Elisa; Ansorena, Eduardo; Lana, Hugo; Carmona-Abellan, María Del Mar; Marcilla, Irene; Lanciego, José Luis; Luquin, María Rosario; Blanco-Prieto, María José

    2016-12-01

    Glial cell line-derived neurotrophic factor (GDNF) remains the most potent neurotrophic factor for dopamine neurons. Despite its potential as treatment for Parkinson's disease (PD), its clinical application has been hampered by safety and efficacy concerns associated with GDNF's short in vivo half-life and with significant brain delivery obstacles. Drug formulation systems such as microparticles (MPs) may overcome these issues providing protein protection from degradation and sustained drug release over time. We therefore sought to evaluate the efficacy and safety of GDNF delivered via injectable biodegradable MPs in a clinically relevant model of PD and to investigate the mechanism contributing to their beneficial effects. MPs were injected unilaterally into the putamen of parkinsonian monkeys with severe nigrostriatal degeneration. Notably, a single administration of the microencapsulated neurotrophic factor achieved sustained GDNF levels in the brain, providing motor improvement and dopaminergic function restoration. This was reflected by a bilateral increase in the density of striatal dopaminergic neurons 9 months after treatment. Moreover, GDNF was retrogradely transported to the substantia nigra increasing bilaterally the number of dopaminergic and total neurons, regardless of the severe degeneration. GDNF-MP injection within the putamen elicited no adverse effects such as immunogenicity, cerebellar degeneration or weight loss. MPs are therefore a safe, efficient vehicle for sustained protein delivery to the brain, supporting the therapeutic benefit of GDNF when encapsulated within MPs for brain repair. Overall, these findings constitute important groundwork for GDNF-MP clinical development. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Multi-functional Electric Module for a Vehicle

    Science.gov (United States)

    Bluethmann, William J. (Inventor); Waligora, Thomas M. (Inventor); Fraser-Chanpong, Nathan (Inventor); Reed, Ryan (Inventor); Akinyode, Akinjide Akinniyi (Inventor); Spain, Ivan (Inventor); Dawson, Andrew D. (Inventor); Figuered, Joshua M. (Inventor); Herrera, Eduardo (Inventor); Markee, Mason M. (Inventor)

    2015-01-01

    A multi-functional electric module (eModule) is provided for a vehicle having a chassis, a master controller, and a drive wheel having a propulsion-braking module. The eModule includes a steering control assembly, mounting bracket, propulsion control assembly, brake controller, housing, and control arm. The steering control assembly includes a steering motor controlled by steering controllers in response to control signals from the master controller. A mounting feature of the bracket connects to the chassis. The propulsion control assembly and brake controller are in communication with the propulsion-braking module. The control arm connects to the lower portion and contains elements of a suspension system, with the control arm being connectable to the drive wheel via a wheel input/output block. The controllers are responsive to the master controller to control a respective steering, propulsion, and braking function. The steering motor may have a dual-wound stator with windings controlled via the respective steering controllers.

  13. Design of lipid nanocapsule delivery vehicles for multivalent display of recombinant Env trimers in HIV vaccination.

    Science.gov (United States)

    Pejawar-Gaddy, Sharmila; Kovacs, James M; Barouch, Dan H; Chen, Bing; Irvine, Darrell J

    2014-08-20

    Immunization strategies that elicit antibodies capable of neutralizing diverse virus strains will likely be an important part of a successful vaccine against HIV. However, strategies to promote robust humoral responses against the native intact HIV envelope trimer structure are lacking. We recently developed chemically cross-linked lipid nanocapsules as carriers of molecular adjuvants and encapsulated or surface-displayed antigens, which promoted follicular helper T-cell responses and elicited high-avidity, durable antibody responses to a candidate malaria antigen. To apply this system to the delivery of HIV antigens, Env gp140 trimers with terminal his-tags (gp140T-his) were anchored to the surface of lipid nanocapsules via Ni-NTA-functionalized lipids. Initial experiments revealed that the large (409 kDa), heavily glycosylated trimers were capable of extracting fluid phase lipids from the membranes of nanocapsules. Thus, liquid-ordered and/or gel-phase lipid compositions were required to stably anchor trimers to the particle membranes. Trimer-loaded nanocapsules combined with the clinically relevant adjuvant monophosphoryl lipid A primed high-titer antibody responses in mice at antigen doses ranging from 5 μg to as low as 100 ng, whereas titers dropped more than 50-fold over the same dose range when soluble trimer was mixed with a strong oil-in-water adjuvant comparator. Nanocapsule immunization also broadened the number of distinct epitopes on the HIV trimer recognized by the antibody response. These results suggest that nanocapsules displaying HIV trimers in an oriented, multivalent presentation can promote key aspects of the humoral response against Env immunogens.

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

    Science.gov (United States)

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

    2015-12-01

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

  15. Fire Detection Tradeoffs as a Function of Vehicle Parameters

    Science.gov (United States)

    Urban, David L.; Dietrich, Daniel L.; Brooker, John E.; Meyer, Marit E.; Ruff, Gary A.

    2016-01-01

    Fire survivability depends on the detection of and response to a fire before it has produced an unacceptable environment in the vehicle. This detection time is the result of interplay between the fire burning and growth rates; the vehicle size; the detection system design; the transport time to the detector (controlled by the level of mixing in the vehicle); and the rate at which the life support system filters the atmosphere, potentially removing the detected species or particles. Given the large differences in critical vehicle parameters (volume, mixing rate and filtration rate) the detection approach that works for a large vehicle (e.g. the ISS) may not be the best choice for a smaller crew capsule. This paper examines the impact of vehicle size and environmental control and life support system parameters on the detectability of fires in comparison to the hazard they present. A lumped element model was developed that considers smoke, heat, and toxic product release rates in comparison to mixing and filtration rates in the vehicle. Recent work has quantified the production rate of smoke and several hazardous species from overheated spacecraft polymers. These results are used as the input data set in the lumped element model in combination with the transport behavior of major toxic products released by overheating spacecraft materials to evaluate the necessary alarm thresholds to enable appropriate response to the fire hazard.

  16. Nanostructured liquid crystalline particles as an alternative delivery vehicle for plant agrochemicals.

    Science.gov (United States)

    Nadiminti, Pavani P; Dong, Yao D; Sayer, Chad; Hay, Phillip; Rookes, James E; Boyd, Ben J; Cahill, David M

    2013-03-13

    Agrochemical spray formulations applied to plants are often mixed with surfactants that facilitate delivery of the active ingredient. However, surfactants cause phytotoxicity and off-target effects in the environment. We propose the use of nanostructured liquid crystalline particles (NLCP) as an alternative to surfactant-based agrochemical delivery. For this, we have compared the application of commercial surfactants, di (2-ethylhexyl) sulfosuccinate and alkyl dimethyl betaine, with NLCP made from phytantriol, at concentrations of 0.1%, 1% and 5% on the adaxial surface of leaves of four plant species Ttriticum aestivum (wheat), Zea mays (maize), Lupinus angustifolius (lupin), and Arabidopsis thaliana. In comparison with the application of surfactants there was less phytotoxicity on leaves of each species following treatment with NLCP. Following treatment of leaves with NLCP analysis of cuticular wax micromorphology revealed less wax solubilization in the monocot species. The results clearly show that there are advantages in the use of NLCP rather than surfactants for agrochemical delivery.

  17. 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.

  18. Exploring Heuristics for the Vehicle Routing Problem with Split Deliveries and Time Windows

    Science.gov (United States)

    2014-09-18

    of Defense, or the United States Government. This material is declared a work of the U.S. Government and is not subject to copyright protection in...M. Gambardella, "Ant Colony Optimisation for vehicle routing problems: from theory to applications," Galleria Rassegna Bimestrale Di Cultura , vol

  19. Dual delivery of hepatocyte and vascular endothelial growth factors via a protease-degradable hydrogel improves cardiac function in rats.

    Directory of Open Access Journals (Sweden)

    Apoorva S Salimath

    Full Text Available Acute myocardial infarction (MI caused by ischemia and reperfusion (IR is the most common cause of cardiac dysfunction due to local cell death and a temporally regulated inflammatory response. Current therapeutics are limited by delivery vehicles that do not address spatial and temporal aspects of healing. The aim of this study was to engineer biotherapeutic delivery materials to harness endogenous cell repair to enhance myocardial repair and function. We have previously engineered poly(ethylene glycol (PEG-based hydrogels to present cell adhesive motifs and deliver VEGF to promote vascularization in vivo. In the current study, bioactive hydrogels with a protease-degradable crosslinker were loaded with hepatocyte and vascular endothelial growth factors (HGF and VEGF, respectively and delivered to the infarcted myocardium of rats. Release of both growth factors was accelerated in the presence of collagenase due to hydrogel degradation. When delivered to the border zones following ischemia-reperfusion injury, there was no acute effect on cardiac function as measured by echocardiography. Over time there was a significant increase in angiogenesis, stem cell recruitment, and a decrease in fibrosis in the dual growth factor delivery group that was significant compared with single growth factor therapy. This led to an improvement in chronic function as measured by both invasive hemodynamics and echocardiography. These data demonstrate that dual growth factor release of HGF and VEGF from a bioactive hydrogel has the capacity to significantly improve cardiac remodeling and function following IR injury.

  20. Mucosal vaccines: a paradigm shift in the development of mucosal adjuvants and delivery vehicles.

    Science.gov (United States)

    Srivastava, Atul; Gowda, Devegowda Vishakante; Madhunapantula, SubbaRao V; Shinde, Chetan G; Iyer, Meenakshi

    2015-04-01

    Mucosal immune responses are the first-line defensive mechanisms against a variety of infections. Therefore, immunizations of mucosal surfaces from which majority of infectious agents make their entry, helps to protect the body against infections. Hence, vaccinization of mucosal surfaces by using mucosal vaccines provides the basis for generating protective immunity both in the mucosal and systemic immune compartments. Mucosal vaccines offer several advantages over parenteral immunization. For example, (i) ease of administration; (ii) non-invasiveness; (iii) high-patient compliance; and (iv) suitability for mass vaccination. Despite these benefits, to date, only very few mucosal vaccines have been developed using whole microorganisms and approved for use in humans. This is due to various challenges associated with the development of an effective mucosal vaccine that can work against a variety of infections, and various problems concerned with the safe delivery of developed vaccine. For instance, protein antigen alone is not just sufficient enough for the optimal delivery of antigen(s) mucosally. Hence, efforts have been made to develop better prophylactic and therapeutic vaccines for improved mucosal Th1 and Th2 immune responses using an efficient and safe immunostimulatory molecule and novel delivery carriers. Therefore, in this review, we have made an attempt to cover the recent advancements in the development of adjuvants and delivery carriers for safe and effective mucosal vaccine production. © 2015 APMIS. Published by John Wiley & Sons Ltd.

  1. Double emulsion electrospun nanofibers as a growth factor delivery vehicle for salivary gland regeneration

    Science.gov (United States)

    Foraida, Zahraa I.; Sharikova, Anna; Peerzada, Lubna N.; Khmaladze, Alexander; Larsen, Melinda; Castracane, James

    2017-08-01

    Sustained delivery of growth factors, proteins, drugs and other biologically active molecules is necessary for tissue engineering applications. Electrospun fibers are attractive tissue engineering scaffolds as they partially mimic the topography of the extracellular matrix (ECM). However, they do not provide continuous nourishment to the tissue. In search of a biomimetic scaffold for salivary gland tissue regeneration, we previously developed a blend nanofiber scaffold composed of the protein elastin and the synthetic polymer polylactic-co-glycolic acid (PLGA). The nanofiber scaffold promoted in vivo-like salivary epithelial cell tissue organization and apicobasal polarization. However, in order to enhance the salivary cell proliferation and biomimetic character of the scaffold, sustained growth factor delivery is needed. The composite nanofiber scaffold was optimized to act as a growth factor delivery system using epidermal growth factor (EGF) as a model protein. The nanofiber/EGF hybrid nanofibers were synthesized by double emulsion electrospinning where EGF is emulsified within a water/oil/water (w/o/w) double emulsion system. Successful incorporation of EGF was confirmed using Raman spectroscopy. EGF release profile was characterized using enzyme-linked immunosorbent assay (ELIZA) of the EGF content. Double emulsion electrospinning resulted in slower release of EGF. We demonstrated the potential of the proposed double emulsion electrospun nanofiber scaffold for the delivery of growth factors and/or drugs for tissue engineering and pharmaceutical applications.

  2. DNA origami as an in vivo drug delivery vehicle for cancer therapy.

    Science.gov (United States)

    Zhang, Qian; Jiang, Qiao; Li, Na; Dai, Luru; Liu, Qing; Song, Linlin; Wang, Jinye; Li, Yaqian; Tian, Jie; Ding, Baoquan; Du, Yang

    2014-07-22

    Many chemotherapeutics used for cancer treatments encounter issues during delivery to tumors in vivo and may have high levels of systemic toxicity due to their nonspecific distribution. Various materials have been explored to fabricate nanoparticles as drug carriers to improve delivery efficiency. However, most of these materials suffer from multiple drawbacks, such as limited biocompatibility and inability to engineer spatially addressable surfaces that can be utilized for multifunctional activity. Here, we demonstrate that DNA origami possessed enhanced tumor passive targeting and long-lasting properties at the tumor region. Particularly, the triangle-shaped DNA origami exhibits optimal tumor passive targeting accumulation. The delivery of the known anticancer drug doxorubicin into tumors by self-assembled DNA origami nanostructures was performed, and this approach showed prominent therapeutic efficacy in vivo. The DNA origami carriers were prepared through the self-assembly of M13mp18 phage DNA and hundreds of complementary DNA helper strands; the doxorubicin was subsequently noncovalently intercalated into these nanostructures. After conducting fluorescence imaging and safety evaluation, the doxorubicin-containing DNA origami exhibited remarkable antitumor efficacy without observable systemic toxicity in nude mice bearing orthotopic breast tumors labeled with green fluorescent protein. Our results demonstrated the potential of DNA origami nanostructures as innovative platforms for the efficient and safe drug delivery of cancer therapeutics in vivo.

  3. TSP model for electric vehicle deliveries, considering speed, loading and path slope.

    OpenAIRE

    Bay, Maud; Limbourg, Sabine

    2015-01-01

    In the current Transport White Paper, the European Union presents a roadmap for a more competitive and sustainable European transport system. Concerning Urban Freight Transport, responsible for about a quarter of CO2 emissions of the transport sector, one of the goals of the EU is to achieve essentially CO2-free city logistics in major urban centres by 2030 by developing and deploying new and sustainable fuels and propulsion systems. The gradual phasing out of ‘conventionally-fuelled’ vehicle...

  4. Transdermal delivery of ondansetron hydrochloride: effects of vehicles and penetration enhancers.

    Science.gov (United States)

    Gwak, Hye Sun; Oh, Ik Sang; Chun, In Koo

    2004-02-01

    The effects of vehicles and penetration enhancers on the in vitro permeation of ondansetron hydrochloride (OS) across dorsal hairless mouse skins were investigated. Various types of vehicles, including ester, alcohol, and ether and their mixtures were used, and then a series of fatty acids and fatty alcohols were employed as enhancers. Among pure vehicles used, water and ethanol showed high permeation fluxes, which were 48.2+/-23.7 and 41.9+/-17.9 microg/cm2 per h, respectively. Even though propylene glycol monocaprylate (PGMC) alone did not show a high permeation rate, the skin permeability of OS was increased by the addition of diethylene glycol monoethyl ether (DGME); the highest flux was achieved at 40% of DGME. Also, the combination of PGMC and ethanol (80:20) or PGMC and propylene glycol (PG) (60:40) increased the permeation flux by six- and two-fold, respectively, compared to PGMC alone. The synergistic enhancement was also obtained by using PG-oleyl alcohol (OAl) cosolvent. The greatest flux was attained by the addition of unsaturated fatty acids at 3% concentration to PG. The enhancement factors with the addition of oleic acid or linoleic acid to PG were about 1250 and 450, respectively. But saturated fatty acids failed to show a significant enhancing effect. When the PGMC-DGME (60:40) cosolvent system was used as a vehicle, all fatty acids, including unsaturated fatty acids, failed to show significant enhancing effects. The results indicate that the combinations of oleic acid, linoleic acid, or oleyl alcohol with PG, or PGMC-DGME (60:40) cosolvent could be used for the design of the OS transdermal system.

  5. BNNTs under the influence of external electric field as potential new drug delivery vehicle of Glu, Lys, Gly and Ser amino acids: A first-principles study

    Energy Technology Data Exchange (ETDEWEB)

    Farmanzadeh, Davood, E-mail: d.farmanzad@umz.ac.ir; Ghazanfary, Samereh

    2014-11-30

    Graphical abstract: - Highlights: • Solvation energies show that the BNNTs/amino acids complex stabilizes in presence of solvent. • The adsorption process is sensitive to the external electric field. • The electric field is a suitable method for adsorption and storage of amino acids on BNNTs. - Abstract: The interaction of Glu (Glutamic acid), Lys (Lysine), Gly (Glycine) and Ser (Serine) amino acids with different polarities and (9, 0) zigzag single-wall boron nitride nanotubes (BNNTs) with various lengths in the presence and absence of external electric field (EF) in gas and solvent phases, are studied using density functional theory. It is found that interaction of Glu, Lys, Gly and Ser amino acids with BNNTs in both phases is energetically favorable. From solvation energy calculations, it can be seen that the BNNTs/amino acid complex dissolution in water is spontaneous. The adsorption energies and quantum molecular descriptors changed in the presence of external EF. Therefore, the study of BNNTs/amino acid complex under influence of external electric field is very important in proposing or designing new drug delivery systems in the presence of external EF. Results indicate that Glu, Lys, Gly and Ser amino acids can be adsorbed considerably on the BNNTs in the existence of external electric field. Our results showed that the BNNTs can act as a suitable drug delivery vehicle of Glu, Lys, Gly and Ser amino acids within biological systems and strength of adsorption and rate of drug release can be controlled by the external EF.

  6. BNNTs under the influence of external electric field as potential new drug delivery vehicle of Glu, Lys, Gly and Ser amino acids: A first-principles study

    International Nuclear Information System (INIS)

    Farmanzadeh, Davood; Ghazanfary, Samereh

    2014-01-01

    Graphical abstract: - Highlights: • Solvation energies show that the BNNTs/amino acids complex stabilizes in presence of solvent. • The adsorption process is sensitive to the external electric field. • The electric field is a suitable method for adsorption and storage of amino acids on BNNTs. - Abstract: The interaction of Glu (Glutamic acid), Lys (Lysine), Gly (Glycine) and Ser (Serine) amino acids with different polarities and (9, 0) zigzag single-wall boron nitride nanotubes (BNNTs) with various lengths in the presence and absence of external electric field (EF) in gas and solvent phases, are studied using density functional theory. It is found that interaction of Glu, Lys, Gly and Ser amino acids with BNNTs in both phases is energetically favorable. From solvation energy calculations, it can be seen that the BNNTs/amino acid complex dissolution in water is spontaneous. The adsorption energies and quantum molecular descriptors changed in the presence of external EF. Therefore, the study of BNNTs/amino acid complex under influence of external electric field is very important in proposing or designing new drug delivery systems in the presence of external EF. Results indicate that Glu, Lys, Gly and Ser amino acids can be adsorbed considerably on the BNNTs in the existence of external electric field. Our results showed that the BNNTs can act as a suitable drug delivery vehicle of Glu, Lys, Gly and Ser amino acids within biological systems and strength of adsorption and rate of drug release can be controlled by the external EF

  7. 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

  8. Poly(ester amide-Poly(ethylene oxide Graft Copolymers: Towards Micellar Drug Delivery Vehicles

    Directory of Open Access Journals (Sweden)

    Gregory J. Zilinskas

    2012-01-01

    Full Text Available Micelles formed from amphiphilic copolymers are promising materials for the delivery of drug molecules, potentially leading to enhanced biological properties and efficacy. In this work, new poly(ester amide-poly(ethylene oxide (PEA-PEO graft copolymers were synthesized and their assembly into micelles in aqueous solution was investigated. It was possible to tune the sizes of the micelles by varying the PEO content of the polymers and the method of micelle preparation. Under optimized conditions, it was possible to obtain micelles with diameters less than 100 nm as measured by dynamic light scattering and transmission electron microscopy. These micelles were demonstrated to encapsulate and release a model drug, Nile Red, and were nontoxic to HeLa cells as measured by an MTT assay. Overall, the properties of these micelles suggest that they are promising new materials for drug delivery systems.

  9. Near-roadway monitoring of vehicle emissions as a function of mode of operation for light-duty vehicles.

    Science.gov (United States)

    Wen, Dongqi; Zhai, Wenjuan; Xiang, Sheng; Hu, Zhice; Wei, Tongchuan; Noll, Kenneth E

    2017-11-01

    Determination of the effect of vehicle emissions on air quality near roadways is important because vehicles are a major source of air pollution. A near-roadway monitoring program was undertaken in Chicago between August 4 and October 30, 2014, to measure ultrafine particles, carbon dioxide, carbon monoxide, traffic volume and speed, and wind direction and speed. The objective of this study was to develop a method to relate short-term changes in traffic mode of operation to air quality near roadways using data averaged over 5-min intervals to provide a better understanding of the processes controlling air pollution concentrations near roadways. Three different types of data analysis are provided to demonstrate the type of results that can be obtained from a near-roadway sampling program based on 5-min measurements: (1) development of vehicle emission factors (EFs) for ultrafine particles as a function of vehicle mode of operation, (2) comparison of measured and modeled CO 2 concentrations, and (3) application of dispersion models to determine concentrations near roadways. EFs for ultrafine particles are developed that are a function of traffic volume and mode of operation (free flow and congestion) for light-duty vehicles (LDVs) under real-world conditions. Two air quality models-CALINE4 (California Line Source Dispersion Model, version 4) and AERMOD (American Meteorological Society/U.S. Environmental Protection Agency Regulatory Model)-are used to predict the ultrafine particulate concentrations near roadways for comparison with measured concentrations. When using CALINE4 to predict air quality levels in the mixing cell, changes in surface roughness and stability class have no effect on the predicted concentrations. However, when using AERMOD to predict air quality in the mixing cell, changes in surface roughness have a significant impact on the predicted concentrations. The paper provides emission factors (EFs) that are a function of traffic volume and mode of

  10. Functional design of heat exchange for pneumatic vehicles

    Science.gov (United States)

    Xu, Z. G.; Yang, D. Y.; Shen, W. D.; Liu, T. T.

    2017-10-01

    With the increasingly serious environmental problems, especially the impact of fog and haze, the development of air powered vehicles has become an important research direction of new energy vehicles. Quadrature test was done with different materials, i.e. stainless steel and aluminum alloy, at different inlet pressures, using different expansion gases, i.e. air, CO2, for heat exchanging properties for pneumatic vehicles. The mathematics as well as simulation methods are used to analyze the different heat exchanging effects in the multistage cylinder. The research results showed that the stainless steel has better effects in heat exchanging than Aluminum Alloy; the intake pressure has little effect on CO2 than the air in heat exchanging effect. CO2 is better in heat exchanging than air.

  11. Automated driving and autonomous functions on road vehicles

    Science.gov (United States)

    Gordon, T. J.; Lidberg, M.

    2015-07-01

    In recent years, road vehicle automation has become an important and popular topic for research and development in both academic and industrial spheres. New developments have received extensive coverage in the popular press, and it may be said that the topic has captured the public imagination. Indeed, the topic has generated interest across a wide range of academic, industry and governmental communities, well beyond vehicle engineering; these include computer science, transportation, urban planning, legal, social science and psychology. While this follows a similar surge of interest - and subsequent hiatus - of Automated Highway Systems in the 1990s, the current level of interest is substantially greater, and current expectations are high. It is common to frame the new technologies under the banner of 'self-driving cars' - robotic systems potentially taking over the entire role of the human driver, a capability that does not fully exist at present. However, this single vision leads one to ignore the existing range of automated systems that are both feasible and useful. Recent developments are underpinned by substantial and long-term trends in 'computerisation' of the automobile, with developments in sensors, actuators and control technologies to spur the new developments in both industry and academia. In this paper, we review the evolution of the intelligent vehicle and the supporting technologies with a focus on the progress and key challenges for vehicle system dynamics. A number of relevant themes around driving automation are explored in this article, with special focus on those most relevant to the underlying vehicle system dynamics. One conclusion is that increased precision is needed in sensing and controlling vehicle motions, a trend that can mimic that of the aerospace industry, and similarly benefit from increased use of redundant by-wire actuators.

  12. Concept for a Lunar Transfer Vehicle for Small Satellite Delivery to the Moon from the International Space Station

    Science.gov (United States)

    Elliott, John; Alkalai, Leon

    2010-01-01

    The International Space Station (ISS) has developed as a very capable center for scientific research in Lower Earth Orbit. An additional potential of the ISS that has not thus far been exploited, is the use of this orbiting plat-form for the assembly and launching of vehicles that could be sent to more distant destinations. This paper reports the results of a recent study that looked at an architecture and conceptual flight system design for a lunar transfer vehicle (LTV) that could be delivered to the ISS in segments, assembled, loaded with payload and launched from the ISS with the objective of delivering multiple small and micro satellites to lunar orbit. The design of the LTV was optimized for low cost and high payload capability, as well as ease of assembly. The resulting design would use solar electric propulsion (SEP) to carry a total payload mass of 250 kg from the ISS to a 100 km lunar orbit. A preliminary concept of operations was developed considering currently available delivery options and ISS capabili-ties that should prove flexible enough to accommodate a variety of payloads and missions. This paper will present an overview of the study, including key trades, mission and flight system design, and notional operational concept.

  13. Transdermal delivery of ketorolac tromethamine: effects of vehicles and penetration enhancers.

    Science.gov (United States)

    Cho, Young Ah; Gwak, Hye Sun

    2004-07-01

    The effects of vehicles and penetration enhancers on the in vitro permeation of ketorolac tromethamine (KT) across excised hairless mouse skins were investigated. Among pure vehicles examined, propylene glycol monolaurate (PGML) showed the highest permeation flux, which was 94.3 +/- 17.3 microg/cm2/h. Even though propylene glycol monocaprylate (PGMC) alone did not show high permeation rate, the skin permeability of KT was markedly increased by the addition of diethylene glycol monoethyl ether (DGME); the enhancement factors were 19.0 and 17.1 at 20% and 40% of DGME, respectively. When DGME was added to PGML, the permeation fluxes were almost two times at 20-60% of DGME compared to PGML alone. In the cosolvent system consisting of propylene glycol (PG)-oleyl alcohol, the permeation rate increased as the ratio of PG increased. In the study to investigate the effect of drug concentration on the permeation rate of KT, the permeation rates increased as the drug concentration increased in all vehicles used, and the dramatic increase in permeation rate was obtained when the drug concentration was higher than its solubility. For the effects of fatty acids on the permeation of KT, five fatty acids were added to PG at concentrations of 1%-, 3%-, 5%- and 10%- caprylic acid, capric acid, lauric acid, oleic acid, and linoleic acid. The enhancing effects of fatty acids were different, depending on the concentration as well as the sort of fatty acids. The highest enhancing effect was attained with 10% caprylic acid in PG; the permeation flux was 113.6 +/- 17.5 microg/cm2/h. The lag time of KT was reduced as the concentration of fatty acids increased except for caprylic acid.

  14. Effect of neat and binary vehicle systems on the solubility and cutaneous delivery of piperine

    Directory of Open Access Journals (Sweden)

    Abdullah Hasan Alomrani

    2018-02-01

    Full Text Available Vitiligo is a skin disease characterized by depigmentation disorders due to lack of melanin production. Piperine, an alkaloid extracted from black piper, is active in melanocytes proliferation. To achieve this, the drug has to reach the melanocytes which exist in the deep layer of the epidermis. Higher drug concentration can be obtained after application of optimized formulation to skin. Accordingly, the aim of this work is to investigate the effect of vehicles on skin penetration of piperine as the first step in development of optimized formulation. The tested vehicles include ethanol (Eth, propylene glycol (PG, polyethylene glycol 400 (PEG, and oleic acid (OA and their combinations. Water was used as the control and skin permeation was monitored using rabbit ear model skin. The highest piperine solubility (48.6 mg/ml and flux (40.8 μg/cm2 h was achieved by Eth and the lowest piperine flux (1.17 μg/cm2 h was reported for PEG. PG and OA showed piperine flux values comparable to that of the control. Among different combination systems, Eth-OA (75:25 binary system had the highest piperine flux (59.3 μg/cm2 h followed by Eth-OA (50:50 (32.3 μg/cm2 h and PG-OA (90:10 (22.7 μg/cm2 h. The study thus introduced a vehicle system as the first step in the development of topical formulation of piperine.

  15. 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.

  16. AC133+ progenitor cells as gene delivery vehicle and cellular probe in subcutaneous tumor models: a preliminary study

    Directory of Open Access Journals (Sweden)

    Knight Robert A

    2009-03-01

    Full Text Available Abstract Background Despite enormous progress in gene therapy for breast cancer, an optimal systemic vehicle for delivering gene products to the target tissue is still lacking. The purpose of this study was to determine whether AC133+ progenitor cells (APC can be used as both gene delivery vehicles and cellular probes for magnetic resonance imaging (MRI. In this study, we used superparamagentic iron oxide (SPIO-labeled APCs to carry the human sodium iodide symporter (hNIS gene to the sites of implanted breast cancer in mouse model. In vivo real time tracking of these cells was performed by MRI and expression of hNIS was determined by Tc-99m pertechnetate (Tc-99m scan. Results Three million human breast cancer (MDA-MB-231 cells were subcutaneously implanted in the right flank of nude mice. APCs, isolated from fresh human cord blood, were genetically transformed to carry the hNIS gene using adenoviral vectors and magnetically labeled with ferumoxides-protamine sulfate (FePro complexes. Magnetically labeled genetically transformed cells were administered intravenously in tumor bearing mice when tumors reached 0.5 cm in the largest dimension. MRI and single photon emission computed tomography (SPECT images were acquired 3 and 7 days after cell injection, with a 7 Tesla animal MRI system and a custom built micro-SPECT using Tc-99m, respectively. Expression of hNIS in accumulated cells was determined by staining with anti-hNIS antibody. APCs were efficiently labeled with ferumoxide-protamine sulfate (FePro complexes and transduced with hNIS gene. Our study showed not only the accumulation of intravenously administered genetically transformed, magnetically labeled APCs in the implanted breast cancer, but also the expression of hNIS gene at the tumor site. Tc-99m activity ratio (tumor/non-tumor was significantly different between animals that received non-transduced and transduced cells (P Conclusion This study indicates that genetically transformed

  17. Myeloid-derived suppressor cells as a Trojan horse: A cellular vehicle for the delivery of oncolytic viruses.

    Science.gov (United States)

    Pan, Ping-Ying; Chen, Hui-Ming; Chen, Shu-Hsia

    2013-08-01

    We have recently demonstrated that oncolytic vesicular stomatitis viruses can be efficiently and selectively delivered to neoplastic lesions by myeloid-derived suppressor cells (MDSCs). Importantly, the loading of viruses onto MDSCs inhibited their immunosuppressive properties and endowed them with immunostimulatory and tumoricidal functions. Our study demonstrates the potential use of MDSCs as a Trojan horse for the tumor-targeted delivery of various anticancer therapeutics.

  18. Chitosan-Poly (I:C-PADRE Based Nanoparticles as Delivery Vehicles for Synthetic Peptide Vaccines

    Directory of Open Access Journals (Sweden)

    Jorge F. Correia-Pinto

    2015-09-01

    Full Text Available The safety and precision of peptide antigens has prompted the search for adjuvants capable of increasing the immune response against these intrinsically poorly immunogenic antigens. The integration of both immunostimulants and peptide antigens within nanometric delivery systems for their co-delivery to immune cells is a promising vaccination strategy. With this in mind, the potential synergistic effect of the immunostimulant poly (I:C (pIC and a T-Helper peptide (PADRE, integrated into a chitosan (CS based nanostructure, was explored. The value of this nanostructured combination of materials was assessed for a peptide antigen (1338aa derived from the HPV-16 L2 protein. These nanoparticles, produced by ionic gelation technique, exhibited a nanometric size (<300 nm, a high positive surface charge (>40 mV and high pIC association efficiency (>96%. They also showed capacity for the association of both the 1338aa and PADRE peptides. The influence of the presence of pIC and PADRE in the nanocomposition, as well as that of the peptide presentation form (encapsulated versus surface adsorbed on the antibody induction was evaluated in a preliminary in vivo study. The data obtained highlights the possibility to engineer nanoparticles through the rational combination of a number of adjuvant molecules together with the antigen.

  19. Investigating the In-Vehicle Crowding Cost Functions for Public Transit Modes

    Directory of Open Access Journals (Sweden)

    Feifei Qin

    2014-01-01

    Full Text Available In the densely populated metropolitan area, empirical studies have found that overcrowding inside transit vehicles has become substantially worse and worse over recent years. Chronic in-vehicle crowding is not only caused by a lack of physical infrastructure, but also triggered by inadequate service provisions. Given the prevalence of overcrowded transit vehicles, this paper conducts both quantitative and qualitative studies, especially focusing on remodeling the in-vehicle crowding cost functions for different transit modes. Three numerical case studies show that applying distinct in-vehicle crowding cost functions to different transit modes has implications not only for the cost structure of transit systems and the magnitude of optimal service provisions but also for the presence of economies of scale in consumption.

  20. 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.

  1. Hyaluronic acid: a unique topical vehicle for the localized delivery of drugs to the skin.

    Science.gov (United States)

    Brown, M B; Jones, S A

    2005-05-01

    Hyaluronic acid (HA) is a naturally occurring polyanionic, polysaccharide that consists of N-acetyl-D-glucosamine and beta-glucoronic acid. It is present in the intercellular matrix of most vertebrate connective tissues especially skin where it has a protective, structure stabilizing and shock-absorbing role. The unique viscoelastic nature of HA along with its biocompatibility and non-immunogenicity has led to its use in a number of clinical applications, which include: the supplementation of joint fluid in arthritis; as a surgical aid in eye surgery; and to facilitate the healing and regeneration of surgical wounds. More recently, HA has been investigated as a drug delivery agent for various routes of administration, including ophthalmic, nasal, pulmonary, parenteral and topical. In fact, regulatory approval in the USA, Canada and Europe was granted recently for 3% diclofenac in 2.5% HA gel, Solaraze, for the topical treatment of actinic keratoses, which is the third most common skin complaint in the USA. The gel is well tolerated, safe and efficacious and provides an attractive, cost-effective alternative to cryoablation, curettage or dermabrasion, or treatment with 5-fluorouracil. The purpose of this review is to describe briefly the physical, chemical and biological properties of HA together with some details of its medical and pharmaceutical uses with emphasis on this more recent topical application.

  2. Novel Hydrogel-Advanced Modified Clay Nanocomposites as Possible Vehicles for Drug Delivery and Controlled Release

    Directory of Open Access Journals (Sweden)

    Raluca Ianchis

    2017-12-01

    Full Text Available Present study refers to the synthesis of new advanced materials based on poly(methacrylic acid (PMAA with previously reported own advanced modified clays by edge covalent bonding. This will create the premises to obtain nanocomposite hydrogels with combined hydrophilic-hydrophobic behavior absolutely necessary for co-delivery of polar/nonpolar substances. For the synthesis, N,N’-methylenebisacrylamide was used as cross-linker and ammonium persulphate as initiator. As a consequence of the inclusion of clay into the polymer matrix and the intercalation of PMAA between the layers as well as the presence of hydrophobic interactions occurred between partners, the final hydrogel nanocomposites possessed greater swelling degrees, slower de-swelling process and enhanced mechanical properties depending on the clay type in comparison with pure hydrogel. In vitro MTS ([3-(4,5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium, inner salt] colorimetric assay showed that direct exposure with PMMA-clay-based constructs did not affect cell viability and proliferation in time (24 and 48 h on either normal or adenocarcinoma cell lines.

  3. Novel Hydrogel-Advanced Modified Clay Nanocomposites as Possible Vehicles for Drug Delivery and Controlled Release.

    Science.gov (United States)

    Ianchis, Raluca; Ninciuleanu, Claudia M; Gifu, Ioana C; Alexandrescu, Elvira; Somoghi, Raluca; Gabor, Augusta R; Preda, Silviu; Nistor, Cristina L; Nitu, Sabina; Petcu, Cristian; Icriverzi, Madalina; Florian, Paula E; Roseanu, Anca M

    2017-12-13

    Present study refers to the synthesis of new advanced materials based on poly(methacrylic acid) (PMAA) with previously reported own advanced modified clays by edge covalent bonding. This will create the premises to obtain nanocomposite hydrogels with combined hydrophilic-hydrophobic behavior absolutely necessary for co-delivery of polar/nonpolar substances. For the synthesis, N , N '-methylenebisacrylamide was used as cross-linker and ammonium persulphate as initiator. As a consequence of the inclusion of clay into the polymer matrix and the intercalation of PMAA between the layers as well as the presence of hydrophobic interactions occurred between partners, the final hydrogel nanocomposites possessed greater swelling degrees, slower de-swelling process and enhanced mechanical properties depending on the clay type in comparison with pure hydrogel. In vitro MTS ([3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H -tetrazolium, inner salt]) colorimetric assay showed that direct exposure with PMMA-clay-based constructs did not affect cell viability and proliferation in time (24 and 48 h) on either normal or adenocarcinoma cell lines.

  4. Use of traditional African fermented beverages as delivery vehicles for Bifidobacterium lactis DSM 10140.

    Science.gov (United States)

    McMaster, L D; Kokott, S A; Reid, S J; Abratt, V R

    2005-07-15

    A microencapsulation delivery system for Bifidobacterium lactis, a possible probiotic suited for use by the rural population of South Africa, was evaluated using two existing traditional fermented foods, amasi and mahewu. Gellan/xanthan microcapsules containing viable B. lactis, were tested under simulated physiological conditions, and added to pasteurized beverages. The capsules protected the organism under simulated low pH conditions associated with the stomach and from the biocidal activity of pancreatic and bile acids. For mahewu, microencapsulation of B. lactis with storage aerobically at 4 degrees C and 22 degrees C enhanced survival over a 21-day period as compared to free cells. In amasi, differences in viability between immobilized and free cells were less noticeable. An analytically trained taste panel was unable to detect a significant difference in texture in any of the samples fortified with microcapsules. Although flavour differences were noted for mahewu containing either free or immobilized cells, after 14 days refrigerated storage, these were not disliked. No significant flavour difference was noted between amasi containing immobilized cells and untreated controls over the period tested.

  5. Future Directions in the Design, Development, and Investigation of Technology as a Service Delivery Vehicle

    Science.gov (United States)

    Jones, Deborah J.

    2013-01-01

    Treatment outcome research with children and adolescents has progressed to such an extent that numerous handbooks have been devoted to reviewing and summarizing the evidence base. Ensuring that consumers of these advancements in state-of-the-field interventions have the opportunity to access, engage in, and benefit from this evidence-base, however, has been wrought with challenge. As such, much discussion exists about innovative strategies for overcoming the gap between research and practice; yet, no other potential solution that has received more attention in both the popular and academic press than technology. The promise of technology is not surprising given the fast-paced evolution in development and, in turn, a seemingly endless range of possibilities for novel service delivery platforms. Yet, this is precisely the most formidable challenge threatening to upset the very promise of this potential solution: The rate of emerging technologies is far outpacing the field’s capacity to demonstrate the conceptual or empirical benefits of such an approach. Accordingly, this paper aims to provide a series of recommendations that better situate empirical enquiry at the core of a collaborative development, testing, and deployment process that must define this line of work if the promise of mental health technologies is going to be a reality for front-line clinicians and the clients they serve. PMID:24400723

  6. Preservation of surface-dependent properties of viral antigens following immobilization on particulate ceramic delivery vehicles.

    Science.gov (United States)

    Kossovsky, N; Gelman, A; Sponsler, E; Rajguru, S; Torres, M; Mena, E; Ly, K; Festekjian, A

    1995-05-01

    B-cell stimulation for the purpose of evoking an effective neutralizing humoral immune response is a surface phenomenon that is exquisitely specific to antigen conformation. Consequently, successful delivery of antigen, such as would be desired in a vaccine, entails preservation of an antigen's apparent native surface (conformational) properties. Prior to testing the actual vaccinating efficacy of delivered antigens, the surface properties could be assessed through a variety of in vitro and in vivo assays in which the measurement standard would be the properties of the antigens in their native state (whole virus). Using surface modified nanocrystalline carbon and calcium-phosphate ceramic particulates (carbon ceramics and brushite), we evaluated the surface activity of immobilized non-nuclear material extracted from HIV-1. Physical characterization showed that the particles with immobilized antigen ("HIV decoys") measured 50 nm in diameter (HIV = 50-100 nm) and exhibited the same zeta potentials as whole (live) HIV. In vitro testing showed that the HIV decoys were recognized by both conformationally nonspecific and specific monoclonal antibodies, were recognized by human IgG from HIV antibody-positive patients, and could promote surface agglomeration among malignant T-cells similar to live HIV. Last, in vivo testing in three vaccinated animal species showed that the HIV decoys elicited humoral and cellular immune responses similar to that evoked by whole (live) HIV.

