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Sample records for proton delivery system

  1. Commissioning of the discrete spot scanning proton beam delivery system at University of Texas M.D. Anderson Cancer Center, Proton Therapy Center, Houston

    SciTech Connect

    Gillin, Michael T.; Sahoo, Narayan; Bues, Martin; Ciangaru, George; Sawakuchi, Gabriel; Poenisch, Falk; Arjomandy, Bijan; Martin, Craig; Titt, Uwe; Suzuki, Kazumichi; Smith, Alfred R.; Zhu, X. Ronald

    2010-01-15

    Purpose: To describe a summary of the clinical commissioning of the discrete spot scanning proton beam at the Proton Therapy Center, Houston (PTC-H). Methods: Discrete spot scanning system is composed of a delivery system (Hitachi ProBeat), an electronic medical record (Mosaiq V 1.5), and a treatment planning system (TPS) (Eclipse V 8.1). Discrete proton pencil beams (spots) are used to deposit dose spot by spot and layer by layer for the proton distal ranges spanning from 4.0 to 30.6 g/cm{sup 2} and over a maximum scan area at the isocenter of 30x30 cm{sup 2}. An arbitrarily chosen reference calibration condition has been selected to define the monitor units (MUs). Using radiochromic film and ion chambers, the authors have measured spot positions, the spot sizes in air, depth dose curves, and profiles for proton beams with various energies in water, and studied the linearity of the dose monitors. In addition to dosimetric measurements and TPS modeling, significant efforts were spent in testing information flow and recovery of the delivery system from treatment interruptions. Results: The main dose monitors have been adjusted such that a specific amount of charge is collected in the monitor chamber corresponding to a single MU, following the IAEA TRS 398 protocol under a specific reference condition. The dose monitor calibration method is based on the absolute dose per MU, which is equivalent to the absolute dose per particle, the approach used by other scanning beam institutions. The full width at half maximum for the spot size in air varies from approximately 1.2 cm for 221.8 MeV to 3.4 cm for 72.5 MeV. The measured versus requested 90% depth dose in water agrees to within 1 mm over ranges of 4.0-30.6 cm. The beam delivery interlocks perform as expected, guarantying the safe and accurate delivery of the planned dose. Conclusions: The dosimetric parameters of the discrete spot scanning proton beam have been measured as part of the clinical commissioning program

  2. Neutron production from beam-modifying devices in a modern double scattering proton therapy beam delivery system

    PubMed Central

    Pérez-Andújar, Angélica; Newhauser, Wayne D; DeLuca, Paul M

    2014-01-01

    In this work the neutron production in a passive beam delivery system was investigated. Secondary particles including neutrons are created as the proton beam interacts with beam shaping devices in the treatment head. Stray neutron exposure to the whole body may increase the risk that the patient develops a radiogenic cancer years or decades after radiotherapy. We simulated a passive proton beam delivery system with double scattering technology to determine the neutron production and energy distribution at 200 MeV proton energy. Specifically, we studied the neutron absorbed dose per therapeutic absorbed dose, the neutron absorbed dose per source particle and the neutron energy spectrum at various locations around the nozzle. We also investigated the neutron production along the nozzle's central axis. The absorbed doses and neutron spectra were simulated with the MCNPX Monte Carlo code. The simulations revealed that the range modulation wheel (RMW) is the most intense neutron source of any of the beam spreading devices within the nozzle. This finding suggests that it may be helpful to refine the design of the RMW assembly, e.g., by adding local shielding, to suppress neutron-induced damage to components in the nozzle and to reduce the shielding thickness of the treatment vault. The simulations also revealed that the neutron dose to the patient is predominated by neutrons produced in the field defining collimator assembly, located just upstream of the patient. PMID:19147903

  3. Delivery Systems.

    ERIC Educational Resources Information Center

    Hutchison, Betty

    This paper on delivery systems for preparing and training early childhood educators focuses on three main topics: (1) adequacy of delivery systems and access; (2) market influences on delivery systems; and (3) linking preparation and professional development components. Questions addressed include the following: Would the current preparation and…

  4. Measurements of lateral penumbra for uniform scanning proton beams under various beam delivery conditions and comparison to the XiO treatment planning system

    SciTech Connect

    Rana, Suresh; Zeidan, Omar; Ramirez, Eric; Rains, Michael; Gao, Junfang; Zheng, Yuanshui

    2013-09-15

    Purpose: The main purposes of this study were to (1) investigate the dependency of lateral penumbra (80%–20% distance) of uniform scanning proton beams on various factors such as air gap, proton range, modulation width, compensator thickness, and depth, and (2) compare the lateral penumbra calculated by a treatment planning system (TPS) with measurements.Methods: First, lateral penumbra was measured using solid–water phantom and radiographic films for (a) air gap, ranged from 0 to 35 cm, (b) proton range, ranged from 8 to 30 cm, (c) modulation, ranged from 2 to 10 cm, (d) compensator thickness, ranged from 0 to 20 cm, and (e) depth, ranged from 7 to 15 cm. Second, dose calculations were computed in a virtual water phantom using the XiO TPS with pencil beam algorithm for identical beam conditions and geometrical configurations that were used for the measurements. The calculated lateral penumbra was then compared with the measured one for both the horizontal and vertical scanning magnets of our uniform scanning proton beam delivery system.Results: The results in the current study showed that the lateral penumbra of horizontal scanning magnet was larger (up to 1.4 mm for measurement and up to 1.0 mm for TPS) compared to that of vertical scanning magnet. Both the TPS and measurements showed an almost linear increase in lateral penumbra with increasing air gap as it produced the greatest effect on lateral penumbra. Lateral penumbra was dependent on the depth and proton range. Specifically, the width of lateral penumbra was found to be always lower at shallower depth than at deeper depth within the spread out Bragg peak (SOBP) region. The lateral penumbra results were less sensitive to the variation in the thickness of compensator, whereas lateral penumbra was independent of modulation. Overall, the comparison between the results of TPS with that of measurements indicates a good agreement for lateral penumbra, with TPS predicting higher values compared to

  5. A Case Study in Proton Pencil-Beam Scanning Delivery

    SciTech Connect

    Kooy, Hanne M.; Clasie, Benjamin M.; Lu, H.-M.; Madden, Thomas M.; Bentefour, Hassan; Depauw, Nicolas M.S.; Adams, Judy A.; Trofimov, Alexei V.; Demaret, Denis; Delaney, Thomas F.; Flanz, Jacob B.