  7. A novel injectable borate bioactive glass cement as an antibiotic delivery vehicle for treating osteomyelitis.

    Science.gov (United States)

    Ding, Hao; Zhao, Cun-Ju; Cui, Xu; Gu, Yi-Fei; Jia, Wei-Tao; Rahaman, Mohamed N; Wang, Yang; Huang, Wen-Hai; Zhang, Chang-Qing

    2014-01-01

    A novel injectable cement composed of chitosan-bonded borate bioactive glass (BG) particles was evaluated as a carrier for local delivery of vancomycin in the treatment of osteomyelitis in a rabbit tibial model. The setting time, injectability, and compressive strength of the borate BG cement, and the release profile of vancomycin from the cement were measured in vitro. The capacity of the vancomycin-loaded BG cement to eradicate methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis in rabbit tibiae in vivo was evaluated and compared with that for a vancomycin-loaded calcium sulfate (CS) cement and for intravenous injection of vancomycin. The BG cement had an injectability of >90% during the first 3 minutes after mixing, hardened within 30 minutes and, after hardening, had a compressive strength of 18 ± 2 MPa. Vancomycin was released from the BG cement into phosphate-buffered saline for up to 36 days, and the cumulative amount of vancomycin released was 86% of the amount initially loaded into the cement. In comparison, vancomycin was released from the CS cement for up 28 days and the cumulative amount released was 89%. Two months post-surgery, radiography and microbiological tests showed that the BG and CS cements had a better ability to eradicate osteomyelitis when compared to intravenous injection of vancomycin, but there was no significant difference between the BG and CS cements in eradicating the infection. Histological examination showed that the BG cement was biocompatible and had a good capacity for regenerating bone in the tibial defects. These results indicate that borate BG cement is a promising material both as an injectable carrier for vancomycin in the eradication of osteomyelitis and as an osteoconductive matrix to regenerate bone after the infection is cured.

  8. A novel injectable borate bioactive glass cement as an antibiotic delivery vehicle for treating osteomyelitis.

    Directory of Open Access Journals (Sweden)

    Hao Ding

    Full Text Available BACKGROUND: A novel injectable cement composed of chitosan-bonded borate bioactive glass (BG particles was evaluated as a carrier for local delivery of vancomycin in the treatment of osteomyelitis in a rabbit tibial model. MATERIALS AND METHODS: The setting time, injectability, and compressive strength of the borate BG cement, and the release profile of vancomycin from the cement were measured in vitro. The capacity of the vancomycin-loaded BG cement to eradicate methicillin-resistant Staphylococcus aureus (MRSA-induced osteomyelitis in rabbit tibiae in vivo was evaluated and compared with that for a vancomycin-loaded calcium sulfate (CS cement and for intravenous injection of vancomycin. RESULTS: The BG cement had an injectability of >90% during the first 3 minutes after mixing, hardened within 30 minutes and, after hardening, had a compressive strength of 18 ± 2 MPa. Vancomycin was released from the BG cement into phosphate-buffered saline for up to 36 days, and the cumulative amount of vancomycin released was 86% of the amount initially loaded into the cement. In comparison, vancomycin was released from the CS cement for up 28 days and the cumulative amount released was 89%. Two months post-surgery, radiography and microbiological tests showed that the BG and CS cements had a better ability to eradicate osteomyelitis when compared to intravenous injection of vancomycin, but there was no significant difference between the BG and CS cements in eradicating the infection. Histological examination showed that the BG cement was biocompatible and had a good capacity for regenerating bone in the tibial defects. CONCLUSIONS: These results indicate that borate BG cement is a promising material both as an injectable carrier for vancomycin in the eradication of osteomyelitis and as an osteoconductive matrix to regenerate bone after the infection is cured.

  9. 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

  10. 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.

  11. Octa-ammonium POSS-conjugated single-walled carbon nanotubes as vehicles for targeted delivery of paclitaxel

    Directory of Open Access Journals (Sweden)

    Naghmeh Naderi

    2015-09-01

    Full Text Available Background: Carbon nanotubes (CNTs have unique physical and chemical properties. Furthermore, novel properties can be developed by attachment or encapsulation of functional groups. These unique properties facilitate the use of CNTs in drug delivery. We developed a new nanomedicine consisting of a nanocarrier, cell-targeting molecule, and chemotherapeutic drug and assessed its efficacy in vitro. Methods: The efficacy of a single-walled carbon nanotubes (SWCNTs-based nanoconjugate system is assessed in the targeted delivery of paclitaxel (PTX to cancer cells. SWCNTs were oxidized and reacted with octa-ammonium polyhedral oligomeric silsesquioxanes (octa-ammonium POSS to render them biocompatible and water dispersable. The functionalized SWCNTs were loaded with PTX, a chemotherapeutic agent toxic to cancer cells, and Tn218 antibodies for cancer cell targeting. The nanohybrid composites were characterized with transmission electron microscopy (TEM, Fourier transform infrared (FTIR, and ultraviolet–visible–near-infrared (UV–Vis–NIR. Additionally, their cytotoxic effects on Colon cancer cell (HT-29 and Breast cancer cell (MCF-7 lines were assessed in vitro. Results: TEM, FTIR, and UV–Vis–NIR studies confirmed side-wall functionalization of SWCNT with COOH-groups, PTX, POSS, and antibodies. Increased cell death was observed with PTX–POSS–SWCNT, PTX–POSS–Ab–SWCNT, and free PTX compared to functionalized-SWCNT (f-SWCNT, POSS–SWCNT, and cell-only controls at 48 and 72 h time intervals in both cell lines. At all time intervals, there was no significant cell death in the POSS–SWCNT samples compared to cell-only controls. Conclusion: The PTX-based nanocomposites were shown to be as cytotoxic as free PTX. This important finding indicates successful release of PTX from the nanocomposites and further reiterates the potential of SWCNTs to deliver drugs directly to targeted cells and tissues.

  12. 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.

  13. Intrinsically disordered amphiphilic peptides as potential targets in drug delivery vehicles.

    Science.gov (United States)

    Vincenzi, Marian; Accardo, Antonella; Costantini, Susan; Scala, Stefania; Portella, Luigi; Trotta, Annamaria; Ronga, Luisa; Guillon, Jean; Leone, Marilisa; Colonna, Giovanni; Rossi, Filomena; Tesauro, Diego

    2015-11-01

    Intrinsically disordered proteins/peptides play a crucial role in many physiological and pathological events and may assume a precise conformation upon binding to a specific target. Recently, we have described the conformational and functional properties of two linear ester peptides provided with the following sequences: Y-G-E-C-P-C-K-OAllyl (PepK) and Y-G-E-C-P-C-E-OAllyl (PepE). Both peptides are characterized by the presence of the "CPC" motif together with a few amino acids able to promote disorder. The CPC sequence is a binding motif for the CXCR4 receptor that represents a well-known target for cancer therapies. In this paper, we report on synthetic amphiphilic peptides that consist of lipophilic derivatives of PepE and PepK bearing two stearic alkyl chains and/or an ethoxylic spacer. These peptide amphiphiles form stable supramolecular aggregates; they present conformational features that are typical of intrinsically disordered molecules as shown by CD spectroscopy. Solution fluorescence and DLS studies have been performed to evaluate Critical Micellar Concentrations and the dimension of supramolecular aggregates. Moreover, preliminary in vitro cell-based assays have been conducted to investigate the molecular recognition processes involving the CXCR4 receptor. In the end, the results obtained have been compared with the previous data generated by the corresponding non-amphiphilic peptides (PepE and PepK).

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

    Directory of Open Access Journals (Sweden)

    Ali Özler

    2013-12-01

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

  15. The Entropy-Cost Function Evaluation Method for Unmanned Ground Vehicles

    Directory of Open Access Journals (Sweden)

    Ya-Nan Zhao

    2015-01-01

    Full Text Available To improve the technology of unmanned ground vehicles, it is necessary to conduct a proper evaluation on various technologies. Previous evaluation methods are mainly based on completion of the task; this may mislead most of teams of unmanned ground vehicles using a conservative strategy during the evaluation. In this paper, a new evaluation method is proposed. Based on typical working conditions including intersection, car-following, and obstacle-avoiding, the new evaluation indicator system is established, and the entropy-cost function method is applied to the comprehensive evaluation of unmanned ground vehicles. As reported in a numerical example, the proposed evaluation method can get a quantitative result that authentically reflects the intelligent behavior level of unmanned ground vehicles.

  16. Microemulsion loaded hydrogel as a promising vehicle for dermal delivery of the antifungal sertaconazole: design, optimization and ex vivo evaluation.

    Science.gov (United States)

    Radwan, Shaimaa Ali Ali; ElMeshad, Aliaa Nabil; Shoukri, Raguia Aly

    2017-08-01

    The purpose of the present study was to develop and optimize sertaconazole microemulsion-loaded hydrogel (STZ ME G) to enhance the dermal delivery and skin retention of the drug. Following screening of various oils for maximum drug solubility, 12 pseudoternary phase diagrams were constructed using oils (Peceol ® , Capryol ® 90), surfactants (Tween ® 80, Cremophor ® EL), a cosurfactant (Transcutol ® P) and water. A 2 1 × 3 1 × 2 1 × 3 1 full factorial design was employed to optimize a ME of desirable characteristics. The MEs were formulated by varying the oil type, oil concentration, surfactant type and surfactant: cosurfactant ratio. Optimized ME formulae F22 [5% Peceol ® , 55% Tween ® 80: Transcutol ® (1:2), 40% water] and F31 [5% Peceol ® , 55% Cremophor ® EL: Transcutol ® (1:2), 40% water] acquired mean droplet size of 75.21 and 8.68 nm, and zeta potential of 34.65 and 24.05 mV, respectively. Since F22 showed higher STZ skin retention during ex vivo studies (686.47 μg/cm 2 ) than F31 (338.11 μg/cm 2 ); hence it was incorporated in 0.5% Carbopol 934 gel to augment STZ skin retention capability. STZ ME G exhibited higher STZ skin retention (1086.1 μg/cm 2 ) than the marketed product "Dermofix ® cream" (270.3 μg/cm 2 ). The antimycotic activity against C.albicans revealed increased zones of inhibition for F22 and STZ ME G (35.75 and 30.5 mm, respectively) compared to Dermofix ® cream (26 mm). No histopathological changes were observed following topical application of STZ ME G on rats' skin (n = 9). Overall, the obtained results confirmed that the fabricated formulation could be a promising vehicle for the dermal delivery of STZ.

  17. Mathematical modelling of active safety system functions as tools for development of driverless vehicles

    Science.gov (United States)

    Ryazantsev, V.; Mezentsev, N.; Zakharov, A.

    2018-02-01

    This paper is dedicated to a solution of the issue of synthesis of the vehicle longitudinal dynamics control functions (acceleration and deceleration control) based on the element base of the vehicle active safety system (ESP) - driverless vehicle development tool. This strategy helps to reduce time and complexity of integration of autonomous motion control systems (AMCS) into the vehicle architecture and allows direct control of actuators ensuring the longitudinal dynamics control, as well as reduction of time for calibration works. The “vehicle+wheel+road” longitudinal dynamics control is complicated due to the absence of the required prior information about the control object. Therefore, the control loop becomes an adaptive system, i.e. a self-adjusting monitoring system. Another difficulty is the driver’s perception of the longitudinal dynamics control process in terms of comfort. Traditionally, one doesn’t pay a lot of attention to this issue within active safety systems, and retention of vehicle steerability, controllability and stability in emergency situations are considered to be the quality criteria. This is mainly connected to its operational limits, since it is activated only in critical situations. However, implementation of the longitudinal dynamics control in the AMCS poses another challenge for the developers - providing the driver with comfortable vehicle movement during acceleration and deceleration - while the possible highest safety level in terms of the road grip is provided by the active safety system (ESP). The results of this research are: universal active safety system - AMCS interaction interface; block diagram for the vehicle longitudinal acceleration and deceleration control as one of the active safety system’s integrated functions; ideology of adaptive longitudinal dynamics control, which enables to realize the deceleration and acceleration requested by the AMCS; algorithms synthesised; analytical experiments proving the

  18. Smart materials on the way to theranostic nanorobots: Molecular machines and nanomotors, advanced biosensors, and intelligent vehicles for drug delivery.

    Science.gov (United States)

    Sokolov, Ilya L; Cherkasov, Vladimir R; Tregubov, Andrey A; Buiucli, Sveatoslav R; Nikitin, Maxim P

    2017-06-01

    Theranostics, a fusion of two key parts of modern medicine - diagnostics and therapy of the organism's disorders, promises to bring the efficacy of medical treatment to a fundamentally new level and to become the basis of personalized medicine. Extrapolating today's progress in the field of smart materials to the long-run prospect, we can imagine future intelligent agents capable of performing complex analysis of different physiological factors inside the living organism and implementing a built-in program thereby triggering a series of therapeutic actions. These agents, by analogy with their macroscopic counterparts, can be called nanorobots. It is quite obscure what these devices are going to look like but they will be more or less based on today's achievements in nanobiotechnology. The present Review is an attempt to systematize highly diverse nanomaterials, which may potentially serve as modules for theranostic nanorobotics, e.g., nanomotors, sensing units, and payload carriers. Biocomputing-based sensing, externally actuated or chemically "fueled" autonomous movement, swarm inter-agent communication behavior are just a few inspiring examples that nanobiotechnology can offer today for construction of truly intelligent drug delivery systems. The progress of smart nanomaterials toward fully autonomous drug delivery nanorobots is an exciting prospect for disease treatment. Synergistic combination of the available approaches and their further development may produce intelligent drugs of unmatched functionality. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Motion planning for autonomous vehicle based on radial basis function neural network in unstructured environment.

    Science.gov (United States)

    Chen, Jiajia; Zhao, Pan; Liang, Huawei; Mei, Tao

    2014-09-18

    The autonomous vehicle is an automated system equipped with features like environment perception, decision-making, motion planning, and control and execution technology. Navigating in an unstructured and complex environment is a huge challenge for autonomous vehicles, due to the irregular shape of road, the requirement of real-time planning, and the nonholonomic constraints of vehicle. This paper presents a motion planning method, based on the Radial Basis Function (RBF) neural network, to guide the autonomous vehicle in unstructured environments. The proposed algorithm extracts the drivable region from the perception grid map based on the global path, which is available in the road network. The sample points are randomly selected in the drivable region, and a gradient descent method is used to train the RBF network. The parameters of the motion-planning algorithm are verified through the simulation and experiment. It is observed that the proposed approach produces a flexible, smooth, and safe path that can fit any road shape. The method is implemented on autonomous vehicle and verified against many outdoor scenes; furthermore, a comparison of proposed method with the existing well-known Rapidly-exploring Random Tree (RRT) method is presented. The experimental results show that the proposed method is highly effective in planning the vehicle path and offers better motion quality.

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

    Directory of Open Access Journals (Sweden)

    Feng Jiang

    2015-10-01

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

  1. Controlling Fungal Biofilms with Functional Drug Delivery Denture Biomaterials

    OpenAIRE

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

    2015-01-01

    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 ...

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

    NARCIS (Netherlands)

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

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

  3. 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.

  4. 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.

  5. 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.

  6. Selective atonal gene delivery improves balance function in a mouse model of vestibular disease.

    Science.gov (United States)

    Schlecker, C; Praetorius, M; Brough, D E; Presler, R G; Hsu, C; Plinkert, P K; Staecker, H

    2011-09-01

    Loss of balance is often due to loss of vestibular hair cells. In mammals, regeneration of functional hair cells in the mature sensory epithelium is limited; therefore, loss of sensory cells can lead to debilitating balance problems. Delivery of the transcription factor atonal (atoh1) after aminoglycoside ototoxicity has previously been shown to induce the transdifferentiation of supporting cells into new hair cells and restore function. A problem with mouse aminoglycoside models is that the partial loss of hair cells seen in human disease is difficult to establish consistently. To more closely mirror human clinical balance dysfunction, we have used systemic application of 3,3'-iminodipropionitrile (IDPN), a vestibulotoxic nitrile compound known to cause vestibular hair cell loss, to induce a consistent partial loss of vestibular hair cells. To determine if balance function could be restored, we delivered atoh1 using a new adenovirus vector, based on Ad28. The Ad28 adenovector is based on a human serotype with a low seroprevalence that appears to target gene delivery to vestibular supporting cells. To further provide cell type selectivity of gene delivery, we expressed atoh1 using the supporting cell-specific glial fibrillary acid protein promoter. Delivery of this vector to IDPN-damaged vestibular organs resulted in a significant recovery of vestibular hair cells and restoration of balance, as measured by time on rotarod compared with untreated controls.

  7. In-Use and Vehicle Dynamometer Evaluation and Comparison of Class 7 Hybrid Electric and Conventional Diesel Delivery Trucks

    Energy Technology Data Exchange (ETDEWEB)

    Burton, J.; Walkowicz, K.; Sindler, P.; Duran, A.

    2013-10-01

    This study compared fuel economy and emissions between heavy-duty hybrid electric vehicles (HEVs) and equivalent conventional diesel vehicles. In-use field data were collected from daily fleet operations carried out at a FedEx facility in California on six HEV and six conventional 2010 Freightliner M2-106 straight box trucks. Field data collection primarily focused on route assessment and vehicle fuel consumption over a six-month period. Chassis dynamometer testing was also carried out on one conventional vehicle and one HEV to determine differences in fuel consumption and emissions. Route data from the field study was analyzed to determine the selection of dynamometer test cycles. From this analysis, the New York Composite (NYComp), Hybrid Truck Users Forum Class 6 (HTUF 6), and California Air Resource Board (CARB) Heavy Heavy-Duty Diesel Truck (HHDDT) drive cycles were chosen. The HEV showed 31% better fuel economy on the NYComp cycle, 25% better on the HTUF 6 cycle and 4% worse on the CARB HHDDT cycle when compared to the conventional vehicle. The in-use field data indicates that the HEVs had around 16% better fuel economy than the conventional vehicles. Dynamometer testing also showed that the HEV generally emitted higher levels of nitric oxides than the conventional vehicle over the drive cycles, up to 77% higher on the NYComp cycle (though this may at least in part be attributed to the different engine certification levels in the vehicles tested). The conventional vehicle was found to accelerate up to freeway speeds over ten seconds faster than the HEV.

  8. Retargeting Clostridium difficile Toxin B to Neuronal Cells as a Potential Vehicle for Cytosolic Delivery of Therapeutic Biomolecules to Treat Botulism

    Directory of Open Access Journals (Sweden)

    Greice Krautz-Peterson

    2012-01-01

    Full Text Available Botulinum neurotoxins (BoNTs deliver a protease to neurons which can cause a flaccid paralysis called botulism. Development of botulism antidotes will require neuronal delivery of agents that inhibit or destroy the BoNT protease. Here, we investigated the potential of engineering Clostridium difficile toxin B (TcdB as a neuronal delivery vehicle by testing two recombinant TcdB chimeras. For AGT-TcdB chimera, an alkyltransferase (AGT was appended to the N-terminal glucosyltransferase (GT of TcdB. Recombinant AGT-TcdB had alkyltransferase activity, and the chimera was nearly as toxic to Vero cells as wild-type TcdB, suggesting efficient cytosolic delivery of the AGT/GT fusion. For AGT-TcdB-BoNT/A-Hc, the receptor-binding domain (RBD of TcdB was replaced by the equivalent RBD from BoNT/A (BoNT/A-Hc. AGT-TcdB-BoNT/A-Hc was >25-fold more toxic to neuronal cells and >25-fold less toxic to Vero cells than AGT-TcdB. Thus, TcdB can be engineered for cytosolic delivery of biomolecules and improved targeting of neuronal cells.

  9. Robust Predictive Functional Control for Flight Vehicles Based on Nonlinear Disturbance Observer

    Directory of Open Access Journals (Sweden)

    Yinhui Zhang

    2015-01-01

    Full Text Available A novel robust predictive functional control based on nonlinear disturbance observer is investigated in order to address the control system design for flight vehicles with significant uncertainties, external disturbances, and measurement noise. Firstly, the nonlinear longitudinal dynamics of the flight vehicle are transformed into linear-like state-space equations with state-dependent coefficient matrices. And then the lumped disturbances are considered in the linear structure predictive model of the predictive functional control to increase the precision of the predictive output and resolve the intractable mismatched disturbance problem. As the lumped disturbances cannot be derived or measured directly, the nonlinear disturbance observer is applied to estimate the lumped disturbances, which are then introduced to the predictive functional control to replace the unknown actual lumped disturbances. Consequently, the robust predictive functional control for the flight vehicle is proposed. Compared with the existing designs, the effectiveness and robustness of the proposed flight control are illustrated and validated in various simulation conditions.

  10. Functional safety for road vehicles new challenges and solutions for e-mobility and automated driving

    CERN Document Server

    Ross, Hans-Leo

    2016-01-01

    This book highlights the current challenges for engineers involved in product development and the associated changes in procedure they make necessary. Methods for systematically analyzing the requirements for safety and security mechanisms are described using examples of how they are implemented in software and hardware, and how their effectiveness can be demonstrated in terms of functional and design safety are discussed. Given today’s new E-mobility and automated driving approaches, new challenges are arising and further issues concerning “Road Vehicle Safety” and “Road Traffic Safety” have to be resolved. To address the growing complexity of vehicle functions, as well as the increasing need to accommodate interdisciplinary project teams, previous development approaches now have to be reconsidered, and system engineering approaches and proven management systems need to be supplemented or wholly redefined. The book presents a continuous system development process, starting with the basic requiremen...

  11. 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.

  12. A Multi-Function Conversion Technique for Vehicle-to-Grid Applications

    Directory of Open Access Journals (Sweden)

    Ying Fan

    2015-07-01

    Full Text Available This paper presents a new multi-function conversion technique for vehicle-to-grid (V2G applications. The proposed bi-directional charger can achieve three functions, including EV battery charging, grid-connection and reactive compensation, which are keys for energy management of the grid. With the proposed multi-function technology, the bi-directional charger will benefit both the grid and electricity customers. A hybrid regulation of energy bi-directional transfer for V2G systems is proposed in this paper, which consists of the battery-side controller and the grid-side controller. This proposed multi-function conversion technique improves the whole system performance with proportional-resonant (PR control and achieves reactive power compensation with instantaneous reactive theory and a deadbeat control scheme. Simulation and experimental results demonstrate the validity of this new multi-function technique in a V2G system.

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

    Science.gov (United States)

    Coyuco, Jurja C; Liu, Yuanjie; Tan, Bee-Jen; Chiu, Gigi NC

    2011-01-01

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

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

    Science.gov (United States)

    Coyuco, Jurja C; Liu, Yuanjie; Tan, Bee-Jen; Chiu, Gigi N C

    2011-01-01

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

  15. 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

  16. Development of Fully Degradable Phosphonium-Functionalized Amphiphilic Diblock Copolymers for Nucleic Acids Delivery.

    Science.gov (United States)

    Borguet, Yannick P; Khan, Sarosh; Noel, Amandine; Gunsten, Sean P; Brody, Steven L; Elsabahy, Mahmoud; Wooley, Karen L

    2018-03-11

    To expand the range of functional polymer materials to include fully hydrolytically degradable systems that bear bioinspired phosphorus-containing linkages both along the backbone and as cationic side chain moieties for packaging and delivery of nucleic acids, phosphonium-functionalized polyphosphoester- block-poly(l-lactide) copolymers of various compositions were synthesized, fully characterized, and their self-assembly into nanoparticles were studied. First, an alkyne-functionalized polyphosphoester- block-poly(l-lactide) copolymer was synthesized via a one pot sequential ring opening polymerization of an alkyne-functionalized phospholane monomer, followed by the addition of l-lactide to grow the second block. Second, the alkynyl side groups of the polyphosphoester block were functionalized via photoinitiated thiol-yne radical addition of a phosphonium-functionalized free thiol. The polymers of varying phosphonium substitution degrees were self-assembled in aqueous buffers to afford formation of well-defined core-shell assemblies with an average size ranging between 30 and 50 nm, as determined by dynamic light scattering. Intracellular delivery of the nanoparticles and their effects on cell viability and capability at enhancing transfection efficiency of nucleic acids (e.g., siRNA) were investigated. Cell viability assays demonstrated limited toxicity of the assembly to RAW 264.7 mouse macrophages, except at high polymer concentrations, where the polymer of high degree of phosphonium functionalization induced relatively higher cytotoxicity. Transfection efficiency was strongly affected by the phosphonium-to-phosphate (P + /P - ) ratios of the polymers and siRNA, respectively. The AllStars Hs Cell Death siRNA complexed to the various copolymers at a P + /P - ratio of 10:1 induced comparable cell death to Lipofectamine. These fully degradable nanoparticles might provide biocompatible nanocarriers for therapeutic nucleic acid delivery.

  17. Hydraulic Hybrid Vehicles

    Science.gov (United States)

    EPA and the United Parcel Service (UPS) have developed a hydraulic hybrid delivery vehicle to explore and demonstrate the environmental benefits of the hydraulic hybrid for urban pick-up and delivery fleets.

  18. Virosome, a hybrid vehicle for efficient and safe drug delivery and its emerging application in cancer treatment

    Directory of Open Access Journals (Sweden)

    Liu Hanqing

    2015-06-01

    Full Text Available A virosome is an innovative hybrid drug delivery system with advantages of both viral and non-viral vectors. Studies have shown that a virosome can carry various biologically active molecules, such as nucleic acids, peptides, proteins and small organic molecules. Targeted drug delivery using virosome-based systems can be achieved through surface modifications of virosomes. A number of virosome- -based prophylactic and therapeutic products with high safety profiles are currently available in the market. Cancer treatment is a big battlefield for virosome-based drug delivery systems. This review provides an overview of the general concept, preparation procedures, working mechanisms, preclinical studies and clinical applications of virosomes in cancer treatment.

  19. A Multi-Depot Two-Echelon Vehicle Routing Problem with Delivery Options Arising in the Last Mile Distribution

    NARCIS (Netherlands)

    Zhou, Lin; Baldacci, Roberto; Vigo, Daniele; Wang, Xu

    2018-01-01

    In this paper, we introduce a new city logistics problem arising in the last mile distribution of e-commerce. The problem involves two levels of routing problems. The first requires a design of the routes for a vehicle fleet located at the depots to transport the customer demands to a subset of the

  20. Implications of Functional Capacity Loss and Fatality for Vehicle Safety Prioritization.

    Science.gov (United States)

    McMurry, Timothy L; Sherwood, Chris; Poplin, Gerald S; Seguí-Gómez, María; Crandall, Jeff

    2015-01-01

    We investigate the use of the Functional Capacity Index (FCI) as a tool for establishing vehicle safety priorities by comparing the life year burden of injuries to the burden of fatality in frontal and side automotive crashes. We demonstrate FCI's utility by investigating in detail the resulting disabling injuries and their life year costs. We selected occupants in the 2000-2013 NASS-CDS database involved in frontal and side crashes, merged their injuries with FCI, and then used the merged data to estimate each occupant's overall functional loss. Lifetime functional loss was assessed by combining this measure of impairment with the occupants' expected future life spans, estimated from the Social Security Administration's Actuarial Life Table. Frontal crashes produce a large number of disabling injuries, particularly to the lower extremities. In our population, these crashes are estimated to account for approximately 400,000 life years lost to disability in comparison with 500,000 life years lost to fatality. Victims of side crashes experienced a higher rate of fatality but a significantly lower rate of disabling injury (0.3 vs. 1.0%), resulting in approximately 370,000 life years lost to fatality versus 50,000 life years lost to disability. The burden of disabling injuries to car crash survivors should be considered when setting vehicle safety design priorities. In frontal crashes this burden in life years is similar to the burden attributable to fatality.

  1. Renewable poly(δ-decalactone) based block copolymer micelles as drug delivery vehicle:in vitroandin vivoevaluation.

    Science.gov (United States)

    Bansal, Kuldeep K; Gupta, Jitendra; Rosling, Ari; Rosenholm, Jessica M

    2018-03-01

    Polymers from natural resources are attracting much attention in various fields including drug delivery as green alternatives to fossil fuel based polymers. In this quest, novel block copolymers based on renewable poly(δ-decalactone) (PDL) were evaluated for their drug delivery capabilities and compared with a fossil fuel based polymer i.e. methoxy-poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-b-PCL). Using curcumin as a hydrophobic drug model, micelles of PDL block copolymers with different orientation i.e. AB (mPEG-b-PDL), ABA (PDL-b-PEG-b-PDL), ABC (mPEG-b-PDL-b-poly(pentadecalactone) and (mPEG-b-PCL) were prepared by nanoprecipitation method. The size, drug loading and curcumin stability studies results indicated that mPEG-b-PDL micelles was comparable to its counterpart mPEG-b-PCL micelles towards improved delivery of curcumin. Therefore, mixed micelles using these two copolymers were also evaluated to see any change in size, loading and drug release. Drug release studies proposed that sustained release can be obtained using poly(pentadecalactone) as crystalline core whereas rapid release can be achieved using amorphous PDL core. Further, mPEG-b-PDL micelles were found to be non-haemolytic, up to the concentration of 40 mg/mL. In vivo toxicity studies on rats advised low-toxic behaviour of these micelles up to 400 mg/kg dose, as evident by histopathological and biochemical analysis. In summary, it is anticipated that mPEG-b-PDL block copolymer micelles could serve as a renewable alternative for mPEG-b-PCL copolymers in drug delivery applications.

  2. Analysis of the Dynamic Response in the Railway Vehicles to the Track Vertical Irregularities. Part I: The Theoretical Model and the Vehicle Response Functions

    Directory of Open Access Journals (Sweden)

    M. Dumitriu

    2015-11-01

    Full Text Available The paper herein focuses on the dynamic response of a two-bogie vehicle to the excitations derived from the track vertical irregularities. The symmetrical and antisymmetrical modes due from the bounce and pitch motions of the axles’ planes in the two bogies are being considered. The analysis of the dynamic response in the vehicle relies on the response functions in three reference points of the carbody, composed by means of these response functions to the symmetrical and antisymmetrical excitation modes. Similarly, the dynamic response of the vehicle to the track stochastic irregularities is examined and expressed as a power spectral density of the carbody vertical acceleration and the root mean square of the acceleration and the index of the partial comfort to the vertical vibrations is calculated. The paper is structured into two parts. The Part I includes all the theoretical elements required for the analysis of the dynamic response in the vehicle, while Part II introduces the results of the numerical analysis.

  3. Comparing Traditional Service Delivery and Telepractice for Speech Sound Production Using a Functional Outcome Measure.

    Science.gov (United States)

    Coufal, Kathy; Parham, Douglas; Jakubowitz, Melissa; Howell, Cassandra; Reyes, Jared

    2018-02-06

    Using American Speech-Language-Hearing Association's (ASHA's) National Outcomes Measurement System (NOMS) Functional Communication Measure (FCM) as a common metric, this investigation compared traditional service delivery and telepractice service delivery for children receiving therapy for the NOMS diagnostic category of "speech sound production." De-identified cases were secured from ASHA's NOMS database and a proprietary database from a private e-learning provider. Cases were included if they met 3 criteria: (a) children received treatment exclusively for speech sound production, (b) they were between 6.0 and 9.5 years old, and (c) they received therapy lasting between 4 and 9 months. A total of 1,331 ASHA NOMS cases and 428 telepractice cases were included. The 2 groups were matched by initial FCM scores. Mann-Whitney U tests were completed to compare differences in the median change scores (the difference between the initial and final FCM scores) between the 2 groups. There were no significant differences in the median change scores between the traditional group and the telepractice group. These results suggest comparable treatment outcomes between traditional service delivery and telepractice for treatment of children exhibiting speech sound disorders. The findings provide support for the use of telepractice for school-age children.

  4. 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.

  5. Functional capacity evaluation of work performance among individuals with pelvic injuries following motor vehicle accidents.

    Science.gov (United States)

    Ratzon, Navah Z; Ari Shevil, Eynat Ben; Froom, Paul; Friedman, Sharon; Amit, Yehuda

    2013-01-01

    Pelvic injuries following motor vehicle accidents (MVA) cause disability and affect work capabilities. This study evaluated functional, self-report, and medical-based factors that could predict work capacity as was reflected in a functional capacity evaluation (FCE) among persons who sustained a pelvic injury. It was hypothesized that self-reported functional status and bio-demographic variables would predict work capacity. Sixty-one community-dwelling adults previously hospitalized following a MVA induced pelvic injury. FCE for work performance was conducted using the Physical Work Performance Evaluation (PWPE). Additional data was collected through a demographics questionnaire and the Functional Status Questionnaire. All participants underwent an orthopedic medical examination of the hip and lower extremities. Most participants self-reported that their work capacity post-injury were lower than their job required. PWPE scores indicated below-range functional performance. Regression models predicted 23% to 51% of PWPE subtests. Participants' self-report of functioning (instrumental activities of daily living and work) and bio-demographic variables (gender and age) were better predictors of PWPE scores than factors originating from the medical examination. Results support the inclusion of FCE, in addition to self-report of functioning and medical examination, to evaluate work capacity among individuals' post-pelvic injury and interventions and discharge planning.

  6. Choline- versus imidazole-based ionic liquids as functional ingredients in topical delivery systems: cytotoxicity, solubility, and skin permeation studies.

    Science.gov (United States)

    Santos de Almeida, Tânia; Júlio, Ana; Saraiva, Nuno; Fernandes, Ana Sofia; Araújo, Maria Eduarda M; Baby, André Rolim; Rosado, Catarina; Mota, Joana Portugal

    2017-11-01

    Poor drug solubility represents a problem for the development of topical formulations. Since ionic liquids (ILs) can be placed in either lipophilic or hydrophilic solutions, they may be advantageous vehicles in such delivery systems. Nonetheless, it is vital to determine their usefulness when used at concentrations were cell viability is maintained, which was considered herein. Five different ILs were prepared-three imidazole-based ILs: [C2mim][Br], [C4mim][Br], and [C6mim][Br]; and two choline-based ILs: [Cho][Phe] and [Cho][Glu]. Their cytotoxicity in human keratinocytes (HaCat cells), their influence in drug solubility and in percutaneous permeation, using pig skin membranes, was evaluated. Caffeine and salicylic acid were used as model actives. Choline-based ILs proved to be more suitable as functional ingredients, since they showed higher impact on drug solubility and a lower cytotoxicity. The major solubility enhancement was observed for caffeine and further solubility studies were carried out with this active in several concentrations of the choline-based ILs (0.1; 0.2; 0.5; 1.0; 3.0 and 5.0%, w/w) at 25 °C and 32 °C. Solubility was greatly influenced by concentrations up to 0.5%. The choline-based ILs showed no significant impact on the skin permeation, for both actives. The size of the imidazole-based ILs alkyl chain enhances the caffeine solubility and permeation, but also the ILs cytotoxicity. Stable O/W emulsions and gels were prepared containing the less toxic choline-based ILs and caffeine. Our results indicate that the choline-based ILs were effective functional ingredients, since, when used at nontoxic concentrations, they allowed a higher drug loading, while maintaining the stability of the formulations.

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    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.

  9. 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.

  10. 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)

  11. 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.

  12. Structured triglyceride vehicles for oral delivery of halofantrine: examination of intestinal lymphatic transport and bioavailability in conscious rats

    DEFF Research Database (Denmark)

    Holm, René; Porter, Christopher J H; Müllertz, Anette

    2002-01-01

    triglycerides; sunflower oil, and two structured triglycerides containing different proportion and position of medium-(M) and long-chain (L) fatty acids on the glycerol backbone. The two structured triglycerides were abbreviated MLM and LML to reflect the structural position on the glycerol. The concentration...... animals, and this was most pronounced for the animals dosed with the structured triglycerides. CONCLUSIONS: Using MLM as vehicle increases the portal absorption of halofantrine and results in similar lymphatic transport levels when compared to sunflower oil. Total absorption when assessed as absorption...... in the blood plus lymphatic transport for halofantrine after administration in the MLM triglyceride was higher than after administration in sunflower oil....

  13. Functional MRI of the pelvic floor: postpartum changes of primiparous women after spontaneous vaginal delivery

    International Nuclear Information System (INIS)

    Lienemann, A.; Fischer, T.; Reiser, M.; Anthuber, C.

    2003-01-01

    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 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.) [de

  14. Nonlinear H∞ Optimal Control Scheme for an Underwater Vehicle with Regional Function Formulation

    Directory of Open Access Journals (Sweden)

    Zool H. Ismail

    2013-01-01

    Full Text Available A conventional region control technique cannot meet the demands for an accurate tracking performance in view of its inability to accommodate highly nonlinear system dynamics, imprecise hydrodynamic coefficients, and external disturbances. In this paper, a robust technique is presented for an Autonomous Underwater Vehicle (AUV with region tracking function. Within this control scheme, nonlinear H∞ and region based control schemes are used. A Lyapunov-like function is presented for stability analysis of the proposed control law. Numerical simulations are presented to demonstrate the performance of the proposed tracking control of the AUV. It is shown that the proposed control law is robust against parameter uncertainties, external disturbances, and nonlinearities and it leads to uniform ultimate boundedness of the region tracking error.

  15. Patient-derived mesenchymal stem cells as delivery vehicles for oncolytic virotherapy: novel state-of-the-art technology.

    Science.gov (United States)

    Ramírez, Manuel; García-Castro, Javier; Melen, Gustavo J; González-Murillo, África; Franco-Luzón, Lidia

    2015-01-01

    Oncolytic virotherapy is gaining interest in the clinic as a new weapon against cancer. In vivo administration of oncolytic viruses showed important limitations that decrease their effectiveness very significantly: the antiviral immune response causes the elimination of the therapeutic effect, and the poor natural ability of oncolytic viruses to infect micrometastatic lesions significantly minimizes the effective dose of virus. This review will focus on updating the technical and scientific foundations of one of the strategies developed to overcome these limitations, ie, using cells as vehicles for oncolytic viruses. Among many candidates, a special type of adult stem cell, mesenchymal stem cells (MSCs), have already been used in the clinic as cell vehicles for oncolytic viruses, partly due to the fact that these cells are actively being evaluated for other indications. MSC carrier cells are used as Trojan horses loaded with oncoviruses, are administered systemically, and release their cargos at the right places. MSCs are equipped with an array of molecules involved in cell arrest in the capillaries (integrins and selectins), migration toward specific parenchymal locations within tissues (chemokine receptors), and invasion and degradation of the extracellular matrix (proteases). In addition to anatomical targeting capacity, MSCs have a well-recognized role in modulating immune responses by affecting cells of the innate (antigen-presenting cells, natural killer cells) and adaptive immune system (effector and regulatory lymphocytes). Therefore, carrier MSCs may also modulate the immune responses taking place after therapy, ie, the antiviral and the antitumor immune responses.

  16. Homing in on an intracellular target for delivery of loaded nanoparticles functionalized with a histone deacetylase inhibitor.

    Science.gov (United States)

    Zhang, Jie; Shi, Yaling; Zheng, Yueqin; Pan, Chengcheng; Yang, Xiaoying; Dou, Taoyan; Wang, Binghe; Lu, Wen

    2017-09-15

    Functionalized nanoparticles (NPs) are usually used to enhance cellular penetration for targeted drug delivery that can improve efficacy and reduce side effects. However, it is difficult to exploit intracellular targets for similar delivery applications. Herein we describe the targeted delivery of functionalized NPs by homing in on an intracellular target, histone deacetylases (HDACs). Specifically, a modified poly-lactide-co-glycolideacid (FPLGA) was yielded by conjugation with an HDAC inhibitor. Subsequently, FPLGA was used to prepare functionalized FPLGA NPs. Compared to unmodified NPs, FPLGA NPs were more efficiently uptaken or retained by MCF-7 cells and showed longer retention time intracellular. In vivo fluorescence imaging also revealed that they had a higher accumulation and a slower elimination than unmodified NPs. FPLGA NPs loaded with paclitaxel exhibited superior anticancer efficacy compared with unmodified NPs. These results offer a promising approach for intracellular drug delivery through elevating the concentration of NPs.

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

    Science.gov (United States)

    Mueller, Noel T; Shin, Hakdong; Pizoni, Aline; Werlang, Isabel C; Matte, Ursula; Goldani, Marcelo Z; Goldani, Helena A S; Dominguez-Bello, Maria G

    2017-12-04

    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 amino and

  18. 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

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

    Science.gov (United States)

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

    2011-01-01

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

  20. Purification and functionalization of nanodiamond to serve as a platform for amoxicillin delivery.

    Science.gov (United States)

    Rouhani, Parvaneh; Govindaraju, Nirmal; Iyer, Janaki K; Kaul, Rashmi; Kaul, Anil; Singh, Raj N

    2016-06-01

    Urinary tract infections (UTIs) cost $0.4-0.5 billion a year in the US and is the second most common disease affecting millions of people. As resistance to antibiotics becomes more common, a greater need for alternative treatments is needed. Nanodiamond particles (NDPs) are actively researched as drug delivery platforms due to their biocompatibility, particle size, and stable inert core. This research is aimed at developing NDPs as antibiotic drug delivery platforms for treating UTIs. To this end, 100 nm, 75 nm, 25 nm and 6 nm size NDPs are purified with acid and heat treatment techniques. Raman spectra of the NDPs showed that the acid treatment method resulted in higher diamond yield. Fourier transform infrared spectroscopy (FTIR) studies showed that both purification techniques result in oxygen terminated surface groups. Efficiency of loading amoxicillin on 25 nm NDPs based on electrostatic interaction of NDPs, functionalizing surfaces of NDPs with hydrogen, and polyethylenimine (PEI) are investigated. It is found that the electrostatic and surface hydrogenation approaches are not efficient in loading amoxicillin on the NDPs. On the other hand, PEI functionalized NDPs produced successful loading with amoxicillin as indicated by the presence of the β-lactam peak at 1770 cm(-1), amide peak at 1680 cm(-1), and bond between PEI NH stretching and amoxicillin -COOH group at 3650 cm(-1) by the FTIR spectra. These results are expected to lay the foundation for developing NDP based targeted drug delivery treatment techniques for treating UTIs and other infectious diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Maturation of the Infant Microbiome Community Structure and Function Across Multiple Body Sites and in Relation to Mode of Delivery

    Science.gov (United States)

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

    2017-01-01

    Human microbial communities are characterized by their taxonomic, metagenomic, and metabolic diversity, which varies by distinct body sites and influences human physiology. However, when and how microbial communities within each body niche acquire unique taxonomical and functional signatures in early life remains underexplored. We thus sought to assess the taxonomic composition and potential metabolic function of the neonatal and early infant microbiota across multiple body sites, and assess the impact of mode of delivery and its potential confounders or modifiers. A cohort of pregnant women in their early 3rd trimester (n=81) were prospectively enrolled for longitudinal sampling through 6 weeks post-delivery, and a second matched cross-sectional cohort (n=81) was additionally recruited for sampling once at delivery. Samples were collected for each maternal-infant dyad across multiple body sites, including stool, oral gingiva, nares, skin and vagina. 16S rRNA gene sequencing analysis and whole genome shotgun sequencing was performed to interrogate the composition and function of the neonatal and maternal microbiota. We found that the neonatal microbiota and its associated functional pathways were relatively homogenous across all body sites at delivery, with the notable exception of neonatal meconium. However, by 6 weeks, the infant microbiota structure and function had significantly expanded and diversified, with body site serving as the primary determinant of the bacterial community composition and its functional capacity. Although minor variations in the neonatal (immediately at birth) microbiota community structure were associated with Cesarean delivery in some body sites (oral, nares, and skin; R2 = 0.038), this was not true in neonatal stool (meconium, Mann-Whitney p>0.05) and there was no observable difference in community function regardless of delivery mode. By 6 weeks of age, the infant microbiota structure and function had expanded and diversified with

  2. 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)

  3. 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.