    2010-02-01

    Purpose: We completed an implementation of pencil-beam scanning (PBS), a technology whereby a focused beam of protons, of variable intensity and energy, is scanned over a plane perpendicular to the beam axis and in depth. The aim of radiotherapy is to improve the target to healthy tissue dose differential. We illustrate how PBS achieves this aim in a patient with a bulky tumor. Methods and Materials: Our first deployment of PBS uses 'broad' pencil-beams ranging from 20 to 35 mm (full-width-half-maximum) over the range interval from 32 to 7 g/cm{sup 2}. Such beam-brushes offer a unique opportunity for treating bulky tumors. We present a case study of a large (4,295 cc clinical target volume) retroperitoneal sarcoma treated to 50.4 Gy relative biological effectiveness (RBE) (presurgery) using a course of photons and protons to the clinical target volume and a course of protons to the gross target volume. Results: We describe our system and present the dosimetry for all courses and provide an interdosimetric comparison. Discussion: The use of PBS for bulky targets reduces the complexity of treatment planning and delivery compared with collimated proton fields. In addition, PBS obviates, especially for cases as presented here, the significant cost incurred in the construction of field-specific hardware. PBS offers improved dose distributions, reduced treatment time, and reduced cost of treatment.

  6. Systems and Components Fuel Delivery System, Water Delivery System, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Systems and Components - Fuel Delivery System, Water Delivery System, Derrick Crane System, and Crane System Details - Marshall Space Flight Center, F-1 Engine Static Test Stand, On Route 565 between Huntsville and Decatur, Huntsville, Madison County, AL

  7. A p-Hydroxyphenacyl-Benzothiazole-Chlorambucil Conjugate as a Real-Time-Monitoring Drug-Delivery System Assisted by Excited-State Intramolecular Proton Transfer.

    PubMed

    Barman, Shrabani; Mukhopadhyay, Sourav K; Biswas, Sandipan; Nandi, Surajit; Gangopadhyay, Moumita; Dey, Satyahari; Anoop, Anakuthil; Pradeep Singh, N D

    2016-03-18

    Among the well-known phototriggers, the p-hydroxyphenacyl (pHP) group has consistently enabled the very fast, efficient, and high-conversion release of active molecules. Despite this unique behavior, the pHP group has been ignored as a delivery agent, particularly in the area of theranostics, because of two major limitations: Its excitation wavelength is below 400 nm, and it is nonfluorescent. We have overcome these limitations by incorporating a 2-(2'-hydroxyphenyl)benzothiazole (HBT) appendage capable of rapid excited-state intramolecular proton transfer (ESIPT). The ESIPT effect also provided two unique advantages: It assisted the deprotonation of the pHP group for faster release, and it was accompanied by a distinct fluorescence color change upon photorelease. In vitro studies showed that the p-hydroxyphenacyl-benzothiazole-chlorambucil conjugate presents excellent properties, such as real-time monitoring, photoregulated drug delivery, and biocompatibility. PMID:26919455

  8. Treatment planning, optimization, and beam delivery technqiues for intensity modulated proton therapy

    NASA Astrophysics Data System (ADS)

    Sengbusch, Evan R.

    Physical properties of proton interactions in matter give them a theoretical advantage over photons in radiation therapy for cancer treatment, but they are seldom used relative to photons. The primary barriers to wider acceptance of proton therapy are the technical feasibility, size, and price of proton therapy systems. Several aspects of the proton therapy landscape are investigated, and new techniques for treatment planning, optimization, and beam delivery are presented. The results of these investigations suggest a means by which proton therapy can be delivered more efficiently, effectively, and to a much larger proportion of eligible patients. An analysis of the existing proton therapy market was performed. Personal interviews with over 30 radiation oncology leaders were conducted with regard to the current and future use of proton therapy. In addition, global proton therapy market projections are presented. The results of these investigations serve as motivation and guidance for the subsequent development of treatment system designs and treatment planning, optimization, and beam delivery methods. A major factor impacting the size and cost of proton treatment systems is the maximum energy of the accelerator. Historically, 250 MeV has been the accepted value, but there is minimal quantitative evidence in the literature that supports this standard. A retrospective study of 100 patients is presented that quantifies the maximum proton kinetic energy requirements for cancer treatment, and the impact of those results with regard to treatment system size, cost, and neutron production is discussed. This study is subsequently expanded to include 100 cranial stereotactic radiosurgery (SRS) patients, and the results are discussed in the context of a proposed dedicated proton SRS treatment system. Finally, novel proton therapy optimization and delivery techniques are presented. Algorithms are developed that optimize treatment plans over beam angle, spot size, spot spacing

  9. Nanosize drug delivery system.

    PubMed

    Mukherjee, Biswajit

    2013-01-01

    Nanosize materials provide hopes, speculations and chances for an unprecedented change in drug delivery in near future. Nanotechnology is an emerging field to produce nanomaterials for drug delivery that can offer a new tool, opportunities and scope to provide more focused and fine-tuned treatment of diseases at a molecular level, enhancing the therapeutic potential of drugs so that they become less toxic and more effective. Nanodimensional drug delivery systems are of great scientific interest as they project their tremendous utility because of their capability of altering biodistribution of therapeutic agents so that they can concentrate more in the target tissues. Nanosize drug delivery systems generally focus on formulating bioactive molecules in biocompatible nanosystems such as nanocrystals, solid lipid nanoparticles, nanostructure lipid carriers, lipid drug conjugates, nanoliposomes, dendrimers, nanoshells, emulsions, nanotubes, quantum dots etc. Extensively versatile molecules like synthetic chemicals to naturally occurring complex macromolecules such as nucleic acids and proteins could be dispensed in such formulations maintaining their stability and efficacy. Empty viral capsids are being tried to deliver drug as these uniformly sized bionanomaterials can be utilized to load drug to improve solubility, reduce toxicity and provide site specific targeting. Nanomedicines offer a wide scope for delivery of smart materials from tissue engineering to more recently artificial RBCs. Nanocomposites are the future hope for tailored and personalized medicines as well as for bone repairing and rectification of cartilage impairment. Nanosize drug delivery systems are addressing the challenges to overcome the delivery problems of wide ranges of drugs through their narrow submicron particle size range, easily manipulatable surface characteristics in achievement of versatile tissue targeting (includes active and passive drug targeting), controlled and sustained drug

  10. SU-D-304-04: Pre-Clinical Feasibility Study for Intensity Modulated Grid Proton Therapy (IMgPT) Using a Newly Developed Delivery System

    SciTech Connect

    Tsiamas, P; Moskvin, V; Shin, J; Axente, M; Pirlepesov, F; Krasin, M; Merchant, T; Farr, J

    2015-06-15

    Purpose: The purpose of the current study was to characterize and evaluate intensity-modulated proton grid therapy (IMgPT) using a clinical proton beam. Methods: A TOPAS MC model of a new developmental mode (pre-clinical) of the Hitachi proton therapy system (PROBEAT) was used for simulation and characterization of proton grid therapy. TOPAS simulations of different energy ranges, depths and spot separation distances were performed. LET spectra for various energies and depths were produced with FLUKA MC code for evaluation potential interplay between planning parameters and their effect on the characterization of areas (valley) between spots. IMgPT planning aspects (spot spacing, skin dose, peak-to-valley ratios, beam selection, etc.) were evaluated for different phantom and patient cases. Raysearch software (v4.51) was used to perform the evaluation. Results: Calculated beam peak-to-valley ratios scenarios showed strong energy and depth dependence with ratios to be larger for higher energies and shallower depths. Peak-to-valley ratios for R90 range and for spot spacing of 1cm varied from 30% (E = 221.3 MeV, depth 30.6 cm) to 80% (E = 70.3 MeV, depth 4 cm). LET spectra calculations showed spectral hardening with depth, which might potential increase, spot separation distance and improve peak-to-valley ratios. IMgPT optimization, using constant spot spacing, showed skin dose reduction between peak regions of dose due to the irradiation of less skin. Single beam for bulky shallower tumors might be a potential candidate for proton grid therapy. Conclusions: Proton grid therapy using a clinical beam is a promising technique that reduces skin dose between peak regions of dose and may be suitable for the treatment of shallow tumors. IMgPT may be considered for use when bystander effects in off peak regions would be appropriate.

  11. Proton driver power supply system

    SciTech Connect

    C. Jach and D. Wolff

    2002-06-03

    This paper describes magnet power supply system for a proposed Proton Driver at Fermilab. The magnet power supply system consists of resonant dipole/quadrupole power supply system, quadrupole tracking, dipole correction (horizontal and vertical) and sextupole power supply systems. This paper also describes preliminary design of the power distribution system supplying 13.8 kV power to all proton Driver electrical systems.

  12. Educational Telecommunications Delivery Systems.

    ERIC Educational Resources Information Center

    Curtis, John A., Ed.; Biedenbach, Joseph M., Ed.

    This monograph is a single volume reference manual providing an overall review of the current status and likely near future application of six major educational telecommunications delivery technologies. The introduction provides an overview to the usage and potential for these systems in the context of the major educational issues involved. Each…

  13. Commissioning a passive-scattering proton therapy nozzle for accurate SOBP delivery

    PubMed Central

    Engelsman, M.; Lu, H.-M.; Herrup, D.; Bussiere, M.; Kooy, H. M.

    2009-01-01

    Proton radiotherapy centers that currently use passively scattered proton beams do field specific calibrations for a non-negligible fraction of treatment fields, which is time and resource consuming. Our improved understanding of the passive scattering mode of the IBA universal nozzle, especially of the current modulation function, allowed us to re-commission our treatment control system for accurate delivery of SOBPs of any range and modulation, and to predict the output for each of these fields. We moved away from individual field calibrations to a state where continued quality assurance of SOBP field delivery is ensured by limited system-wide measurements that only require one hour per week. This manuscript reports on a protocol for generation of desired SOBPs and prediction of dose output. PMID:19610306

  14. Mucoadhesive drug delivery systems

    PubMed Central

    Shaikh, Rahamatullah; Raj Singh, Thakur Raghu; Garland, Martin James; Woolfson, A David; Donnelly, Ryan F.

    2011-01-01

    Mucoadhesion is commonly defined as the adhesion between two materials, at least one of which is a mucosal surface. Over the past few decades, mucosal drug delivery has received a great deal of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release for improved therapeutic outcome. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, and finally various mucoadhesive drug delivery systems (buccal, nasal, ocular, gastro, vaginal, and rectal). PMID:21430958

  15. MEMS: Enabled Drug Delivery Systems.

    PubMed

    Cobo, Angelica; Sheybani, Roya; Meng, Ellis

    2015-05-01

    Drug delivery systems play a crucial role in the treatment and management of medical conditions. Microelectromechanical systems (MEMS) technologies have allowed the development of advanced miniaturized devices for medical and biological applications. This Review presents the use of MEMS technologies to produce drug delivery devices detailing the delivery mechanisms, device formats employed, and various biomedical applications. The integration of dosing control systems, examples of commercially available microtechnology-enabled drug delivery devices, remaining challenges, and future outlook are also discussed.

  16. Nanovehicular Intracellular Delivery Systems

    PubMed Central

    PROKOP, ALES; DAVIDSON, JEFFREY M.

    2013-01-01

    This article provides an overview of principles and barriers relevant to intracellular drug and gene transport, accumulation and retention (collectively called as drug delivery) by means of nanovehicles (NV). The aim is to deliver a cargo to a particular intracellular site, if possible, to exert a local action. Some of the principles discussed in this article apply to noncolloidal drugs that are not permeable to the plasma membrane or to the blood–brain barrier. NV are defined as a wide range of nanosized particles leading to colloidal objects which are capable of entering cells and tissues and delivering a cargo intracelullarly. Different localization and targeting means are discussed. Limited discussion on pharmacokinetics and pharmacodynamics is also presented. NVs are contrasted to micro-delivery and current nanotechnologies which are already in commercial use. Newer developments in NV technologies are outlined and future applications are stressed. We also briefly review the existing modeling tools and approaches to quantitatively describe the behavior of targeted NV within the vascular and tumor compartments, an area of particular importance. While we list “elementary” phenomena related to different level of complexity of delivery to cancer, we also stress importance of multi-scale modeling and bottom-up systems biology approach. PMID:18200527

  17. Novel antigen delivery systems

    PubMed Central

    Trovato, Maria; Berardinis, Piergiuseppe De

    2015-01-01

    Vaccines represent the most relevant contribution of immunology to human health. However, despite the remarkable success achieved in the past years, many vaccines are still missing in order to fight important human pathologies and to prevent emerging and re-emerging diseases. For these pathogens the known strategies for making vaccines have been unsuccessful and thus, new avenues should be investigated to overcome the failure of clinical trials and other important issues including safety concerns related to live vaccines or viral vectors, the weak immunogenicity of subunit vaccines and side effects associated with the use of adjuvants. A major hurdle of developing successful and effective vaccines is to design antigen delivery systems in such a way that optimizes antigen presentation and induces broad protective immune responses. Recent advances in vector delivery technologies, immunology, vaccinology and system biology, have led to a deeper understanding of the molecular and cellular mechanisms by which vaccines should stimulate both arms of the adaptive immune responses, offering new strategies of vaccinations. This review is an update of current strategies with respect to live attenuated and inactivated vaccines, DNA vaccines, viral vectors, lipid-based carrier systems such as liposomes and virosomes as well as polymeric nanoparticle vaccines and virus-like particles. In addition, this article will describe our work on a versatile and immunogenic delivery system which we have studied in the past decade and which is derived from a non-pathogenic prokaryotic organism: the “E2 scaffold” of the pyruvate dehydrogenase complex from Geobacillus stearothermophilus. PMID:26279977

  18. Secondary fuel delivery system

    DOEpatents

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

    2010-02-23

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

  19. Shortening Delivery Times of Intensity Modulated Proton Therapy by Reducing Proton Energy Layers During Treatment Plan Optimization

    SciTech Connect

    Water, Steven van de; Kooy, Hanne M.; Heijmen, Ben J.M.; Hoogeman, Mischa S.