  4. Oligodendrocytes in the Mouse Corpus Callosum Maintain Axonal Function by Delivery of Glucose

    Directory of Open Access Journals (Sweden)

    Niklas Meyer

    2018-02-01

    Full Text Available In the optic nerve, oligodendrocytes maintain axonal function by supplying lactate as an energy substrate. Here, we report that, in acute brain slices of the mouse corpus callosum, exogenous glucose deprivation (EGD abolished compound action potentials (CAPs, which neither lactate nor pyruvate could prevent. Loading an oligodendrocyte with 20 mM glucose using a patch pipette prevented EGD-mediated CAP reduction in about 70% of experiments. Loading oligodendrocytes with lactate rescued CAPs less efficiently than glucose. In mice lacking connexin 47, oligodendrocyte filling with glucose did not prevent CAP loss, emphasizing the importance of glial networks for axonal energy supply. Compared with the optic nerve, the astrocyte network in the corpus callosum was less dense, and loading astrocytes with glucose did not prevent CAP loss during EGD. We suggest that callosal oligodendrocyte networks provide energy to sustain axonal function predominantly by glucose delivery, and mechanisms of metabolic support vary across different white matter regions.

  5. Delivery of completed irradiation vehicles and the quality assurance document to the High Flux Isotope Reactor for irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Petrie, Christian M. [Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States); McDuffee, Joel Lee [Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States); Katoh, Yutai [Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States); Terrani, Kurt A. [Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

    2015-10-01

    This report details the initial fabrication and delivery of two Fuel Cycle Research and Development (FCRD) irradiation capsules (ATFSC01 and ATFSC02), with associated quality assurance documentation, to the High Flux Isotope Reactor (HFIR). The capsules and documentation were delivered by September 30, 2015, thus meeting the deadline for milestone M3FT-15OR0202268. These irradiation experiments are testing silicon carbide composite tubes in order to obtain experimental validation of thermo-mechanical models of stress states in SiC cladding irradiated under a prototypic high heat flux. This document contains a copy of the completed capsule fabrication request sheets, which detail all constituent components, pertinent drawings, etc., along with a detailed summary of the capsule assembly process performed by the Thermal Hydraulics and Irradiation Engineering Group (THIEG) in the Reactor and Nuclear Systems Division (RNSD). A complete fabrication package record is maintained by the THIEG and is available upon request.

  6. 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

  7. Vehicle Development Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Supports the development of prototype deployment platform vehicles for offboard countermeasure systems.DESCRIPTION: The Vehicle Development Laboratory is...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-20

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

  9. 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.

  10. Simulation of vertical dynamic vehicle-track interaction in a railway crossing using Green's functions

    Science.gov (United States)

    Li, X.; Torstensson, P. T.; Nielsen, J. C. O.

    2017-12-01

    Vertical dynamic vehicle-track interaction in the through route of a railway crossing is simulated in the time domain based on a Green's function approach for the track in combination with an implementation of Kalker's variational method to solve the non-Hertzian, and potentially multiple, wheel-rail contact. The track is described by a linear, three-dimensional and non-periodic finite element model of a railway turnout accounting for the variations in rail cross-sections and sleeper lengths, and including baseplates and resilient elements. To reduce calculation time due to the complexity of the track model, involving a large number of elements and degrees-of-freedom, a complex-valued modal superposition with a truncated mode set is applied before the impulse response functions are calculated at various positions along the crossing panel. The variation in three-dimensional contact geometry of the crossing and wheel is described by linear surface elements. In each time step of the contact detection algorithm, the lateral position of the wheelset centre is prescribed but the contact positions on wheel and rail are not, allowing for an accurate prediction of the wheel transition between wing rail and crossing rail. The method is demonstrated by calculating the wheel-rail impact load and contact stress distribution for a nominal S1002 wheel profile passing over a nominal crossing geometry. A parameter study is performed to determine the influence of vehicle speed, rail pad stiffness, lateral wheelset position and wheel profile on the impact load generated at the crossing. It is shown that the magnitude of the impact load is more influenced the wheel-rail contact geometry than by the selection of rail pad stiffness.

  11. Biodegradable PLGA85/15 nanoparticles as a delivery vehicle for Chlamydia trachomatis recombinant MOMP-187 peptide

    Science.gov (United States)

    Taha, Murtada A.; Singh, Shree R.; Dennis, Vida A.

    2012-08-01

    Development of a Chlamydia trachomatis vaccine has been a formidable task partly because of an ineffective delivery system. Our laboratory has generated a recombinant peptide of C. trachomatis major outer membrane protein (MOMP) (rMOMP-187) and demonstrated that it induced at 20 μg ml-1 maximal interleukin (IL)-6 and IL-12p40 Th1 cytokines in mouse J774 macrophages. In a continuous pursuit of a C. trachomatis effective vaccine-delivery system, we encapsulated rMOMP-187 in poly(d,l-lactic-co-glycolic acid) (PLGA, 85:15 PLA/PGA ratio) to serve as a nanovaccine candidate. Physiochemical characterizations were assessed by Fourier transform-infrared spectroscopy, atomic force microscopy, Zetasizer, Zeta potential, transmission electron microcopy and differential scanning calorimetry. The encapsulated rMOMP-187 was small (˜200 nm) with an apparently smooth uniform oval structure, thermally stable (54 °C), negatively charged ( - 27.00 mV) and exhibited minimal toxicity at concentrations 95% viable cells) over a 24-72 h period. We achieved a high encapsulation efficiency of rMOMP-187 (˜98%) in PLGA, a loading peptide capacity of 2.7% and a slow release of the encapsulated peptide. Stimulation of J774 macrophages with a concentration as low as 1 μg ml -1 of encapsulated rMOMP-187 evoked high production levels of the Th1 cytokines IL-6 (874 pg ml-1) and IL-12p40 (674 pg ml-1) as well as nitric oxide (8 μM) at 24 h post-stimulation, and in a dose-response and time-kinetics manner. Our data indicate the successful encapsulation and characterization of rMOMP-187 in PLGA and, more importantly, that PLGA enhanced the capacity of the peptide to induce Th1 cytokines and NO in vitro. These findings make this nanovaccine an attractive candidate in pursuit of an efficacious vaccine against C. trachomatis.

  12. Biodegradable PLGA85/15 nanoparticles as a delivery vehicle for Chlamydia trachomatis recombinant MOMP-187 peptide

    International Nuclear Information System (INIS)

    Taha, Murtada A; Singh, Shree R; Dennis, Vida A

    2012-01-01

    Development of a Chlamydia trachomatis vaccine has been a formidable task partly because of an ineffective delivery system. Our laboratory has generated a recombinant peptide of C. trachomatis major outer membrane protein (MOMP) (rMOMP-187) and demonstrated that it induced at 20 μg ml −1 maximal interleukin (IL)-6 and IL-12p40 Th1 cytokines in mouse J774 macrophages. In a continuous pursuit of a C. trachomatis effective vaccine-delivery system, we encapsulated rMOMP-187 in poly(d,l-lactic-co-glycolic acid) (PLGA, 85:15 PLA/PGA ratio) to serve as a nanovaccine candidate. Physiochemical characterizations were assessed by Fourier transform-infrared spectroscopy, atomic force microscopy, Zetasizer, Zeta potential, transmission electron microcopy and differential scanning calorimetry. The encapsulated rMOMP-187 was small (∼200 nm) with an apparently smooth uniform oval structure, thermally stable (54 °C), negatively charged ( − 27.00 mV) and exhibited minimal toxicity at concentrations −1 to eukaryotic cells (>95% viable cells) over a 24–72 h period. We achieved a high encapsulation efficiency of rMOMP-187 (∼98%) in PLGA, a loading peptide capacity of 2.7% and a slow release of the encapsulated peptide. Stimulation of J774 macrophages with a concentration as low as 1 μg ml −1 of encapsulated rMOMP-187 evoked high production levels of the Th1 cytokines IL-6 (874 pg ml −1 ) and IL-12p40 (674 pg ml −1 ) as well as nitric oxide (8 μM) at 24 h post-stimulation, and in a dose-response and time-kinetics manner. Our data indicate the successful encapsulation and characterization of rMOMP-187 in PLGA and, more importantly, that PLGA enhanced the capacity of the peptide to induce Th1 cytokines and NO in vitro. These findings make this nanovaccine an attractive candidate in pursuit of an efficacious vaccine against C. trachomatis. (paper)

  13. Rhesus Cochlear and Vestibular Functions Are Preserved After Inner Ear Injection of Saline Volume Sufficient for Gene Therapy Delivery.

    Science.gov (United States)

    Dai, Chenkai; Lehar, Mohamed; Sun, Daniel Q; Rvt, Lani Swarthout; Carey, John P; MacLachlan, Tim; Brough, Doug; Staecker, Hinrich; Della Santina, Alexandra M; Hullar, Timothy E; Della Santina, Charles C

    2017-08-01

    Sensorineural losses of hearing and vestibular sensation due to hair cell dysfunction are among the most common disabilities. Recent preclinical research demonstrates that treatment of the inner ear with a variety of compounds, including gene therapy agents, may elicit regeneration and/or repair of hair cells in animals exposed to ototoxic medications or other insults to the inner ear. Delivery of gene therapy may also offer a means for treatment of hereditary hearing loss. However, injection of a fluid volume sufficient to deliver an adequate dose of a pharmacologic agent could, in theory, cause inner ear trauma that compromises functional outcome. The primary goal of the present study was to assess that risk in rhesus monkeys, which closely approximates humans with regard to middle and inner ear anatomy. Secondary goals were to identify the best delivery route into the primate ear from among two common surgical approaches (i.e., via an oval window stapedotomy and via the round window) and to determine the relative volumes of rhesus, rodent, and human labyrinths for extrapolation of results to other species. We measured hearing and vestibular functions before and 2, 4, and 8 weeks after unilateral injection of phosphate-buffered saline vehicle (PBSV) into the perilymphatic space of normal rhesus monkeys at volumes sufficient to deliver an atoh1 gene therapy vector. To isolate effects of injection, PBSV without vector was used. Assays included behavioral observation, auditory brainstem responses, distortion product otoacoustic emissions, and scleral coil measurement of vestibulo-ocular reflexes during whole-body rotation in darkness. Three groups (N = 3 each) were studied. Group A received a 10 μL transmastoid/trans-stapes injection via a laser stapedotomy. Group B received a 10 μL transmastoid/trans-round window injection. Group C received a 30 μL transmastoid/trans-round window injection. We also measured inner ear fluid space volume via 3D

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

    Science.gov (United States)

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

    2013-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Sanaz Motamedi

    2011-06-01

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

  16. Functionalized graphene oxide nanoparticles for cancer cell-specific delivery of antitumor drug.

    Science.gov (United States)

    Zhao, Xubo; Yang, Liangwei; Li, Xiaorui; Jia, Xu; Liu, Lei; Zeng, Jin; Guo, Jinshan; Liu, Peng

    2015-01-21

    The unique reduction-triggered functional graphene oxide nanoparticles (GON) with well-defined size and uniform distribution were designed as an innovative drug delivery platform for cancer treatment for the first time, via the redox radical polymerization of methacrylic acid from the polyethylene glycol (PEG) modified GON (GON-PEG), following by cross-linking with cystamine. Thermogravimetric analysis demonstrates that the typical PMAA2-GON-PEG carriers contain about 16 wt % PEG segments and 33 wt % poly(methacrylic acid) (PMAA) brushes. PEG moieties are incorporated to make the drug delivery platforms stealthy during blood circulation. Notably, introducing the cross-linked PMAA brushes efficiently minimizes the premature release of doxorubicin (DOX) in the stimulated normal tissues, and accelerates DOX release in the stimulated tumor tissues through response to reduce agent. The carriers showed a 6-fold faster releasing rate at pH 5.0 in the presence of 10 mM glutathione (GSH) (stimulated tumor tissues) than at pH 7.4 with 10 μM GSH (stimulated normal tissues). In vitro cytotoxicity test also showed that the cross-linked PMAA2-GON-PEG (CPMAA2-GON-PEG) carriers had remarkable cytocompatibility, and that the DOX-loaded CPMAA2-GON-PEG had excellent killing capability to SiHa cells.

  17. Self-Assembled Modified Soy Protein/Dextran Nanogel Induced by Ultrasonication as a Delivery Vehicle for Riboflavin

    Directory of Open Access Journals (Sweden)

    Bei Jin

    2016-03-01

    Full Text Available A simple and green approach was developed to produce a novel nanogel via self-assembly of modified soy protein and dextran, to efficiently deliver riboflavin. First, modified soy protein was prepared by heating denaturation at 60 °C for 30 min or Alcalase hydrolysis for 40 min. Second, modified soy protein was mixed with dextran and ultrasonicated for 70 min so as to assemble nanogels. The modified soy protein-dextran nanogels were characterized by Fourier-transform infrared spectroscopy (FTIR and X-ray photoelectron spectroscopy (XPS and ζ-potential studies to confirm the formation of NGs. Transmission electron microscopy (TEM revealed the NGs to be spherical with core-shell structures, in the range of 32–40 nm size. The nanogels were stable against various environmental conditions. Furthermore, the particle size of the nanogels hardly changed with the incorporation of riboflavin. The encapsulation efficiency of nanogels was found to be up to 65.9% at a riboflavin concentration of 250 μg/mL. The nanogels exhibited a faster release in simulated intestine fluid (SIF compared with simulated gastric fluid (SGF. From the results obtained it can be concluded that modified soy protein-dextran nanogels can be considered a promising carrier for drugs and other bioactive molecule delivery purposes.

  18. Future of human Chlamydia vaccine: potential of self-adjuvanting biodegradable nanoparticles as safe vaccine delivery vehicles.

    Science.gov (United States)

    Sahu, Rajnish; Verma, Richa; Dixit, Saurabh; Igietseme, Joseph U; Black, Carolyn M; Duncan, Skyla; Singh, Shree R; Dennis, Vida A

    2018-03-01

    There is a persisting global burden and considerable public health challenge by the plethora of ocular, genital and respiratory diseases caused by members of the Gram-negative bacteria of the genus Chlamydia. The major diseases are conjunctivitis and blinding trachoma, non-gonococcal urethritis, cervicitis, pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, and interstitial pneumonia. The failures in screening and other prevention programs led to the current medical opinion that an efficacious prophylactic vaccine is the best approach to protect humans from chlamydial infections. Unfortunately, there is no human Chlamydia vaccine despite successful veterinary vaccines. A major challenge has been the effective delivery of vaccine antigens to induce safe and effective immune effectors to confer long-term protective immunity. The dawn of the era of biodegradable polymeric nanoparticles and the adjuvanted derivatives may accelerate the realization of the dream of human vaccine in the foreseeable future. Areas covered: This review focuses on the current status of human chlamydial vaccine research, specifically the potential of biodegradable polymeric nanovaccines to provide efficacious Chlamydia vaccines in the near future. Expert commentary: The safety of biodegradable polymeric nanoparticles-based experimental vaccines with or without adjuvants and the array of available chlamydial vaccine candidates would suggest that clinical trials in humans may be imminent. Also, the promising results from vaccine testing in animal models could lead to human vaccines against trachoma and reproductive diseases simultaneously.

  19. Atoxic derivative of botulinum neurotoxin A as a prototype molecular vehicle for targeted delivery to the neuronal cytoplasm.

    Directory of Open Access Journals (Sweden)

    Edwin J Vazquez-Cintron

    Full Text Available We have previously described genetic constructs and expression systems that enable facile production of recombinant derivatives of botulinum neurotoxins (BoNTs that retain the structural and trafficking properties of wt BoNTs. In this report we describe the properties of one such derivative, BoNT/A ad, which was rendered atoxic by introducing two amino acid mutations to the light chain (LC of wt BoNT/A, and which is being developed as a molecular vehicle for delivering drugs to the neuronal cytoplasm. The neuronal binding, internalization, and intracellular trafficking of BoNT/A ad in primary hippocampal cultures was evaluated using three complimentary techniques: flow cytometry, immunohistochemistry, and Western blotting. Neuronal binding of BoNT ad was significantly increased when neurons were incubated in depolarizing medium. Flow cytometry demonstrated that BoNT/A ad internalized into neurons but not glia. After 24 hours, the majority of the neuron-bound BoNT/A ad became internalized, as determined by its resistance to pronase E-induced proteolytic degradation of proteins associated with the plasma membrane of intact cells. Significant amounts of the atoxic LC accumulated in a Triton X-100-extractable fraction of the neurons, and persisted as such for at least 11 days with no evidence of degradation. Immunocytochemical analysis demonstrated that the LC of BoNT/A ad was translocated to the neuronal cytoplasm after uptake and was specifically targeted to SNARE proteins. The atoxic LC consistently co-localized with synaptic markers SNAP-25 and VAMP-2, but was rarely co-localized with markers for early or late endosomes. These data demonstrate that BoNT/A ad mimics the trafficking properties of wt BoNT/A, confirming that our platform for designing and expressing BoNT derivatives provides an accessible system for elucidating the molecular details of BoNT trafficking, and can potentially be used to address multiple medical and biodefense needs.

  20. Hydrogen-bonding layer-by-layer-assembled biodegradable polymeric micelles as drug delivery vehicles from surfaces.

    Science.gov (United States)

    Kim, Byeong-Su; Park, Sang Wook; Hammond, Paula T

    2008-02-01

    We present the integration of amphiphilic block copolymer micelles as nanometer-sized vehicles for hydrophobic drugs within layer-by-layer (LbL) films using alternating hydrogen bond interactions as the driving force for assembly for the first time, thus enabling the incorporation of drugs and pH-sensitive release. The film was constructed based on the hydrogen bonding between poly(acrylic acid) (PAA) as an H-bond donor and biodegradable poly(ethylene oxide)-block-poly(epsilon-caprolactone) (PEO-b-PCL) micelles as the H-bond acceptor when assembled under acidic conditions. By taking advantage of the weak interactions of the hydrogen-bonded film on hydrophobic surfaces, it is possible to generate flexible free-standing films of these materials. A free-standing micelle LbL film of (PEO-b-PCL/PAA)60 with a thickness of 3.1 microm was isolated, allowing further characterization of the bulk film properties, including morphology and phase transitions, using transmission electron microscopy and differential scanning calorimetry. Because of the sensitive nature of the hydrogen bonding employed to build the multilayers, the film can be rapidly deconstructed to release micelles upon exposure to physiological conditions. However, we could also successfully control the rate of film deconstruction by cross-linking carboxylic acid groups in PAA through thermally induced anhydride linkages, which retard the drug release to the surrounding medium to enable sustained release over multiple days. To demonstrate efficacy in delivering active therapeutics, in vitro Kirby-Bauer assays against Staphylococcus aureus were used to illustrate that the drug-loaded micelle LbL film can release significant amounts of an active antibacterial drug, triclosan, to inhibit the growth of bacteria. Because the micellar encapsulation of hydrophobic therapeutics does not require specific chemical interactions, we believe this noncovalent approach provides a new route to integrating active small

  1. Communications data delivery system analysis task 2 report : high-level options for secure communications data delivery systems.

    Science.gov (United States)

    2012-05-16

    This Communications Data Delivery System Analysis Task 2 report describes and analyzes options for Vehicle to Vehicle (V2V) and Vehicle to Infrastructure (V2I) communications data delivery systems using various communication media (Dedicated Short Ra...

  2. Sensor Fusion Based on an Integrated Neural Network and Probability Density Function (PDF) Dual Kalman Filter for On-Line Estimation of Vehicle Parameters and States.

    Science.gov (United States)

    Vargas-Melendez, Leandro; Boada, Beatriz L; Boada, Maria Jesus L; Gauchia, Antonio; Diaz, Vicente

    2017-04-29

    Vehicles with a high center of gravity (COG), such as light trucks and heavy vehicles, are prone to rollover. This kind of accident causes nearly 33 % of all deaths from passenger vehicle crashes. Nowadays, these vehicles are incorporating roll stability control (RSC) systems to improve their safety. Most of the RSC systems require the vehicle roll angle as a known input variable to predict the lateral load transfer. The vehicle roll angle can be directly measured by a dual antenna global positioning system (GPS), but it is expensive. For this reason, it is important to estimate the vehicle roll angle from sensors installed onboard in current vehicles. On the other hand, the knowledge of the vehicle's parameters values is essential to obtain an accurate vehicle response. Some of vehicle parameters cannot be easily obtained and they can vary over time. In this paper, an algorithm for the simultaneous on-line estimation of vehicle's roll angle and parameters is proposed. This algorithm uses a probability density function (PDF)-based truncation method in combination with a dual Kalman filter (DKF), to guarantee that both vehicle's states and parameters are within bounds that have a physical meaning, using the information obtained from sensors mounted on vehicles. Experimental results show the effectiveness of the proposed algorithm.

  3. Novel borate glass/chitosan composite as a delivery vehicle for teicoplanin in the treatment of chronic osteomyelitis.

    Science.gov (United States)

    Jia, Wei-Tao; Zhang, Xin; Luo, Shi-Hua; Liu, Xin; Huang, Wen-Hai; Rahaman, Mohamed N; Day, Delbert E; Zhang, Chang-Qing; Xie, Zong-Ping; Wang, Jian-Qiang

    2010-03-01

    Composite materials composed of borate bioactive glass and chitosan (designated BGC) were investigated in vitro and in vivo as a new delivery system for teicoplanin in the treatment of chronic osteomyelitis induced by methicillin-resistant Staphylococcus aureus (MRSA). In vitro, the release of teicoplanin from BGC pellets into phosphate-buffered saline (PBS), as well as its antibacterial activity, were determined. The compressive strength of the pellets was measured after specific immersion times, and the structure of the pellets was characterized using scanning electron microscopy and X-ray diffraction. In vivo, the tibial cavity of New Zealand White rabbits was injected with MRSA strain to induce chronic osteomyelitis, treated by debridement after 4weeks, implanted with teicoplanin-loaded BGC pellets (designated TBGC) or BGC pellets, or injected intravenously with teicoplanin. After 12weeks' implantation, the efficacy of the TBGC pellets for treating osteomyelitis was evaluated using hematological, radiological, microbiological and histological techniques. When immersed in PBS, the TBGC pellets provided a sustained release of teicoplanin, while the surface of the pellets was converted to hydroxyapatite (HA). In vivo, the best therapeutic effect was observed in animals implanted with TBGC pellets, resulting in significantly lower radiological and histological scores, a lower positive rate of MRSA culture, and an excellent bone defect repair, without local or systemic side effects. The results indicate that TBGC pellets are effective in treating chronic osteomyelitis by providing a sustained release of teicoplanin, in addition to participating in bone regeneration. Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  4. 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

  5. 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.

  6. Mango-bagasse functional-confectionery: vehicle for enhancing bioaccessibility and permeability of phenolic compounds.

    Science.gov (United States)

    Herrera-Cazares, Luz Abril; Hernández-Navarro, Fátima; Ramírez-Jiménez, Aurea K; Campos-Vega, Rocío; Reyes-Vega, María de la Luz; Loarca-Piña, Guadalupe; Morales-Sánchez, Eduardo; Wall-Medrano, Abraham; Gaytán-Martínez, Marcela

    2017-11-15

    Functional confectionery can be exploited as a vehicle for the protection of phenolic compounds (PCs) and for enhancing absorption during the gastrointestinal (GI) process. In this study, a confection containing 20% of mango bagasse (MB), gelatin and pectin was formulated. The PC profile, antioxidant capacity, in vitro bioaccessibility and apparent permeability (Papp) during mouth-stomach-intestine digestion (15, 30, 60, 120 min) and in vitro colonic fermentation (6, 12, 24 h) were evaluated for MB and the mango bagasse confection (MBC). HPLC-DAD analysis showed that mangiferin (830.69 μg g -1 ) was the most abundant compound in MBC. Total PCs (4.14 mg g -1 ), quercetin (244.83 μg g -1 ), and gallic acid (GA) (285.43 μg g -1 ) were highly bioaccessible mainly at the intestine at 60-120 min of digestion. GA was the most bioaccessible compound. Total flavonoids (TFs) and condensed tannins (CTs) had the maximum bioaccessibility in the mouth and stomach, respectively. For the permeability studies, PCs showed efflux rather than uptake in the intestine. Those compounds that exhibited intestinal absorption were mangiferin > GA > total PCs > TFs, whereas quercetin and CT absorption was negligible. The antioxidant capacity remained unchanged along the GI, mangiferin and quercetin being the most likely compounds to exert this activity. Overall results indicate that MBC has higher bioaccessibility, absorption and antioxidant capacity than MB, suggesting an effective protective role of gelatin and pectin, giving insight into the potential of MBC as a functional food.

  7. Self-assembly of core-polyethylene glycol-lipid shell (CPLS) nanoparticles and their potential as drug delivery vehicles

    Science.gov (United States)

    Shen, Zhiqiang; Loe, David T.; Awino, Joseph K.; Kröger, Martin; Rouge, Jessica L.; Li, Ying

    2016-08-01

    potential of simulation-driven approaches for guiding the design of more efficient nanomaterial delivery platforms.Herein a new multifunctional formulation, referred to as a core-polyethylene glycol-lipid shell (CPLS) nanoparticle, has been proposed and studied in silico via large scale coarse-grained molecular dynamics simulations. A PEGylated core with surface tethered polyethylene glycol (PEG) chains is used as the starting configuration, where the free ends of the PEG chains are covalently bonded with lipid molecules (lipid heads). A complete lipid bilayer is formed at the surface of the PEGylated particle core upon addition of free lipids, driven by the hydrophobic properties of the lipid tails, leading to the formation of a CPLS nanoparticle. The self-assembly process is found to be sensitive to the grafting density and molecular weight of the tethered PEG chains, as well as the amount of free lipids added. At low grafting densities the assembly of CPLS nanoparticles cannot be accomplished. As demonstrated by simulations, a lipid bud/vesicle can be formed on the surface when an excess amount of free lipids is added at high grafting density. Therefore, the CPLS nanoparticles can only be formed under appropriate conditions of both PEG and free lipids. The CPLS nanoparticle has been recognized to be able to store a large quantity of water molecules, particularly with high molecular weight of PEG chains, indicating its capacity for carrying hydrophilic molecules such as therapeutic biomolecules or imaging agents. Under identical size and surface chemistry conditions of a liposome, it has been observed that the CPLS particle can be more efficiently wrapped by the lipid membrane, indicating its potential for a greater efficiency in delivering its hydrophilic cargo. As a proof-of-concept, the experimental realization of CPLS nanoparticles is explicitly demonstrated in this study. To test the capacity of the CPLS to store small molecule cargo a hydrophilic dye was

  8. Galactose-functionalized multi-responsive nanogels for hepatoma-targeted drug delivery

    Science.gov (United States)

    Lou, Shaofeng; Gao, Shan; Wang, Weiwei; Zhang, Mingming; Zhang, Ju; Wang, Chun; Li, Chen; Kong, Deling; Zhao, Qiang

    2015-02-01

    We report here a hepatoma-targeting multi-responsive biodegradable crosslinked nanogel, poly(6-O-vinyladipoyl-d-galactose-ss-N-vinylcaprolactam-ss-methacrylic acid) P(ODGal-VCL-MAA), using a combination of enzymatic transesterification and emulsion copolymerization for intracellular drug delivery. The nanogel exhibited redox, pH and temperature-responsive properties, which can be adjusted by varying the monomer feeding ratio. Furthermore, the volume phase transition temperature (VPTT) of the nanogels was close to body temperature and can result in rapid thermal gelation at 37 °C. Scanning electron microscopy also revealed that the P(ODGal-VCL-MAA) nanogel showed uniform spherical monodispersion. With pyrene as a probe, the fluorescence excitation spectra demonstrated nanogel degradation in response to glutathione (GSH). X-ray diffraction (XRD) showed an amorphous property of DOX within the nanogel, which was used in this study as a model anti-cancer drug. Drug-releasing characteristics of the nanogel were examined in vitro. The results showed multi-responsiveness of DOX release by the variation of environmental pH values, temperature or the availability of GSH, a biological reductase. An in vitro cytotoxicity assay showed a higher anti-tumor activity of the galactose-functionalized DOX-loaded nanogels against human hepatoma HepG2 cells, which was, at least in part, due to specific binding between the galactose segments and the asialoglycoprotein receptors (ASGP-Rs) in hepatic cells. Confocal laser scanning microscopy (CLSM) and flow cytometric profiles further confirmed elevated cellular uptake of DOX by the galactose-functionalised nanogels. Thus, we report here a multi-responsive P(ODGal-VCL-MAA) nanogel with a hepatoma-specific targeting ability for anti-cancer drug delivery.We report here a hepatoma-targeting multi-responsive biodegradable crosslinked nanogel, poly(6-O-vinyladipoyl-d-galactose-ss-N-vinylcaprolactam-ss-methacrylic acid) P(ODGal-VCL-MAA), using

  9. Solar Electric Propulsion System Integration Technology (SEPSIT). Volume 2: Encke rendezvous mission and space vehicle functional description

    Science.gov (United States)

    Gardner, J. A.

    1972-01-01

    A solar electric propulsion system integration technology study is discussed. Detailed analyses in support of the solar electric propulsion module were performed. The thrust subsystem functional description is presented. The space vehicle and the space mission to which the propulsion system is applied are analyzed.

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

    Science.gov (United States)

    Thula, Taili T.

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

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

    Science.gov (United States)

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

    2013-08-01

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

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

    Science.gov (United States)

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

    2012-03-05

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

  13. 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.

  14. 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

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

    Science.gov (United States)

    Thangavel, Prakash; Viswanath, Buddolla; Kim, Sanghyo

    2017-01-01

    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.

  16. 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.

  17. 40 CFR 610.21 - Device functional category and vehicle system effects.

    Science.gov (United States)

    2010-07-01

    ...., engine heaters) 1. Lubrication Oil filters 3. Vehicle Body Aerodynamic drag reduction devices 1...) Interaction between the device and specific vehicle/engine operating characteristics; and (3) Constraints with... each characteristic is as follows: Exhaust emissions 1 Driveability 2 Durability 3 Performance 4 Table...

  18. Thyroid Function and Premature Delivery in TPO Antibody-Negative Women: The Added Value of hCG.

    Science.gov (United States)

    Korevaar, Tim I M; Steegers, Eric A P; Chaker, Layal; Medici, Marco; Jaddoe, Vincent W V; Visser, Theo J; de Rijke, Yolanda B; Peeters, Robin P

    2017-09-01

    Human chorionic gonadotropin (hCG) stimulates thyroid function during pregnancy. We recently showed that thyroid autoimmunity severely attenuated the thyroidal response to hCG stimulation and that this may underlie the higher risk of premature delivery in thyroperoxidase antibody (TPOAb)-positive women. We hypothesized that a lower thyroidal response to hCG stimulation in TPOAb-negative women is also associated with a higher risk of premature delivery and preterm premature rupture of membranes (pPROM). Thyrotropin (TSH), free thyroxine (FT4), and hCG concentrations were available in 5644 TPOAb-negative women from a prospective cohort. We tested for interaction between TSH or FT4 and hCG in linear regression models for duration of pregnancy and logistic regression models for premature delivery/pPROM. Accordingly, analyses were stratified per TSH percentile (TSH ≥ 85th percentile) and hCG per 10,000 IU/L. Women with high TSH and low hCG concentrations did not have a higher risk of premature delivery or pPROM, with protective effect estimates. In contrast, women with a high TSH concentration despite a high hCG concentration had twofold to 10-fold higher risk of premature delivery (Pdifference = 0.022) and an up to fourfold higher risk of pPROM (Pdifference = 0.079). hCG concentrations were not associated with premature delivery or pPROM. In TPOAb-negative women with high-normal TSH concentrations, only women with high hCG concentrations had a higher risk of premature delivery or pPROM. These results suggest a lower thyroidal response to hCG stimulation is also associated with premature delivery in TPOAb-negative women and that an additional measurement of hCG may improve thyroid-related risk assessments during pregnancy. Copyright © 2017 Endocrine Society

  19. ASSESSMENT OF THE GENERAL PSYCHOLOGICAL AND FUNCTIONAL CHARACTERISTICS CAUSED BY VIBRATIONS AT DRIVERS OF HEAVY MOTOR VEHICLES

    Directory of Open Access Journals (Sweden)

    Sanela Čajlaković Kurtalić

    2014-09-01

    Full Text Available In this paper we presented a research that estimates general psychological and functional characteristics of motor vehicle drivers, with the goal of determining the adverse effects of noise and vibration on the drivers. The study was conducted on a sample of 56 participants, professional drivers of motor vehicles, randomly chosen from companies of various types operating in transport of passengers and goods. For the evaluation of the results,we used descriptive and correlational analysis. The results showed that there were significant negative side effects caused by the nature of work of drivers, especially those under the influence of noise and vibration, which are even more significant in older participants and those with more years of service and those who spend more time driving during the interval of 24 hours , as well as those who drive heavier vehicles.

  20. 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

  1. Enhanced release and drug delivery of celecoxib into physiological environment by the different types of nanoscale vehicles

    Science.gov (United States)

    Khazraei, Avideh; Tarlani, Aliakbar; Naderi, Nima; Muzart, Jacques; Abdulhameed (Kaabi), Zahra; Eslami-Moghadam, Mahbube

    2017-11-01

    Celecoxib (CEL) as the very low water soluble drug was loaded 16 and 50% (w/w) through an impregnation method on varieties of alumina nanostructures such as synthetic sol-gel γ-alumina (Gam-Al), functionalized sol-gel γ-alumina (Gam-Al-NH2), organized nano porous alumina (Onp-Al) and then the results compared with commercial alumina (Com-Al) and SBA-15 (SBA). Analyses of the samples were carried out by FT-IR, X-ray diffraction (XRD) and N2-sorption. in vitro studies were accomplished in simulated body fluid (SBF), simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). In vivo study was carried out on male wistar rats under standard conditions. The N2-sorption revealed the initial pore characteristics of the nanocarriers. XRD patterns showed that the 50% loaded samples contain bulk celecoxib and its solubility in body fluids is lower than that of 16% loaded samples. In the case of 16% loaded samples, the drug solubility in three simulated body fluids drug was found to decrease in the following order: Gam-Al-CEL > Onp-Al-CEL > Com-Al-CEL > SBA-CEL. Gam-Al-CEL showed the highest release (96%) in SBF after 60 min in vivo study showed significant decrease in pain score in rats for Gam-Al-NH2-CEL-16% and Gam-Al-CEL-50%. It could be concluded that the synthetic aluminas have a developing future potential compared to the formal SBA and commercial alumina.

  2. Predicting Light-Duty Vehicle Fuel Economy as a Function of Highway Speed

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, John [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hwang, Ho-Ling [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); West, Brian [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Huff, Shean [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2013-04-08

    The www.fueleconomy.gov website offers information such as window label fuel economy for city, highway, and combined driving for all U.S.-legal light-duty vehicles from 1984 to the present. The site is jointly maintained by the U.S. Department of Energy and the U.S. Environmental Protection Agency (EPA), and also offers a considerable amount of consumer information and advice pertaining to vehicle fuel economy and energy related issues. Included with advice pertaining to driving styles and habits is information concerning the trend that as highway cruising speed is increased, fuel economy will degrade. An effort was undertaken to quantify this conventional wisdom through analysis of dynamometer testing results for 74 vehicles at steady state speeds from 50 to 80 mph. Using this experimental data, several simple models were developed to predict individual vehicle fuel economy and its rate of change over the 50-80 mph speed range interval. The models presented require a minimal number of vehicle attributes. The simplest model requires only the EPA window label highway mpg value (based on the EPA specified estimation method for 2008 and beyond). The most complex of these simple model uses vehicle coast-down test coefficients (from testing prescribed by SAE Standard J2263) known as the vehicle Target Coefficients, and the raw fuel economy result from the federal highway test. Statistical comparisons of these models and discussions of their expected usefulness and limitations are offered.

  3. 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.

  4. 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.

  5. Targeted Delivery of Functionalized Upconversion Nanoparticles for Externally Triggered Photothermal/Photodynamic Therapies of Brain Glioblastoma.

    Science.gov (United States)

    Tsai, Yuan-Chung; Vijayaraghavan, Priya; Chiang, Wen-Hsuan; Chen, Hsin-Hung; Liu, Te-I; Shen, Ming-Yin; Omoto, Ayumu; Kamimura, Masao; Soga, Kohei; Chiu, Hsin-Cheng

    2018-01-01

    Therapeutic efficacy of glioblastoma multiforme (GBM) is often severely limited by poor penetration of therapeutics through blood-brain barrier (BBB) into brain tissues and lack of tumor targeting. In this regard, a functionalized upconversion nanoparticle (UCNP)-based delivery system which can target brain tumor and convert deep tissue-penetrating near-infrared (NIR) light into visible light for precise phototherapies on brain tumor was developed in this work. Methods : The UCNP-based phototherapy delivery system was acquired by assembly of oleic acid-coated UCNPs with angiopep-2/cholesterol-conjugated poly(ethylene glycol) and the hydrophobic photosensitizers. The hybrid nanoparticles (ANG-IMNPs) were characterized by DLS, TEM, UV/vis and fluorescence spectrophotometer. Cellular uptake was examined by laser scanning confocal microscopy and flow cytometry. The PDT/PTT effect of ANG-IMNPs was evaluated using MTT assay. Tumor accumulation of NPs was determined by a non-invasive in vivo imaging system (IVIS). The in vivo anti-glioma effect of ANG-IMNPs was evaluated by immunohistochemical (IHC) examination of tumor tissues and Kaplan-Meier survival analysis. Results : In vitro data demonstrated enhanced uptake of ANG-IMNPs by murine astrocytoma cells (ALTS1C1) and pronounced cytotoxicity by combined NIR-triggered PDT and PTT. In consistence with the increased penetration of ANG-IMNPs through endothelial monolayer in vitro , the NPs have also shown significantly enhanced accumulation at brain tumor by IVIS. The IHC tissue examination confirmed prominent apoptotic and necrotic effects on tumor cells in mice receiving targeted dual photo-based therapies, which also led to enhanced median survival (24 days) as compared to the NP treatment without angiopep-2 (14 days). Conclusion : In vitro and in vivo data strongly indicate that the ANG-IMNPs were capable of selectively delivering dual photosensitizers to brain astrocytoma tumors for effective PDT/PTT in conjugation with

  6. Automotive Security Functions; The Use of New Technologies to Tackle Vehicle-Related Crime

    NARCIS (Netherlands)

    Knapik, Peter

    2016-01-01

    Daily life is increasingly penetrated by new technologies. Advanced driver assistance systems with sophisticated sensors are increasingly available in all classes of vehicles. Moreover, mobile devices, such as smartphones, have become our daily companions. With the help of wireless communication

  7. Photovoltaic Power System with MPPT Functionality for a Small-Size Electric Vehicle

    OpenAIRE

    Xu, Jianming; Kang, Longyun; Zhong, Changyi; Cao, Binggang

    2014-01-01

    Electric vehicles are recognized as the best replacement of petrol vehicles in the future. However, there are several problems hampering their development, such as the short life span of batteries, poor performance of start-up, and a short driving range. In order to resolve these problems, a hybrid power system based on photovoltaic (PV) cells, supercapacitors, and batteries is proposed. This paper focuses on PV cells using a maximum power point track (MPPT) system based on a BUCK chopper cir...

  8. The Entropy-Cost Function Evaluation Method for Unmanned Ground Vehicles

    OpenAIRE

    Ya-Nan Zhao; Kai-Wen Meng; Li Gao

    2015-01-01

    To improve the technology of unmanned ground vehicles, it is necessary to conduct a proper evaluation on various technologies. Previous evaluation methods are mainly based on completion of the task; this may mislead most of teams of unmanned ground vehicles using a conservative strategy during the evaluation. In this paper, a new evaluation method is proposed. Based on typical working conditions including intersection, car-following, and obstacle-avoiding, the new evaluation indicator system ...

  9. A General Method for Intracellular Protein Delivery through 'E-tag' Protein Engineering and Arginine Functionalized Gold Nanoparticles.