    2015-06-01

    Purpose: To shorten delivery times of intensity modulated proton therapy by reducing the number of energy layers in the treatment plan. Methods and Materials: We have developed an energy layer reduction method, which was implemented into our in-house-developed multicriteria treatment planning system “Erasmus-iCycle.” The method consisted of 2 components: (1) minimizing the logarithm of the total spot weight per energy layer; and (2) iteratively excluding low-weighted energy layers. The method was benchmarked by comparing a robust “time-efficient plan” (with energy layer reduction) with a robust “standard clinical plan” (without energy layer reduction) for 5 oropharyngeal cases and 5 prostate cases. Both plans of each patient had equal robust plan quality, because the worst-case dose parameters of the standard clinical plan were used as dose constraints for the time-efficient plan. Worst-case robust optimization was performed, accounting for setup errors of 3 mm and range errors of 3% + 1 mm. We evaluated the number of energy layers and the expected delivery time per fraction, assuming 30 seconds per beam direction, 10 ms per spot, and 400 Giga-protons per minute. The energy switching time was varied from 0.1 to 5 seconds. Results: The number of energy layers was on average reduced by 45% (range, 30%-56%) for the oropharyngeal cases and by 28% (range, 25%-32%) for the prostate cases. When assuming 1, 2, or 5 seconds energy switching time, the average delivery time was shortened from 3.9 to 3.0 minutes (25%), 6.0 to 4.2 minutes (32%), or 12.3 to 7.7 minutes (38%) for the oropharyngeal cases, and from 3.4 to 2.9 minutes (16%), 5.2 to 4.2 minutes (20%), or 10.6 to 8.0 minutes (24%) for the prostate cases. Conclusions: Delivery times of intensity modulated proton therapy can be reduced substantially without compromising robust plan quality. Shorter delivery times are likely to reduce treatment uncertainties and costs.

  20. Evaluation of monitor unit calculation based on measurement and calculation with a simplified Monte Carlo method for passive beam delivery system in proton beam therapy.

    PubMed

    Hotta, Kenji; Kohno, Ryosuke; Nagafuchi, Kohsuke; Yamaguchi, Hidenori; Tansho, Ryohei; Takada, Yoshihisa; Akimoto, Tetsuo

    2015-01-01

    Calibrating the dose per monitor unit (DMU) for individual patients is important to deliver the prescribed dose in radiation therapy. We have developed a DMU calculation method combining measurement data and calculation with a simplified Monte Carlo method for the double scattering system in proton beam therapy at the National Cancer Center Hospital East in Japan. The DMU calculation method determines the clinical DMU by the multiplication of three factors: a beam spreading device factor FBSD, a patient-specific device factor FPSD, and a field-size correction factor FFS(A). We compared the calculated and the measured DMU for 75 dose fields in clinical cases. The calculated DMUs were in agreement with measurements in ± 1.5% for all of 25 fields in prostate cancer cases, and in ± 3% for 94% of 50 fields in head and neck (H&N) and lung cancer cases, including irregular shape fields and small fields. Although the FBSD in the DMU calculations is dominant as expected, we found that the patient-specific device factor and field-size correction also contribute significantly to the calculated DMU. This DMU calculation method will be able to substitute the conventional DMU measurement for the majority of clinical cases with a reasonable calculation time required for clinical use. PMID:26699303

  1. WE-D-17A-03: Improvement of Accuracy of Spot-Scanning Proton Beam Delivery for Liver Tumor by Real-Time Tumor-Monitoring and Gating System: A Simulation Study

    SciTech Connect

    Matsuura, T; Shimizu, S; Miyamoto, N; Takao, S; Toramatsu, C; Nihongi, H; Yamada, T; Shirato, H; Fujii, Y; Umezawa, M; Umegaki, K

    2014-06-15

    Purpose: To improve the accuracy of spot-scanning proton beam delivery for target in motion, a real-time tumor-monitoring and gating system using fluoroscopy images was developed. This study investigates the efficacy of this method for treatment of liver tumors using simulation. Methods: Three-dimensional position of a fiducial marker inserted close to the tumor is calculated in real time and proton beam is gated according to the marker's distance from the planned position (Shirato, 2012). The efficient beam delivery is realized even for the irregular and sporadic motion signals, by employing the multiple-gated irradiations per operation cycle (Umezawa, 2012). For each of two breath-hold CTs (CTV=14.6cc, 63.1cc), dose distributions were calculated with internal margins corresponding to freebreathing (FB) and real-time gating (RG) with a 2-mm gating window. We applied 8 trajectories of liver tumor recorded during the treatment of RTRT in X-ray therapy and 6 initial timings. Dmax/Dmin in CTV, mean liver dose (MLD), and irradiation time to administer 3 Gy (RBE) dose were estimated assuming rigid motion of targets by using in-house simulation tools and VQA treatment planning system (Hitachi, Ltd., Tokyo). Results: Dmax/Dmin was degraded by less than 5% compared to the prescribed dose with all motion parameters for smaller CTV and less than 7% for larger CTV with one exception. Irradiation time showed only a modest increase if RG was used instead of FB; the average value over motion parameters was 113 (FB) and 138 s (RG) for smaller CTV and 120 (FB) and 207 s (RG) for larger CTV. In RG, it was within 5 min for all but one trajectory. MLD was markedly decreased by 14% and 5–6% for smaller and larger CTVs respectively, if RG was applied. Conclusions: Spot-scanning proton beam was shown to be delivered successfully to liver tumor without much lengthening of treatment time. This research was supported by the Cabinet Office, Government of Japan and the Japan Society for

  2. Proton beam therapy control system

    DOEpatents

    Baumann, Michael A; Beloussov, Alexandre V; Bakir, Julide; Armon, Deganit; Olsen, Howard B; Salem, Dana

    2013-06-25

    A tiered communications architecture for managing network traffic in a distributed system. Communication between client or control computers and a plurality of hardware devices is administered by agent and monitor devices whose activities are coordinated to reduce the number of open channels or sockets. The communications architecture also improves the transparency and scalability of the distributed system by reducing network mapping dependence. The architecture is desirably implemented in a proton beam therapy system to provide flexible security policies which improve patent safety and facilitate system maintenance and development.