    Science.gov (United States)

    Mout, Rubul; Rotello, Vincent M

    2017-12-20

    In this protocol, we describe a method for direct cytosolic protein delivery that avoids endosomal entrapment of the delivered proteins. We achieved this by tagging the desired protein with an oligo glutamic acid tag (E-tag), and subsequently using carrier gold nanoparticles to deliver these E-tagged proteins. When E-tagged proteins and nanoparticles were mixed, they formed nanoassemblies, which got fused to cell membrane upon incubation and directly released the E-tagged protein into cell cytosol. We used this method to deliver a wide variety of proteins with different sizes, charges, and functions in various cell lines (Mout et al ., 2017). To use this protocol, the first step is to generate the required materials (gold nanoparticles, recombinant E-tagged proteins). Laboratory-synthesis of gold nanoparticles has been previously described (Yang et al ., 2011). Desired E-tagged proteins can be cloned from the corresponding genes, and expressed and purified using standard laboratory procedures. We will use E-tagged green fluorescent protein (GFP) as a reference protein here. Users can simply insert an E-tag into their protein of interest, at either terminus. To achieve maximum delivery efficiency, we suggest users testing different length of E-tags. For example, we inserted E = 0 to 20 (E0 means no E-tag insertion, and E20 means 20 glutamic acids insertion in a row) to most of the proteins we tested, and screened for optimal E-tagged length for highest delivery efficiency. E10-tagged proteins gave us the highest delivery efficiency for most of the proteins (except for Cas9, where E20 tag showed highest delivery efficiency). Once these materials are ready, it takes about ~10 min to make the E-tagged protein and nanoparticle nanoassemblies, which are immediately used for delivery. Complete delivery (~100% for GFP-E10) is achieved in less than 3 h.

  10. 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.

  11. Dual-functional Polyurea Microcapsules for Chronic Wound Care Dressings: Sustained Drug Delivery and Non-leaching Infection Control

    Science.gov (United States)

    He, Wei

    A new design of dual-functional polyurea microcapsules was proposed for chronic wound dressings to provide both non-leaching infection control and sustained topical drug delivery functionalities. Quaternary ammonium functionalized polyurea microcapsules (MCQs) were synthesized under mild conditions through an interfacial crosslinking reaction between branched polyethylenimine (PEI) and 2,4-toluene diisocyanate (TDI) in a dimethylformamide/cyclohexane emulsion. An in-situ modification method was developed to endow non-leaching surface antimicrobial properties to MCQs via bonding antimicrobial surfactants to surface isocyanate residues on the polyurea shells. The resultant robust MCQs with both non-leaching antimicrobial properties and sustained drug releasing properties have potential applications in medical textiles, such as chronic wound dressings, for infection control and drug delivery.

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

    DEFF Research Database (Denmark)

    Bentin, Thomas

    2012-01-01

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

  13. 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.

  14. Modeling and predicting low-speed vehicle emissions as a function of driving kinematics.

    Science.gov (United States)

    Hao, Lijun; Chen, Wei; Li, Lei; Tan, Jianwei; Wang, Xin; Yin, Hang; Ding, Yan; Ge, Yunshan

    2017-05-01

    An instantaneous emission model was developed to model and predict the real driving emissions of the low-speed vehicles. The emission database used in the model was measured by using portable emission measurement system (PEMS) under actual traffic conditions in the rural area, and the characteristics of the emission data were determined in relation to the driving kinematics (speed and acceleration) of the low-speed vehicle. The input of the emission model is driving cycle, and the model requires instantaneous vehicle speed and acceleration levels as input variables and uses them to interpolate the pollutant emission rate maps to calculate the transient pollutant emission rates, which will be accumulated to calculate the total emissions released during the whole driving cycle. And the vehicle fuel consumption was determined through the carbon balance method. The model predicted the emissions and fuel consumption of an in-use low-speed vehicle type model, which agreed well with the measured data. Copyright © 2016. Published by Elsevier B.V.

  15. Road load simulator tests of the Gould phase 1 functional model silicon controlled rectifier ac motor controller for electric vehicles

    Science.gov (United States)

    Gourash, F.

    1984-01-01

    The test results for a functional model ac motor controller for electric vehicles and a three-phase induction motor which were dynamically tested on the Lewis Research Center road load simulator are presented. Results show that the controller has the capability to meet the SAE-J227a D cycle test schedule and to accelerate a 1576-kg (3456-lb) simulated vehicle to a cruise speed of 88.5 km/hr (55 mph). Combined motor controller efficiency is 72 percent and the power inverter efficiency alone is 89 percent for the cruise region of the D cycle. Steady state test results for motoring, regeneration, and thermal data obtained by operating the simulator as a conventional dynamometer are in agreement with the contractor's previously reported data. The regeneration test results indicate that a reduction in energy requirements for urban driving cycles is attainable with regenerative braking. Test results and data in this report serve as a data base for further development of ac motor controllers and propulsion systems for electric vehicles. The controller uses state-of-the-art silicon controlled rectifier (SCR) power semiconductors and microprocessor-based logic and control circuitry. The controller was developed by Gould Laboratories under a Lewis contract for the Department of Energy's Electric and Hybrid Vehicle program.

  16. Road load simulator tests of the Gould phase 1 functional model silicon controlled rectifier ac motor controller for electric vehicles

    Science.gov (United States)

    Gourash, F.

    1984-02-01

    The test results for a functional model ac motor controller for electric vehicles and a three-phase induction motor which were dynamically tested on the Lewis Research Center road load simulator are presented. Results show that the controller has the capability to meet the SAE-J227a D cycle test schedule and to accelerate a 1576-kg (3456-lb) simulated vehicle to a cruise speed of 88.5 km/hr (55 mph). Combined motor controller efficiency is 72 percent and the power inverter efficiency alone is 89 percent for the cruise region of the D cycle. Steady state test results for motoring, regeneration, and thermal data obtained by operating the simulator as a conventional dynamometer are in agreement with the contractor's previously reported data. The regeneration test results indicate that a reduction in energy requirements for urban driving cycles is attainable with regenerative braking. Test results and data in this report serve as a data base for further development of ac motor controllers and propulsion systems for electric vehicles. The controller uses state-of-the-art silicon controlled rectifier (SCR) power semiconductors and microprocessor-based logic and control circuitry. The controller was developed by Gould Laboratories under a Lewis contract for the Department of Energy's Electric and Hybrid Vehicle program.

  17. 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.

  18. On the chemical synthesis and drug delivery response of folate receptor-activated, polyethylene glycol-functionalized magnetite nanoparticles.

    Science.gov (United States)

    Zhang, J; Rana, S; Srivastava, R S; Misra, R D K

    2008-01-01

    We describe here the chemical synthesis and in vitro drug delivery response of polyethylene glycol (PEG)-functionalized magnetite (Fe(3)O(4)) nanoparticles, which were activated with a stable ligand, folic acid, and conjugated with an anticancer drug, doxorubicin. The functionalization and conjugation steps in the chemical synthesis were confirmed using Fourier transform infrared spectroscopy. The drug-release behavior of PEG-functionalized and folic acid-doxorubicin-conjugated magnetic nanoparticles was characterized by two stages involving an initial rapid release, followed by a controlled release.

  19. Functional outcomes of motor vehicle crash head injuries in pediatric and adult occupants.

    Science.gov (United States)

    Schoell, Samantha L; Weaver, Ashley A; Talton, Jennifer W; Baker, Gretchen; Doud, Andrea N; Barnard, Ryan T; Stitzel, Joel D; Zonfrillo, Mark R

    2016-09-01

    The objective of the study was to develop a disability-based metric for motor vehicle crash (MVC) injuries, with a focus on head injuries, and compare the functional outcomes between the pediatric and adult populations. Disability risk (DR) was quantified using Functional Independence Measure (FIM) scores within the National Trauma Data Bank-Research Data System (NTDB-RDS) for the top 95% most frequently occurring Abbreviated Injury Scale (AIS) 3, 4, and 5 head injuries in NASS-CDS 2000-2011. Pediatric (ages 7-18), adult (19-45), middle-aged (46-65), and older adult (66+) patients with an FIM score available who were alive at discharge and had an AIS 3, 4, or 5 injury were included in the study. The NTDB-RDS contains a truncated form of the FIM instrument, including 3 items (self-feed, locomotion, and verbal expression), each graded on a scale of 1 (full functional dependence) to 4 (full functional independence). Patients within each age group were classified as disabled or not disabled based on the FIM scale. The DR was calculated for each age group by dividing the number of patients who sustained a specific injury and were disabled by the number of patients who sustained the specific injury. To account for the impact of more severe associated coinjuries, a maximum AIS (MAIS) adjusted DR (DRMAIS) was also calculated for each injury. DR and DRMAIS ranged from 0 (0% disability risk) to 1 (100% disability risk). An analysis of the most frequent FIM components associated with disabling MVC head injuries revealed that disability across all 3 items (self-feed, locomotion, and expression) was the most frequent for pediatric and adult patients. Only locomotion was the most frequent for middle-aged and older adults. The mean DRMAIS for MVC head injuries was 35% for pediatric patients, 36% for adults, 38% for middle-aged adults, and 44% for older adults. Further analysis was conducted by grouping the head injuries into 8 groups based on the structure of injury and injury

  20. Developing Functional Parameters for a Science-Based Vehicle Cleaning Program to Reduce Transport of Non-Indigenous Invasive Plant Species

    Science.gov (United States)

    2011-06-01

    indigenous . Some species were grouped due to identification similarity and some could not be identified beyond genus due to lack of flowering under...FINAL REPORT Developing Functional Parameters for a Science-Based Vehicle Cleaning Program to Reduce Transport of Non- Indigenous Invasive...vehicles .............................. 15  4.3.2 Non- indigenous plant survey to create occupancy maps

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

    Science.gov (United States)

    McClements, David Julian

    2013-12-01

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

  2. Biodegradable Eri silk nanoparticles as a delivery vehicle for bovine lactoferrin against MDA-MB-231 and MCF-7 breast cancer cells

    Directory of Open Access Journals (Sweden)

    Roy K

    2015-12-01

    Full Text Available Kislay Roy,1,* Yogesh S Patel,1,* Rupinder K Kanwar,1 Rangam Rajkhowa,2 Xungai Wang,2 Jagat R Kanwar1 1Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR, Centre for Molecular and Medical Research (C-MMR, School of Medicine (SoM, Faculty of Health, 2Institute for Frontier Materials (IFM, Deakin University, Waurn Ponds, VIC, Australia *These authors contributed equally to this work Abstract: This study used the Eri silk nanoparticles (NPs for delivering apo-bovine lactoferrin (Apo-bLf (~2% iron saturated and Fe-bLf (100% iron saturated in MDA-MB-231 and MCF-7 breast cancer cell lines. Apo-bLf and Fe-bLf-loaded Eri silk NPs with sizes between 200 and 300 nm (±10 nm showed a significant internalization within 4 hours in MDA-MB-231 cells when compared to MCF-7 cells. The ex vivo loop assay with chitosan-coated Fe-bLf-loaded silk NPs was able to substantiate its future use in oral administration and showed the maximum absorption within 24 hours by ileum. Both Apo-bLf and Fe-bLf induced increase in expression of low-density lipoprotein receptor-related protein 1 and lactoferrin receptor in epidermal growth factor (EGFR-positive MDA-MB-231 cells, while transferrin receptor (TfR and TfR2 in MCF-7 cells facilitated the receptor-mediated endocytosis of NPs. Controlled and sustained release of both bLf from silk NPs was shown to induce more cancer-specific cytotoxicity in MDA-MB-231 and MCF-7 cells compared to normal MCF-10A cells. Due to higher degree of internalization, the extent of cytotoxicity and apoptosis was significantly higher in MDA-MB-231 (EGFR+ cells when compared to MCF-7 (EGFR- cells. The expression of a prominent anti-cancer target, survivin, was found to be downregulated at both gene and protein levels. Taken together, all the observations suggest the potential use of Eri silk NPs as a delivery vehicle for an anti-cancer milk protein, and indicate bLf for the treatment of breast cancer. Keywords: breast

  3. Recovery of HPA Axis Function After Successful Gonadotropin-Induced Pregnancy and Delivery in a Woman With Panhypopituitarism

    OpenAIRE

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

    2015-01-01

    Abstract 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 o...

  4. Vehicle perceptibilty : reflectorized registration plates and alternative means : function, design and application.

    NARCIS (Netherlands)

    Griep, D.J. Thoenes, E. Schreuder, D.A. & Kranenburg, A.

    1970-01-01

    In November 1967 the Minister of Transport and Waterways in the Netherlands asked the Institute for Road Safety Research SWOV to examine the advisable design of reflectorized registration plates from the aspect of perceptibility. Allowance had to be made for the identification of motor vehicles.

  5. Dynamics and Control of a Biomimetic Vehicle Using Biased Wingbeat Forcing Functions: Part 2 - Controller (Postprint)

    Science.gov (United States)

    2010-01-01

    NUMBER 5c. PROGRAM ELEMENT NUMBER 62201F 6. AUTHOR(S) David B. Doman, Michael W. Oppenheimer, and David O. Sigthorsson (AFRL/ RBCA ) 5d...REPORT NUMBER Control Design and Analysis Branch (AFRL/ RBCA ) Control Sciences Division Air Force Research Laboratory, Air Vehicles

  6. A New Method to Optimize Semiactive Hybrid Energy Storage System for Hybrid Electrical Vehicle by Using PE Function

    Directory of Open Access Journals (Sweden)

    Cong Zhang

    2015-01-01

    Full Text Available Although both battery and super-capacitor are important power sources for hybrid electric vehicles, there is no accurate configuration theory to match the above two kinds of power sources which have significantly different characteristics on energy and power storage for the goal of making good use of their individual features without size wasting. In this paper, a new performance is presented that is used for analysis and optimal design method of battery and super-capacitor for hybrid energy storage system of a parallel hybrid electrical vehicle. In order to achieve optimal design with less consumption, the power-energy function is applied to establish direct mathematical relationship between demand power and the performance. During matching process, firstly, three typical operating conditions are chosen as the basis of design; secondly, the energy and power capacity evaluation methods for the parameters of battery and super-capacitor in hybrid energy storage system are proposed; thirdly, the mass, volume, and cost of the system are optimized simultaneously by using power-energy function. As a result, there are significant advantages on mass, volume, and cost for the hybrid energy storage system with the matching method. Simulation results fit well with the results of analysis, which confirms that the optimized design can meet the demand of hybrid electric vehicle well.

  7. Do changes in anal sphincter anatomy correlate with anal function in women with a history of vaginal delivery?

    Science.gov (United States)

    Murad-Regadas, Sthela Maria; Dealcanfreitas, Iris Daiana; Regadas, Francisco Sergio Pinheiro; Rodrigues, Lusmar Veras; Fernandes, Graziela Olivia da Silva; Pereira, Jacyara de Jesus Rosa

    2014-01-01

    To evaluate anal sphincter anatomy using three-dimensional ultrasonography (3-DAUS) in incontinent women with vaginal delivery, correlate anatomical findings with symptoms of fecal incontinence and determine the effect of vaginal delivery on anal canal anatomy and function. Female with fecal incontinence and vaginal delivery were assessed with Wexner's score, manometry, and 3DAUS. A control group comprising asymptomatic nulliparous was included. Anal pressure, the angle of the defect and length of the external anal sphincter (EAS), the anterior and posterior internal anal sphincter (IAS), the EAS + puborectal and the gap were measured and correlated with score. Of the 62, 49 had fecal incontinence and 13 were asymptomatic. Twenty five had EAS defects, 8 had combined EAS+IAS defects, 16 had intact sphincters and continence scores were similar. Subjects with sphincter defects had a shorter anterior EAS, IAS and longer gap than women without defects. Those with a vaginal delivery and intact sphincters had a shorter anterior EAS and longer gap than nulliparous. We found correlations between resting pressure and anterior EAS and IAS length in patients with defects. Fecal incontinence symptoms did not correlate with anal pressures and anal sphincter anatomy changes, but women with sphincter defects have shorter anterior EAS and IAS and a longer gap.

  8. 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...

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

    Science.gov (United States)

    Scanlan, Martin

    2009-01-01

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

  10. 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...

  11. Protein kinase A inhibition modulates the intracellular routing of gene delivery vehicles in HeLa cells, leading to productive transfection

    NARCIS (Netherlands)

    Rehman, Zia Ur; Hoekstra, Dick; Zuhorn, Inge S.

    2011-01-01

    Cellular entry of nanoparticles for drug- and gene delivery relies on various endocytic pathways, including clathrin-and caveolae-mediated endocytosis. To improve delivery, i.e., the therapeutic and/or cell biological impact, current efforts are aimed at avoiding processing of the carriers along the

  12. Photovoltaic Power System with MPPT Functionality for a Small-Size Electric Vehicle

    Directory of Open Access Journals (Sweden)

    Jianming Xu

    2014-01-01

    Full Text Available Electric vehicles are recognized as the best replacement of petrol vehicles in the future. However, there are several problems hampering their development, such as the short life span of batteries, poor performance of start-up, and a short driving range. In order to resolve these problems, a hybrid power system based on photovoltaic (PV cells, supercapacitors, and batteries is proposed. This paper focuses on PV cells using a maximum power point track (MPPT system based on a BUCK chopper circuit. Moreover, a novel MPPT algorithm named sectional variable step climbing (SVSC algorithm was proposed. To validate the proposed system, two main experiments have been done. The first experiment showed that the MPP of PV cells was tracked perfectly by use of this photovoltaic power system. The second one showed that the efficiency of SVSC was higher than two existing MPPT methods, the climbing algorithm and the open-circuit voltage (OCV algorithm.

  13. A review of construction and functionality of photogrammetric unmanned aerial vehicles

    Directory of Open Access Journals (Sweden)

    Paweł Burdziakowski

    2016-12-01

    Full Text Available A photogrammetry from an unmanned aerial vehicle (UAV can be understood as a new measurement tool. It introduces low-cost alternatives for a traditional aerial photogrammetry, combining terrestrial, aerial, and satellite photogrammetry techniques. This paper presents a photogrammetric UAV construction basics, a recommended platform analysis, and a review of commercially available components and systems’ elements designed for photogrammetric UAV purposes. As the results show, a motoglider can be recommended as a platform for a photogrammetric task, where the priority is to execute the maximum area coverage during one flight. That platform type is resistant to windy conditions and is able to execute long flight, opposite to multirotor platforms.[b]Keywords:[/b] photogrammetry, remote sensing, navigation, unmanned aerial vehicle, commercial of-the-shelf

  14. Quillaja saponaria extract as mucosal adjuvant with chitosan functionalized gold nanoparticles for mucosal vaccine delivery: stability and immunoefficiency studies.

    Science.gov (United States)

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

    2013-01-30

    Carrier mediated delivery of vaccines along with adjuvants can possibly address the issue related to oral vaccines like inadequate immune potentiation. In this study, chitosan functionalized gold nanoparticles (CsAuNPs) were used as a carrier for the model antigen tetanus toxoid (TT) along with immunostimulant Quillaja saponaria extract (QS). Physicochemical properties (size, zeta potential, pH value) of formulation were investigated as stability indicating parameters. The synthesized CsAuNPs were spherical in shape, around 40 nm in size, positively charged (around +35 mV) and had TT and QS payload of 65% and 0.01%, respectively. Formulation parameters did not alter the secondary structure of TT, as determined by FTIR, fluorescence and CD spectroscopy. Antigen specificity, determined by an ELISA, was also not compromised. The CsAuNPs conferred protection to TT against gastric hydrolysis as studied in vitro. TT-QS-CsAuNPs induced up to 28-fold immune responses compared to control formulations (TT, TT-QS) after oral administration of formulations in BALB/c mice. The immune responses were quantified by measuring the TT-specific IgG and IgA titers using ELISA. Findings herein demonstrate that co-delivery of TT and QS with functionalized CsAuNPs promotes better systemic and local immune responses and hence can be considered as a sound approach for oral vaccine delivery. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. DFT computational study on the phosphate functionalized SWCNTs as efficient drug delivery systems for anti-osteoporosis zolendronate and risedronate drugs

    Science.gov (United States)

    Nikfar, Zahra; Shariatinia, Zahra

    2017-07-01

    The pristine (4,4)-armchair SWCNT as well as its three phosphate functionalized (CNT-nH2PO4, n=1-3) forms were studied as novel drug delivery systems for the two commercially famous anti-osteoporosis drugs including risedronate (RIS) and zolendronate (ZOL) using the density functional theory (DFT) computations at both B3LYP and B3PW91 levels. Results revealed that the binding energy was increased by increasing number of H2PO4 moieties attached on the CNT with the most negative binding energy was measured for the CNT-3H2PO4 carrier. The dipole moments of all phosphate containing CNTs were much greater ( 1.5-4.5 D) than that of pristine CNT ( 0 D). The contour maps verified that when the CNT was functionalized by H2PO4 groups, the symmetric distribution of electric charge was vanished so that the highest and the lowest asymmetric charge distributions were achieved for the CNT-2H2PO4 and CNT-3H2PO4, respectively, leading to the greatest and the smallest dipole moments for the CNT-2H2PO4 (4.177 D) and the CNT-3H2PO4 (1.614 D). The compounds RIS-CNT-3H2PO4 and ZOL-CNT-3H2PO4 displayed the greatest electronegativity and electrophilicity index which were appropriate for the binding of drugs onto the bone surface (having partial positive charge due to the presence of Ca2+) and therefore effectively inhibiting the osteoporosis. Consequently, it was proposed that the drug-CNT-3H2PO4 was the most appropriate drug-carrier system for both of the RIS and ZOL drugs which could be employed as the most efficient vehicle.

  16. Oral delivery of diabetes peptides - Comparing standard formulations incorporating functional excipients and nanotechnologies in the translational context.

    Science.gov (United States)

    Lakkireddy, Harivardhan Reddy; Urmann, Matthias; Besenius, Melissa; Werner, Ulrich; Haack, Torsten; Brun, Priscilla; Alié, Jean; Illel, Brigitte; Hortala, Laurent; Vogel, Rachel; Bazile, Didier

    2016-11-15

    While some orally delivered diabetes peptides are moving to late development with standard formulations incorporating functional excipients, the demonstration of the value of nanotechnology in clinic is still at an early stage. The goal of this review is to compare these two drug delivery approaches from a physico-chemical and a biopharmaceutical standpoint in an attempt to define how nanotechnology-based products can be differentiated from standard oral dosage forms for oral bioavailability of diabetes peptides. Points to consider in a translational approach are outlined to seize the opportunities offered by a better understanding of both the intestinal barrier and of nano-carriers designed for oral delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. 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.

  18. Functional requirements for the man-vehicle systems research facility. [identifying and correcting human errors during flight simulation

    Science.gov (United States)

    Clement, W. F.; Allen, R. W.; Heffley, R. K.; Jewell, W. F.; Jex, H. R.; Mcruer, D. T.; Schulman, T. M.; Stapleford, R. L.

    1980-01-01

    The NASA Ames Research Center proposed a man-vehicle systems research facility to support flight simulation studies which are needed for identifying and correcting the sources of human error associated with current and future air carrier operations. The organization of research facility is reviewed and functional requirements and related priorities for the facility are recommended based on a review of potentially critical operational scenarios. Requirements are included for the experimenter's simulation control and data acquisition functions, as well as for the visual field, motion, sound, computation, crew station, and intercommunications subsystems. The related issues of functional fidelity and level of simulation are addressed, and specific criteria for quantitative assessment of various aspects of fidelity are offered. Recommendations for facility integration, checkout, and staffing are included.

  19. Recovery of HPA Axis Function After Successful Gonadotropin-Induced Pregnancy and Delivery in a Woman With Panhypopituitarism

    Science.gov (United States)

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

    2015-01-01

    Abstract 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 cotisol 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

  20. 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.

  1. Tracked vehicles in hazardous environments

    International Nuclear Information System (INIS)

    Jones, S.; Walton, P.J.

    1993-01-01

    A programme of remote inspections has been conducted on the Magnox steel reactor pressure vessel at Trawsfynydd Power Station using climbing vehicles. Tracked remotely operated vehicles supported the inspection programme by assisting with the delivery and recovery of the climbing vehicles and facilitating the use of various accessory packages. This paper presents details of the support project, the tracked vehicles and of the uses made of them during the inspection programme. (author)

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

    Science.gov (United States)

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

    2017-01-01

    Therapeutic delivery of regeneration-promoting biological factors directly to the site of injury has demonstrated its efficacy in various injury models. Several reports describe improved tissue regeneration following local injection of tissue specific growth factors, cytokines and chemokines. Evidence exists that combined cytokine/growth factor treatment is superior for optimizing tissue repair by targeting different aspects of the regeneration response. The purpose of this study was to evaluate the therapeutic potential of the controlled delivery of stromal cell-derived factor-1alpha (SDF-1α) alone or in combination with insulin-like growth factor-I (SDF-1α/IGF-I) for the treatment of tourniquet-induced ischemia/reperfusion injury (TK-I/R) of skeletal muscle. We hypothesized that SDF-1α will promote sustained stem cell recruitment to the site of muscle injury, while IGF-I will induce progenitor cell differentiation to effectively restore muscle contractile function after TK-I/R injury while concurrently reducing apoptosis. Utilizing a novel poly-ethylene glycol PEGylated fibrin gel matrix (PEG-Fib), we incorporated SDF-1α alone (PEG-Fib/SDF-1α) or in combination with IGF-I (PEG-Fib/SDF-1α/IGF-I) for controlled release at the site of acute muscle injury. Despite enhanced cell recruitment and revascularization of the regenerating muscle after SDF-1α treatment, functional analysis showed no benefit from PEG-Fib/SDF-1α therapy, while dual delivery of PEG-Fib/SDF-1α/IGF-I resulted in IGF-I-mediated improvement of maximal force recovery and SDF-1α-driven in vivo neovasculogenesis. Histological data supported functional data, as well as highlighted the important differences in the regeneration process among treatment groups. This study provides evidence that while revascularization may be necessary for maximizing muscle force recovery, without modulation of other effects of inflammation it is insufficient. PMID:26247892

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

    Science.gov (United States)

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

    2015-11-01

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

  4. 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

  5. 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

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

    Science.gov (United States)

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

    2014-10-08

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

  7. 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.

  8. Bleomycin loaded magnetite nanoparticles functionalized by polyacrylic acid as a new antitumoral drug delivery system.

    Science.gov (United States)

    Xu, Yue; Lin, Yi; Zhuang, Lin; Lin, Jiong; Lv, Jiahong; Huang, Qin; Sun, Jiadong

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yue Xu

    2013-01-01

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

  10. Functional Foods Programs Serve as a Vehicle to Provide Nutrition Education to Groups

    Science.gov (United States)

    Cirignano, Sherri M.

    2011-01-01

    An increase in consumer interest in functional foods provides an opportunity for FCS educators to use this topic in Extension programming to promote current nutrition recommendations. The Functional Foods for Life Educational Programs (FFL) are a curriculum of six evidence-based mini-seminars that highlight specific functional foods that have the…

  11. Definition of technology development missions for early space stations orbit transfer vehicle serving. Phase 2, task 1: Space station support of operational OTV servicing

    Science.gov (United States)

    1983-01-01

    Representative space based orbital transfer vehicles (OTV), ground based vehicle turnaround assessment, functional operational requirements and facilities, mission turnaround operations, a comparison of ground based versus space based tasks, activation of servicing facilities prior to IOC, fleet operations requirements, maintenance facilities, OTV servicing facilities, space station support requirements, and packaging for delivery are discussed.

  12. Using CPE Function to Size Capacitor Storage for Electric Vehicles and Quantifying Battery Degradation during Different Driving Cycles

    Directory of Open Access Journals (Sweden)

    Cong Zhang

    2016-11-01

    Full Text Available Range anxiety and battery cycle life are two major factors which restrict the development of electric vehicles. Battery degradation can be reduced by adding supercapacitors to create a Hybrid Energy Storage System. This paper proposes a systematic approach to configure the hybrid energy storage system and quantifies the battery degradation for electric vehicles when using supercapacitors. A continuous power-energy function is proposed to establish supercapacitor size based on national household travel survey statistics. By analyzing continuous driving action in standard driving cycles and special driving phases (start up and acceleration, the supercapacitor size is calculated to provide a compromise between the capacitor size and battery degradation. Estimating the battery degradation after 10 years, the battery capacity loss value decreases 17.55% and 21.6%, respectively, under the urban dynamometer driving schedule and the US06. Furthermore, the battery lifespan of the continuous power-energy configured system is prolonged 28.62% and 31.39%, respectively, compared with the battery alone system.

  13. On the use of liposome controls in studies investigating the clinical potential of extracellular vesicle-based drug delivery systems - A commentary

    DEFF Research Database (Denmark)

    Johnsen, Kasper Bendix; Gudbergsson, Johann Mar; Duroux, Meg

    2018-01-01

    The field of extracellular vesicle (EV)-based drug delivery systems has evolved significantly through the recent years, and numerous studies suggest that these endogenous nanoparticles can function as efficient drug delivery vehicles in a variety of diseases. Many characteristics of these EV...

  14. α, ω-Cholesterol-Functionalized Low Molecular Weight Polyethylene Glycol as a Novel Modifier of Cationic Liposomes for Gene Delivery

    Directory of Open Access Journals (Sweden)

    Cui-Cui Ma

    2014-11-01

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

  15. The Effect of Chewing Sugar Free Gum after Elective Cesarean-Delivery on Return of Bowel Function in Primiparous Women:

    Directory of Open Access Journals (Sweden)

    Gangi F

    2011-01-01

    Full Text Available Background and Objectives: An important cause of delayed recovery from abdominal surgery is delay in return of bowel Function. The aim of the present study was to assess the effects of chewing sugar free gum after elective Cesarean-delivery on return of bowel function in primiparous women in Hajar hospital of Shahrekord.Methods: In a randomized clinical trial, 120 patients, who were scheduled for elective cesarean were randomly allocated to 2 groups of gum-chewing group (n=60 and control group (n=60 postoperatively. The patients in the gum-chewing group chewed postoperatively sugar free gum 4 times daily as soon as they recovered from anesthesia till the time they passed flatus or defecated. Control group recieved routine postoperative dietary management. The mean scores of postoperative time interval to first hearing of normal bowel sounds, passage of flatus, defecation and sensation of bowel movement were compared between the two groups. The data were then analyzed using chi square and t-test (p<0.05.Results: The mean postoperative time interval to first hearing of normal intestinal sounds (6.5+/-1.5 versus 12.5+/- 2.5 hours, the first passage of flatus (12.2+/-2.0 vs.22.4+/-4.1 hours, first sensation of bowel movement (7.4+/-1.7 versus 15.7+/-3.4 hours and defecation (15.5+/-2.5 versus 23.4+/-4.8 hours were significantly lower in the gum-chewing group compared with control group. (p<0.001. The staying period in the hospital (0.96+/-0.18 versus 1.1+/-34 days was significantly shorter in gum-chewing group. (p<0.001.Conclusion: Chewing gum after elective Cesarean-Delivery is safe, inexpensive and helpful which is well tolerated, and associated with rapid resumption of intestinal function and speeds recovery shorter hospital stay.

  16. The Effect of Chewing Sugar Free Gum after Elective Cesarean-Delivery on Return of Bowel Function in Primiparous Women:

    Directory of Open Access Journals (Sweden)

    Safdari Dehcheshmeh F

    Full Text Available Background and Objectives: An important cause of delayed recovery from abdominal surgery is delay in return of bowel Function. The aim of the present study was to assess the effects of chewing sugar free gum after elective Cesarean-delivery on return of bowel function in primiparous women in Hajar hospital of Shahrekord.Methods: In a randomized clinical trial, 120 patients, who were scheduled for elective cesarean were randomly allocated to 2 groups of gum-chewing group (n=60 and control group (n=60 postoperatively. The patients in the gum-chewing group chewed postoperatively sugar free gum 4 times daily as soon as they recovered from anesthesia till the time they passed flatus or defecated. Control group recieved routine postoperative dietary management. The mean scores of postoperative time interval to first hearing of normal bowel sounds, passage of flatus, defecation and sensation of bowel movement were compared between the two groups. The data were then analyzed using chi square and t-test (p<0.05.Results: The mean postoperative time interval to first hearing of normal intestinal sounds (6.5+/-1.5 versus 12.5+/- 2.5 hours, the first passage of flatus (12.2+/-2.0 vs.22.4+/-4.1 hours, first sensation of bowel movement (7.4+/-1.7 versus 15.7+/-3.4 hours and defecation (15.5+/-2.5 versus 23.4+/-4.8 hours were significantly lower in the gum-chewing group compared with control group. (p<0.001. The staying period in the hospital (0.96+/-0.18 versus 1.1+/-34 days was significantly shorter in gum-chewing group. (p<0.001.Conclusion: Chewing gum after elective Cesarean-Delivery is safe, inexpensive and helpful which is well tolerated, and associated with rapid resumption of intestinal function and speeds recovery shorter hospital stay.

  17. Probing potassium channel function in vivo by intracellular delivery of antibodies in a rat model of retinal neurodegeneration

    Science.gov (United States)

    Raz-Prag, Dorit; Grimes, William N.; Fariss, Robert N.; Vijayasarathy, Camasamudram; Campos, Maria M.; Bush, Ronald A.; Diamond, Jeffrey S.; Sieving, Paul A.

    2010-01-01

    Inward rectifying potassium (Kir) channels participate in regulating potassium concentration (K+) in the central nervous system (CNS), including in the retina. We explored the contribution of Kir channels to retinal function by delivering Kir antibodies (Kir-Abs) into the rat eye in vivo to interrupt channel activity. Kir-Abs were coupled to a peptide carrier to reach intracellular epitopes. Functional effects were evaluated by recording the scotopic threshold response (STR) and photopic negative response (PhNR) of the electroretinogram (ERG) noninvasively with an electrode on the cornea to determine activity of the rod and cone pathways, respectively. Intravitreal delivery of Kir2.1-Ab coupled to the peptide carrier diminished these ERG responses equivalent to dimming the stimulus 10- to 100-fold. Immunohistochemistry (IHC) showed Kir2.1 immunostaining of retinal bipolar cells (BCs) matching the labeling pattern obtained with conventional IHC of applying Kir2.1-Ab to fixed retinal sections postmortem. Whole-cell voltage-clamp BC recordings in rat acute retinal slices showed suppression of barium-sensitive Kir2.1 currents upon inclusion of Kir2.1-Ab in the patch pipette. The in vivo functional and structural results implicate a contribution of Kir2.1 channel activity in these electronegative ERG potentials. Studies with Kir4.1-Ab administered in vivo also suppressed the ERG components and showed immunostaining of Müller cells. The strategy of administering Kir antibodies in vivo, coupled to a peptide carrier to facilitate intracellular delivery, identifies roles for Kir2.1 and Kir4.1 in ERG components arising in the proximal retina and suggests this approach could be of further value in research. PMID:20616020

  18. Plant Food Residues as a Source of Nutraceuticals and Functional Foods.

    Science.gov (United States)

    Varzakas, Theodoros; Zakynthinos, George; Verpoort, Francis

    2016-12-10

    This chapter describes the use of different plant and vegetable food residues as nutraceuticals and functional foods. Different nutraceuticals are mentioned and explained. Their uses are well addressed along with their disease management and their action as nutraceutical delivery vehicles.

  19. Ultrasound in Radiology: from Anatomic, Functional, Molecular Imaging to Drug Delivery and Image-Guided Therapy

    Science.gov (United States)

    Klibanov, Alexander L.; Hossack, John A.

    2015-01-01

    During the past decade, ultrasound has expanded medical imaging well beyond the “traditional” radiology setting - a combination of portability, low cost and ease of use makes ultrasound imaging an indispensable tool for radiologists as well as for other medical professionals who need to obtain imaging diagnosis or guide a therapeutic intervention quickly and efficiently. Ultrasound combines excellent ability for deep penetration into soft tissues with very good spatial resolution, with only a few exceptions (i.e. those involving overlying bone or gas). Real-time imaging (up to hundreds and thousands frames per second) enables guidance of therapeutic procedures and biopsies; characterization of the mechanical properties of the tissues greatly aids with the accuracy of the procedures. The ability of ultrasound to deposit energy locally brings about the potential for localized intervention encompassing: tissue ablation, enhancing penetration through the natural barriers to drug delivery in the body and triggering drug release from carrier micro- and nanoparticles. The use of microbubble contrast agents brings the ability to monitor and quantify tissue perfusion, and microbubble targeting with ligand-decorated microbubbles brings the ability to obtain molecular biomarker information, i.e., ultrasound molecular imaging. Overall, ultrasound has become the most widely used imaging modality in modern medicine; it will continue to grow and expand. PMID:26200224

  20. 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

  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. 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

  3. Adaptive terminal sliding mode control for hypersonic flight vehicles with strictly lower convex function based nonlinear disturbance observer.

    Science.gov (United States)

    Wu, Yun-Jie; Zuo, Jing-Xing; Sun, Liang-Hua

    2017-11-01

    In this paper, the altitude and velocity tracking control of a generic hypersonic flight vehicle (HFV) is considered. A novel adaptive terminal sliding mode controller (ATSMC) with strictly lower convex function based nonlinear disturbance observer (SDOB) is proposed for the longitudinal dynamics of HFV in presence of both parametric uncertainties and external disturbances. First, for the sake of enhancing the anti-interference capability, SDOB is presented to estimate and compensate the equivalent disturbances by introducing a strictly lower convex function. Next, the SDOB based ATSMC (SDOB-ATSMC) is proposed to guarantee the system outputs track the reference trajectory. Then, stability of the proposed control scheme is analyzed by the Lyapunov function method. Compared with other HFV control approaches, key novelties of SDOB-ATSMC are that a novel SDOB is proposed and drawn into the (virtual) control laws to compensate the disturbances and that several adaptive laws are used to deal with the differential explosion problem. Finally, it is illustrated by the simulation results that the new method exhibits an excellent robustness and a better disturbance rejection performance than the convention approach. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  4. Disruption management of the vehicle routing problem with vehicle breakdown

    DEFF Research Database (Denmark)

    Mu, Q; Fu, Z; Lysgaard, Jens

    2011-01-01

    This paper introduces a new class of problem, the disrupted vehicle routing problem (VRP), which deals with the disruptions that occur at the execution stage of a VRP plan. The paper then focuses on one type of such problem, in which a vehicle breaks down during the delivery and a new routing...

  5. A modular function architecture for adaptive and predictive energy management in hybrid electric vehicles; Eine modulare Funktionsarchitektur fuer adaptives und vorausschauendes Energiemanagement in Hybridfahrzeugen

    Energy Technology Data Exchange (ETDEWEB)

    Wilde, Andreas

    2009-10-27

    Due to the relatively low energy density of electrical energy storage devices, the control strategy of hybrid electric vehicles has to fulfil a variety of requirements in order to provide both, the availability of hybrid functions, and their efficient execution. Energy consuming functions such as electric drive or electric boost need a high amount of energy stored in the battery. On the other hand for the optimum use of the energy regeneration function a lower state of charge is preferable in order to enable storage of the kinetic energy of the vehicle in all situations, including upon deceleration from high speeds or downhill driving. These diverging requirements yield a conflict of objectives for the charging strategy of hybrid electric vehicles. This work proposes a way to overcome the restrictions on efficiency in hybrid electric vehicles without deteriorating overall driving performance by charging or discharging the traction battery, and by setting the energy management parametres according to the current and forthcoming driving situation. Specific charging and electric drive strategies are presented for various driving situations which are identified by sensors such as navigation systems, cameras or radar. Necessary sensor data fusion methods for driving situation identification are described and a modular function architecture for predictive energy management is derived that is plug-and-play compatible with a broad fleet of vehicles. In order to evaluate its potential, this work also focuses on the simulation of the energy functions and their implementation into an experimental vehicle. This allows measurements under real traffic conditions and a sensivity analysis of the main module interactions within the architecture. (orig.)

  6. Degradable Polymersomes for Targeted Drug Delivery

    Science.gov (United States)

    Petersen, Matthew Alan

    Chemotherapy today is often accompanied by major side effects due to delivery of toxic drugs to healthy tissue in addition to diseased cells. Targeted drug delivery offers the possibility of minimizing these side effects by specific delivery to cancer cells using targeted nanocarriers that enhance drug accumulation in tumors and facilitate target-specific cellular uptake. Polymersomes, vesicles self-assembled from polymeric amphiphiles, are an attractive targeted vehicle, as they are capable of encapsulating both hydrophobic and hydrophilic drugs, have lengthy circulation times in vivo, and can employ degradable functionality for triggered release of payload and clearance from the body. This thesis reports on efforts to enhance the capabilities of degradable polymersomes for targeted delivery. First, targeting functionality is incorporated into polymersomes of the block copolymer poly(ethylene oxide)-b-poly(gamma-methyl-epsilon-caprolactone) by incorporating the reactive vinyl sulfone group into the amphiphile's hydrophilic terminus, allowing site-selective reaction with cysteine-functionalized targeting peptides following self-assembly. The performance of targeted delivery using this polymersome is then evaluated in vitro. Binding and delivery to model cell lines for targeted and bystander cells is tracked using nontargeted polymersomes and compared to that for polymersomes using a high- or low-affinity ligand. Polymer degradation is also tracked both in simple media and during cellular delivery. Finally, a new monomer is developed incorporating acid-labile acetal functionality into a cyclic polyester. The polymerization of this monomer to two distinct polymers is also characterized and the degradation behavior of both polymers evaluated.