  3. Proton beam therapy control system

    DOEpatents

    Baumann, Michael A.; Beloussov, Alexandre V.; Bakir, Julide; Armon, Deganit; Olsen, Howard B.; Salem, Dana

    2008-07-08

    A tiered communications architecture for managing network traffic in a distributed system. Communication between client or control computers and a plurality of hardware devices is administered by agent and monitor devices whose activities are coordinated to reduce the number of open channels or sockets. The communications architecture also improves the transparency and scalability of the distributed system by reducing network mapping dependence. The architecture is desirably implemented in a proton beam therapy system to provide flexible security policies which improve patent safety and facilitate system maintenance and development.

  4. Proton beam therapy control system

    DOEpatents

    Baumann, Michael A.; Beloussov, Alexandre V.; Bakir, Julide; Armon, Deganit; Olsen, Howard B.; Salem, Dana

    2010-09-21

    A tiered communications architecture for managing network traffic in a distributed system. Communication between client or control computers and a plurality of hardware devices is administered by agent and monitor devices whose activities are coordinated to reduce the number of open channels or sockets. The communications architecture also improves the transparency and scalability of the distributed system by reducing network mapping dependence. The architecture is desirably implemented in a proton beam therapy system to provide flexible security policies which improve patent safety and facilitate system maintenance and development.

  5. Proton beam therapy control system

    DOEpatents

    Baumann, Michael A; Beloussov, Alexandre V; Bakir, Julide; Armon, Deganit; Olsen, Howard B; Salem, Dana

    2013-12-03

    A tiered communications architecture for managing network traffic in a distributed system. Communication between client or control computers and a plurality of hardware devices is administered by agent and monitor devices whose activities are coordinated to reduce the number of open channels or sockets. The communications architecture also improves the transparency and scalability of the distributed system by reducing network mapping dependence. The architecture is desirably implemented in a proton beam therapy system to provide flexible security policies which improve patent safety and facilitate system maintenance and development.

  6. Why new delivery systems?

    PubMed

    Calkins, J M

    1984-01-01

    Although anesthetists have accomplished a remarkable safety record with commercially available anesthetic machines, these results have been obtained in spite of machine design, which could best be described as a nonsystem. In cases involving severely compromised patients, surgical procedures that severely alter patient physiology, and untoward events during "routine" anesthesia, it is a tribute to the flexibility and resourcefulness of anesthetists that more incidents do not occur. Industry has long sought precision, reliability, automatic control, and human-factors engineering in nonmedical applications, such as aircraft cockpit design, word-processing stations, and manufacturing processes. The relentless accretion of more and more nonintegrated gadgets onto an antiquated technology has exceeded the boundaries of proper function. Neither the patient nor the anesthetist is being served well by failure to implement state-of-the-art technology in anesthesic delivery systems. Anesthesiologists and others who are vitally interested in the welfare of their patients must insist that development of radically new integrated modular systems proceed at full speed. Their checkbooks can speak as loudly as the facts; it is time the manufacturers are aware that deep concern will be translated into purchasing decisions.

  7. The M. D. Anderson proton therapy system

    SciTech Connect

    Smith, Alfred; Gillin, Michael; Bues, Martin; Zhu, X. Ronald; Suzuki, Kazumichi; Mohan, Radhe; Woo, Shiao; Lee, Andrew; Komaki, Ritsko; Cox, James; Hiramoto, Kazuo; Akiyama, Hiroshi; Ishida, Takayuki; Sasaki, Toshie; Matsuda, Koji

    2009-09-15

    Purpose: The purpose of this study is to describe University of Texas M. D. Anderson proton therapy system (PTC-H) including the accelerator, beam transport, and treatment delivery systems, the functionality and clinical parameters for passive scattering and pencil beam scanning treatment modes, and the results of acceptance tests. Methods: The PTC-H has a synchrotron (70-250 MeV) and four treatment rooms. An overall control system manages the treatment, physics, and service modes of operation. An independent safety system ensures the safety of patients, staff, and equipment. Three treatment rooms have isocentric gantries and one room has two fixed horizontal beamlines, which include a large-field treatment nozzle, used primarily for prostate treatments, and a small-field treatment nozzle for ocular treatments. Two gantry treatment rooms and the fixed-beam treatment room have passive scattering nozzles. The third gantry has a pencil beam scanning nozzle for the delivery of intensity modulated proton treatments (IMPT) and single field uniform dose (SFUD) treatments. The PTC-H also has an experimental room with a fixed horizontal beamline and a passive scattering nozzle. The equipment described above was provided by Hitachi, Ltd. Treatment planning is performed using the Eclipse system from Varian Medical Systems and data management is handled by the MOSAIQ system from IMPAC Medical Systems, Inc. The large-field passive scattering nozzles use double scattering systems in which the first scatterers are physically integrated with the range modulation wheels. The proton beam is gated on the rotating range modulation wheels at gating angles designed to produce spread-out-Bragg peaks ranging in size from 2 to 16 g/cm{sup 2}. Field sizes of up to 25x25 cm{sup 2} can be achieved with the double scattering system. The IMPT delivery technique is discrete spot scanning, which has a maximum field size of 30x30 cm{sup 2}. Depth scanning is achieved by changing the energy

  8. Polymers for Drug Delivery Systems

    PubMed Central

    Liechty, William B.; Kryscio, David R.; Slaughter, Brandon V.; Peppas, Nicholas A.

    2012-01-01

    Polymers have played an integral role in the advancement of drug delivery technology by providing controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and tunable release of both hydrophilic and hydrophobic drugs. From early beginnings using off-the-shelf materials, the field has grown tremendously, driven in part by the innovations of chemical engineers. Modern advances in drug delivery are now predicated upon the rational design of polymers tailored for specific cargo and engineered to exert distinct biological functions. In this review, we highlight the fundamental drug delivery systems and their mathematical foundations and discuss the physiological barriers to drug delivery. We review the origins and applications of stimuli-responsive polymer systems and polymer therapeutics such as polymer-protein and polymer-drug conjugates. The latest developments in polymers capable of molecular recognition or directing intracellular delivery are surveyed to illustrate areas of research advancing the frontiers of drug delivery. PMID:22432577

  9. Delivery methods for LVSD systems

    NASA Astrophysics Data System (ADS)

    Kasner, James H.; Brower, Bernard V.

    2011-06-01

    In this paper we present formats and delivery methods of Large Volume Streaming Data (LVSD) systems. LVSD systems collect TBs of data per mission with aggregate camera sizes in the 100 Mpixel to several Gpixel range at temporal rates of 2 - 60 Hz. We present options and recommendations for the different stages of LVSD data collection and delivery, to include the raw (multi-camera) data, delivery of processed (stabilized mosaic) data, and delivery of user-defined region of interest windows. Many LVSD systems use JPEG 2000 for the compression of raw and processed data. We explore the use of the JPEG 2000 Interactive Protocol (JPIP) for interactive client/server delivery to thick-clients (desktops and laptops) and MPEG-2 and H.264 to handheld thin-clients (tablets, cell phones). We also explore the use of 3D JPEG 2000 compression, defined in ISO 15444-2, for storage and delivery as well. The delivery of raw, processed, and region of interest data requires different metadata delivery techniques and metadata content. Beyond the format and delivery of data and metadata we discuss the requirements for a client/server protocol that provides data discovery and retrieval. Finally, we look into the future as LVSD systems perform automated processing to produce "information" from the original data. This information may include tracks of moving targets, changes of the background, snap shots of targets, fusion of multiple sensors, and information about "events" that have happened.

  10. Transcutaneous antigen delivery system

    PubMed Central

    Lee, Mi-Young; Shin, Meong-Cheol; Yang, Victor C.

    2013-01-01

    Transcutaneous immunization refers to the topical application of antigens onto the epidermis. Transcutaneous immunization targeting the Langerhans cells of the skin has received much attention due to its safe, needle-free, and noninvasive antigen delivery. The skin has important immunological functions with unique roles for antigen-presenting cells such as epidermal Langerhans cells and dermal dendritic cells. In recent years, novel vaccine delivery strategies have continually been developed; however, transcutaneous immunization has not yet been fully exploited due to the penetration barrier represented by the stratum corneum, which inhibits the transport of antigens and adjuvants. Herein we review recent achievements in transcutaneous immunization, focusing on the various strategies for the enhancement of antigen delivery and vaccination efficacy. [BMB Reports 2013; 46(1): 17-24] PMID:23351379

  11. Radiation delivery system and method

    DOEpatents

    Sorensen, Scott A.; Robison, Thomas W.; Taylor, Craig M. V.

    2002-01-01

    A radiation delivery system and method are described. The system includes a treatment configuration such as a stent, balloon catheter, wire, ribbon, or the like, a portion of which is covered with a gold layer. Chemisorbed to the gold layer is a radiation-emitting self-assembled monolayer or a radiation-emitting polymer. The radiation delivery system is compatible with medical catheter-based technologies to provide a therapeutic dose of radiation to a lesion following an angioplasty procedure.

  12. Fluid delivery control system

    DOEpatents

    Hoff, Brian D.; Johnson, Kris William; Algrain, Marcelo C.; Akasam, Sivaprasad

    2006-06-06

    A method of controlling the delivery of fluid to an engine includes receiving a fuel flow rate signal. An electric pump is arranged to deliver fluid to the engine. The speed of the electric pump is controlled based on the fuel flow rate signal.

  13. Adenosine-Associated Delivery Systems

    PubMed Central

    Kazemzadeh-Narbat, Mehdi; Annabi, Nasim; Tamayol, Ali; Oklu, Rahmi; Ghanem, Amyl; Khademhosseini, Ali

    2016-01-01

    Adenosine is a naturally occurring purine nucleoside in every cell. Many critical treatments such as modulating irregular heartbeat (arrhythmias), regulation of central nervous system (CNS) activity, and inhibiting seizural episodes can be carried out using adenosine. Despite the significant potential therapeutic impact of adenosine and its derivatives, the severe side effects caused by their systemic administration have significantly limited their clinical use. In addition, due to adenosine’s extremely short half-life in human blood (less than 10 s), there is an unmet need for sustained delivery systems to enhance efficacy and reduce side effects. In this paper, various adenosine delivery techniques, including encapsulation into biodegradable polymers, cell-based delivery, implantable biomaterials, and mechanical-based delivery systems, are critically reviewed and the existing challenges are highlighted. PMID:26453156

  14. Maximum proton kinetic energy and patient-generated neutron fluence considerations in proton beam arc delivery radiation therapy.

    PubMed

    Sengbusch, E; Pérez-Andújar, A; DeLuca, P M; Mackie, T R

    2009-02-01

    Several compact proton accelerator systems for use in proton therapy have recently been proposed. Of paramount importance to the development of such an accelerator system is the maximum kinetic energy of protons, immediately prior to entry into the patient, that must be reached by the treatment system. The commonly used value for the maximum kinetic energy required for a medical proton accelerator is 250 MeV, but it has not been demonstrated that this energy is indeed necessary to treat all or most patients eligible for proton therapy. This article quantifies the maximum kinetic energy of protons, immediately prior to entry into the patient, necessary to treat a given percentage of patients with rotational proton therapy, and examines the impact of this energy threshold on the cost and feasibility of a compact, gantry-mounted proton accelerator treatment system. One hundred randomized treatment plans from patients treated with IMRT were analyzed. The maximum radiological pathlength from the surface of the patient to the distal edge of the treatment volume was obtained for 180 degrees continuous arc proton therapy and for 180 degrees split arc proton therapy (two 90 degrees arcs) using CT# profiles from the Pinnacle (Philips Medical Systems, Madison, WI) treatment planning system. In each case, the maximum kinetic energy of protons, immediately prior to entry into the patient, that would be necessary to treat the patient was calculated using proton range tables for various media. In addition, Monte Carlo simulations were performed to quantify neutron production in a water phantom representing a patient as a function of the maximum proton kinetic energy achievable by a proton treatment system. Protons with a kinetic energy of 240 MeV, immediately prior to entry into the patient, were needed to treat 100% of patients in this study. However, it was shown that 90% of patients could be treated at 198 MeV, and 95% of patients could be treated at 207 MeV. Decreasing the

  15. Maximum proton kinetic energy and patient-generated neutron fluence considerations in proton beam arc delivery radiation therapy

    SciTech Connect

    Sengbusch, E.; Perez-Andujar, A.; DeLuca, P. M. Jr.; Mackie, T. R.