  7. Effects of physiotherapy on pain and functional activities after cesarean delivery.

    Science.gov (United States)

    Çıtak Karakaya, İlkim; Yüksel, İnci; Akbayrak, Türkan; Demirtürk, Funda; Karakaya, Mehmet Gürhan; Ozyüncü, Özgür; Beksaç, Sinan

    2012-03-01

    To investigate the effects of a physiotherapy program on incision pain and functional activities in the early post-cesarean period. Fifty women were evaluated after Cesarean operation with regard to times of ambulation and return of bowel activity, intensity of incision pain, difficulty in functional activities and number of analgesics required additional to routine pain control procedure. Twenty-four women received only routine nursing care, and a physiotherapy program was applied to the study group (n = 26), additionally. Postoperative ambulation and return of bowel activity were earlier in the study group (p physiotherapy program in the early post-cesarean period in a wider perspective than the current literature, and are considered to be valuable for increasing the quality and productivity of the postnatal care, therefore improving well-being after childbirth.

  8. Drug delivery to the bone-implant interface: Functional hydroxyapatite surfaces and particles

    OpenAIRE

    Schüssele, Andrea

    2007-01-01

    With the goal of controlling the events at the bone-implant interface, it was the main objective of this thesis to provide a basis for the conjugation of cell stimulating molecules or targeting motifs to the surface of hydroxyapatite ceramic discs and particles. To this end, methods for surface functionalization have been investigated for the attachment of biomolecules. The approach focused on combining three approved and effective principles for enhanced osseointegration of implants: hydroxy...

  9. 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.

  10. Rapid screening of gene function by systemic delivery of morpholino oligonucleotides to live mouse embryos.

    Directory of Open Access Journals (Sweden)

    Kathryn S McClelland

    Full Text Available Traditional gene targeting methods in mice are complex and time consuming, especially when conditional deletion methods are required. Here, we describe a novel technique for assessing gene function by injection of modified antisense morpholino oligonucleotides (MOs into the heart of mid-gestation mouse embryos. After allowing MOs to circulate through the embryonic vasculature, target tissues were explanted, cultured and analysed for expression of key markers. We established proof-of-principle by partially phenocopying known gene knockout phenotypes in the fetal gonads (Stra8, Sox9 and pancreas (Sox9. We also generated a novel double knockdown of Gli1 and Gli2, revealing defects in Leydig cell differentiation in the fetal testis. Finally, we gained insight into the roles of Adamts19 and Ctrb1, genes of unknown function in sex determination and gonadal development. These studies reveal the utility of this method as a means of first-pass analysis of gene function during organogenesis before committing to detailed genetic analysis.

  11. The role of the International Classification of Functioning, Disability, and Health and quality criteria for improving assistive technology service delivery in Europe.

    Science.gov (United States)

    Steel, Emily J; Gelderblom, Gert Jan; de Witte, Luc P

    2012-02-01

    People with disabilities are entitled to access assistive technology (AT) to facilitate their full and effective participation in society and may reasonably expect to be central to the decision-making processes of services that provide these technologies. European projects have improved the knowledge and resources available for AT service delivery in many countries, but the outputs are not consistently implemented or published in scientific literature. This article examines European developments in AT service delivery and the barriers to its effective provision. Specifically, it analyzes the role of the International Classification of Functioning, Disability, and Health in service delivery improvement. Published scientific papers, as well as reports from and descriptions of European projects related to AT service delivery, were reviewed. The publications were analyzed in relation to six criteria for AT service delivery described in an earlier, major European project. The findings and recommendations from the publications are synthesized in this article to identify advances and gaps in AT service delivery and to assess the current status and direction of AT service delivery improvement in Europe. Multicountry projects have brought together AT researchers from across Europe to work together and produced promising results that are contextually relevant. Access to AT information and training of practitioners has improved, and efforts are being made to facilitate user involvement. More effort should be put into integrating research and resources from European projects into practice. Use of the International Classification of Functioning, Disability, and Health model and terminology may support coordination of service delivery systems. The AT research and practice communities in Europe may be able to learn from developments in North America, while continuing to work together, sharing resources and strategies, and communicating results internationally.

  12. Design and Control of a Multi-Functional Energy Recovery Power Accumulator Battery Pack Testing System for Electric Vehicles

    Directory of Open Access Journals (Sweden)

    Bo Long

    2014-03-01

    Full Text Available In this paper, aiming at the energy loss and harmonic problems in the conventional power accumulator battery pack testing system (PABPTS, an improved multi-functional energy recovery PABPTS (ERPABPTS for electric vehicles (EVs was proposed. The improved system has the functions of harmonic detection, suppression, reactive compensation and energy recovery. The ERPABPTS, which contains a bi-directional buck-boost direct current (DC-DC converter and a bi-directional alternating current (AC-DC converter with an inductor-capacitor-inductor (LCL type filter interfacing to the AC-grid, is proposed. System configuration and operation principle of the combined system are discussed first, then, the reactive compensation and harmonic suppression controller under balanced grid-voltage condition are presented. Design of a fourth order band-pass Butterworth filter for current harmonic detection is put forward, and the reactive compensator design procedure considering the non-linear load is also illustrated. The proposed scheme is implemented in a 175-kW prototype in the laboratory. Simulation and experimental results show that the combined configuration can effectively realize energy recovery for high accuracy current test requirement, meanwhile, can effectively achieve reactive compensation and current harmonic suppression.

  13. Vehicle Detection Tool - VDtect

    OpenAIRE

    Prateek, GV; Hari, KVS

    2012-01-01

    The report talks about the implementation of Vehicle Detection tool using opensource software - WxPython. The main functionality of this tool includes collection of data, plotting of magnetometer data and the count of the vehicles detected. The report list about how installation process and various functionality of the tool.

  14. Solid emulsion gel as a vehicle for delivery of polyunsaturated fatty acids: implications for tissue repair, dermal angiogenesis and wound healing.

    Science.gov (United States)

    Shingel, Kirill I; Faure, Marie-Pierre; Azoulay, Laurent; Roberge, Christophe; Deckelbaum, Richard J

    2008-10-01

    The paper describes preparation and biological characterization of the solid hybrid biomaterial that was designed for cell-targeted lipid delivery in healing tissues. The material referred to as 'solid emulsion gel' combines a protein-stabilized lipid emulsion and a hydrogel structure in a single compartment. The potential of the omega-3 (n-3)-fatty acids rich solid emulsion gel for tissue repair applications was investigated at the macro-, micro-, molecular and gene expression levels, using human fibroblasts and endothelial cells and a porcine model of full-thickness wounds. Being non-cytotoxic in vitro and in vivo, the biomaterial was found to affect cell metabolism, modulate expression of certain genes, stimulate early angiogenesis and promote wound repair in vivo. The neovascular response in vivo was correlated with upregulated expression of the genes involved in lipid transport (e.g. adipophilin), anti-apoptosis (e.g. heat shock proteins, haem oxygenase 1) and angiogenesis (vascular endothelial growth factor, placental growth factor). Collectively, the results of this study provide first evidence that the angiogenic response provided by solid emulsion gel-mediated delivery of n-3 fatty acids is an alternative to the topical administration of exogenous growth factors or gene therapy, and can be advantageously used for the stimulation of tissue repair in complex wounds. Copyright (c) 2008 John Wiley & Sons, Ltd.

  15. The Effect of Chewing Sugar Free Gum after Elective Cesarean-Delivery on Return of Bowel Function in Primiparous Women:

    Directory of Open Access Journals (Sweden)

    F Safdari Dehcheshmeh

    2012-05-01

    Full Text Available

    Background and Objectives: An important cause of delayed recovery from abdominal surgery is delay in return of bowel Function. The aim of the present study was to assess the effects of chewing sugar free gum after elective Cesarean-delivery on return of bowel function in primiparous women in Hajar hospital of Shahrekord. Methods: In a randomized clinical trial, 120 patients, who were scheduled for elective cesarean were randomly allocated to 2 groups of gum-chewing group (n=60 and control group (n=60 postoperatively. The patients in the gum-chewing group chewed postoperatively sugar free gum 4 times daily as soon as they recovered from anesthesia till the time they passed flatus or defecated. Control group recieved routine postoperative dietary management. The mean scores of postoperative time interval to first hearing of normal bowel sounds, passage of flatus, defecation and sensation of bowel movement were compared between the two groups. The data were then analyzed using chi square and t-test (p<0.05. Results: The mean postoperative time interval to first hearing of normal intestinal sounds (6.5+/-1.5 versus 12.5+/- 2.5 hours, the first passage of flatus (12.2+/-2.0 vs.22.4+/-4.1 hours, first sensation of bowel movement (7.4+/-1.7 versus 15.7+/-3.4 hours and defecation (15.5+/-2.5 versus 23.4+/-4.8 hours were significantly lower in the gum-chewing group compared with control group. (p<0.001. The staying period in the hospital (0.96+/-0.18 versus 1.1+/-34 days was significantly shorter in gum-chewing group. (p<0.001. Conclusion: Chewing gum after elective Cesarean-Delivery is safe, inexpensive and helpful which is well tolerated, and associated with rapid resumption of intestinal function and speeds recovery shorter hospital stay.

  16. 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.

  17. 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

  18. 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.

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

    Science.gov (United States)

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

    2013-04-01

    The non-biorecognition of general biomaterials and inherent biospecificity of biological systems pose key challenges to the optimal functions of medical devices. In this study, we constructed the surface-mediated functional gene delivery through layer-by-layer self-assembly of protamine sulfate (PrS) and plasmid DNA encoding hepatocyte growth factor (HGF), aiming at specific enhancing endothelial cells (EC) compeititiveness over smooth muscle cells (SMC). Characterizations of the (PrS/HGF-pDNA) multilayered films present the linear buildup with homogeneous and flat topographical feature. The amount of DNA can be easily controlled. By using these multilayered films, both human umbilical vein endothelial cells (HUVEC) and human umbilical artery smooth muscle cells (HUASMC) can be directly transfected when they contact with the multilayered films. On transfection, increasing secretion of HGF has been detected in both HUVEC and HUASMC culture, which leads to selective promotion of HUVEC proliferation. In the co-culture experiment, we also exhibit the promoted and hindered growth of HUVEC and HUASMC, respectively, which could be attributed to the inverse influence of HUVEC on HUASMC. These results collectively demonstrate that our system can be served as a powerful tool for enhancing competitiveness of EC over SMC, which opens perspectives for the regulation of intercellular competitiveness in the field of interventional therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. A retrospective: Use of Escherichia coli as a vehicle to study phospholipid synthesis and function

    Science.gov (United States)

    Dowhan, William

    2012-01-01

    Although the study of individual phospholipids and their synthesis began in the 1920’s first in plants and then mammals, it was not until the early 1960’s that Eugene Kennedy using Escherichia coli initiated studies of bacterial phospholipid metabolism. With the base of information already available from studies of mammalian tissue, the basic blueprint of phospholipid biosynthesis in E. coli was worked out by the late 1960’s. In 1970’s and 1980’s most of the enzymes responsible for phospholipid biosynthesis were purified and many of the genes encoding these enzymes were identified. By the late 1990’s conditional and null mutants were available along with clones of the genes for every step of phospholipid biosynthesis. Most of these genes had been sequenced before the complete E. coli genome sequence was available. Strains of E. coli were developed in which phospholipid composition could be changed in a systematic manner while maintaining cell viability. Null mutants, strains in which phospholipid metabolism was artificially regulated, and strains synthesizing foreign lipids not found in E. coli have been used to this day to define specific roles for individual phospholipid. This review will trace the findings that have led to the development of E. coli as an excellent model system to study mechanisms underlying the synthesis and function of phospholipids that are widely applicable to other prokaryotic and eukaryotic systems. PMID:22925633

  1. Mitigation Conducted Emission Strategy Based on Transfer Function from a DC-Fed Wireless Charging System for Electric Vehicles

    Directory of Open Access Journals (Sweden)

    Li Zhai

    2018-02-01

    Full Text Available The large dv/dt and di/dt outputs of power devices in wireless charging system (WCS in electric vehicles (EVs always introduce conducted electromagnetic interference (EMI emissions. This paper proposes a mitigation conducted emission strategy based on transfer function from a direct current fed (DC-fed WCS for EVs. A complete test for the DC-fed WCS is set up to measure the conducted emission of DC power cables in a frequency range of 150 kHz–108 MHz. An equivalent circuit with high-frequency parasitic parameters for WCS for EV is built based on measurement results to obtain the characteristics of conducted emission from WCS. The transfer functions of differential mode (DM interference and common mode (CM interference were established. A judgment method of using transfer functions to determine the dominated interference mode responsible for EMI is proposed. From the comparison of simulation results between CM or DM and CM+DM interference, it can be seen that the CM interference is the dominated interference mode which causes the conducted EMI in WCS in EVs. A strategy of giving priority to the dominated interference mode is proposed for designing the CM interference filter. Finally, the conducted voltage experiment is performed to verify the mitigation conducted emission strategy. The conducted voltage of simulation and experiment is decreased respectively by 21.17 and 21.4 dBμV at resonance frequency 30 MHz. The conduced voltage at frequency range of 150 kHz–108 MHz can be mitigated to below the limit level-3 of CISPR25 standard (GB/T 18655-2010 by adding the CM interference filters.

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

    Science.gov (United States)

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

    2016-11-01

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

  3. Folate receptor-mediated boron-10 containing carbon nanoparticles as potential delivery vehicles for boron neutron capture therapy of nonfunctional pituitary adenomas.

    Science.gov (United States)

    Dai, Congxin; Cai, Feng; Hwang, Kuo Chu; Zhou, Yongmao; Zhang, Zizhu; Liu, Xiaohai; Ma, Sihai; Yang, Yakun; Yao, Yong; Feng, Ming; Bao, Xinjie; Li, Guilin; Wei, Junji; Jiao, Yonghui; Wei, Zhenqing; Ma, Wenbin; Wang, Renzhi

    2013-02-01

    Invasive nonfunctional pituitary adenomas (NFPAs) are difficult to completely resect and often develop tumor recurrence after initial surgery. Currently, no medications are clinically effective in the control of NFPA. Although radiation therapy and radiosurgery are useful to prevent tumor regrowth, they are frequently withheld because of severe complications. Boron neutron capture therapy (BNCT) is a binary radiotherapy that selectively and maximally damages tumor cells without harming the surrounding normal tissue. Folate receptor (FR)-targeted boron-10 containing carbon nanoparticles is a novel boron delivery agent that can be selectively taken up by FR-expressing cells via FR-mediated endocytosis. In this study, FR-targeted boron-10 containing carbon nanoparticles were selectively taken up by NFPAs cells expressing FR but not other types of non-FR expressing pituitary adenomas. After incubation with boron-10 containing carbon nanoparticles and following irradiation with thermal neutrons, the cell viability of NFPAs was significantly decreased, while apoptotic cells were simultaneously increased. However, cells administered the same dose of FR-targeted boron-10 containing carbon nanoparticles without neutron irradiation or received the same neutron irradiation alone did not show significant decrease in cell viability or increase in apoptotic cells. The expression of Bcl-2 was down-regulated and the expression of Bax was up-regulated in NFPAs after treatment with FR-mediated BNCT. In conclusion, FR-targeted boron-10 containing carbon nanoparticles may be an ideal delivery system of boron to NFPAs cells for BNCT. Furthermore, our study also provides a novel insight into therapeutic strategies for invasive NFPA refractory to conventional therapy, while exploring these new applications of BNCT for tumors, especially benign tumors.

  4. Hollow-core magnetic colloidal nanocrystal clusters with ligand-exchanged surface modification as delivery vehicles for targeted and stimuli-responsive drug release.

    Science.gov (United States)

    Li, Dian; Tang, Jing; Guo, Jia; Wang, Shilong; Chaudhary, Deeptangshu; Wang, Changchun

    2012-12-14

    The fabrication of hierarchical magnetic nanomaterials with well-defined structure, high magnetic response, excellent colloidal stability, and biocompatibility is highly sought after for drug-delivery systems. Herein, a new kind of hollow-core magnetic colloidal nanocrystal cluster (HMCNC) with porous shell and tunable hollow chamber is synthesized by a one-pot solvothermal process. Its novelty lies in the "tunability" of the hollow chamber and of the pore structure within the shell through controlled feeding of sodium citrate and water, respectively. Furthermore, by using the ligand-exchange method, folate-modified poly(acrylic acid) was immobilized on the surface of HMCNCs to create folate-targeted HMCNCs (folate-HMCNCs), which endowed them with excellent colloidal stability, pH sensitivity, and, more importantly, folate receptor-targeting ability. These assemblages exhibited excellent colloidal stability in plasma solution. Doxorubicin (DOX), as a model anticancer agent, was loaded within the hollow core of these folate-HMCNCs (folate-HMCNCs-DOX), and drug-release experiments proved that the folate-HMCNCs-DOX demonstrated pH-dependent release behavior. The folate-HMCNCs-DOX assemblages also exhibited higher potent cytotoxicity to HeLa cells than free doxorubicin. Moreover, folate-HMCNCs-DOX showed rapid cell uptake apart from the enhanced cytotoxicity to HeLa cells. Experimental results confirmed that the synthesized folate-HMCNCs are smart nanovehicles as a result of their improved folate receptor-targeting abilities and also because of their combined pH- and magnetic-stimuli response for applications in drug delivery. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Science.gov (United States)

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

    2014-11-01

    Approaches based on combined use of delivery systems and adjuvants are being favored to maximize efficient mucosal delivery of antigens. Here, we describe a novel delivery system comprised of chitosan-functionalized gold nanoparticles (CsAuNPs) and saponin-containing botanical adjuvant; Asparagus racemosus extract (ARE) for oral delivery of tetanus toxoid (TT). A significant increase in TT-specific IgG (34.53-fold) and IgA (43.75-fold) was observed when TT-CsAuNPs were formulated with ARE (TT-ARE-CsAuNPs). The local IgA immune responses for TT also showed a significant increase (106.5-fold in intestine washes and 99.74-fold in feces) with ARE-based formulations as compared with plain TT group. No effect of ARE was observed on size, charge, and loading properties of CsAuNPs. Additionally, no effect of ARE and CsAuNPs was observed on antigenicity and secondary structure of TT as determined by fluorescence, circular dichroism, and Fourier transform infrared spectroscopy. The stability studies demonstrated excellent stability profile of formulation at recommended storage conditions. The study establishes the possible role of immunomodulatory adjuvants in particulate delivery systems for mucosal delivery of vaccines. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  6. 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.

  7. Bisphosphonate-Functionalized Hydroxyapatite Nanoparticles for the Delivery of the Bromodomain Inhibitor JQ1 in the Treatment of Osteosarcoma.

    Science.gov (United States)

    Wu, Victoria M; Mickens, Jarrett; Uskoković, Vuk

    2017-08-09

    intracellular delivery and sustained release of the drug enabled by HAp. In addition to the reduction of the OS cell viability, the reduction of the migration and invasion radii was observed in OS tumor spheroids challenged with even JQ1-free medronate-functionalized HAp nanoparticles, demonstrating a definite anticancer activity of medronate alone when combined with HAp. The effect of medronate-functionalized JQ1-loaded HAp nanoparticles was most noticeable against OS cells differentiated into an osteoblastic lineage, in which case they surpassed in effect pure JQ1 and medronate-free compositions. The activity of JQ1 was mediated through increased Ezrin expression and decreased RUNX2 expression and was MYC and FOSL1 independent, but these patterns of gene expression changed in cells challenged with the nanoparticulate form of delivery, having been accompanied by the upregulation of RUNX2 and downregulation of Ezrin in OS cells treated with medronate-functionalized JQ1-loaded HAp nanoparticles.

  8. Vehicle to Vehicle Services

    DEFF Research Database (Denmark)

    Brønsted, Jeppe Rørbæk

    2008-01-01

    As computing devices, sensors, and actuators pervade our surroundings, new applications emerge with accompanying research challenges. In the transportation domain vehicles are being linked by wireless communication and equipped with an array of sensors and actuators that make is possible to provide...... location aware infotainment, increase safety, and lessen environmental strain. This dissertation is about service oriented architecture for pervasive computing with an emphasis on vehicle to vehicle applications. If devices are exposed as services, applications can be created by composing a set of services......, mobility, and availability of services. The dissertation consists of two parts. Part I gives an overview of service oriented architecture for pervasive computing systems and describes the contributions of the publications listed in part II. We investigate architecture for vehicular technology applications...

  9. Delivery of a functional anti-trypanosome Nanobody in different tsetse fly tissues via a bacterial symbiont, Sodalis glossinidius.

    Science.gov (United States)

    De Vooght, Linda; Caljon, Guy; De Ridder, Karin; Van Den Abbeele, Jan

    2014-11-07

    Sodalis glossinidius, a vertically transmitted microbial symbiont of the tsetse fly, is currently considered as a potential delivery system for anti-trypanosomal components that reduce or eliminate the capability of the tsetse fly host to transmit parasitic trypanosomes, an approach also known as paratransgenesis. An essential step in developing paratransgenic tsetse is the stable colonization of adult flies and their progeny with recombinant Sodalis bacteria, expressing trypanocidal effector molecules in tissues where the parasite resides. In this study, Sodalis was tested for its ability to deliver functional anti-trypanosome nanobodies (Nbs) in Glossina morsitans morsitans. We characterized the in vitro and in vivo stability of recombinant Sodalis (recSodalis) expressing a potent trypanolytic nanobody, i.e. Nb_An46. We show that recSodalis is competitive with WT Sodalis in in vivo conditions and that tsetse flies transiently cleared of their endogenous WT Sodalis population can be successfully repopulated with recSodalis at high densities. In addition, vertical transmission to the offspring was observed. Finally, we demonstrated that recSodalis expressed significant levels (ng range) of functional Nb_An46 in different tsetse fly tissues, including the midgut where an important developmental stage of the trypanosome parasite occurs. We demonstrated the proof-of-concept that the Sodalis symbiont can be genetically engineered to express and release significant amounts of functional anti-trypanosome Nbs in different tissues of the tsetse fly. The application of this innovative concept of using pathogen-targeting nanobodies delivered by insect symbiotic bacteria could be extended to other vector-pathogen systems.

  10. 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.

  11. Biodegradable glycopolymer-b-poly(ε-caprolactone) block copolymer micelles: Versatile construction, tailored lactose functionality, and hepatoma-targeted drug delivery

    NARCIS (Netherlands)

    Chen, Wei; Meng, Fenghua; Cheng, Ru; Deng, Chao; Feijen, Jan; Zhong, Zhiyuan

    2015-01-01

    Glycopolymer-b-poly(ε-caprolactone) (GP-PCL) block copolymer micelles (‘glycomicelles’) with tailored lactose functionalities were developed and investigated for hepatoma-targeted doxorubicin (DOX) delivery. Amphiphilic GP-PCL copolymers were readily prepared with controlled lactobionic acid (LBA)

  12. 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

  13. Thyroid Function and Premature Delivery in TPO Antibody-Negative Women: The Added Value of hCG

    NARCIS (Netherlands)

    T.I.M. Korevaar (Tim); E.A.P. Steegers (Eric); L. Chaker (Layal); M. Medici (Marco); V.W.V. Jaddoe (Vincent); T.J. Visser (Theo); Y.B. de Rijke (Yolanda); R.P. Peeters (Robin)

    2017-01-01

    textabstractConclusion: In TPOAb-negative women with high-normal TSH concentrations, only women with high hCG concentrations had a higher risk of premature delivery or pPROM. These results suggest a lower thyroidal response to hCG stimulation is also associated with premature delivery in

  14. Physiorack: an integrated MRI safe/conditional, gas delivery, respiratory gating, and subject monitoring solution for structural and functional assessments of pulmonary function.

    Science.gov (United States)

    Halaweish, Ahmed F; Charles, H Cecil

    2014-03-01

    To evaluate the use of a modular MRI conditional respiratory monitoring and gating solution, designed to facilitate proper monitoring of subjects' vital signals and their respiratory efforts, during free-breathing and breathheld 19F, oxygen-enhanced, and Fourier-decomposition MRI-based acquisitions. All Imaging was performed on a Siemens TIM Trio 3 Tesla MRI scanner, following Institutional Review Board approval. Gas delivery is accomplished through the use of an MR compatible pneumotachometer, in conjunction with two three-way pneumatically controlled Hans Rudolph Valves. The pneumatic valves are connected to Douglas bags used as the gas source. A mouthpiece (+nose clip) or an oro-nasal Hans Rudolph disposable mask is connected following the pneumatic valve to minimize dead-space and provide an airtight seal. Continuous monitoring/sampling of inspiratory and expiratory oxygen and carbon dioxide levels at the mouthpiece/mask is achieved through the use of an Oxigraf gas analyzer. Forty-four imaging sessions were successfully monitored, during Fourier-decomposition (n=3), fluorine-enhanced (n=29), oxygen-enhanced, and ultra short echo (n=12) acquisitions. The collected waveforms, facilitated proper monitoring and coaching of the subjects. We demonstrate an inexpensive, off-the-shelf solution for monitoring these signals, facilitating assessments of lung function. Monitoring of respiratory efforts and exhaled gas concentrations assists in understanding the heterogeneity of lung function visualized by gas imaging. Copyright © 2013 Wiley Periodicals, Inc.

  15. Self-Assembled Cationic Biodegradable Nanoparticles from pH-Responsive Amino-Acid-Based Poly(Ester Urea Urethane)s and Their Application As a Drug Delivery Vehicle.

    Science.gov (United States)

    He, Mingyu; Potuck, Alicia; Kohn, Julie C; Fung, Katharina; Reinhart-King, Cynthia A; Chu, Chih-Chang

    2016-02-08

    The objective of this study is to develop a new family of biodegradable and biologically active copolymers and their subsequent self-assembled cationic nanoparticles as better delivery vehicles for anticancer drugs to achieve the synergism between the cytotoxicity effects of the loaded drugs and the macrophage inflammatory response of the delivery vehicle. This family of cationic nanoparticles was formulated from a new family of amphiphilic cationic Arginine-Leucine (Arg-Leu)-based poly(ester urea urethane) (Arg-Leu PEUU) synthesized from four building blocks (amino acids, diols, glycerol α-monoallyl ether, and 1,6 hexamethylene diisocyanate). The chemical, physical, and biological properties of Arg-Leu PEUU biomaterials can be tuned by controlling the feed ratio of the four building blocks. The Arg-Leu PEUU copolymers have weight-average molecular weights from 13.4 to 16.8 kDa and glass-transition temperatures from -3.4 to -4.6 °C. The self-assembled cationic nanoparticles (Arg-Leu PEUU NPs) were prepared using a facile dialysis method. Arg-Leu PEUU NPs have average diameters ranging from 187 to 272 nm, show good biocompatibility with 3T3 fibroblasts, and they support bovine aortic endothelial cell (BAEC) proliferation and adhesion. Arg-Leu PEUU NPs also enhanced the macrophages' production of tumor necrosis factor-α (TNF-α) and nitric oxide (NO), but produced relatively low levels of interleukin-10 (IL-10), and therefore, the antitumor activity of macrophages might be enhanced. Arg-Leu PEUU NPs were taken up by HeLa cells after 4 h of incubation. The in vitro hemolysis assay showed the cationic Arg-Leu PEUU NPs increased their chance of endosomal escape at a more acidic pH. Doxorubicin (DOX) was successfully incorporated into the Arg-Leu PEUU NPs, and the DOX-loaded Arg-Leu PEUU NPs exhibited a pH-dependent drug release profile with accelerated release kinetics in a mild acidic condition. The DOX-loaded 6-Arg-4-Leu-4 A/L-2/1 NPs showed higher HeLa cell

  16. 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.

  17. 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.

  18. 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.

  19. 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 ...

  20. 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.

  1. Structure-function relationship among Quillaja saponins serving as excipients for nasal and ocular delivery of insulin.

    Science.gov (United States)

    Pillion, D J; Amsden, J A; Kensil, C R; Recchia, J

    1996-05-01

    The purpose of this investigation was to explore the structure-function relationship among naturally occurring Quillaja saponins and derivatives for their ability to stimulate insulin delivery from nosedrops and eyedrops and to test the hypothesis that stimulation of peptide drug delivery was correlated with surfactant strength. Native saponins, including QS-21, were purified from an aqueous extract of Quillaja saponaria bark by adsorption chromatography and HPLC. Native saponins were then deacylated by mild alkaline hydrolysis to form DS-1 and DS-2, derivatives that are smaller and more hydrophilic than their parent compounds. DS-1 was further treated either to reduce an aldehyde residue to form DS-1(R) or to remove the fucose-containing oligosaccharide to form QH-957. Rats receiving eyedrops or nosedrops formulated with insulin, but without any Quillaja saponins, showed no hypoglycemic response. Rats receiving eyedrops or nosedrops formulated with insulin plus saponins showed a dose-dependent hypoglycemic response, with the following rank order: QS-21 > DS-1 > DS-1(R) > DS-2 > QH-957. Surfactant strength was determined by measurement of the critical micellar concentration (cmc) and hemolysis of sheep erythrocytes. The cmc was lowest for the parent saponins QS-21 and QS-18, and increased for the deacylated saponin derivatives DS-1, DS-2, and QH-957; hemolysis of sheep erythrocytes was observed at low concentrations (approximately 0.006 mM) of the parent saponins, QS-21 and QS-18, at intermediate concentrations (0.06-0.08 mM) of DS-1 and DS-2, and at higher concentrations of DS-1(R) (0.45 mM) and QH-957 (1.5 mM). Hence, efficacy as an absorption-enhancing agent was greatest in those saponins with the lowest hemolytic titers and cmc values. However, this relationship was not a strict one, because DS-1, which differs from DS-2 only in the absence of one glucose residue, was significantly more potent than DS-2 in stimulating the absorption of insulin. DS-1 and DS-2

  2. 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.

  3. 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.

  4. Hydrogen vehicle fueling station

    Energy Technology Data Exchange (ETDEWEB)

    Daney, D.E.; Edeskuty, F.J.; Daugherty, M.A. [Los Alamos National Lab., NM (United States)] [and others

    1995-09-01

    Hydrogen fueling stations are an essential element in the practical application of hydrogen as a vehicle fuel, and a number of issues such as safety, efficiency, design, and operating procedures can only be accurately addressed by a practical demonstration. Regardless of whether the vehicle is powered by an internal combustion engine or fuel cell, or whether the vehicle has a liquid or gaseous fuel tank, the fueling station is a critical technology which is the link between the local storage facility and the vehicle. Because most merchant hydrogen delivered in the US today (and in the near future) is in liquid form due to the overall economics of production and delivery, we believe a practical refueling station should be designed to receive liquid. Systems studies confirm this assumption for stations fueling up to about 300 vehicles. Our fueling station, aimed at refueling fleet vehicles, will receive hydrogen as a liquid and dispense it as either liquid, high pressure gas, or low pressure gas. Thus, it can refuel any of the three types of tanks proposed for hydrogen-powered vehicles -- liquid, gaseous, or hydride. The paper discusses the fueling station design. Results of a numerical model of liquid hydrogen vehicle tank filling, with emphasis on no vent filling, are presented to illustrate the usefulness of the model as a design tool. Results of our vehicle performance model illustrate our thesis that it is too early to judge what the preferred method of on-board vehicle fuel storage will be in practice -- thus our decision to accommodate all three methods.

  5. Air Vehicle Integration and Technology Research (AVIATR). Delivery Order 0002: Condition-Based Maintenance Plus Structural Integrity (CBM+SI) Strategy Development

    Science.gov (United States)

    2010-11-01

    overpopulated with piezoelectric elements to allow for a trade study related to sensor density to be conducted. Figure 34. Ring-shaped SMART Layer...include but are not limited to: density , corrosion resistance, defect population , reflectivity, and surface roughness. 5.1.8.4 Supportability...Methodology to optimize sensor layout for detecting area-type damages ...................94 Figure 88. POD Curves are a Function of Sensor Density

  6. Emissions from light and medium goods vehicles in Denmark

    DEFF Research Database (Denmark)

    Jørgensen, Kaj

    1996-01-01

    The article analyses atmospheric pollution of light goods vehicles (i.e. freight vehicles lighter than 6 tonnes) and medium goods vehicles (i.e. 6-24 t delivery trucks) in Denmark, and evaluated the scope for emission reductions. Light goods vehicles are very inefficient vehicles, and moreover have...... inappropriate utilisation patterns, while medium goods vehicles, in comparison, are more efficient with regard to both construction and utilisation. An emission inventory of these vehicles is produced, covering fuel consumption and a range of emissions, and including heavy goods vehicles (i.e. vehicles over 24...

  7. Paclitaxel controlled delivery using a pH-responsive functional-AuNP/block-copolymer vesicular nanocarrier composite system.

    Science.gov (United States)

    Liaskoni, Athina; Angelopoulou, Athina; Voulgari, Efstathia; Popescu, Maria-Teodora; Tsitsilianis, Constantinos; Avgoustakis, Konstantinos

    2018-02-26

    Paclitaxel (PTX)-loaded gold nanoparticles functionalized with mercaptooctanoic acid (MOA) and folic acid (FA) (AuMOA-FA) were encapsulated within pH-sensitive poly(2-vinylpyridine)-b-poly(ethylene oxide) (P2VP-PEO) vesicles with the aim to develop a more selective injectable nano-formulation for PTX, lacking the side effects of the conventional PTX delivery system. The size of the resulting composite vesicles was lower than 200 nm, i.e. it is suitable for tumor targeting applications taking advantage of the enhanced permeability and retention (EPR) effect. The vesicles did not aggregate in the presence of high electrolyte concentrations, indicating the colloidal stability of the vesicles. The vesicles did not leak their AuMOA-FA or PTX content at physiological pH of 7.4. However, AuMOA-FA and PTX release were significantly accelerated at acidic pHs resembling tumor environment and acidic intracellular compartments. PTX release from the vesicles at acidic pH apparently follows AuMOA-FA release from the vesicles. Flow cytometry measurements and confocal laser scanning microscopy images showed that the vesicles could enter A549 cancer cells in culture and that cellular uptake increased with time. Blank vesicles did not exhibit cytotoxicity and did not induce apoptosis in A549 cancer cells. The PTX currying vesicles exhibited comparable or a little higher cytotoxicity than free PTX. Both the PTX currying vesicles and free PTX induced A549 cells apoptosis, however the vesicle-encapsulated PTX induced a higher percentage of late apoptotic cells than free PTX. Copyright © 2018. Published by Elsevier B.V.

  8. Localized delivery of brain-derived neurotrophic factor-expressing mesenchymal stem cells enhances functional recovery following cervical spinal cord injury.

    Science.gov (United States)

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

    2015-02-01

    Neurotrophins, such as brain-derived neurotrophic factor (BDNF), are important in modulating neuroplasticity and promoting recovery after spinal cord injury. Intrathecal delivery of BDNF enhances functional recovery following unilateral spinal cord hemisection (SH) at C2, a well-established model of incomplete cervical spinal cord injury. We hypothesized that localized delivery of BDNF-expressing mesenchymal stem cells (BDNF-MSCs) would promote functional recovery of rhythmic diaphragm activity after SH. In adult rats, bilateral diaphragm electromyographic (EMG) activity was chronically monitored to determine evidence of complete SH at 3 days post-injury, and recovery of rhythmic ipsilateral diaphragm EMG activity over time post-SH. Wild-type, bone marrow-derived MSCs (WT-MSCs) or BDNF-MSCs (2×10(5) cells) were injected intraspinally at C2 at the time of injury. At 14 days post-SH, green fluorescent protein (GFP) immunoreactivity confirmed MSCs presence in the cervical spinal cord. Functional recovery in SH animals injected with WT-MSCs was not different from untreated SH controls (n=10; overall, 20% at 7 days and 30% at 14 days). In contrast, functional recovery was observed in 29% and 100% of SH animals injected with BDNF-MSCs at 7 days and 14 days post-SH, respectively (n=7). In BDNF-MSCs treated SH animals at 14 days, root-mean-squared EMG amplitude was 63±16% of the pre-SH value compared with 12±9% in the control/WT-MSCs group. We conclude that localized delivery of BDNF-expressing MSCs enhances functional recovery of diaphragm muscle activity following cervical spinal cord injury. MSCs can be used to facilitate localized delivery of trophic factors such as BDNF in order to promote neuroplasticity following spinal cord injury.

  9. Applications of nanodiamonds in drug delivery and catalysis

    KAUST Repository

    Moosa, Basem

    2014-01-01

    The interest of researchers in utilizing nanomaterials as carriers for a wide spectrum of molecules has exploded in the last two decades. Nanodiamonds are one class of carbon-based nanomaterials that have emerged as promising drug delivery vehicles and imaging probes. Their ease of functionalization also led to the generation of stimuli-responsive nanodiamonds that deliver drugs on demand in a controlled manner. The ample surface area of NDs allowed for a higher loading of not only small molecules but also macromolecules like genes and proteins. Recently, the unique surface of NDs has attracted more attention as catalyst support in a huge range of organic modification and C-C bond formation reactions. Herein, recent advances in the utilization of nanodiamonds as a drug delivery vehicle and catalytical support are highlighted and summarized to illustrate the potential and versatility of this cheap and commercially available nanomaterial. Copyright © 2014 American Scientific Publishers All rights reserved.

  10. Responsive crosslinked polymer nanogels for imaging and therapeutics delivery

    NARCIS (Netherlands)

    Ekkelenkamp, Antonie E.; Elzes, Marie-Louise Rachel; Engbersen, Johan F.J.; Paulusse, Jos M.J.

    2018-01-01

    Water-soluble, nano-sized crosslinked polymer networks, or nanogels, are delivery vehicles, which have highly interesting properties for therapeutic delivery and imaging. Nanogels may also possess responsive properties, depending on the employed polymers, allowing controlled release of therapeutics

  11. Regional frontal gray matter volume associated with executive function capacity as a risk factor for vehicle crashes in normal aging adults.

    Directory of Open Access Journals (Sweden)

    Hiroyuki Sakai

    Full Text Available Although low executive functioning is a risk factor for vehicle crashes among elderly drivers, the neural basis of individual differences in this cognitive ability remains largely unknown. Here we aimed to examine regional frontal gray matter volume associated with executive functioning in normal aging individuals, using voxel-based morphometry (VBM. To this end, 39 community-dwelling elderly volunteers who drove a car on a daily basis participated in structural magnetic resonance imaging, and completed two questionnaires concerning executive functioning and risky driving tendencies in daily living. Consequently, we found that participants with low executive function capacity were prone to risky driving. Furthermore, VBM analysis revealed that lower executive function capacity was associated with smaller gray matter volume in the supplementary motor area (SMA. Thus, the current data suggest that SMA volume is a reliable predictor of individual differences in executive function capacity as a risk factor for vehicle crashes among elderly persons. The implication of our results is that regional frontal gray matter volume might underlie the variation in driving tendencies among elderly drivers. Therefore, detailed driving behavior assessments might be able to detect early neurodegenerative changes in the frontal lobe in normal aging adults.

  12. Targeted drug delivery into reversibly injured myocardium with silica nanoparticles: surface functionalization,  natural biodistribution, and acute toxicity

    Directory of Open Access Journals (Sweden)

    Michael M Galagudza

    2010-03-01

    Full Text Available Michael M Galagudza1, Dmitry V Korolev1, Dmitry L Sonin1, Viktor N Postnov2, Garry V Papayan3, Ivan S Uskov1, Anastasia V Belozertseva1, Eugene V Shlyakhto11Institute of Experimental Medicine, VA. Almazov Federal Heart, Blood and Endocrinology Center, St-Petersburg, Russian Federation; 2Chemical Faculty, St-Petersburg State University, St-Petersburg, Russian Federation;  3Department of Pathophysiology, IP. Pavlov State Medical University, St-Petersburg, Russian FederationAbstract: The clinical outcome of patients with ischemic heart disease can be significantly improved with the implementation of targeted drug delivery into the ischemic myocardium. In this paper, we present our original findings relevant to the problem of therapeutic heart targeting with use of nanoparticles. Experimental approaches included fabrication of carbon and silica nanoparticles, their characterization and surface modification. The acute hemodynamic effects of nanoparticle formulation as well as nanoparticle biodistribution were studied in male Wistar rats. Carbon and silica nanoparticles are non-toxic materials that can be used as carriers for heart-targeted drug delivery. Concepts of passive and active targeting can be applied to the development of targeted drug delivery to the ischemic myocardial cells. Provided that ischemic heart-targeted drug delivery can be proved to be safe and efficient, the results of this research may contribute to the development of new technologies in the pharmaceutical industry.Keywords: nanocarriers, targeted drug delivery, myocardial ischemia

  13. 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.

  14. Underwater Vehicle

    National Research Council Canada - National Science Library

    Dick, James L

    2007-01-01

    There is thus provided an underwater vehicle having facility for maneuvering alongside a retrieving vehicle, as by manipulation of bow and stern planes, for engaging a hull surface of the retrieving...

  15. Intelligent Vehicle Health Management

    Science.gov (United States)

    Paris, Deidre E.; Trevino, Luis; Watson, Michael D.

    2005-01-01

    As a part of the overall goal of developing Integrated Vehicle Health Management systems for aerospace vehicles, the NASA Faculty Fellowship Program (NFFP) at Marshall Space Flight Center has performed a pilot study on IVHM principals which integrates researched IVHM technologies in support of Integrated Intelligent Vehicle Management (IIVM). IVHM is the process of assessing, preserving, and restoring system functionality across flight and ground systems (NASA NGLT 2004). The framework presented in this paper integrates advanced computational techniques with sensor and communication technologies for spacecraft that can generate responses through detection, diagnosis, reasoning, and adapt to system faults in support of INM. These real-time responses allow the IIVM to modify the affected vehicle subsystem(s) prior to a catastrophic event. Furthermore, the objective of this pilot program is to develop and integrate technologies which can provide a continuous, intelligent, and adaptive health state of a vehicle and use this information to improve safety and reduce costs of operations. Recent investments in avionics, health management, and controls have been directed towards IIVM. As this concept has matured, it has become clear the INM requires the same sensors and processing capabilities as the real-time avionics functions to support diagnosis of subsystem problems. New sensors have been proposed, in addition, to augment the avionics sensors to support better system monitoring and diagnostics. As the designs have been considered, a synergy has been realized where the real-time avionics can utilize sensors proposed for diagnostics and prognostics to make better real-time decisions in response to detected failures. IIVM provides for a single system allowing modularity of functions and hardware across the vehicle. The framework that supports IIVM consists of 11 major on-board functions necessary to fully manage a space vehicle maintaining crew safety and mission

  16. 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.