    2009-02-15

    Several compact proton accelerator systems for use in proton therapy have recently been proposed. Of paramount importance to the development of such an accelerator system is the maximum kinetic energy of protons, immediately prior to entry into the patient, that must be reached by the treatment system. The commonly used value for the maximum kinetic energy required for a medical proton accelerator is 250 MeV, but it has not been demonstrated that this energy is indeed necessary to treat all or most patients eligible for proton therapy. This article quantifies the maximum kinetic energy of protons, immediately prior to entry into the patient, necessary to treat a given percentage of patients with rotational proton therapy, and examines the impact of this energy threshold on the cost and feasibility of a compact, gantry-mounted proton accelerator treatment system. One hundred randomized treatment plans from patients treated with IMRT were analyzed. The maximum radiological pathlength from the surface of the patient to the distal edge of the treatment volume was obtained for 180 deg. continuous arc proton therapy and for 180 deg. split arc proton therapy (two 90 degree sign arcs) using CT profiles from the Pinnacle (Philips Medical Systems, Madison, WI) treatment planning system. In each case, the maximum kinetic energy of protons, immediately prior to entry into the patient, that would be necessary to treat the patient was calculated using proton range tables for various media. In addition, Monte Carlo simulations were performed to quantify neutron production in a water phantom representing a patient as a function of the maximum proton kinetic energy achievable by a proton treatment system. Protons with a kinetic energy of 240 MeV, immediately prior to entry into the patient, were needed to treat 100% of patients in this study. However, it was shown that 90% of patients could be treated at 198 MeV, and 95% of patients could be treated at 207 MeV. Decreasing the

  16. Maximum proton kinetic energy and patient-generated neutron fluence considerations in proton beam arc delivery radiation therapy

    PubMed Central

    Sengbusch, E.; Pérez-Andújar, A.; DeLuca, P. M.; Mackie, T. R.

    2009-01-01

    Several compact proton accelerator systems for use in proton therapy have recently been proposed. Of paramount importance to the development of such an accelerator system is the maximum kinetic energy of protons, immediately prior to entry into the patient, that must be reached by the treatment system. The commonly used value for the maximum kinetic energy required for a medical proton accelerator is 250 MeV, but it has not been demonstrated that this energy is indeed necessary to treat all or most patients eligible for proton therapy. This article quantifies the maximum kinetic energy of protons, immediately prior to entry into the patient, necessary to treat a given percentage of patients with rotational proton therapy, and examines the impact of this energy threshold on the cost and feasibility of a compact, gantry-mounted proton accelerator treatment system. One hundred randomized treatment plans from patients treated with IMRT were analyzed. The maximum radiological pathlength from the surface of the patient to the distal edge of the treatment volume was obtained for 180° continuous arc proton therapy and for 180° split arc proton therapy (two 90° arcs) using CT# profiles from the Pinnacle™ (Philips Medical Systems, Madison, WI) treatment planning system. In each case, the maximum kinetic energy of protons, immediately prior to entry into the patient, that would be necessary to treat the patient was calculated using proton range tables for various media. In addition, Monte Carlo simulations were performed to quantify neutron production in a water phantom representing a patient as a function of the maximum proton kinetic energy achievable by a proton treatment system. Protons with a kinetic energy of 240 MeV, immediately prior to entry into the patient, were needed to treat 100% of patients in this study. However, it was shown that 90% of patients could be treated at 198 MeV, and 95% of patients could be treated at 207 MeV. Decreasing the proton kinetic

  17. Nanoparticulate systems for polynucleotide delivery

    PubMed Central

    Basarkar, Ashwin; Singh, Jagdish

    2007-01-01

    Nanotechnology has tremendously influenced gene therapy research in recent years. Nanometer-size systems have been extensively investigated for delivering genes at both local and systemic levels. These systems offer several advantages in terms of tissue penetrability, cellular uptake, systemic circulation, and cell targeting as compared to larger systems. They can protect the polynucleotide from a variety of degradative and destabilizing factors and enhance delivery efficiency to the cells. A variety of polymeric and non-polymeric nanoparticles have been investigated in an effort to maximize the delivery efficiency while minimizing the toxic effects. This article provides a review on the most commonly used nanoparticulate systems for gene delivery. We have discussed frequently used polymers, such as, polyethyleneimine, poly (lactide-co-glycolide), chitosan, as well as non-polymeric materials such as cationic lipids and metallic nanoparticles. The advantages and limitations of each system have been elaborated. PMID:18019834

  18. Novel central nervous system drug delivery systems.

    PubMed

    Stockwell, Jocelyn; Abdi, Nabiha; Lu, Xiaofan; Maheshwari, Oshin; Taghibiglou, Changiz

    2014-05-01

    For decades, biomedical and pharmaceutical researchers have worked to devise new and more effective therapeutics to treat diseases affecting the central nervous system. The blood-brain barrier effectively protects the brain, but poses a profound challenge to drug delivery across this barrier. Many traditional drugs cannot cross the blood-brain barrier in appreciable concentrations, with less than 1% of most drugs reaching the central nervous system, leading to a lack of available treatments for many central nervous system diseases, such as stroke, neurodegenerative disorders, and brain tumors. Due to the ineffective nature of most treatments for central nervous system disorders, the development of novel drug delivery systems is an area of great interest and active research. Multiple novel strategies show promise for effective central nervous system drug delivery, giving potential for more effective and safer therapies in the future. This review outlines several novel drug delivery techniques, including intranasal drug delivery, nanoparticles, drug modifications, convection-enhanced infusion, and ultrasound-mediated drug delivery. It also assesses possible clinical applications, limitations, and examples of current clinical and preclinical research for each of these drug delivery approaches. Improved central nervous system drug delivery is extremely important and will allow for improved treatment of central nervous system diseases, causing improved therapies for those who are affected by central nervous system diseases.

  19. Career Information Delivery Systems Inventory.

    ERIC Educational Resources Information Center

    Olson, Gerald T.; Whitman, Patricia D.

    This inventory highlights similarities and differences between 19 computerized career information delivery systems (CIDS) so practitioners may make more informed choices concerning the adoption of such systems, and policymakers may monitor the developing scope of system features and costs. It was developed through a survey of computer products…

  20. Quantitative analysis of beam delivery parameters and treatment process time for proton beam therapy

    SciTech Connect

    Suzuki, Kazumichi; Gillin, Michael T.; Sahoo, Narayan; Zhu, X. Ronald; Lee, Andrew K.; Lippy, Denise