  17. 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

  18. 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.

  19. Yosemite Waters Vehicle Evaluation Report: Final Results

    Energy Technology Data Exchange (ETDEWEB)

    Eudy, L.; Barnitt, R.; Alleman, T. L.

    2005-08-01

    Document details the evaluation of Fischer-Tropsch diesel, a gas-to-liquid fuel, in medium-duty delivery vehicles at Yosemite Waters. The study was conducted by NREL at the company's Fullerton, California, bottling headquarters.

  20. After Delivery

    Science.gov (United States)

    ... Size: A A A Listen En Español After Delivery After your baby arrives, your body begins to recover from the hard work of pregnancy and delivery. Some new mothers have better blood glucose control ...

  1. A star-shaped porphyrin-arginine functionalized poly(L-lysine) copolymer for photo-enhanced drug and gene co-delivery.

    Science.gov (United States)

    Ma, Dong; Lin, Qian-Ming; Zhang, Li-Ming; Liang, Yuan-Yuan; Xue, Wei

    2014-05-01

    The co-delivery of drug and gene has become the primary strategy in cancer and other disease therapy. To co-deliver hydrophobic drug and functional gene efficiently into tumor cells, a star-shaped copolymer (PP-PLLD-Arg) with a photochemical internalization effect consisting of a porphyrin (PP) core and arginine-functionalized poly(L-lysine) dendron (PLLD-Arg) arms has been designed, and used to co-deliver docetaxel (DOC) and MMP-9 shRNA plasmid for nasopharyngeal cancer therapy. It was found that PP-PLLD-Arg/MMP-9 nanocomplex showed the photo-enhanced gene transfection efficiency in vitro, and could mediate a significant reduce of MMP-9 protein expression in HNE-1 cells. For co-delivery analysis, the obtained PP-PLLD-Arg/DOC/MMP-9 complexes could induce a more significant apoptosis than DOC or MMP-9 used only, and decreased invasive capacity of HNE-1 cells. Moreover, the star-shaped copolymer exhibited better blood compatibility and lower cytotoxicity compared to PEI-25k in the hemolysis and MTT assays, and also showed a good biocompatibility in vivo. Therefore, PP-PLLD-Arg with suited irradiation is a promising non-toxic and photo-inducible effective drug and gene delivery strategy, which should be encouraged in tumor therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Modeling and Deployment of Model-Based Decentralized Embedded Diagnosis inside Vehicles: Application to Smart Distance Keeping Function

    Directory of Open Access Journals (Sweden)

    Othman Nasri

    2012-01-01

    Full Text Available The deployment of a fault diagnosis strategy in the Smart Distance Keeping (SDK system with a decentralized architecture is presented. The SDK system is an advanced Adaptive Cruise Control (ACC system implemented in a Renault-Volvo Trucks vehicle to increase safety by overcoming some ACC limitations. One of the main differences between this new system and the classical ACC is the choice of the safe distance. This latter is the distance between the vehicle equipped with the ACC or the SDK system and the obstacle-in-front (which may be another vehicle. It is supposed fixed in the case of the ACC, while variable in the case of the SDK. The variation of this distance depends essentially on the relative velocity between the vehicle and the obstacle-in-front. The main goal of this work is to analyze measurements, issued from the SDK elements, in order to detect, to localize, and to identify some faults that may occur. Our main contribution is the proposition of a decentralized approach permitting to carry out an on-line diagnosis without computing the global model and to achieve most of the work locally avoiding huge extra diagnostic information traffic between components. After a detailed description of the SDK system, this paper explains the model-based decentralized solution and its application to the embedded diagnosis of the SDK system inside Renault-Volvo Truck with five control units connected via a CAN-bus using “Hardware in the Loop” (HIL technique. We also discuss the constraints that must be fulfilled.

  3. Mechanically refuelable zinc/air electric vehicle cells

    Science.gov (United States)

    Noring, J.; Gordon, S.; Maimoni, A.; Spragge, M.; Cooper, J. F.

    1992-12-01

    Refuelable zinc/air batteries have long been considered for motive as well as stationary power because of a combination of high specific energy, low initial cost, and the possibility of mechanical recharge by electrolyte exchange and additions of metallic zinc. In this context, advanced slurry batteries, stationary packed bed cells, and batteries offering replaceable cassettes have been reported recently. The authors are developing self-feeding, particulate-zinc/air batteries for electric vehicle applications. Emissionless vehicle legislation in California motivated efforts to consider a new approach to providing an electric vehicle with long range (400 km), rapid refueling (10 minutes) and highway safe acceleration - factors which define the essential functions of common automobiles. Such an electric vehicle would not compete with emerging secondary battery vehicles in specialized applications (commuting vehicles, delivery trucks). Rather, different markets would be sought where long range or rapid range extension are important. Examples are: taxis, continuous-duty fork-lift trucks and shuttle busses, and general purpose automobiles having modest acceleration capabilities. In the long range, a mature fleet would best use regional plants to efficiently recover zinc from battery reaction products. One option would be to use chemical/thermal reduction to recover the zinc. The work described focuses on development of battery configurations which efficiently and completely consume zinc particles, without clogging or changing discharge characteristics.

  4. 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.

  5. Injectable supramolecular hydrogel formed from α-cyclodextrin and PEGylated arginine-functionalized poly(l-lysine) dendron for sustained MMP-9 shRNA plasmid delivery.

    Science.gov (United States)

    Lin, Qianming; Yang, Yumeng; Hu, Qian; Guo, Zhong; Liu, Tao; Xu, Jiake; Wu, Jianping; Kirk, Thomas Brett; Ma, Dong; Xue, Wei

    2017-02-01

    Hydrogels have attracted much attention in cancer therapy and tissue engineering due to their sustained gene delivery ability. To obtain an injectable and high-efficiency gene delivery hydrogel, methoxypolyethylene glycol (MPEG) was used to conjugate with the arginine-functionalized poly(l-lysine) dendron (PLLD-Arg) by click reaction, and then the synthesized MPEG-PLLD-Arg interacted with α-cyclodextrin (α-CD) to form the supramolecular hydrogel by the host-guest interaction. The gelation dynamics, hydrogel strength and shear viscosity could be modulated by α-CD content in the hydrogel. MPEG-PLLD-Arg was confirmed to bind and deliver gene effectively, and its gene transfection efficiency was significantly higher than PEI-25k under its optimized condition. After gelation, MMP-9 shRNA plasmid (pMMP-9) could be encapsulated into the hydrogel matrix in situ and be released from the hydrogels sustainedly, as the release rate was dependent on α-CD content. The released MPEG-PLLD-Arg/pMMP-9 complex still showed better transfection efficiency than PEI-25k and induced sustained tumor cell apoptosis. Also, in vivo assays indicated that this pMMP-9-loaded supramolecular hydrogel could result in the sustained tumor growth inhibition meanwhile showed good biocompatibility. As an injectable, sustained and high-efficiency gene delivery system, this supramolecular hydrogel is a promising candidate for long-term gene therapy. To realize the sustained gene delivery for gene therapy, a supramolecular hydrogel with high-efficiency gene delivery ability was prepared through the host-guest interaction between α-cyclodextrin and PEGylated arginine-functionalized poly(l-lysine) dendron. The obtained hydrogel was injectable and biocompatible with adjustable physicochemical property. More importantly, the hydrogel showed the high-efficiency and sustained gene transfection to our used cells, better than PEI-25k. The supramolecular hydrogel resulted in the sustained tumor growth

  6. Albumin-mediated delivery of siRNA

    DEFF Research Database (Denmark)

    Bienk, Konrad

    2015-01-01

    in autoimmune disorders, neurodegenerative disorders and cancer by specific gene silencing. The effective delivery of the therapeutic to target cells and tissues is currently a great challenge for successful siRNA therapy. In the bloodstream, free siRNA is rapidly cleared by renal excretion or degraded by serum...... been used to create a range of albumin variants with FcRn affinity both lower and higher than that of wild-type albumin. The aim of this project is to develop a siRNA carrier system utilizing albumin as a natural delivery vehicle. Cholesteryl functionalized siRNA was designed to facilitate binding...... formulation with albumin. Furthermore, the experiments revealed a preferential accumulation of the 2- cholesteryl siRNA in the liver after 6 hours. The finding of accumulation in the liver was utilized in vivo to illustrate liver specific Factor VII silencing of ~30%, mediated only by albumin as a delivery...

  7. Analysis of axisymmetrical vibration of a partially liquid-filled elastic sphere by the method of Green's function. [with application to launch vehicle propellant tanks

    Science.gov (United States)

    Glaser, R. F.

    1973-01-01

    The longitudinal dynamic behavior of launch vehicles is largely determined by their huge liquid propellant masses which are spring supported by the elastic tank walls. Throughout much of the powered flight time, these masses constitute a high percentage of the entire vehicle mass and, therefore, may dominate the fundamental modes of the vehicle. In this report, a spherical container is considered. The analysis is based on a Galerkin approach, in the course of which a second-order differential equation must be solved. The solution has been obtained by the method of Green's function. This method is favorable because it displays the manner in which the analysis can be extended to partially liquid-filled general shells of revolution. The computer programs currently available for partially liquid-filled propellant tanks are based on the finite element methods and result in analytical models having as many as several hundred degrees of freedom. The method applied in this report results in a model having less than 10 degrees of freedom as can be shown by numerical evaluation. Therefore, it will be possible to analyze propellant tanks using much less computer time with comparable accuracy.

  8. Vehicle barrier systems

    International Nuclear Information System (INIS)

    Sena, P.A.

    1986-01-01

    The ground vehicle is one of the most effective tools available to an adversary force. Vehicles can be used to penetrate many types of perimeter barriers, transport equipment and personnel rapidly over long distances, and deliver large amounts of explosives directly to facilities in suicide missions. The function of a vehicle barrier system is to detain or disable a defined threat vehicle at a selected distance from a protected facility. Numerous facilities are installing, or planning to install, vehicle barrier systems and many of these facilities are requesting guidance to do so adequately. Therefore, vehicle barriers are being evaluated to determine their stopping capabilities so that systems can be designed that are both balanced and capable of providing a desired degree of protection. Equally important, many of the considerations that should be taken into account when establishing a vehicle barrier system have been identified. These considerations which pertain to site preparation, barrier selection, system integration and operation, and vehicle/barrier interaction, are discussed in this paper

  9. (BSA) nanoparticles as drug delivery vehicles

    African Journals Online (AJOL)

    SERVER

    2008-02-19

    Feb 19, 2008 ... Since the pore size of poly acrylamide is limited, proteins higher than 800 kDa cannot permeate into the gel. An acrylamide concentration of 10% has been selected to enable optimal resolution for the soluble proteins. The molecular weight markers and protein samples were separated by SDS–PAGE using.

  10. Synthetic LDL as targeted drug delivery vehicle

    Science.gov (United States)

    Forte, Trudy M [Berkeley, CA; Nikanjam, Mina [Richmond, CA

    2012-08-28

    The present invention provides a synthetic LDL nanoparticle comprising a lipid moiety and a synthetic chimeric peptide so as to be capable of binding the LDL receptor. The synthetic LDL nanoparticle of the present invention is capable of incorporating and targeting therapeutics to cells expressing the LDL receptor for diseases associated with the expression of the LDL receptor such as central nervous system diseases. The invention further provides methods of using such synthetic LDL nanoparticles.

  11. Local Delivery of High-Dose Chondroitinase ABC in the Sub-Acute Stage Promotes Axonal Outgrowth and Functional Recovery after Complete Spinal Cord Transection.

    Directory of Open Access Journals (Sweden)

    Chu-Hsun Cheng

    Full Text Available Chondroitin sulfate proteoglycans (CSPGs are glial scar-associated molecules considered axonal regeneration inhibitors and can be digested by chondroitinase ABC (ChABC to promote axonal regeneration after spinal cord injury (SCI. We previously demonstrated that intrathecal delivery of low-dose ChABC (1 U in the acute stage of SCI promoted axonal regrowth and functional recovery. In this study, high-dose ChABC (50 U introduced via intrathecal delivery induced subarachnoid hemorrhage and death within 48 h. However, most SCI patients are treated in the sub-acute or chronic stages, when the dense glial scar has formed and is minimally digested by intrathecal delivery of ChABC at the injury site. The present study investigated whether intraparenchymal delivery of ChABC in the sub-acute stage of complete spinal cord transection would promote axonal outgrowth and improve functional recovery. We observed no functional recovery following the low-dose ChABC (1 U or 5 U treatments. Furthermore, animals treated with high-dose ChABC (50 U or 100 U showed decreased CSPGs levels. The extent and area of the lesion were also dramatically decreased after ChABC treatment. The outgrowth of the regenerating axons was significantly increased, and some partially crossed the lesion site in the ChABC-treated groups. In addition, retrograde Fluoro-Gold (FG labeling showed that the outgrowing axons could cross the lesion site and reach several brain stem nuclei involved in sensory and motor functions. The Basso, Beattie and Bresnahan (BBB open field locomotor scores revealed that the ChABC treatment significantly improved functional recovery compared to the control group at eight weeks after treatment. Our study demonstrates that high-dose ChABC treatment in the sub-acute stage of SCI effectively improves glial scar digestion by reducing the lesion size and increasing axonal regrowth to the related functional nuclei, which promotes locomotor recovery. Thus, our results

  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. Functional health status in subjects after a motor vehicle accident, with emphasis on whiplash associated disorders: design of a descriptive, prospective inception cohort study

    Directory of Open Access Journals (Sweden)

    Helders Paul JM

    2008-12-01

    Full Text Available Abstract Background The clinical consequences of whiplash injuries resulting from a motor vehicle accident (MVA are poorly understood. Thereby, there is general lack of research on the development of disability in patients with acute and chronic Whiplash Associated Disorders. Methods/Design The objective is to describe the design of an inception cohort study with a 1-year follow-up to determine risk factors for the development of symptoms after a low-impact motor vehicle accident, the prognosis of chronic disability, and costs. Victims of a low-impact motor vehicle accident will be eligible for participation. Participants with a Neck Disability Index (NDI score of 7 or more will be classified as experiencing post-traumatic neck pain and will enter the experimental group. Participants without complaints (a NDI score less than 7 will enter the reference group. The cohort will be followed up by means of postal questionnaires and physical examinations at baseline, 3 months, 6 months, and 12 months. Recovery from whiplash-associated disorders will be measured in terms of perceived functional health, and employment status (return to work. Life tables will be generated to determine the 1-year prognosis of whiplash-associated disorders, and risk factors and prognostic factors will be assessed using multiple logistic regression analysis. Discussion Little is known about the development of symptoms and chronic disability after a whiplash injury. In the clinical setting, it is important to identify those people who are at risk of developing chronic symptoms. This inception prospective cohort study will provide insight in the influence of risk factors, of the development of functional health problems, and costs in people with whiplash-associated disorders.

  14. Effect of the Use and Timing of Bone Marrow Mononuclear Cell Delivery on Left Ventricular Function After Acute Myocardial Infarction: The TIME Randomized Trial

    Science.gov (United States)

    Traverse, Jay H.; Henry, Timothy D.; Pepine, Carl J.; Willerson, James T.; Zhao, David X.M.; Ellis, Stephen G.; Forder, John R.; Anderson, R. David; Hatzopoulos, Antonis K.; Penn, Marc S.; Perin, Emerson C.; Chambers, Jeffrey; Baran, Kenneth W.; Raveendran, Ganesh; Lambert, Charles; Lerman, Amir; Simon, Daniel I.; Vaughan, Douglas E.; Lai, Dejian; Gee, Adrian P.; Taylor, Doris A.; Cogle, Christopher R.; Thomas, James D.; Olson, Rachel E.; Bowman, Sherry; Francescon, Judy; Geither, Carrie; Handberg, Eileen; Kappenman, Casey; Westbrook, Lynette; Piller, Linda B.; Simpson, Lara M.; Baraniuk, Sarah; Loghin, Catalin; Aguilar, David; Richman, Sara; Zierold, Claudia; Spoon, Daniel B.; Bettencourt, Judy; Sayre, Shelly L.; Vojvodic, Rachel W.; Skarlatos, Sonia I.; Gordon, David J.; Ebert, Ray F.; Kwak, Minjung; Moyé, Lemuel A.; Simari, Robert D.

    2013-01-01

    Context While the delivery of cell therapy following ST segment myocardial infarction (STEMI) has been evaluated in previous clinical trials, the influence of the timing of cell delivery on the effect on left ventricular (LV) function has not been analyzed in a trial that randomly designated the time of delivery. Objective To determine 1) the effect of intracoronary autologous bone marrow mononuclear cell (BMC) delivery following STEMI on recovery of global and regional LV function and 2) if timing of BMC delivery (3 versus 7 days following reperfusion) influences this effect. Design, Setting, and Patients Between July 17, 2008 and November 15, 2011, 120 patients were enrolled in a randomized, 2×2 factorial, double-blind, placebo-controlled trial of the National Heart, Lung, and Blood Institute (NHLBI)-sponsored Cardiovascular Cell Therapy Research Network (CCTRN) of patients with LV dysfunction (LV Ejection Fraction (LVEF) ≤45%) following successful primary percutaneous coronary intervention (PCI) of anterior STEMI. Interventions Intracoronary infusion of 150 × 106 BMCs or placebo (randomized 2:1 BMC:placebo) within 12 hours of aspiration and processing administered at Day 3 or Day 7 (randomized 1:1) post-PCI. Main Outcome Measures Co-primary endpoints were: 1) Change in global (LVEF) and regional (wall motion) LV function in infarct and border zones at 6 months measured by cardiac magnetic resonance imaging and 2) Change in LV function as affected by timing of treatment on Day 3 versus Day 7. Secondary endpoints included major adverse cardiovascular events as well as changes in LV volumes and infarct size. Results Patient mean age was 56.9±10.9 years with 87.5% male. At 6 months, LVEF increased similarly in both BMC (45.2±10.6 to 48.3±13.3 %) and placebo groups (44.5±10.8 to 47.8±13.6 %). No detectable treatment effect on regional LV function was observed in either infarct or border zones. Differences between therapy groups in the change in global LV

  15. 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.

  16. Influence of microemulsions on cutaneous drug delivery

    DEFF Research Database (Denmark)

    Kreilgaard, Mads

    2002-01-01

    In attempt to increase cutaneous drug delivery, microemulsion vehicles have been more and more frequently employed over recent years. Microemulsion formulations have been shown to be superior for both transdermal and dermal delivery of particularly lipophilic compounds, but also hydrophilic compo...

  17. Protein nanoparticles for therapeutic protein delivery.

    Science.gov (United States)

    Herrera Estrada, L P; Champion, J A

    2015-06-01

    Therapeutic proteins can face substantial challenges to their activity, requiring protein modification or use of a delivery vehicle. Nanoparticles can significantly enhance delivery of encapsulated cargo, but traditional small molecule carriers have some limitations in their use for protein delivery. Nanoparticles made from protein have been proposed as alternative carriers and have benefits specific to therapeutic protein delivery. This review describes protein nanoparticles made by self-assembly, including protein cages, protein polymers, and charged or amphipathic peptides, and by desolvation. It presents particle fabrication and delivery characterization for a variety of therapeutic and model proteins, as well as comparison of the features of different protein nanoparticles.

  18. 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.

  19. 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.

  20. The effect of side-chain functionality and hydrophobicity on the gene delivery capabilities of cationic helical polypeptides.

    Science.gov (United States)

    Zhang, Rujing; Zheng, Nan; Song, Ziyuan; Yin, Lichen; Cheng, Jianjun

    2014-03-01

    The rational design of effective and safe non-viral gene vectors is largely dependent on the understanding of the structure-property relationship. We herein report the design of a new series of cationic, α-helical polypeptides with different side charged groups (amine and guanidine) and hydrophobicity, and mechanistically unraveled the effect of polypeptide structure on the gene delivery capability. Guanidine-containing polypeptides displayed superior membrane activities to their amine-containing analogues via the pore formation mechanism, and thus possessed notably higher transfection efficiencies. Elongating the hydrophobic side chain also potentiated the membrane activities of the polypeptides, while at the meantime caused higher cytotoxicities. Upon an optimal balance between membrane activity and cytotoxicity, maximal transfection efficiency was achieved which outperformed commercial reagent Lipofectamine™ 2000 (LPF2000) by 3-6 folds. This study thus provides mechanistic insights into the rational design of non-viral gene delivery vectors, and the best-performing materials identified also serve as a promising addition to the existing systems. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. 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.

  2. 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.

  3. 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.

  4. Sistem Pengantaran Makanan dengan Pendayagunaan Vehicle Menggunakan Geographical Information System (GIS) dan Algoritma A Star (A*)

    OpenAIRE

    Lubis, Elita Sari

    2016-01-01

    Food delivery system is one various of geographical information systems (GIS) that can be applied through digitation process. The main case in food delivery service is the way to acquire shortest path and movement tracking of food delivery vehicle. Therefore, to accomplish the efficient food delivery system digitation process, it is needed to add facility of shortest path determination and food delivery vehicle tracking. This research uses A* shortest path algorithm to determine shortest path...

  5. Handbook of Intelligent Vehicles

    CERN Document Server

    2012-01-01

    The Handbook of Intelligent Vehicles provides a complete coverage of the fundamentals, new technologies, and sub-areas essential to the development of intelligent vehicles; it also includes advances made to date, challenges, and future trends. Significant strides in the field have been made to date; however, so far there has been no single book or volume which captures these advances in a comprehensive format, addressing all essential components and subspecialties of intelligent vehicles, as this book does. Since the intended users are engineering practitioners, as well as researchers and graduate students, the book chapters do not only cover fundamentals, methods, and algorithms but also include how software/hardware are implemented, and demonstrate the advances along with their present challenges. Research at both component and systems levels are required to advance the functionality of intelligent vehicles. This volume covers both of these aspects in addition to the fundamentals listed above.

  6. Co-delivery of platelet-derived growth factor (PDGF-BB) and bone morphogenic protein (BMP-2) coated onto heparinized titanium for improving osteoblast function and osteointegration.

    Science.gov (United States)

    Kim, Sung Eun; Yun, Young-Pil; Lee, Jae Yong; Shim, June-Sung; Park, Kyeongsoon; Huh, Jung-Bo

    2015-12-01

    The aim of this study was to improve osteoblast function by delivering two growth factors, PDGF-BB and BMP-2, incorporated onto heparinized titanium (Hep-Ti) substrate. To achieve co-delivery of PDGF-BB and BMP-2, the surface of anodized Ti was immobilized with heparin, and then the two growth factors were coated onto the Hep-Ti surface. Incorporation of the two growth factors onto Hep-Ti was evaluated by SEM and XPS. Incorporated PDGF-BB and BMP-2 were released from the Hep-Ti substrate in a sustained manner. In vitro studies revealed that osteoblasts grown on PDGF-BB- and BMP-2-immobilized Hep-Ti increased ALP activity, calcium deposition, osteocalcin and osteopontin levels as compared to those grown on PDGF-BB alone- or BMP-2 alone-immobilized Hep-Ti. These results suggested that co-delivery of PDGF-BB and BMP-2 using Hep-Ti substrate will be a promising material for the enhancement of osteoblast function and osteointegration. Copyright © 2013 John Wiley & Sons, Ltd.

  7. 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.

  8. 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

  9. Influence of microemulsions on cutaneous drug delivery

    DEFF Research Database (Denmark)

    Kreilgaard, Mads

    2002-01-01

    In attempt to increase cutaneous drug delivery, microemulsion vehicles have been more and more frequently employed over recent years. Microemulsion formulations have been shown to be superior for both transdermal and dermal delivery of particularly lipophilic compounds, but also hydrophilic...... compounds appear to benefit from application in microemulsions compared to conventional vehicles, like hydrogels, emulsions and liposomes. The favourable drug delivery properties of microemulsions appear to mainly be attributed to the excellent solubility properties. However, the vehicles may also act...... as penetration enhancers depending on the oil/surfactant constituents, which involves a risk of inducing local irritancy. The correlation between microemulsion structure/composition and drug delivery potential is not yet fully elucidated. However, a few studies have indicated that the internal structure...

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

    Science.gov (United States)

    Liu, Ge; Li, Li; Huo, Da; Li, Yanzhao; Wu, Yangxiao; Zeng, Lingqing; Cheng, Panke; Xing, Malcolm; Zeng, Wen; Zhu, Chuhong

    2017-05-01

    Myocardial infarction (MI) is a serious ischemic condition affecting many individuals around the world. Vascular endothelial growth factor (VEGF) is considered a promising factor for enhancing cardiac function by promoting angiogenesis. However, the lack of a suitable method of VEGF delivery to the MI area is a serious challenge. In this study, we screened a suitable delivery carrier with favorable biocompatibility that targeted the MI area using the strategy of an inherent structure derived from the body and that was based on characteristics of the MI. Mesenchymal stem cells (MSCs) are important infiltrating cells that are derived from blood and have an inherent tropism for the MI zone. We hypothesized that VEGF-encapsulated MSCs targeting MI tissue could improve cardiac function by angiogenesis based on the tropism of the MSCs to the MI area. We first developed VEGF-encapsulated MSCs using self-assembled gelatin and alginate polyelectrolytes to improve angiogenesis and cardiac function. In vitro, the results showed that VEGF-encapsulated MSCs had a sustained release of VEGF and tropism to SDF-1. In vivo, VEGF-encapsulated MSCs migrated to the MI area, enhanced cardiac function, perfused the infarcted area and promoted angiogenesis. These preclinical findings suggest that VEGF-loaded layer-by-layer self-assembled encapsulated MSCs may be a promising and minimally invasive therapy for treating MI. Furthermore, other drugs loaded to layer-by-layer self-assembled encapsulated MSCs may be promising therapies for treating other diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. The pickup and delivery problem with cross-docking opportunity

    DEFF Research Database (Denmark)

    Petersen, Hanne Løhmann; Røpke, Stefan

    2011-01-01

    delivery by one truck, or by being picked up and transported to the cross-dock by one vehicle, and subsequently delivered at its final destination by another vehicle. Handling times at customers sites and terminal are given. A typical daily instance includes 500-1,000 requests. We solve the problem using......In this paper, we consider the pickup and delivery problem with cross-docking opportunity (PDPCD). The problem arises from an industry application, and includes pickup requests, delivery requests, and pickup-and-delivery requests. Each pickup-and-delivery request can be served either as direct...

  12. Nanocomposite Hydrogels: 3D Polymer-Nanoparticle Synergies for On-Demand Drug Delivery.

    Science.gov (United States)

    Merino, Sonia; Martín, Cristina; Kostarelos, Kostas; Prato, Maurizio; Vázquez, Ester

    2015-05-26

    Considerable progress in the synthesis and technology of hydrogels makes these materials attractive structures for designing controlled-release drug delivery systems. In particular, this review highlights the latest advances in nanocomposite hydrogels as drug delivery vehicles. The inclusion/incorporation of nanoparticles in three-dimensional polymeric structures is an innovative means for obtaining multicomponent systems with diverse functionality within a hybrid hydrogel network. Nanoparticle-hydrogel combinations add synergistic benefits to the new 3D structures. Nanogels as carriers for cancer therapy and injectable gels with improved self-healing properties have also been described as new nanocomposite systems.

  13. Robotic vehicle

    Science.gov (United States)

    Box, W. Donald

    1997-01-01

    A robotic vehicle for travel through a conduit. The robotic vehicle includes forward and rear housings each having a hub portion, and each being provided with surface engaging mechanisms for selectively engaging the walls of the conduit such that the housings can be selectively held in stationary positions within the conduit. The surface engaging mechanisms of each housing includes a plurality of extendable appendages, each of which is radially extendable relative to the operatively associated hub portion between a retracted position and a radially extended position. The robotic vehicle also includes at least three selectively extendable members extending between the forward and rear housings, for selectively changing the distance between the forward and rear housings to effect movement of the robotic vehicle.

  14. Abandoned vehicles

    CERN Multimedia

    Relations with the Host States Service

    2004-01-01

    The services in charge of managing the CERN site have recently noted an increase in the number of abandoned vehicles. This poses a risk from the point of view of safety and security and, on the eve of several important events in honour of CERN's fiftieth anniversary, is detrimental to the Organization's image. Owners of vehicles that have been left immobile for some time on the CERN site, including on the external car park by the flags, are therefore invited to contact the Reception and Access Control Service (service-parking-longterm@cern.ch) before 1st October 2004 and, where appropriate, move their vehicle to a designated long-term parking area. After this date, any vehicle whose owner has failed to respond to this request and which is without a number plate, has been stationary for several weeks or is out of service, may be impounded at the owner's risk and expense. Relations with the Host States Service Tel. 72848

  15. Anionic clay as the drug delivery vehicle: tumor targeting function of layered double hydroxide-methotrexate nanohybrid in C33A orthotopic cervical cancer model.

    Science.gov (United States)

    Choi, Goeun; Piao, Huiyan; Alothman, Zeid A; Vinu, Ajayan; Yun, Chae-Ok; Choy, Jin-Ho

    2016-01-01

    Methotrexate (MTX), an anticancer agent, was successfully intercalated into the anionic clay, layered double hydroxides to form a new nanohybrid drug. The coprecipitation and subsequent hydrothermal method were used to prepare chemically, structurally, and morphologically well-defined two-dimensional drug-clay nanohybrid. The resulting two-dimensional drug-clay nanohybrid showed excellent colloidal stability not only in deionized water but also in an electrolyte solution of Dulbecco's Modified Eagle's Medium with 10% fetal bovine serum, in which the average particle size in colloid and the polydispersity index were determined to be around 100 and 0.250 nm, respectively. The targeting property of the nanohybrid drug was confirmed by evaluating the tumor-to-blood and tumor-to-liver ratios of the MTX with anionic clay carrier, and these ratios were compared to those of free MTX in the C33A orthotopic cervical cancer model. The biodistribution studies indicated that the mice treated with the former showed 3.5-fold higher tumor-to-liver ratio and fivefold higher tumor-to-blood ratio of MTX than those treated with the latter at 30 minutes postinjection.

  16. Anionic clay as the drug delivery vehicle: tumor targeting function of layered double hydroxide-methotrexate nanohybrid in C33A orthotopic cervical cancer model

    Directory of Open Access Journals (Sweden)

    Choi G

    2016-01-01

    Full Text Available Goeun Choi,1 Huiyan Piao,1 Zeid A Alothman,2 Ajayan Vinu,3 Chae-Ok Yun,4 Jin-Ho Choy1 1Center for Intelligent Nano-Bio Materials, Department of Chemistry and Nano Science, Ewha Womans University, Seoul, Korea; 2Advanced Materials Research Chair, Chemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia; 3Future Industries Institute, University of South Australia, Mawson Lakes, SA, Australia; 4Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Korea Abstract: Methotrexate (MTX, an anticancer agent, was successfully intercalated into the anionic clay, layered double hydroxides to form a new nanohybrid drug. The coprecipitation and subsequent hydrothermal method were used to prepare chemically, structurally, and morphologically well-defined two-dimensional drug-clay nanohybrid. The resulting two-dimensional drug-clay nanohybrid showed excellent colloidal stability not only in deionized water but also in an electrolyte solution of Dulbecco’s Modified Eagle’s Medium with 10% fetal bovine serum, in which the average particle size in colloid and the polydispersity index were determined to be around 100 and 0.250 nm, respectively. The targeting property of the nanohybrid drug was confirmed by evaluating the tumor-to-blood and tumor-to-liver ratios of the MTX with anionic clay carrier, and these ratios were compared to those of free MTX in the C33A orthotopic cervical cancer model. The biodistribution studies indicated that the mice treated with the former showed 3.5-fold higher tumor-to-liver ratio and fivefold higher tumor-to-blood ratio of MTX than those treated with the latter at 30 minutes postinjection. Keywords: anionic clay, biodistribution, cervical cancer, colloidal stability, layered double hydroxide, methotrexate 

  17. Describing Function Techniques for the Non-Linear Analysis of the Dynamics of a Rail Vehicle Wheelset

    Science.gov (United States)

    1975-07-01

    The describing function method of analysis is applied to investigate the influence of parametric variations on wheelset critical velocity. In addition, the relationship between the amplitude of sustained lateral oscillations and critical speed is der...

  18. 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

  19. 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.

  20. Connected vehicle applications : safety.

    Science.gov (United States)

    2016-01-01

    Connected vehicle safety applications are designed to increase situational awareness : and reduce or eliminate crashes through vehicle-to-infrastructure, vehicle-to-vehicle, : and vehicle-to-pedestrian data transmissions. Applications support advisor...

  1. 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.

  2. 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

  3. Forceps Delivery

    Science.gov (United States)

    ... 2015. Related Signs of labor Forceps delivery About Advertisement Mayo Clinic does not endorse companies or products. ... a Job Site Map About This Site Twitter Facebook Google YouTube Pinterest Mayo Clinic is a not- ...

  4. Oil components modulate physical characteristics and function of the natural oil emulsions as drug or gene delivery system.

    Science.gov (United States)

    Chung, H; Kim, T W; Kwon, M; Kwon, I C; Jeong, S Y

    2001-04-28

    Oil-in-water (o/w) type lipid emulsions were formulated by using 18 different natural oils and egg phosphatidylcholine (egg PC) to investigate how emulsion particle size and stability change with different oils. Cottonseed, linseed and evening primrose oils formed emulsions with very large and unstable particles. Squalene, light mineral oil and jojoba bean oil formed stable emulsions with small particles. The remaining natural oils formed moderately stable emulsions. Emulsions with smaller initial particle size were more stable than those with larger particles. The correlation between emulsion size made with different oils and two physical properties of the oils was also investigated. The o/w interfacial tension and particle size of the emulsion were inversely proportional. The effect of viscosity was less pronounced. To study how the oil component in the emulsion modulates the in vitro release characteristics of lipophilic drugs, three different emulsions loaded with two different drugs were prepared. Squalene, soybean oil and linseed oil emulsions represented the most, medium and the least stable systems, respectively. For the lipophilic drugs, release was the slowest from the most stable squalene emulsion, followed by soybean oil and then by linseed oil emulsions. Cationic emulsions were also prepared with the above three different oils as gene carriers. In vitro transfection activity was the highest for the most stable squalene emulsion followed by soybean oil and then by linseed oil emulsions. Even though the in vitro transfection activity of emulsions were lower than the liposome in the absence of serum, the activity of squalene emulsion, for instance, was ca. 30 times higher than that of liposome in the presence of 80% (v/v) serum. In conclusion, the choice of oil component in o/w emulsion is important in formulating emulsion-based drug or gene delivery systems.

  5. 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.

  6. The effect of hydrochloric acid addition to increase carbon nanotubes dispersibility as drug delivery system by covalent functionalization

    Science.gov (United States)

    Wulan, P. P. D. K.; Ulwani, S. H.; Wulandari, H.; Purwanto, W. W.; Mulia, K.

    2018-03-01

    This study is to obtain the effect of adding hydrochloric acid (HCl) to the mixture of sulfuric acid (H2SO4) and HNO3 in CNT covalent functionalization. HCl expected to increase the dispersibility of functionalized CNT by improving the dispersion time period done with H2SO4 or HNO3. Functionalization used mixture of H2SO4 and HNO3 with volume ratio of 3:1. Covalent functionalization used 0.5 grams of MWCNT ultra sonicated in 50mL HNO3 with and mixture of H2SO4 and HNO3. Additions of 200 mL HCl used variation of molarity from 1M, 2M, 3M, 4M, 5M to 6M. CNT were oxidized to form carboxylic and hydroxyl bonds on the surface that increase dispersibility of CNT. FTIR spectrums showed the existences of carboxyl and hydroxyl group on spectra of 2600-3700 cm-1 and 900-1400 cm-1. Dispersion tests, which showed functionalized CNT (f-CNT) dispersion capabilities, were done by dissolving f-CNT in water. The study resulted that 6M f-CNT (NSC6) gave the best dispersion with zeta potential value of -37.1mV. NSC6 gave the longest dispersion time which was 20 days until f-CNT settle again. SEM-EDS micrographs showed the surface structure of 6M f-CNT without significant damage and no longer contain impurities of Fe, Ni, and Cl.

  7. Hybrid FSAE Vehicle Realization

    Science.gov (United States)

    2010-12-01

    The goal of this multi-year project is to create a fully functional University of Idaho entry in the hybrid FSAE competition. Vehicle integration is underway as part of a variety of 2010-11 senior design projects. This leverages a variety of analytic...

  8. 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.

  9. Intramyocardial Delivery of Mesenchymal Stem Cell-Seeded Hydrogel Preserves Cardiac Function and Attenuates Ventricular Remodeling after Myocardial Infarction

    Science.gov (United States)

    Mathieu, Eva; Lamirault, Guillaume; Toquet, Claire; Lhommet, Pierre; Rederstorff, Emilie; Sourice, Sophie; Biteau, Kevin; Hulin, Philippe; Forest, Virginie; Weiss, Pierre

    2012-01-01

    Background To improve the efficacy of bone marrow-derived mesenchymal stem cell (MSC) therapy targeted to infarcted myocardium, we investigated whether a self-setting silanized hydroxypropyl methylcellulose (Si-HPMC) hydrogel seeded with MSC (MSC+hydrogel) could preserve cardiac function and attenuate left ventricular (LV) remodeling during an 8-week follow-up study in a rat model of myocardial infarction (MI). Methodology/Principal Finding Si-HPMC hydrogel alone, MSC alone or MSC+hydrogel were injected into the myocardium immediately after coronary artery ligation in female Lewis rats. Animals in the MSC+hydrogel group showed an increase in cardiac function up to 28 days after MI and a mid-term prevention of cardiac function alteration at day 56. Histological analyses indicated that the injection of MSC+hydrogel induced a decrease in MI size and an increase in scar thickness and ultimately limited the transmural extent of MI. These findings show that intramyocardial injection of MSC+hydrogel induced short-term recovery of ventricular function and mid-term attenuation of remodeling after MI. Conclusion/Significance These beneficial effects may be related to the specific scaffolding properties of the Si-HPMC hydrogel that may provide the ability to support MSC injection and engraftment within myocardium. PMID:23284842

  10. General Strategy for Direct Cytosolic Protein Delivery via Protein-Nanoparticle Co-engineering.

    Science.gov (United States)

    Mout, Rubul; Ray, Moumita; Tay, Tristan; Sasaki, Kanae; Yesilbag Tonga, Gulen; Rotello, Vincent M

    2017-06-27

    Endosomal entrapment is a key hurdle for most intracellular protein-based therapeutic strategies. We report a general strategy for efficient delivery of proteins to the cytosol through co-engineering of proteins and nanoparticle vehicles. The proteins feature an oligo(glutamate) sequence (E-tag) that binds arginine-functionalized gold nanoparticles, generating hierarchical spherical nanoassemblies. These assemblies fuse with cell membranes, releasing the E-tagged protein directly into the cytosol. Five different proteins with diverse charges, sizes, and functions were effectively delivered into cells, demonstrating the generality of our method. Significantly, the engineered proteins retained activity after cytosolic delivery, as demonstrated through the delivery of active Cre recombinase, and granzyme A to kill cancer cells.

  11. FedEx Express Gasoline Hybrid Electric Delivery Truck Evaluation: 12-Month Report

    Energy Technology Data Exchange (ETDEWEB)

    Barnitt, R.

    2011-01-01

    This report summarizes the data obtained in a 12-month comparison of three gasoline hybrid electric delivery vehicles with three comparable diesel vehicles. The data show that there was no statistical difference between operating cost per mile of the two groups of vehicles. As expected, tailpipe emissions were considerably lower across all drive cycles for the gHEV than for the diesel vehicle.

  12. Periodic Heterogeneous Vehicle Routing Problem With Driver Scheduling

    Science.gov (United States)

    Mardiana Panggabean, Ellis; Mawengkang, Herman; Azis, Zainal; Filia Sari, Rina

    2018-01-01

    The paper develops a model for the optimal management of logistic delivery of a given commodity. The company has different type of vehicles with different capacity to deliver the commodity for customers. The problem is then called Periodic Heterogeneous Vehicle Routing Problem (PHVRP). The goal is to schedule the deliveries according to feasible combinations of delivery days and to determine the scheduling of fleet and driver and routing policies of the vehicles. The objective is to minimize the sum of the costs of all routes over the planning horizon. We propose a combined approach of heuristic algorithm and exact method to solve the problem.

  13. 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.

  14. Electric-Drive Vehicles

    Energy Technology Data Exchange (ETDEWEB)

    None

    2017-09-01

    Electric-drive vehicles use electricity as their primary fuel or to improve the efficiency of conventional vehicle designs. These vehicles can be divided into three categories: Hybrid electric vehicles (HEVs), Plug-in hybrid electric vehicles (PHEVs), All-electric vehicles (EVs). Together, PHEVs and EVs can also be referred to as plug-in electric vehicles (PEVs).

  15. Electric-Drive Vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Septon, Kendall K [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-09-11

    Electric-drive vehicles use electricity as their primary fuel or to improve the efficiency of conventional vehicle designs. These vehicles can be divided into three categories: Hybrid electric vehicles (HEVs), Plug-in hybrid electric vehicles (PHEVs), All-electric vehicles (EVs). Together, PHEVs and EVs can also be referred to as plug-in electric vehicles (PEVs).

  16. Light vehicle crash avoidance needs and countermeasure profiles for safety applications based on vehicle-to-vehicle communications

    Science.gov (United States)

    2013-04-30

    This report discusses light-vehicle crash countermeasure profiles and functions for five target pre-crash scenario groups based on vehicle-to-vehicle (V2V) communications. Target pre-crash scenario groups include rear-end, lane change, opposite direc...

  17. 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

  18. Assisted Vaginal Delivery

    Science.gov (United States)

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

  19. Mobile robot vehicles for physical security

    International Nuclear Information System (INIS)

    McGovern, D.E.

    1987-07-01

    A fleet of vehicles is being developed and maintained by Sandia National Labs for studies in remote control and autonomous operation. These vehicles range from modified commercial vehicles to specially constructed mobile platforms and are utilized as test beds for developing concepts in the application of robotics to interior and exterior physical security. Actuators control the vehicle speed, brakes, and steering through manual input from a remote driving station or through some level of digital computer control. On-board processing may include simple vehicle control functions or may allow for unmanned, autonomous operation. communication links are provided for digital communication between control computers, television transmission for vehicle vision, and voice for local control. With these vehicles, SNL can develop, test, and evaluate sensors, processing requirements, various methods of actuator implementation, operator controlled feedback requirements, and vehicle operations. A description of the major features and uses for each of the vehicles in the fleet is provided

  20. Mobile robot vehicles for physical security

    International Nuclear Information System (INIS)

    Mc Govern, D.E.

    1987-01-01

    A fleet of vehicles is being developed and maintained by Sandia National Labs for studies in remote control and autonomous operation. These vehicles range from modified commercial vehicles to specially constructed mobile platforms and are utilized as test beds for developing concepts in the application of robotics to interior and exterior physical security. Actuators control the vehicle speed, brakes, and steering through manual input from a remote driving station or through some level of digital computer control. On-board processing may include simple vehicle control functions or may allow for unmanned, autonomous operation. Communication links are provided for digital communication between control computers, television transmission for vehicle vision, and voice for local control. With these vehicles, SNL can develop, test, and evaluate sensors, processing requirements, various methods of actuator implementation, operator controlled feedback requirements, and vehicle operations. A description of the major features and uses for each of the vehicles in the fleet is provided

  1. Mobile robot vehicles for physical security

    International Nuclear Information System (INIS)

    McGovern, D.E.

    1987-06-01

    A fleet of vehicles is being developed and maintained by Sandia National Labs for studies in remote control and autonomous operation. These vehicles range from modified commercial vehicles to specially constructed mobile platforms and are utilized as test beds for developing concepts in the application of robotics to interior and exterior physical security. Actuators control the vehicle speed, brakes, and steering through manual input from a remote driving station or through some level of digital computer control. On-board processing may include simple vehicle control functions or may allow for unmanned, autonomous operation. Communication links are provided for digital communication between control computers, television transmission for vehicle vision, and voice for local control. With these vehicles, SNL can develop, test, and evaluate sensors, processing requirements, various methods of actuator implementation, operator controlled feedback requirements, and vehicle operations. A description of the major features and uses for each of the vehicles in the fleet is provided. 4 refs., 1 fig., 1 tab

  2. Latency Estimation-Based Data Delivery Scheme for Vehicular Ad Hoc Networks

    OpenAIRE

    Gong, Haigang; Yu, Lingfei; Liu, Ke; Xu, Fulong; Wang, Xiaomin

    2012-01-01

    Data delivery is the most compelling issue for the applications in vehicular ad hoc networks. The characteristics of VAENTs such as highly dynamic topology and the road-constrained mobility pose great challenges for data delivery in vehicular ad hoc networks. In this paper, a latency estimation-based data delivery (LED) scheme is presented. According to the current location and the moving direction of the vehicles, LED calculates the expected delivery latency (EDL) of each vehicle and chooses...

  3. Counterselection and co-delivery of transposon and transposase functions for Sleeping Beauty-mediated transposition in cultured mammalian cells.

    Science.gov (United States)

    Converse, Andrea D; Belur, Lalitha R; Gori, Jennifer L; Liu, Geyi; Amaya, Felipe; Aguilar-Cordova, Estuardo; Hackett, Perry B; McIvor, R Scott

    2004-12-01

    Sleeping Beauty (SB) is a gene-insertion system reconstructed from transposon sequences found in teleost fish and is capable of mediating the transposition of DNA sequences from transfected plasmids into the chromosomes of vertebrate cell populations. The SB system consists of a transposon, made up of a gene of interest flanked by transposon inverted repeats, and a source of transposase. Here we carried out a series of studies to further characterize SB-mediated transposition as a tool for gene transfer to chromosomes and ultimately for human gene therapy. Transfection of mouse 3T3 cells, HeLa cells, and human A549 lung carcinoma cells with a transposon containing the neomycin phosphotransferase (NEO) gene resulted in a several-fold increase in drug-resistant colony formation when co-transfected with a plasmid expressing the SB transposase. A transposon containing a methotrexate-resistant dihydrofolate reductase gene was also found to confer an increased frequency of methotrexate-resistant colony formation when co-transfected with SB transposase-encoding plasmid. A plasmid containing a herpes simplex virus thymidine kinase gene as well as a transposon containing a NEO gene was used for counterselection against random recombinants (NEO+TK+) in medium containing G418 plus ganciclovir. Effective counterselection required a recovery period of 5 days after transfection before shifting into medium containing ganciclovir to allow time for transiently expressed thymidine kinase activity to subside in cells not stably transfected. Southern analysis of clonal isolates indicated a shift from random recombination events toward transposition events when clones were isolated in medium containing ganciclovir as well as G418. We found that including both transposon and transposase functions on the same plasmid substantially increased the stable gene transfer frequency in Huh7 human hepatoma cells. The results from these experiments contribute technical and conceptual insight into

  4. Silica-Coated Liposomes for Insulin Delivery

    Directory of Open Access Journals (Sweden)

    Neelam Dwivedi

    2010-01-01

    Full Text Available Liposomes coated with silica were explored as protein delivery vehicles for their enhanced stability and improved encapsulation efficiency. Insulin was encapsulated within the fluidic phosphatidylcholine lipid vesicles by thin film hydration at pH 2.5, and layer of silica was formed above lipid bilayer by acid catalysis. The presence of silica coating and encapsulated insulin was identified using confocal and electron microscopy. The native state of insulin present in the formulation was evident from Confocal Micro-Raman spectroscopy. Silica coat enhances the stability of insulin-loaded delivery vehicles. In vivo study shows that these silica coated formulations were biologically active in reducing glucose levels.

  5. Intracellular cleavable poly(2-dimethylaminoethyl methacrylate) functionalized mesoporous silica nanoparticles for efficient siRNA delivery in vitro and in vivo

    Science.gov (United States)

    Lin, Daoshu; Cheng, Qiang; Jiang, Qian; Huang, Yuanyu; Yang, Zheng; Han, Shangcong; Zhao, Yuning; Guo, Shutao; Liang, Zicai; Dong, Anjie

    2013-05-01

    A low cytotoxicity and high efficiency delivery system with the advantages of low cost and facile fabrication is needed for the application of small interfering RNA (siRNA) delivery both in vitro and in vivo. For these prerequisites, cationic polymer-mesoporous silica nanoparticles (ssCP-MSNs) were prepared by surface functionalized mesoporous silica nanoparticles with disulfide bond cross-linked poly(2-dimethylaminoethyl methacrylate) (PDMAEMA). In vitro and in vivo evaluations were performed. The synthesized ssCP-MSNs are 100-150 nm in diameter with a pore size of 10 nm and a positively charged surface with a high zeta potential of 27 mV. Consequently, the ssCP-MSNs showed an excellent binding capacity for siRNA, and an enhancement in the cell uptake and cytosolic availability of siRNA. Furthermore, the intracellular reducing cleavage of the disulfide bonds cross-linking the PDMAEMA segments led to intracellular cleavage of PDMAEMA from ssCP-MSNs, which facilitated the intracellular triggered release of siRNA. Therefore, promoted RNA interference was observed in HeLa-Luc cells, which was equal to that of Lipofectamine 2000. Significantly, compared to Lipofectamine 2000, the ssCP-MSNs were more biocompatible, with low cytotoxicity (even non-cytotoxicity) and promotion of cell proliferation to HeLa-Luc cells. The in vivo systemic distribution studies certified that ssCP-MSNs/siRNA could prolong the duration of siRNA in vivo, and that they accumulated in the adrenal gland, liver, lung, spleen, kidney, heart and thymus after intravenous injection. Encouragingly, with the ability to deliver siRNA to a tumor, ssCP-MSNs/siRNA showed a tumor suppression effect in the HeLa-Luc xenograft murine model after intravenous injection. Therefore, the ssCP-MSNs cationic polymer-mesoporous silica nanoparticles with low cytotoxicity are promising for siRNA delivery.A low cytotoxicity and high efficiency delivery system with the advantages of low cost and facile fabrication is needed

  6. Vehicle Controller

    Science.gov (United States)

    1985-01-01

    UNISTICK is an airplane-like joystick being developed by Johnson Engineering under NASA and VA sponsorship. It allows a driver to control a vehicle with one hand, and is based upon technology developed for the Apollo Lunar Landings of the 1970's. It allows severely handicapped drivers to operate an automobile or van easily. The system is expected to be in production by March 1986.

  7. Gelatin device for the delivery of growth factors involved in endochondral ossification

    Science.gov (United States)

    Ahrens, Lucas A. J.; Vonwil, Daniel; Christensen, Jon

    2017-01-01

    Controlled release drug delivery systems are well established as oral and implantable dosage forms. However, the controlled release paradigm can also be used to present complex soluble signals responsible for cellular organization during development. Endochondral ossification (EO), the developmental process of bone formation from a cartilage matrix is controlled by several soluble signals with distinct functions that vary in structure, molecular weight and stability. This makes delivering them from a single vehicle rather challenging. Herein, a gelatin-based delivery system suitable for the delivery of small molecules as well as recombinant human (rh) proteins (rhWNT3A, rhFGF2, rhVEGF, rhBMP4) is reported. The release behavior and biological activity of the released molecules was validated using analytical and biological assays, including cell reporter systems. The simplicity of fabrication of the gelatin device should foster its adaptation by the diverse scientific community interested in interrogating developmental processes, in vivo. PMID:28380024

  8. Hybrid dendrimer hydrogel/poly(lactic-co-glycolic acid) nanoparticle platform: an advanced vehicle for topical delivery of antiglaucoma drugs and a likely solution to improving compliance and adherence in glaucoma management.

    Science.gov (United States)

    Yang, Hu; Leffler, Christopher T

    2013-03-01

    Glaucoma therapy typically begins with topical medications, of which there are 4 major classes in common use in the United States: beta-adrenergic antagonists, alpha-agonists, carbonic anhydrase inhibitors, and prostaglandin analogs. Unfortunately, all 4 classes require at least daily dosing, and 3 of the 4 classes are approved to be administered 2 or 3 times daily. This need for frequent dosing with multiple medications makes compliance difficult. Longer-acting formulations and combinations that require less frequent administration might improve compliance and therefore medication effectiveness. Recently, we developed an ocular drug delivery system, a hybrid dendrimer hydrogel/poly(lactic-co-glycolic acid) nanoparticle platform for delivering glaucoma therapeutics topically. This platform is designed to deliver glaucoma drugs to the eye efficiently and release the drug in a slow fashion. Furthermore, this delivery platform is designed to be compatible with many of the glaucoma drugs that are currently approved for use. In this article, we review this new delivery system with in-depth discussion of its structural features, properties, and preclinical application in glaucoma treatment. In addition, future directions and translational efforts for marketing this technology are elaborated.

  9. 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.

  10. From bacterial avirulence genes to effector functions via the hrp delivery system: an overview of 25 years of progress in our understanding of plant innate immunity.

    Science.gov (United States)

    Mansfield, John W

    2009-11-01

    Cloning the first avirulence (avr) gene has led not only to a deeper understanding of gene-for-gene interactions in plant disease, but also to fundamental insights into the suppression of basal defences against microbial attack. This article (focusing on Pseudomonas syringae) charts the development of ideas and research progress over the 25 years following the breakthrough achieved by Staskawicz and coworkers. Advances in gene cloning technology underpinned the identification of both avr and hrp genes, the latter being required for the activation of the defensive hypersensitive reaction (HR) and pathogenicity. The delivery of Avr proteins through the type III secretion machinery encoded by hrp gene clusters was demonstrated, and the activity of the proteins inside plant cells as elicitors of the HR was confirmed. Key roles for avr genes in pathogenic fitness have now been established. The rebranding of Avr proteins as effectors, proteins that suppress the HR and cell wall-based defences, has led to the ongoing search for their targets, and is generating new insights into the co-ordination of plant resistance against diverse microbes. Bioinformatics-led analysis of effector gene distribution in genomes has provided a remarkable view of the interchange of effectors and also their functional domains, as the arms race of attack and defence drives the evolution of microbial pathogenicity. The application of our accrued knowledge for the development of disease control strategies is considered.

  11. Hydraulic Hybrid Parcel Delivery Truck Deployment, Testing & Demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Gallo, Jean-Baptiste [Calstart Incorporated, Pasadena, CA (United States)

    2014-03-07

    Although hydraulic hybrid systems have shown promise over the last few years, commercial deployment of these systems has primarily been limited to Class 8 refuse trucks. In 2005, the Hybrid Truck Users Forum initiated the Parcel Delivery Working Group including the largest parcel delivery fleets in North America. The goal of the working group was to evaluate and accelerate commercialization of hydraulic hybrid technology for parcel delivery vehicles. FedEx Ground, Purolator and United Parcel Service (UPS) took delivery of the world’s first commercially available hydraulic hybrid parcel delivery trucks in early 2012. The vehicle chassis includes a Parker Hannifin hydraulic hybrid drive system, integrated and assembled by Freightliner Custom Chassis Corp., with a body installed by Morgan Olson. With funding from the U.S. Department of Energy, CALSTART and its project partners assessed the performance, reliability, maintainability and fleet acceptance of three pre-production Class 6 hydraulic hybrid parcel delivery vehicles using information and data from in-use data collection and on-road testing. This document reports on the deployment of these vehicles operated by FedEx Ground, Purolator and UPS. The results presented provide a comprehensive overview of the performance of commercial hydraulic hybrid vehicles in parcel delivery applications. This project also informs fleets and manufacturers on the overall performance of hydraulic hybrid vehicles, provides insights on how the technology can be both improved and more effectively used. The key findings and recommendations of this project fall into four major categories: -Performance, -Fleet deployment, -Maintenance, -Business case. Hydraulic hybrid technology is relatively new to the market, as commercial vehicles have been introduced only in the past few years in refuse and parcel delivery applications. Successful demonstration could pave the way for additional purchases of hydraulic hybrid vehicles throughout the

  12. Advanced technology mobile robotics vehicle fleet

    International Nuclear Information System (INIS)

    McGovern, D.E.

    1987-03-01

    A fleet of vehicles is being developed and maintained by Sandia National Laboratories for studies in remote control and autonomous operation. The vehicles range from modified commercial vehicles to specially constructed mobile platforms and are utilized as testbeds for developing concepts in the areas of remote control (teleoperation) and computer control (autonomy). Actuators control the vehicle speed, brakes, and steering via manual input from a remote driving station or through some level of digital computer control. On-board processing may include simple vehicle control functions or may allow for unmanned, autonomous operation. Communication links are provided for digital communication between control computers, television transmission for vehicle vision, and voice for local control. SNL can develop, test, and evaluate sensors, processing requirements, various methods of actuator implementation, operator controlled feedback requirements, and vehicle operations. A description of the major features and uses for each of the vehicles in the fleet is provided

  13. A COOPERATIVE ASSISTANCE SYSTEM BETWEEN VEHICLES FOR ELDERLY DRIVERS

    Directory of Open Access Journals (Sweden)

    Naohisa HASHIMOTO

    2009-01-01

    Full Text Available This paper proposes a new concept of elderly driver assistance systems, which performs the assistance by cooperative driving between two vehicles, and describes some experiments with elderly drivers. The assistance consists of one vehicle driven by an elderly driver called a guest vehicle and the other driven by a assisting driver called a host vehicle, and the host vehicle assists or escorts the guest vehicle through the inter-vehicle communications. The functions of the systems installed on a single-seat electric vehicle are highly evaluated by subjects of elderly drivers in virtual streets on a test track.

  14. 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

  15. 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

  16. Improved Ant Colony Optimization for Seafood Product Delivery Routing Problem

    Directory of Open Access Journals (Sweden)

    Baozhen Yao

    2014-02-01

    Full Text Available This paper deals with a real-life vehicle delivery routing problem, which is a seafood product delivery routing problem. Considering the features of the seafood product delivery routing problem, this paper formulated this problem as a multi-depot open vehicle routing problem. Since the multi-depot open vehicle routing problem is a very complex problem, a method is used to reduce the complexity of the problem by changing the multi-depot open vehicle routing problem into an open vehicle routing problem with a dummy central depot in this paper. Then, ant colony optimization is used to solve the problem. To improve the performance of the algorithm, crossover operation and some adaptive strategies are used. Finally, the computational results for the benchmark problems of the multi-depot vehicle routing problem indicate that the proposed ant colony optimization is an effective method to solve the multi-depot vehicle routing problem. Furthermore, the computation results of the seafood product delivery problem from Dalian, China also suggest that the proposed ant colony optimization is feasible to solve the seafood product delivery routing problem.

  17. A Study of Vehicle Detection and Counting System Based on Video

    OpenAIRE

    Shuang XU; Lingbin PANG; Huairuo YIN

    2014-01-01

    About the video image processing's vehicle detection and counting system research, which has video vehicle detection, vehicle targets' image processing, and vehicle counting function. Vehicle detection is the use of inter-frame difference method and vehicle shadow segmentation techniques for vehicle testing. Image processing functions is the use of color image gray processing, image segmentation, mathematical morphology analysis and image fills, etc. on target detection to be processed, and t...

  18. An optimization algorithm for a capacitated vehicle routing problem ...

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... In logistic management, determining the locations of delivery points and deciding the path are the vital components that should be considered. Deciding the paths of vehicles provides companies to use their vehicles efficiently. And with utilizing optimized paths, big amounts of cost and time savings will be ...

  19. Repair costs and the intensity of vehicle use

    Directory of Open Access Journals (Sweden)

    Paweł DROŹDZIEL

    2013-01-01

    Full Text Available This paper presents correlation analyses of real-life data associated with the intensity of use of vehicles and the costs of replacement of operating materials and components performed in a three-year period for delivery vans, which was operated by the Poczta Polska (Polish Mail delivery office in Lublin.

  20. An approach to communications security for a communications data delivery system for V2V/V2I safety : technical description and identification of policy and institutional issues.

    Science.gov (United States)

    This report identifies the security approach associated with a communications data delivery system that supports vehicle-to-vehicle (V2V) and vehicle-to-infrastructure (V2I) communications. The report describes the risks associated with communication...

  1. 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.

  2. Biocompatible chitosan nanoparticles as an efficient delivery vehicle for Mycobacterium tuberculosis lipids to induce potent cytokines and antibody response through activation of γδ T cells in mice

    Science.gov (United States)

    Das, Ishani; Padhi, Avinash; Mukherjee, Sitabja; Dash, Debi P.; Kar, Santosh; Sonawane, Avinash

    2017-04-01

    The activation of cell-mediated and humoral immune responses to Mycobacterium tuberculosis (Mtb) is critical for protection against the pathogen and nanoparticle-mediated delivery of antigens is a more potent way to induce different immune responses. Herein, we show that mice immunized with Mtb lipid-bound chitosan nanoparticles (NPs) induce secretion of prominent type-1 T-helper (Th-1) and type-2 T-helper (Th-2) cytokines in lymph node and spleen cells, and also induces significantly higher levels of IgG, IgG1, IgG2 and IgM in comparison to control mice. Furthermore, significantly enhanced γδ-T-cell activation was observed in lymph node cells isolated from mice immunized with Mtb lipid-coated chitosan NPs as compared to mice immunized with chitosan NPs alone or Mtb lipid liposomes. In comparison to CD8+ cells, significantly higher numbers of CD4+ cells were present in both the lymph node and spleen cells isolated from mice immunized with Mtb lipid-coated chitosan NPs. In conclusion, this study represents a promising new strategy for the efficient delivery of Mtb lipids using chitosan NPs to trigger an enhanced cell-mediated and antibody response against Mtb lipids.

  3. Electric vehicle drive train with rollback detection and compensation

    Science.gov (United States)

    Konrad, C.E.

    1994-12-27

    An electric vehicle drive train includes a controller for detecting and compensating for vehicle rollback, as when the vehicle is started upward on an incline. The vehicle includes an electric motor rotatable in opposite directions corresponding to opposite directions of vehicle movement. A gear selector permits the driver to select an intended or desired direction of vehicle movement. If a speed and rotational sensor associated with the motor indicates vehicle movement opposite to the intended direction of vehicle movement, the motor is driven to a torque output magnitude as a nonconstant function of the rollback speed to counteract the vehicle rollback. The torque function may be either a linear function of speed or a function of the speed squared. 6 figures.

  4. Electric vehicle drive train with rollback detection and compensation

    Science.gov (United States)

    Konrad, Charles E.

    1994-01-01

    An electric vehicle drive train includes a controller for detecting and compensating for vehicle rollback, as when the vehicle is started upward on an incline. The vehicle includes an electric motor rotatable in opposite directions corresponding to opposite directions of vehicle movement. A gear selector permits the driver to select an intended or desired direction of vehicle movement. If a speed and rotational sensor associated with the motor indicates vehicle movement opposite to the intended direction of vehicle movement, the motor is driven to a torque output magnitude as a nonconstant function of the rollback speed to counteract the vehicle rollback. The torque function may be either a linear function of speed or a function of the speed squared.

  5. Assessment of Extension Service Delivery on Improved Cassava ...

    African Journals Online (AJOL)

    Extension service delivery is too often merely seen as a vehicle for spreading scientific and technical progress and technology transfer. In the real sense, however, dissemination of knowledge is not a one way affair from scientists to producers. The study was conducted to assess extension service delivery on improved ...

  6. Connected vehicle application : safety.

    Science.gov (United States)

    2015-01-01

    Connected vehicle safety applications are designed to increase situational awareness : and reduce or eliminate crashes through vehicle-to-infrastructure (V2I), vehicle-to-vehicle (V2V), and vehicle-to-pedestrian (V2P) data transmissions. Applications...

  7. Forestry Vehicle

    Science.gov (United States)

    1982-01-01

    Power Pack II provides an economical means of moving a power source into remote roadless forest areas. It was developed by Prof. Miles and his associates, working in cooperation with the University of California's Department of Forestry. The team combined its own design of an all-terrain vehicle with a suspension system based on the NASA load equalization technology. Result is an intermediate-sized unit which carries a power source and the powered tools to perform a variety of forest management tasks which cannot be done economically with current equipment. Power Pack II can traverse very rough terrain and climb a 60 degree slope; any one of the wheels can move easily over an obstacle larger than itself. Work is being done on a more advanced Power Pack III.

  8. Intravitreal delivery of a novel AAV vector targets ON bipolar cells and restores visual function in a mouse model of complete congenital stationary night blindness.

    Science.gov (United States)

    Scalabrino, Miranda L; Boye, Sanford L; Fransen, Kathryn M H; Noel, Jennifer M; Dyka, Frank M; Min, Seok Hong; Ruan, Qing; De Leeuw, Charles N; Simpson, Elizabeth M; Gregg, Ronald G; McCall, Maureen A; Peachey, Neal S; Boye, Shannon E

    2015-11-01

    Adeno-associated virus (AAV) effectively targets therapeutic genes to photoreceptors, pigment epithelia, Müller glia and ganglion cells of the retina. To date, no one has shown the ability to correct, with gene replacement, an inherent defect in bipolar cells (BCs), the excitatory interneurons of the retina. Targeting BCs with gene replacement has been difficult primarily due to the relative inaccessibility of BCs to standard AAV vectors. This approach would be useful for restoration of vision in patients with complete congenital stationary night blindness (CSNB1), where signaling through the ON BCs is eliminated due to mutations in their G-protein-coupled cascade genes. For example, the majority of CSNB1 patients carry a mutation in nyctalopin (NYX), which encodes a protein essential for proper localization of the TRPM1 cation channel required for ON BC light-evoked depolarization. As a group, CSNB1 patients have a normal electroretinogram (ERG) a-wave, indicative of photoreceptor function, but lack a b-wave due to defects in ON BC signaling. Despite retinal dysfunction, the retinas of CSNB1 patients do not degenerate. The Nyx(nob) mouse model of CSNB1 faithfully mimics this phenotype. Here, we show that intravitreally injected, rationally designed AAV2(quadY-F+T-V) containing a novel 'Ple155' promoter drives either GFP or YFP_Nyx in postnatal Nyx(nob) mice. In treated Nyx(nob) retina, robust and targeted Nyx transgene expression in ON BCs partially restored the ERG b-wave and, at the cellular level, signaling in ON BCs. Our results support the potential for gene delivery to BCs and gene replacement therapy in human CSNB1. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Artificial Virus as Trump-card to Resolve Exigencies in Targeted Gene Delivery.

    Science.gov (United States)

    Ajithkumar, K C; Pramod, Kannissery

    2018-01-01

    Viruses are potent pathogens that can effectively deliver the genetic material to susceptible host cells. This capability is beneficially utilized to successfully deliver the genetic material. However, the use of virus mediated gene delivery is considered divisive, because the potentially replicable genomes recombine or integrate with the cell DNA resulting in immunogenicity, ranging from inflammation to death. Thus, the need for potentially effective non-viral gene delivery vehicles arises. Non-viral vectors, protein only particles and virus like particles (VLP) can be constructed which contain all the necessary functional moieties. These resemble viruses and are called artificial or synthetic virus. The artificial virus eliminates the disadvantages of viral vectors but retain the beneficial effects of the viruses. Need for further functionalization can be avoided by this approach because incorporation of requisite agents such as cell ligands, membrane active peptides, etc. into proteins is possible. The protein- DNA complexes resemble bacterial inclusion bodies. Nucleic acids influence conformation of protein units which subsequently result in cell uptake and finally to the cell nucleus. Such tunable systems mimic the activities of infected viruses and are used for the safe and effective delivery of drugs and genetic material in gene therapy. The versatility, stability and biocompatible nature of artificial virus along with high transfection efficacy have made it favorite for gene delivery purposes, in addition to being useful for various biomedical and drug delivery applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Exogenous DNA Loading into Extracellular Vesicles via Electroporation is Size-Dependent and Enables Limited Gene Delivery.

    Science.gov (United States)

    Lamichhane, Tek N; Raiker, Rahul S; Jay, Steven M

    2015-10-05

    Extracellular vesicles (EVs) hold immense promise for utilization as biotherapeutics and drug delivery vehicles due to their nature as biological nanoparticles that facilitate intercellular molecular transport. Specifically, EVs have been identified as natural carriers of nucleic acids, sparking interest in their use for gene therapy and RNA interference applications. So far, small RNAs (siRNA and miRNA) have been successfully loaded into EVs for a variety of delivery applications, but the potential use of EVs for DNA delivery has scarcely been explored. Here, we report that exogenous linear DNA can be associated with EVs via electroporation in quantities sufficient to yield an average of hundreds of DNA molecules per vesicle. We determined that loading efficiency and capacity of DNA in EVs is dependent on DNA size, with linear DNA molecules less than 1000 bp in length being more efficiently associated with EVs compared to larger linear DNAs and plasmid DNAs using this approach. We further showed that EV size is also determinant with regard to DNA loading, as larger microvesicles encapsulated more linear and plasmid DNA than smaller, exosome-like EVs. Additionally, we confirmed the ability of EVs to transfer foreign DNA loaded via electroporation into recipient cells, although functional gene delivery was not observed. These results establish critical parameters that inform the potential use of EVs for gene therapy and, in agreement with other recent results, suggest that substantial barriers must be overcome to establish EVs as broadly applicable DNA delivery vehicles.

  11. Connected vehicles and cybersecurity.

    Science.gov (United States)

    2016-01-01

    Connected vehicles are a next-generation technology in vehicles and in infrastructure : that will make travel safer, cleaner, and more efficient. The advanced wireless : technology enables vehicles to share and communicate information with each other...

  12. T cells enhance gold nanoparticle delivery to tumors in vivo

    Directory of Open Access Journals (Sweden)

    Bear Adham

    2011-01-01

    Full Text Available Abstract Gold nanoparticle-mediated photothermal therapy (PTT has shown great potential for the treatment of cancer in mouse studies and is now being evaluated in clinical trials. For this therapy, gold nanoparticles (AuNPs are injected intravenously and are allowed to accumulate within the tumor via the enhanced permeability and retention (EPR effect. The tumor is then irradiated with a near infrared laser, whose energy is absorbed by the AuNPs and translated into heat. While reliance on the EPR effect for tumor targeting has proven adequate for vascularized tumors in small animal models, the efficiency and specificity of tumor delivery in vivo, particularly in tumors with poor blood supply, has proven challenging. In this study, we examine whether human T cells can be used as cellular delivery vehicles for AuNP transport into tumors. We first demonstrate that T cells can be efficiently loaded with 45 nm gold colloid nanoparticles without affecting viability or function (e.g. migration and cytokine production. Using a human tumor xenograft mouse model, we next demonstrate that AuNP-loaded T cells retain their capacity to migrate to tumor sites in vivo. In addition, the efficiency of AuNP delivery to tumors in vivo is increased by more than four-fold compared to injection of free PEGylated AuNPs and the use of the T cell delivery system also dramatically alters the overall nanoparticle biodistribution. Thus, the use of T cell chaperones for AuNP delivery could enhance the efficacy of nanoparticle-based therapies and imaging applications by increasing AuNP tumor accumulation.

  13. 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.

  14. Functional

    Directory of Open Access Journals (Sweden)

    Fedoua Gandia

    2014-07-01

    Full Text Available The study was carried out to investigate the effects of inhaled Mg alone and associated with F in the treatment of bronchial hyperresponsiveness. 43 male Wistar rats were randomly divided into four groups and exposed to inhaled NaCl 0.9%, MeCh, MgSO4 and MgF2. Pulmonary changes were assessed by means of functional tests and quantitative histological examination of lungs and trachea. Results revealed that delivery of inhaled Mg associated with F led to a significant decrease of total lung resistance better than inhaled Mg alone (p < 0.05. Histological examinations illustrated that inhaled Mg associated with F markedly suppressed muscular hypertrophy (p = 0.034 and bronchoconstriction (p = 0.006 in MeCh treated rats better than inhaled Mg alone. No histological changes were found in the trachea. This study showed that inhaled Mg associated with F attenuated the main principle of the central components of changes in MeCh provoked experimental asthma better than inhaled Mg alone, potentially providing a new therapeutic approach against asthma.

  15. The pitch-heave dynamics of transportation vehicles

    Science.gov (United States)

    Sweet, L. M.; Richardson, H. H.

    1975-01-01

    The analysis and design of suspensions for vehicles of finite length using pitch-heave models is presented. Dynamic models for the finite length vehicle include the spatial distribution of the guideway input disturbance over the vehicle length, as well as both pitch and heave degrees-of-freedom. Analytical results relate the vehicle front and rear accelerations to the pitch and heave natural frequencies, which are functions of vehicle suspension geometry and mass distribution. The effects of vehicle asymmetry and suspension contact area are evaluated. Design guidelines are presented for the modification of vehicle and suspension parameters to meet alternative ride quality criteria.

  16. Functional health status in subjects after a motor vehicle accident, with emphasis on whiplash associated disorders: design of a descriptive, prospective inception cohort study.

    NARCIS (Netherlands)

    Schmitt, Manfred; Meeteren, N.L. van; Wijer, A. de; Helders, P.J.M.; Graaf, Y. van der

    2008-01-01

    BACKGROUND: The clinical consequences of whiplash injuries resulting from a motor vehicle accident (MVA) are poorly understood. Thereby, there is general lack of research on the development of disability in patients with acute and chronic Whiplash Associated Disorders. METHODS/DESIGN: The objective

  17. Interest of general tools of functional simulation in the idea of `mecatronic` groups: an application to energy management of hybrid vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Esteve, D.; Jammes, B.; Vinassa, J.M.; Marpinard, J.C.

    1994-04-01

    This report is a first approach of the simulation to validate the structure of the traction chain of a hybrid vehicle. This first step relies on the use of existing models in libraries of simulation programs. The next steps are going to consist in improving these models, in writing others one more performing and to test this simulation about energy management. (N.C.).

  18. Optimization of a truck-drone in tandem delivery network using k-means and genetic algorithm

    Directory of Open Access Journals (Sweden)

    Sergio Mourelo Ferrandez

    2016-04-01

    Full Text Available Purpose: The purpose of this paper is to investigate the effectiveness of implementing unmanned aerial delivery vehicles in delivery networks. We investigate the notion of the reduced overall delivery time, energy, and costs for a truck-drone network by comparing the in-tandem system with a stand-alone delivery effort. The objectives are (1 to investigate the time, energy, and costs associated to a truck-drone delivery network compared to standalone truck or drone, (2 to propose an optimization algorithm that determines the optimal number of launch sites and locations given delivery requirements, and drones per truck, (3 to develop mathematical formulations for closed form estimations for the optimal number of launch locations, optimal total time, as well as the associated cost for the system. Design/methodology/approach: The design of the algorithm herein computes the minimal time of delivery utilizing K-means clustering to find launch locations, as well as a genetic algorithm to solve the truck route as a traveling salesmen problem (TSP. The optimal solution is determined by finding the minimum cost associated to the parabolic convex cost function. The optimal min-cost is determined by finding the most efficient launch locations using K-means algorithms to determine launch locations and a genetic algorithm to determine truck route between those launch locations.  Findings: Results show improvements with in-tandem delivery efforts as opposed to standalone systems. Further, multiple drones per truck are more optimal and contribute to savings in both energy and time. For this, we sampled various initialization variables to derive closed form mathematical solutions for the problem. Originality/value: Ultimately, this provides the necessary analysis of an integrated truck-drone delivery system which could be implemented by a company in order to maximize deliveries while minimizing time and energy. Closed-form mathematical solutions can be used as

  19. Optimization of a truck-drone in tandem delivery network using k-means and genetic algorithm

    Energy Technology Data Exchange (ETDEWEB)

    Ferrandez, S. M.; Harbison, T.; Weber, T.; Sturges, R.; Rich, R.

    2016-07-01

    The purpose of this paper is to investigate the effectiveness of implementing unmanned aerial delivery vehicles in delivery networks. We investigate the notion of the reduced overall delivery time, energy, and costs for a truck-drone network by comparing the in-tandem system with a stand-alone delivery effort. The objectives are (1) to investigate the time, energy, and costs associated to a truck-drone delivery network compared to standalone truck or drone, (2) to propose an optimization algorithm that determines the optimal number of launch sites and locations given delivery requirements, and drones per truck, (3) to develop mathematical formulations for closed form estimations for the optimal number of launch locations, optimal total time, as well as the associated cost for the system. The design of the algorithm herein computes the minimal time of delivery utilizing K-means clustering to find launch locations, as well as a genetic algorithm to solve the truck route as a traveling salesmen problem (TSP). The optimal solution is determined by finding the minimum cost associated to the parabolic convex cost function. The optimal min-cost is determined by finding the most efficient launch locations using K-means algorithms to determine launch locations and a genetic algorithm to determine truck route between those launch locations. Results show improvements with in-tandem delivery efforts as opposed to standalone systems. Further, multiple drones per truck are more optimal and contribute to savings in both energy and time. For this, we sampled various initialization variables to derive closed form mathematical solutions for the problem. Ultimately, this provides the necessary analysis of an integrated truck-drone delivery system which could be implemented by a company in order to maximize deliveries while minimizing time and energy. Closed-form mathematical solutions can be used as close estimators for final costs and time. (Author)

  20. Suborbital freight delivery concept exploration

    Science.gov (United States)

    Andrews, Dana; Paris, Steve; Rubeck, Mark

    1997-01-01

    Suborbital Freight, sometimes called Fast Freight, is delivery of high priority packages over intercontinental distances in periods of approximately one hour. The vehicles required are usually rocket-powered and have total ideal velocities of around 7.5 km/second. Analysis of this market indicates that there are niches where commercial operations are possible and might even be profitable using today's state-of-the-art technologies. The key requirements to capture this market are low nonrecurring costs, quick turnaround (draft is a report on work in progress. The Fast Freight study will be completed before the STAIF-97 conference and results will be presented at that time.

  1. A high-density ammonia storage/delivery system based on Mg(NH3)6Cl2 for SCR-DeNOx in vehicles

    DEFF Research Database (Denmark)

    Elmøe, Tobias Dokkedal; Sørensen, Rasmus Zink; Quaade, Ulrich

    2006-01-01

    ammonia density of up to 93% of that of liquid ammonia. This provides a long lasting ammonia storage (approximate to 20000 km of driving per 6.2 L Mg(NH(3))(6)Cl(2) for an average medium-sized vehicle). The controlled thermal decomposition of Mg(NH(3))(6)Cl(2) was demonstrated. A small reactor...... to simulate a varying NO, signal. It was demonstrated that it was possible to control the desorption using a simple ON-OFF controller with the buffer pressure as the control variable. Approximately 99% of the ammonia contained in the salt could be desorped and dosed, while maintaining the 5 bars used...... as the set-point pressure. The low density was improved by compressing the Mg(NH(3))(6)Cl(2) powder to a density of 1219 kg/m(3), which is very close to the theoretical crystal density of 1252 kg/m(3). Temperature programmed desorption showed that the ammonia could easily be desorped by heating the densified...

  2. Integrated production and distribution scheduling problems related to fixed delivery departure dates and weights of late orders.

    Science.gov (United States)

    Li, Shanlin; Li, Maoqin

    2015-01-01

    We consider an integrated production and distribution scheduling problem faced by a typical make-to-order manufacturer which relies on a third-party logistics (3PL) provider for finished product delivery to customers. In the beginning of a planning horizon, the manufacturer has received a set of orders to be processed on a single production line. Completed orders are delivered to customers by a finite number of vehicles provided by the 3PL company which follows a fixed daily or weekly shipping schedule such that the vehicles have fixed departure dates which are not part of the decisions. The problem is to find a feasible schedule that minimizes one of the following objective functions when processing times and weights are oppositely ordered: (1) the total weight of late orders and (2) the number of vehicles used subject to the condition that the total weight of late orders is minimum. We show that both problems are solvable in polynomial time.

  3. Electric vehicle drive systems

    Science.gov (United States)

    Appleyard, M.

    1992-01-01

    New legislation in the State of California requires that 2% of vehicles sold there from 1998 will be 'zero-emitting'. This provides a unique market opportunity for developers of electric vehicles but substantial improvements in the technology are probably required if it is to be successfully exploited. There are around a dozen types of battery that are potentially relevant to road vehicles but, at the present, lead/acid and sodium—sulphur come closest to combining acceptable performance, life and cost. To develop an efficient, lightweight electric motor system requires up-to-date techniques of magnetics design, and the latest power-electronic and microprocessor control methods. Brushless machines, coupled with solid-state inverters, offer the most economical solution for mass production, even though their development costs are higher than for direct-current commutator machines. Fitted to a small car, even the highest energy-density batteries will only provide around 200 km average range before recharging. Therefore, some form of supplementary on-board power generation will probably be needed to secure widespread acceptance by the driving public. Engine-driven generators of quite low power can achieve useful increases in urban range but will fail to qualify as 'zero-emitting'. On the other hand, if the same function could be economically performed by a small fuel-cell using hydrogen derived from a methanol reformer, then most of the flexibility provided by conventional vehicles would be retained. The market prospects for electric cars would then be greatly enhanced and their dependence on very advanced battery technology would be reduced.

  4. Biolistic DNA delivery to mice with the low pressure gene gun.

    Science.gov (United States)

    Yen, Meng-Chi; Lai, Ming-Derg

    2013-01-01

    Biolistic DNA delivery is an approach to deliver plasmid to culture cells, plants, or animals. Plasmid DNA is usually transferred through bombardment of DNA-coated particles by highly pressurized gas in various kinds of delivery vehicles. The low pressure gene gun can deliver plasmid at lower pressure. Here, we describe methods of biolistic DNA delivery to mice using the low pressure gene gun.

  5. Delivery of Gemcitabine Prodrugs Employing Mesoporous Silica Nanoparticles

    Directory of Open Access Journals (Sweden)

    Alessio Malfanti

    2016-04-01

    Full Text Available In this paper, mesoporous silica nanoparticles (MSNs were studied as vehicles for the delivery of the antitumoral drug gemcitabine (GEM and of its 4-(N-acyl derivatives, (4-(N-valeroyl-(C5GEM, 4-(N-lauroyl-(C12GEM and 4-(N-stearoyl-gemcitabine (C18GEM. The loading of the GEM lipophilic prodrugs on MSNs was explored with the aim to obtain both a physical and a chemical protection of GEM from rapid plasmatic metabolization. For this purpose, MSNs as such or with grafted aminopropyl and carboxyethyl groups were prepared and characterized. Then, their different drug loading capacity in relation to the nature of the functional group was evaluated. In our experimental conditions, GEM was not loaded in any MSNs, while C12GEM was the most efficiently encapsulated and employed for further evaluation. The results showed that loading capacity increased with the presence of functional groups on the nanoparticles; similarly, the presence of functional groups on MSNs’ surface influenced the drug release profile. Finally, the cytotoxicity of the different preparations was evaluated and data showed that C12GEM loaded MSNs are less cytotoxic than the free drug with an activity that increased with the incubating time, indicating that all these systems are able to release the drug in a controlled manner. Altogether, the results demonstrate that these MSNs could be an interesting system for the delivery of anticancer drugs.

  6. 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 ( ...

  7. Vaginal delivery - discharge

    Science.gov (United States)

    Pregnancy - discharge after vaginal delivery ... return in: 4 to 9 weeks after your delivery if you're not breastfeeding 3 to 12 ... can start sexual activity around 6 weeks after delivery, if the discharge or lochia has stopped. Women ...

  8. Biodegradable nanocomplex from hyaluronic acid and arginine based poly(ester amide)s as the delivery vehicles for improved photodynamic therapy of multidrug resistant tumor cells: An in vitro study of the performance of chlorin e6 photosensitizer.

    Science.gov (United States)

    Ji, Ying; Zhao, Jihui; Chu, Chih-Chang

    2017-05-01

    Photodynamic therapy (PDT), which enables the localized therapeutic effect by light irradiation, provides an alternative and complementary modality for the treatment of tumor. However, the aggregation of photosensitizers in acidic microenvironment of tumor and the non-targeted distribution of photosensitizers in normal tissues significantly affect the PDT efficiency. In this study, we developed a biodegradable nanocomplex HA-Arg-PEA from hyaluronic acid (HA) and arginine based poly(ester amide)s (Arg-PEA) as the nanocarrier for chlorin e6 (Ce6). HA enhanced the tumor-specific endocytosis mediated by the overexpression of CD44 receptor. Arg-PEA not only provide electrostatic interaction with HA to form self-assembled nanostructure, but also improve the monomerization of Ce6 at physiological pH as well as mildly acidic pH. The biodegradable characteristic of HA-Arg-PEA nanocomplex enabled the intracellular delivery of Ce6, in which its release and generation of singlet oxygen can be accelerated by enzymatic degradation of the carrier. The in vitro PDT efficiency of Ce6-loaded HA-Arg-PEA nanocomplex was examined in CD44 positive MDA-MB-435/MDR multidrug resistant melanoma cells. CD44-mediated uptake of Ce6-loaded HA-Arg-PEA nanocomplex significantly improved Ce6 level in MDA-MB-435/MDR cells within short incubation time, and the PDT efficiency in inhibiting multidrug resistant tumor cells was also enhanced at higher Ce6 concentrations. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1487-1499, 2017. © 2017 Wiley Periodicals, Inc.

  9. 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...

  10. Polymer nanogels: a versatile nanoscopic drug delivery platform

    Science.gov (United States)

    Chacko, Reuben T.; Ventura, Judy; Zhuang, Jiaming; Thayumanavan, S.

    2012-01-01

    In this review we put the spotlight on crosslinked polymer nanogels, a promising platform that has the characteristics of an “ideal” drug delivery vehicle. Some of the key aspects of drug delivery vehicle design like stability, response to biologically relevant stimuli, passive targeting, active targeting, toxicity and ease of synthesis are discussed. We discuss several delivery systems in this light and highlight some examples of systems, which satisfy some or all of these design requirements. In particular, we point to the advantages that crosslinked polymeric systems bring to drug delivery. We review some of the synthetic methods of nanogel synthesis and conclude with the diverse applications in drug delivery where nanogels have been fruitfully employed. PMID:22342438

  11. Effect of Intracoronary Delivery of Autolologous Bone Marrow Mononuclear Cells Two to Three Weeks Following Acute Myocardial Infarction on Left-Ventricular Function: The LateTIME Randomized Trial

    Science.gov (United States)

    Traverse, Jay H.; Henry, Timothy D.; Ellis, Stephen G.; Pepine, Carl J.; Willerson, James T.; Zhao, David X.M.; Forder, John R.; Byrne, Barry J.; Hatzopoulos, Antonis K.; Penn, Marc S.; Perin, Emerson C.; Baran, Kenneth W.; Chambers, Jeffrey; Lambert, Charles; Raveendran, Ganesh; Simon, Daniel I.; Vaughan, Douglas E.; Simpson, Lara M.; Gee, Adrian P.; Taylor, Doris A.; Cogle, Christopher R.; Thomas, James D.; Silva, Guilherme V.; Jorgenson, Beth C.; Olson, Rachel E.; Bowman, Sherry; Francescon, Judy; Geither, Carrie; Handberg, Eileen; Smith, Deirdre X.; Baraniuk, Sarah; Piller, Linda B.; Loghin, Catalin; Aguilar, David; Richman, Sara; Zierold, Claudia; Bettencourt, Judy; Sayre, Shelly L.; Vojvodic, Rachel W.; Skarlatos, Sonia I.; Gordon, David J.; Ebert, Ray F.; Kwak, Minjung; Moyé, Lemuel A.; Simari, Robert D.

    2013-01-01

    Context Clinical trial results suggest that intracoronary delivery of autologous bone marrow mononuclear cells (BMCs) may improve left ventricular (LV) function when administered within the first week following myocardial infarction (MI). However, since a substantial number of patients may not present for early cell delivery, we investigated the efficacy of autologous BMC delivery 2–3 weeks post-MI. Objective To determine if intracoronary delivery of autologous BMCs improves global and regional LV function when delivered 2–3 weeks following first MI. Design, Setting, and Patients LateTIME is a randomized, double-blind, placebo-controlled trial of the National Heart, Lung, and Blood Institute - sponsored Cardiovascular Cell Therapy Research Network (CCTRN) of 87 patients with significant LV dysfunction (LVEF ≤ 45%) following successful primary percutaneous coronary intervention (PCI). Interventions Intracoronary infusion of 150 × 106 autologous BMCs (total nucleated cells) or placebo (2:1 BMC:placebo) was performed within 12 hours of bone marrow aspiration after local automated cell processing. Main Outcome Measures The primary endpoints were changes in global (LVEF) and regional (wall motion) LV function in the infarct and border zone from baseline to 6 months as measured by cardiac MRI at a core lab blinded to treatment assignment Secondary endpoints included changes in LV volumes and infarct size. Results 87 patients were randomized between July 2008 and February 2011: mean age = 57 ± 11 yrs, 83% male. Harvesting, processing, and intracoronary delivery of BMCs in this setting was feasible and safe. The change from baseline to six months in the BMC group, when compared to the placebo group, for LVEF (48.7 to 49.2% vs. 45.3 to 48.8%; Difference = −3.0, 95% CI −7.0 to 0.9), wall motion in the infarct zone (6.2 to 6.5 vs. 4.9 to 5.9 mm; Difference = −0.7, 95% CI −2.8 to 1.3), and wall motion in the border zone (16.0 to 16.6 mm vs. 16.1 to 19.3 mm

  12. Consumer Vehicle Choice Model Documentation

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Changzheng [ORNL; Greene, David L [ORNL

    2012-08-01

    In response to the Fuel Economy and Greenhouse Gas (GHG) emissions standards, automobile manufacturers will need to adopt new technologies to improve the fuel economy of their vehicles and to reduce the overall GHG emissions of their fleets. The U.S. Environmental Protection Agency (EPA) has developed the Optimization Model for reducing GHGs from Automobiles (OMEGA) to estimate the costs and benefits of meeting GHG emission standards through different technology packages. However, the model does not simulate the impact that increased technology costs will have on vehicle sales or on consumer surplus. As the model documentation states, “While OMEGA incorporates functions which generally minimize the cost of meeting a specified carbon dioxide (CO2) target, it is not an economic simulation model which adjusts vehicle sales in response to the cost of the technology added to each vehicle.” Changes in the mix of vehicles sold, caused by the costs and benefits of added fuel economy technologies, could make it easier or more difficult for manufacturers to meet fuel economy and emissions standards, and impacts on consumer surplus could raise the costs or augment the benefits of the standards. Because the OMEGA model does not presently estimate such impacts, the EPA is investigating the feasibility of developing an adjunct to the OMEGA model to make such estimates. This project is an effort to develop and test a candidate model. The project statement of work spells out the key functional requirements for the new model.

  13. An operating system for future aerospace vehicle computer systems

    Science.gov (United States)

    Foudriat, E. C.; Berman, W. J.; Will, R. W.; Bynum, W. L.

    1984-01-01

    The requirements for future aerospace vehicle computer operating systems are examined in this paper. The computer architecture is assumed to be distributed with a local area network connecting the nodes. Each node is assumed to provide a specific functionality. The network provides for communication so that the overall tasks of the vehicle are accomplished. The O/S structure is based upon the concept of objects. The mechanisms for integrating node unique objects with node common objects in order to implement both the autonomy and the cooperation between nodes is developed. The requirements for time critical performance and reliability and recovery are discussed. Time critical performance impacts all parts of the distributed operating system; e.g., its structure, the functional design of its objects, the language structure, etc. Throughout the paper the tradeoffs - concurrency, language structure, object recovery, binding, file structure, communication protocol, programmer freedom, etc. - are considered to arrive at a feasible, maximum performance design. Reliability of the network system is considered. A parallel multipath bus structure is proposed for the control of delivery time for time critical messages. The architecture also supports immediate recovery for the time critical message system after a communication failure.

  14. Improved and targeted delivery of bioactive molecules to cells with magnetic layer-by-layer assembled microcapsules.

    Science.gov (United States)

    Pavlov, Anton M; Gabriel, Samantha A; Sukhorukov, Gleb B; Gould, David J

    2015-06-07

    Despite our increasing knowledge of cell biology and the recognition of an increasing repertoire of druggable intracellular therapeutic targets, there remain a limited number of approaches to deliver bioactive molecules to cells and even fewer that enable targeted delivery. Layer-by-layer (LbL) microcapsules are assembled using alternate layers of oppositely charged molecules and are potential cell delivery vehicles for applications in nanomedicine. There are a wide variety of charged molecules that can be included in the microcapsule structure including metal nanoparticles that introduce physical attributes. Delivery of bioactive molecules to cells with LbL microcapsules has recently been demonstrated, so in this study we explore the delivery of bioactive molecules (luciferase enzyme and plasmid DNA) to cells using biodegradable microcapsules containing a layer of magnetite nanoparticles. Interestingly, significantly improved intracellular luciferase enzyme activity (25 fold) and increased transfection efficiency with plasmid DNA (3.4 fold) was observed with magnetic microcapsules. The use of a neodymium magnet enabled efficient targeting of magnetic microcapsules which further improved the delivery efficiency of the cargoes as a consequence of increased microcapsule concentration at the magnetic site. Microcapsules were well tolerated by cells in these experiments and only displayed signs of toxicity at a capsule : cell ratio of 100 : 1 and with extended exposure. These studies illustrate how multi-functionalization of LbL microcapsules can improve and target delivery of bioactive molecules to cells.

  15. Improved and targeted delivery of bioactive molecules to cells with magnetic layer-by-layer assembled microcapsules

    Science.gov (United States)

    Pavlov, Anton M.; Gabriel, Samantha A.; Sukhorukov, Gleb B.; Gould, David J.

    2015-05-01

    Despite our increasing knowledge of cell biology and the recognition of an increasing repertoire of druggable intracellular therapeutic targets, there remain a limited number of approaches to deliver bioactive molecules to cells and even fewer that enable targeted delivery. Layer-by-layer (LbL) microcapsules are assembled using alternate layers of oppositely charged molecules and are potential cell delivery vehicles for applications in nanomedicine. There are a wide variety of charged molecules that can be included in the microcapsule structure including metal nanoparticles that introduce physical attributes. Delivery of bioactive molecules to cells with LbL microcapsules has recently been demonstrated, so in this study we explore the delivery of bioactive molecules (luciferase enzyme and plasmid DNA) to cells using biodegradable microcapsules containing a layer of magnetite nanoparticles. Interestingly, significantly improved intracellular luciferase enzyme activity (25 fold) and increased transfection efficiency with plasmid DNA (3.4 fold) was observed with magnetic microcapsules. The use of a neodymium magnet enabled efficient targeting of magnetic microcapsules which further improved the delivery efficiency of the cargoes as a consequence of increased microcapsule concentration at the magnetic site. Microcapsules were well tolerated by cells in these experiments and only displayed signs of toxicity at a capsule : cell ratio of 100 : 1 and with extended exposure. These studies illustrate how multi-functionalization of LbL microcapsules can improve and target delivery of bioactive molecules to cells.

  16. 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.

  17. Nanodiamonds as novel nanomaterials for biomedical applications: drug delivery and imaging systems

    Directory of Open Access Journals (Sweden)

    Kaur R

    2013-01-01

    Full Text Available Randeep Kaur, Ildiko BadeaDrug Design and Discovery Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, CanadaAbstract: Detonation nanodiamonds (NDs are emerging as delivery vehicles for small chemical drugs and macromolecular biotechnology products due to their primary particle size of 4 to 5 nm, stable inert core, reactive surface, and ability to form hydrogels. Nanoprobe technology capitalizes on the intrinsic fluorescence, high refractive index, and unique Raman signal of the NDs, rendering them attractive for in vitro and in vivo imaging applications. This review provides a brief introduction of the various types of NDs and describes the development of procedures that have led to stable single-digit-sized ND dispersions, a crucial feature for drug delivery systems and nanoprobes. Various approaches used for functionalizing the surface of NDs are highlighted, along with a discussion of their biocompatibility status. The utilization of NDs to provide sustained release and improve the dispersion of hydrophobic molecules, of which chemotherapeutic drugs are the most investigated, is described. The prospects of improving the intracellular delivery of nucleic acids by using NDs as a platform are exemplified. The photoluminescent and optical scattering properties of NDs, together with their applications in cellular labeling, are also reviewed. Considering the progress that has been made in understanding the properties of NDs, they can be envisioned as highly efficient drug delivery and imaging biomaterials for use in animals and humans.Keywords: dispersion, surface functionalization, toxicity, carriers, fluorescence, light scattering

  18. Magnetic nanoparticles: A multifunctional vehicle for modern theranostics.

    Science.gov (United States)

    Angelakeris, M

    2017-06-01

    Magnetic nanoparticles provide a unique multifunctional vehicle for modern theranostics since they can be remotely and non-invasively employed as imaging probes, carrier vectors and smart actuators. Additionally, special delivery schemes beyond the typical drug delivery such as heat or mechanical stress may be magnetically triggered to promote certain cellular pathways. To start with, we need magnetic nanoparticles with several well-defined and reproducible structural, physical, and chemical features, while bio-magnetic nanoparticle design imposes several additional constraints. Except for the intrinsic requirement for high quality of magnetic properties in order to obtain the maximum efficiency with the minimum dose, the surface manipulation of the nanoparticles is a key aspect not only for transferring them from the growth medium to the biological environment but also to bind functional molecules that will undertake specific targeting, drug delivery, cell-specific monitoring and designated treatment without sparing biocompatibility and sustainability in-vivo. The ability of magnetic nanoparticles to interact with matter at the nanoscale not only provides the possibility to ascertain the molecular constituents of a disease, but also the way in which the totality of a biological function may be affected as well. The capacity to incorporate an array of structural and chemical functionalities onto the same nanoscale architecture also enables more accurate, sensitive and precise screening together with cure of diseases with significant pathological heterogeneity such as cancer. This article is part of a Special Issue entitled "Recent Advances in Bionanomaterials" Guest Editor: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Sodium alginate-polyvinyl alcohol-bovin serum albumin coated Fe3O4 nanoparticles as anticancer drug delivery vehicle: Doxorubicin loading and in vitro release study and cytotoxicity to HepG2 and L02 cells.

    Science.gov (United States)

    Prabha, G; Raj, V

    2017-10-01

    The challenging part of this work was to research the potential aspects of sodium alginate (SA)-polyvinyl alcohol (PVA)-bovin serum albumin (BSA) coated Fe 3 O 4 nanoparticles (Fe 3 O 4 -SA-PVA-BSA) as a drug delivery system for doxorubicin (DOX). The anticancer drug doxorubicin was selected as a model drug which is powerful for numerous cancer treatments. Superparamagnetic Fe 3 O 4 nanoparticles were prepared by co-precipitation method. The mixture solution of Fe 3 O 4 -sodium alginate (SA) - doxorubicin (DOX) was crosslinked with Ca 2+ to form (Fe 3 O 4 -SA-DOX) nanoparticles and addition of PVA and BSA with (Fe 3 O 4 -SA-DOX) nanoparticles was prepared by coating procedure. Doxorubicin drug loaded NPs were prepared by a simple crosslinking method by calcium chloride solution. The prepared polymer coated magnetic nanoparticles (Fe 3 O 4 -SA-PVA-BSA) were characterized by using SEM, AFM, FT-IR, XRD and VSM. The mean sizes of the obtained drug loaded nanoparticles (Fe 3 O 4 -SA-DOX, Fe 3 O 4 -SA-DOX-PVA and Fe 3 O 4 -SA-DOX-PVA-BSA) were between 240±8.3 and 460±8.7nm and zeta potential of the particles also was evaluated using Malvern Zetasizer which ranged between -48.1±2.3 and -22.4±4.1mV. The encapsulation efficiency, was between 36.2±0.01 and 96.45±2.12. Moreover drug loading and drug release properties of the polymer coated magnetic nanoparticles loaded with doxorubicin (Fe 3 O 4 -SA-DOX-PVA-BSA) were also studied. In addition, the cytotoxicity of the created nanoparticles was performed by using MTT assay analysis which showed that DOX loaded nanoparticles (Fe 3 O 4 -SA-DOX-PVA-BSA) were toxic to HepG2 cell lines and non-toxic to L02 cell lines. The in-vitro drug release was studied by using UV-Visible spectrophotometer at acidic environment (pH5.0) and basic environment (pH7.4) as well as at different temperatures (37°C and 42°C). It was found that DOX drug is released much faster in acidic environment (pH5.0) than in the basic environment (pH7

  20. A Study of Vehicle Detection and Counting System Based on Video

    Directory of Open Access Journals (Sweden)

    Shuang XU

    2014-10-01

    Full Text Available About the video image processing's vehicle detection and counting system research, which has video vehicle detection, vehicle targets' image processing, and vehicle counting function. Vehicle detection is the use of inter-frame difference method and vehicle shadow segmentation techniques for vehicle testing. Image processing functions is the use of color image gray processing, image segmentation, mathematical morphology analysis and image fills, etc. on target detection to be processed, and then the target vehicle extraction. Counting function is to count the detected vehicle. The system is the use of inter-frame video difference method to detect vehicle and the use of the method of adding frame to vehicle and boundary comparison method to complete the counting function, with high recognition rate, fast, and easy operation. The purpose of this paper is to enhance traffic management modernization and automation levels. According to this study, it can provide a reference for the future development of related applications.

  1. Hydrogen-fueled postal vehicle performance evaluation

    Science.gov (United States)

    Hall, R. A.

    1979-01-01

    Fuel consumption, range, and emissions data were obtained while operating a hydrogen-fueled postal delivery vehicle over a defined Postal Service Driving Cycle and the 1975 Urban Driving Cycle. The vehicle's fuel consumption was 0.366 pounds of hydrogen per mile over the postal driving cycle and 0.22 pounds of hydrogen per mile over the urban driving cycle. These data correspond to 6.2 and 10.6 mpg equivalent gasoline mileage for the two driving cycles, respectively. The vehicle's range was 24.2 miles while being operated on the postal driving cycle. Vehicle emissions were measured over the urban driving cycle. HC and CO emissions were quite low, as would be expected. The oxides of nitrogen were found to be 4.86 gm/mi, a value which is well above the current Federal and California standards. Vehicle limitations discussed include excessive engine flashbacks, inadequate acceleration capability the engine air/fuel ratio, the water injection systems, and the cab temperature. Other concerns are safety considerations, iron-titanium hydride observed in the fuel system, evidence of water in the engine rocker cover, and the vehicle maintenance required during the evaluation.

  2. Causes of visual impairment among commercial motor vehicle ...

    African Journals Online (AJOL)

    Background: Commercial motor vehicles are a very important means of transport in Nigeria where most people do not own personal vehicles and the railway system is not functioning. Aims and Objectives: The aim of the study is to assess the ocular health status of commercial motor vehicle drivers in Uyo metropolis and to ...

  3. Macromolecules for the Delivery of Cancer Chemotherapeutics

    OpenAIRE

    van der Poll, Derek Gregory

    2010-01-01

    Chemotherapy is the practice of treating cancer with antineoplastic drugs. In general, these drugs are highly toxic, and in many patients the side effects from therapy become so severe that treatment is stopped before full tumor remission has occurred. Further, chemotherapeutics usually have poor water solubility and very short circulation lifetimes, which makes it difficult to get a significant fraction of the injected dose to the tumor site. The use of polymers as delivery vehicles for drug...

  4. The Electric Vehicle Development

    DEFF Research Database (Denmark)

    Wang, Jingyu; Liu, Yingqi; Kokko, Ari

    2014-01-01

    In order to respond to the energy crisis and environment problem, countries carry out their research and promotion about electric vehicles. As the ten cities one thousand new energy buses started in 2009, the new energy vehicles have been greatly developed in China, while the development...... of electric vehicles is not that good. This paper selects four cities-Los Angeles, Kanagawa, Hamburg, Amsterdam-that promote electric vehicles successfully and deeply analyzes the development of electric vehicles in these four cities and analyzes the factors that affect the development of electric vehicles...... in three aspects-city environment, government and stakeholders. Then the paper discusses the promotion ways and role of government and consumer. Finally, the paper offers some suggestions to promote electric vehicles in China: focusing on feasibility and adaptability of electric vehicles, playing...

  5. Bridge vehicle impact assessment.

    Science.gov (United States)

    2011-12-01

    Bridges in New York State have been experiencing close to 200 bridge hits a year. These : accidents are attributed to numerous factors including: improperly stored equipment on trucks; : violation of vehicle posting signs; illegal commercial vehicles...

  6. Fuel cells for vehicle applications in cars - bringing the future closer

    Science.gov (United States)

    Panik, Ferdinand

    Among all alternative drive systems, the fuel cell electric propulsion system has the highest potential to compete with the internal combustion engine. For this reason, Daimler-Benz AG has entered into a co-operative alliance with Ballard Power Systems, with the objectives of bringing fuel cell vehicles to the market. Apart from the fuel cell itself, fuel cell vehicles require comprehensive system technology to provide fuel and air supply, cooling, energy management, electric and electronic functions. The system technology determines to a large extent the cost, weight, efficiency, performance and overall customer benefit of fuel cell vehicles. Hence, Daimler-Benz and Ballard are pooling their expertise in fuel cell system technology in a joint company, with the aim of bringing their fuel cell vehicular systems to the stage of maturity required for market entry as early as possible. Hydrogen-fuelled zero-emission fuel cell transit `buses' will be the first market segment addressed, with an emphasis on the North American and European markets. The first buses are already scheduled for delivery to customers in late 1997. Since a liquid fuel like methanol is easier to handle in passenger cars, fuel reforming technologies are developed and will shortly be demonstrated in a prototype, as well. The presentation will cover concepts of fuel cell vehicles with an emphasis on system technology, the related testing procedures and results as well as an outline of market entry strategies.

  7. 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.

  8. Discovery of a Unique Clp Component, ClpF, in Chloroplasts: A Proposed Binary ClpF-ClpS1 Adaptor Complex Functions in Substrate Recognition and Delivery.

    Science.gov (United States)

    Nishimura, Kenji; Apitz, Janina; Friso, Giulia; Kim, Jitae; Ponnala, Lalit; Grimm, Bernhard; van Wijk, Klaas J

    2015-10-01

    Clp proteases are found in prokaryotes, mitochondria, and plastids where they play crucial roles in maintaining protein homeostasis (proteostasis). The plant plastid Clp machinery comprises a hetero-oligomeric ClpPRT proteolytic core, ATP-dependent chaperones ClpC and ClpD, and an adaptor protein, ClpS1. ClpS1 selects substrates to the ClpPR protease-ClpC chaperone complex for degradation, but the underlying substrate recognition and delivery mechanisms are currently unclear. Here, we characterize a ClpS1-interacting protein in Arabidopsis thaliana, ClpF, which can interact with the Clp substrate glutamyl-tRNA reductase. ClpF and ClpS1 mutually stimulate their association with ClpC. ClpF, which is only found in photosynthetic eukaryotes, contains bacterial uvrB/C and YccV protein domains and a unique N-terminal domain. We propose a testable model in which ClpS1 and ClpF form a binary adaptor for selective substrate recognition and delivery to ClpC, reflecting an evolutionary adaptation of the Clp system to the plastid proteome. © 2015 American Society of Plant Biologists. All rights reserved.

  9. Electric Vehicle Charging Modeling

    OpenAIRE

    Grahn, Pia

    2014-01-01

    With an electrified passenger transportation fleet, carbon dioxide emissions could be reduced significantly depending on the electric power production mix. Increased electric power consumption due to electric vehicle charging demands of electric vehicle fleets may be met by increased amount of renewable power production in the electrical systems. With electric vehicle fleets in the transportation system there is a need for establishing an electric vehicle charging infrastructure that distribu...

  10. Bypassing the need for pre-sensitization of cancer cells for anticancer TRAIL therapy with secretion of novel cell penetrable form of Smac from hA-MSCs as cellular delivery vehicle.

    Science.gov (United States)

    Khorashadizadeh, Mohsen; Soleimani, Masoud; Khanahmad, Hossein; Fallah, Ali; Naderi, Mahmood; Khorramizadeh, Mohammadreza

    2015-06-01

    TNF-related apoptosis inducing ligand (TRAIL) is a novel anticancer agent with selective apoptosis-inducing activity on cancer cells. However, many malignant tumors still remain unresponsive. Although cells can bypass apoptosis by different functions, the defect in the blocking role of second mitochondria-derived activator of caspase (Smac) on X-linked inhibitor of apoptosis protein (XIAP) is known to be an important hub for immortal characteristic of malignant cells. Actually, XIAP is known as an apoptosis inhibitor. To date, the sensitization of cancerous cells to TRAIL was successfully performed with different protocols, mainly through blocking XIAP with Smac administration. However, all these sensitization methodologies need to be performed prior to TRAIL administration on cancerous cells which in turn limit their practical application in clinics. Therefore, we hypothesized that concurrent expression of Smac and TRAIL on human adipose-derived mesenchymal stem cells (hA-MSC-ST) could both sensitize and destroy cancerous cells. To this aim, we generated hA-MSC-ST, secreting a novel cell penetrable form of Smac and a trimeric form of TRAIL. Indeed, the cell penetrable form of Smac obviates the need for any pretreatment of cancerous cells. Our data depicted that individual overexpression of TRAIL or Smac in different breast cancer cell types induced limited or no apoptosis, respectively. Conversely, their concomitant overexpression markedly increased cell death even for a resistant type of breast cancer cells, MCF-7. Notably, we observed no cytotoxicity of our methodology on normal cells. In summary, this is the first demonstration that a dual approach using simultaneous overexpression of a cell penetrable form of Smac and TRAIL sensitize and promote apoptotic process even in resistant breast cancer cells.

  11. MRV - Modular Robotic Vehicle

    Science.gov (United States)

    Ridley, Justin; Bluethmann, Bill

    2015-01-01

    The Modular Robotic Vehicle, or MRV, completed in 2013, was developed at the Johnson Space Center in order to advance technologies which have applications for future vehicles both in space and on Earth. With seating for two people, MRV is a fully electric vehicle modeled as a "city car", suited for busy urban environments.

  12. Electric Vehicle Technician

    Science.gov (United States)

    Moore, Pam

    2011-01-01

    With President Obama's goal to have one million electric vehicles (EV) on the road by 2015, the electric vehicle technician should have a promising and busy future. "The job force in the car industry is ramping up for a revitalized green car industry," according to Greencareersguide.com. An electric vehicle technician will safely troubleshoot and…

  13. Automotive vehicle sensors

    Energy Technology Data Exchange (ETDEWEB)

    Sheen, S.H.; Raptis, A.C.; Moscynski, M.J.

    1995-09-01

    This report is an introduction to the field of automotive vehicle sensors. It contains a prototype data base for companies working in automotive vehicle sensors, as well as a prototype data base for automotive vehicle sensors. A market analysis is also included.

  14. Optimal Path Determination for Flying Vehicle to Search an Object

    Science.gov (United States)

    Heru Tjahjana, R.; Heri Soelistyo U, R.; Ratnasari, L.; Irawanto, B.

    2018-01-01

    In this paper, a method to determine optimal path for flying vehicle to search an object is proposed. Background of the paper is controlling air vehicle to search an object. Optimal path determination is one of the most popular problem in optimization. This paper describe model of control design for a flying vehicle to search an object, and focus on the optimal path that used to search an object. In this paper, optimal control model is used to control flying vehicle to make the vehicle move in optimal path. If the vehicle move in optimal path, then the path to reach the searched object also optimal. The cost Functional is one of the most important things in optimal control design, in this paper the cost functional make the air vehicle can move as soon as possible to reach the object. The axis reference of flying vehicle uses N-E-D (North-East-Down) coordinate system. The result of this paper are the theorems which say that the cost functional make the control optimal and make the vehicle move in optimal path are proved analytically. The other result of this paper also shows the cost functional which used is convex. The convexity of the cost functional is use for guarantee the existence of optimal control. This paper also expose some simulations to show an optimal path for flying vehicle to search an object. The optimization method which used to find the optimal control and optimal path vehicle in this paper is Pontryagin Minimum Principle.

  15. A random search algorithm for cyclic delivery synchronization problem

    Directory of Open Access Journals (Sweden)

    Katarzyna Gdowska

    2017-09-01

    Full Text Available Background: The paper is devoted to the cyclic delivery synchronization problem with vehicles serving fixed routes. Each vehicle is assigned to a fixed route: the series of supplier’s and logistic centers to be visited one after another. For each route the service frequency is fixed and known in advance. A vehicle loads at a supplier’s, then it delivers goods to a logistic center and either loads other goods there and delivers them to the next logistic center along the route or goes to another logistic center. Each logistic center can belong to several routes, so goods are delivered there with one vehicle and then they departure for the further journey with another truck. The objective of this cyclic delivery synchronization problem is to maximize the total number of synchronizations of vehicles arrivals in logistic centers and their load times, so that it is possible to organize their arrivals in repeatable blocks. Methods: Basing on the previously developed mathematical model for the cyclic delivery synchronization problem we built a random search algorithm for cyclic delivery synchronization problem. The random heuristic search utilizes objective-oriented randomizing. In the paper the newly-developed random search algorithm for cyclic delivery synchronization problem is presented. Results: A computational experiment consisted of employing the newly-developed random search algorithm for solving a series of cyclic delivery synchronization problems. Results obtained with the algorithm were compared with solutions computed with the exact method. Conclusions: The newly-developed random search algorithm for cyclic delivery synchronization problem gives results which are considerably close to the ones obtained with mixed-integer programming. The main advantage of the algorithm is reduction of computing time; it is relevant for utilization of this method in practice, especially for large-sized problems.

  16. A Comparative Analysis of the Environmental Benefits of Drone-Based Delivery Services in Urban and Rural Areas

    OpenAIRE

    Jiyoon Park; Solhee Kim; Kyo Suh

    2018-01-01

    Unmanned aerial vehicles (UAV, drones) used as delivery vehicles have received increasing attention due to their mobility and accessibility to remote areas. The purpose of this study is to evaluate the environmental impacts of drone versus motorcycle delivery and to compare the expected environmental improvements due to drone delivery in urban and rural areas. In addition, the potential environmental contributions of electric motorcycles were assessed to determine the effects of introducing t...

  17. Rich Vehicle Routing Problems and Applications

    DEFF Research Database (Denmark)

    Wen, Min

    in the sense that consolidation decisions have to be made at the depot and these decisions interact with the planning of pickup and delivery routes. We presented a mathematical model and proposed a Tabu Search based heuristic to solve it. It is shown that the approach can produce near-optimal solutions within...... incrementally over the planning horizon. The delivery plan must be made and executed in every period without knowing the future orders. We modeled the problem as a mixed integer linear program and solved it by means of a three-phase heuristic that works over a rolling planning horizon. The method improves...... are considered, such as the multi-period horizon, the time windows for the delivery, the heterogeneous vehicles, the drivers’ predefined working regulations, the driving rule etc. The problem is formulated as a mixed integer linear program and treated by a multilevel variable neighborhood search algorithm...

  18. Procurement Policy for Armored Vehicles

    National Research Council Canada - National Science Library

    Jolliffe, Richard B; Burton, Bruce A; Carros, Deborah L; Schaefer, Beth K; Truong, Linh; Palmer, Kevin A; Chun, Judy M; Smith, Jessica M; Abraham, Amanda M; Peters, Anthony R

    2007-01-01

    ...., and Armor Holdings, Inc., for armored vehicles. This report addresses armored vehicles, specifically the Buffalo Mine Protected Clearance Vehicle, the Cougar, the Joint Explosive Ordnance Disposal Rapid Response Vehicle (JERRV...

  19. Modeling of electric vehicle battery for vehicle-to-grid applications

    DEFF Research Database (Denmark)

    Pang, Ying; Brady, Cormac; Pellegrino, Giustino

    2013-01-01

    Electric vehicle battery models are essential when performing analysis of EV systems. The battery package of electric vehicles is complicated and unpredictable because of its chemical based functioning. In this paper, a battery model is presented with a number of internal and external factors taken...

  20. Ariane transfer vehicle scenario

    Science.gov (United States)

    Deutscher, Norbert; Cougnet, Claude

    1990-10-01

    ESA's Ariane Transfer Vehicle (ATV) is a vehicle design concept for the transfer of payloads from Ariane 5 launch vehicle orbit insertion to a space station, on the basis of the Ariane 5 program-developed Upper Stage Propulsion Module and Vehicle Equipment Bay. The ATV is conceived as a complement to the Hermes manned vehicle for lower cost unmanned carriage of logistics modules and other large structural elements, as well as waste disposal. It is also anticipated that the ATV will have an essential role in the building block transportation logistics of any prospective European space station.

  1. Space vehicle chassis

    Science.gov (United States)

    Judd, Stephen; Dallmann, Nicholas; Seitz, Daniel; Martinez, John; Storms, Steven; Kestell, Gayle

    2017-07-18

    A modular space vehicle chassis may facilitate convenient access to internal components of the space vehicle. Each module may be removable from the others such that each module may be worked on individually. Multiple panels of at least one of the modules may swing open or otherwise be removable, exposing large portions of the internal components of the space vehicle. Such chassis architectures may reduce the time required for and difficulty of performing maintenance or modifications, may allow multiple space vehicles to take advantage of a common chassis design, and may further allow for highly customizable space vehicles.

  2. VEHICLE FOR SLAVE ROBOT

    Science.gov (United States)

    Goertz, R.C.; Lindberg, J.F.

    1962-01-30

    A reeling device is designed for an electrical cable supplying power to the slave slde of a remote control manipulator mounted on a movable vehicle. As the vehicle carries the slave side about in a closed room, the device reels the cable in and out to maintain a variable length of the cable between the vehicle and a cable inlet in the wall of the room. The device also handles a fixed length of cable between the slave side and the vehicle, in spite of angular movement of the slave side with respect to the vehicle. (AEC)

  3. Hyaluronic acid functional amphipathic and redox-responsive polymer particles for the co-delivery of doxorubicin and cyclopamine to eradicate breast cancer cells and cancer stem cells

    Science.gov (United States)

    Hu, Kelei; Zhou, Huige; Liu, Ying; Liu, Zhu; Liu, Jing; Tang, Jinglong; Li, Jiayang; Zhang, Jiakun; Sheng, Wang; Zhao, Yuliang; Wu, Yan; Chen, Chunying

    2015-04-01

    Cancer stem cells (CSCs) have the ability to transform into bulk cancer cells, to promote tumor growth and establish tumor metastasis. To effectively inhibit tumor growth and prevent metastasis, treatments with conventional chemotherapy drugs should be combined with CSC targeted drugs. In this study, we describe the synthesis and characterization of a new amphiphilic polymer, hyaluronic acid-cystamine-polylactic-co-glycolic acid (HA-SS-PLGA), composed of a hydrophobic PLGA head and a hydrophilic HA segment linked by a bioreducible disulfide bond. With a double emulsion method, a nano delivery system was constructed to deliver doxorubicin (DOX) and cyclopamine (CYC, a primary inhibitor of the hedgehog signaling pathway of CSCs) to both a CD44-overexpressing breast CSC subpopulation and bulk breast cancer cells and allow an on-demand release. The resulting drug-loaded NPs exhibited a redox-responsive drug release profile. Dual drug-loaded particles potently diminished the number and size of tumorspheres and HA showed a targeting effect towards breast CSCs. In vivo combination therapy further demonstrated a remarkable synergistic anti-tumor effect and prolonged survival compared to mono-therapy using the orthotopic mammary fat pad tumor growth model. The co-delivery of drug and the CSC specific inhibitor towards targeted cancer chemotherapeutics provides an insight into anticancer strategy with facile control and high efficacy.Cancer stem cells (CSCs) have the ability to transform into bulk cancer cells, to promote tumor growth and establish tumor metastasis. To effectively inhibit tumor growth and prevent metastasis, treatments with conventional chemotherapy drugs should be combined with CSC targeted drugs. In this study, we describe the synthesis and characterization of a new amphiphilic polymer, hyaluronic acid-cystamine-polylactic-co-glycolic acid (HA-SS-PLGA), composed of a hydrophobic PLGA head and a hydrophilic HA segment linked by a bioreducible disulfide bond

  4. Ultrasound triggered image-guided drug delivery

    International Nuclear Information System (INIS)

    Boehmer, Marcel R.; Klibanov, Alexander L.; Tiemann, Klaus; Hall, Christopher S.; Gruell, Holger; Steinbach, Oliver C.

    2009-01-01

    The integration of therapeutic interventions with diagnostic imaging has been recognized as one of the next technological developments that will have a major impact on medical treatments. Important advances in this field are based on a combination of progress in guiding and monitoring ultrasound energy, novel drug classes becoming available, the development of smart delivery vehicles, and more in depth understanding of the mechanisms of the cellular and molecular basis of diseases. Recent research demonstrates that both pressure sensitive and temperature sensitive delivery systems hold promise for local treatment. The use of ultrasound for the delivery of drugs has been demonstrated in particular the field of cardiology and oncology for a variety of therapeutics ranging from small drug molecules to biologics and nucleic acids.

  5. Synthesis, characterization and in vitro study of biocompatible cinnamaldehyde functionalized magnetite nanoparticles (CPGF Nps) for hyperthermia and drug delivery applications in breast cancer.

    Science.gov (United States)

    Wani, Kirtee D; Kadu, Brijesh S; Mansara, Prakash; Gupta, Preeti; Deore, Avinash V; Chikate, Rajeev C; Poddar, Pankaj; Dhole, Sanjay D; Kaul-Ghanekar, Ruchika

    2014-01-01

    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. 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.

  7. Determining the lowest-cost hydrogen delivery mode

    OpenAIRE

    Yang, Christopher; Ogden, Joan M

    2007-01-01

    Hydrogen delivery is a critical contributor to the cost, energy use and emissions associated with hydrogen pathways involving central plant production. The choice of the lowest-cost delivery mode (compressed gas trucks, cryogenic liquid trucks or gas pipelines) will depend upon specific geographic and market characteristics (e.g. city population and radius, population density, size and number of refueling stations and market penetration of fuel cell vehicles). We developed models to character...

  8. Seaweed Polysaccharide-Based Nanoparticles: Preparation and Applications for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Jayachandran Venkatesan

    2016-01-01

    Full Text Available In recent years, there have been major advances and increasing amounts of research on the utilization of natural polymeric materials as drug delivery vehicles due to their biocompatibility and biodegradability. Seaweed polysaccharides are abundant resources and have been extensively studied for several biological, biomedical, and functional food applications. The exploration of seaweed polysaccharides for drug delivery applications is still in its infancy. Alginate, carrageenan, fucoidan, ulvan, and laminarin are polysaccharides commonly isolated from seaweed. These natural polymers can be converted into nanoparticles (NPs by different types of methods, such as ionic gelation, emulsion, and polyelectrolyte complexing. Ionic gelation and polyelectrolyte complexing are commonly employed by adding cationic molecules to these anionic polymers to produce NPs of a desired shape, size, and charge. In the present review, we have discussed the preparation of seaweed polysaccharide-based NPs using different types of methods as well as their usage as carriers for the delivery of various therapeutic molecules (e.g., proteins, peptides, anti-cancer drugs, and antibiotics. Seaweed polysaccharide-based NPs exhibit suitable particle size, high drug encapsulation, and sustained drug release with high biocompatibility, thereby demonstrating their high potential for safe and efficient drug delivery.

  9. Nanodiamonds as novel nanomaterials for biomedical applications: drug delivery and imaging systems.

    Science.gov (United States)

    Kaur, Randeep; Badea, Ildiko

    2013-01-01

    Detonation nanodiamonds (NDs) are emerging as delivery vehicles for small chemical drugs and macromolecular biotechnology products due to their primary particle size of 4 to 5 nm, stable inert core, reactive surface, and ability to form hydrogels. Nanoprobe technology capitalizes on the intrinsic fluorescence, high refractive index, and unique Raman signal of the NDs, rendering them attractive for in vitro and in vivo imaging applications. This review provides a brief introduction of the various types of NDs and describes the development of procedures that have led to stable single-digit-sized ND dispersions, a crucial feature for drug delivery systems and nanoprobes. Various approaches used for functionalizing the surface of NDs are highlighted, along with a discussion of their biocompatibility status. The utilization of NDs to provide sustained release and improve the dispersion of hydrophobic molecules, of which chemotherapeutic drugs are the most investigated, is described. The prospects of improving the intracellular delivery of nucleic acids by using NDs as a platform are exemplified. The photoluminescent and optical scattering properties of NDs, together with their applications in cellular labeling, are also reviewed. Considering the progress that has been made in understanding the properties of NDs, they can be envisione