    2011-07-15

    Purpose: To evaluate patient census, equipment clinical availability, maximum daily treatment capacity, use factor for major beam delivery parameters, and treatment process time for actual treatments delivered by proton therapy systems. Methods: The authors have been recording all beam delivery parameters, including delivered dose, energy, range, spread-out Bragg peak widths, gantry angles, and couch angles for every treatment field in an electronic medical record system. We analyzed delivery system downtimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the use factor of beam delivery parameters, the size of the patient census, and the equipment clinical availability of the facility. The duration of each treatment session from patient walk-in and to patient walk-out of the treatment room was measured for 82 patients with cancers at various sites. Results: The yearly average equipment clinical availability in the last 3 yrs (June 2007-August 2010) was 97%, which exceeded the target of 95%. Approximately 2200 patients had been treated as of August 2010. The major disease sites were genitourinary (49%), thoracic (25%), central nervous system (22%), and gastrointestinal (2%). Beams have been delivered in approximately 8300 treatment fields. The use factor for six beam delivery parameters was also evaluated. Analysis of the treatment process times indicated that approximately 80% of this time was spent for patient and equipment setup. The other 20% was spent waiting for beam delivery and beam on. The total treatment process time can be expressed by a quadratic polynomial of the number of fields per session. The maximum daily treatment capacity of our facility using the current treatment processes was estimated to be 133 {+-} 35 patients. Conclusions: This analysis shows that the facility has operated at a high performance level and has treated a large number of patients with a variety of diseases. The use

  1. Delivery System, 2003-2004.

    ERIC Educational Resources Information Center

    Office of Federal Student Aid (ED), Washington, DC.

    This workshop guide for financial aid administrators provides training in the federal student financial aid delivery system. An introduction enables the participant to share some information about his or her responsibilities and to reflect on the relevance of the training to the job. Session 1, "Application Systems," identifies methods of applying…

  2. Teleteach Expanded Delivery System: Evaluation.

    ERIC Educational Resources Information Center

    Christopher, G. Ronald; Milam, Alvin L.

    In order to meet the demand for Air Force Institute of Technology (AFIT) professional continuing education (PCE) courses within the School of Systems and Logistics and the School of Engineering, the Teleteach Expanded Delivery System (TEDS) for instruction of Air Force personnel at remote locations was developed and evaluated. TEDS uses a device…

  3. Insulin Delivery System

    NASA Technical Reports Server (NTRS)

    1988-01-01

    When Programmable Implantable Medication System (PIMS) is implanted in human body, it delivers precise programmed amounts of insulin over long periods of time. Mini-Med Technologies has been refining the Technologies since initial development at APL. The size of a hockey puck, and encased in titanium shell, PIMS holds about 2 1/2 teaspoons of insulin at a programmed basal rate. If a change in measured blood sugar level dictates a different dose, the patient can vary the amount of insulin delivered by holding a small radio transceiver over the implanted system and dialing in a specific program held in the PIMS computer memory. Insulin refills are accomplished approximately 4 times a year by hypodermic needle.

  4. Sterile Product Packaging and Delivery Systems.

    PubMed

    Akers, Michael J

    2015-01-01

    Both conventional and more advanced product container and delivery systems are the focus of this brief article. Six different product container systems will be discussed, plus advances in primary packaging for special delivery systems and needle technology. PMID:26891564

  5. Sterile Product Packaging and Delivery Systems.

    PubMed

    Akers, Michael J

    2015-01-01

    Both conventional and more advanced product container and delivery systems are the focus of this brief article. Six different product container systems will be discussed, plus advances in primary packaging for special delivery systems and needle technology.

  6. TH-C-BRD-07: Minimizing Dose Uncertainty for Spot Scanning Beam Proton Therapy of Moving Tumor with Optimization of Delivery Sequence

    SciTech Connect

    Li, H; Zhang, X; Zhu, X; Li, Y

    2014-06-15

    Purpose: Intensity modulated proton therapy (IMPT) has been shown to be able to reduce dose to normal tissue compared to intensity modulated photon radio-therapy (IMRT), and has been implemented for selected lung cancer patients. However, respiratory motion-induced dose uncertainty remain one of the major concerns for the radiotherapy of lung cancer, and the utility of IMPT for lung patients was limited because of the proton dose uncertainty induced by motion. Strategies such as repainting and tumor tracking have been proposed and studied but repainting could result in unacceptable long delivery time and tracking is not yet clinically available. We propose a novel delivery strategy for spot scanning proton beam therapy. Method: The effective number of delivery (END) for each spot position in a treatment plan was calculated based on the parameters of the delivery system, including time required for each spot, spot size and energy. The dose uncertainty was then calculated with an analytical formula. The spot delivery sequence was optimized to maximize END and minimize the dose uncertainty. 2D Measurements with a detector array on a 1D moving platform were performed to validate the calculated results. Results: 143 2D measurements on a moving platform were performed for different delivery sequences of a single layer uniform pattern. The measured dose uncertainty is a strong function of the delivery sequence, the worst delivery sequence results in dose error up to 70% while the optimized delivery sequence results in dose error of <5%. END vs. measured dose uncertainty follows the analytical formula. Conclusion: With optimized delivery sequence, it is feasible to minimize the dose uncertainty due to motion in spot scanning proton therapy.

  7. Proton-dependent multidrug efflux systems.

    PubMed Central

    Paulsen, I T; Brown, M H; Skurray, R A

    1996-01-01

    Multidrug efflux systems display the ability to transport a variety of structurally unrelated drugs from a cell and consequently are capable of conferring resistance to a diverse range of chemotherapeutic agents. This review examines multidrug efflux systems which use the proton motive force to drive drug transport. These proteins are likely to operate as multidrug/proton antiporters and have been identified in both prokaryotes and eukaryotes. Such proton-dependent multidrug efflux proteins belong to three distinct families or superfamilies of transport proteins: the major facilitator superfamily (MFS), the small multidrug resistance (SMR) family, and the resistance/ nodulation/cell division (RND) family. The MFS consists of symporters, antiporters, and uniporters with either 12 or 14 transmembrane-spanning segments (TMS), and we show that within the MFS, three separate families include various multidrug/proton antiport proteins. The SMR family consists of proteins with four TMS, and the multidrug efflux proteins within this family are the smallest known secondary transporters. The RND family consists of 12-TMS transport proteins and includes a number of multidrug efflux proteins with particularly broad substrate specificity. In gram-negative bacteria, some multidrug efflux systems require two auxiliary constituents, which might enable drug transport to occur across both membranes of the cell envelope. These auxiliary constituents belong to the membrane fusion protein and the outer membrane factor families, respectively. This review examines in detail each of the characterized proton-linked multidrug efflux systems. The molecular basis of the broad substrate specificity of these transporters is discussed. The surprisingly wide distribution of multidrug efflux systems and their multiplicity in single organisms, with Escherichia coli, for instance, possessing at least nine proton-dependent multidrug efflux systems with overlapping specificities, is examined. We also

  8. Bioengineered Silk Gene Delivery System for Nuclear Targeting

    PubMed Central

    Yigit, Sezin; Tokareva, Olena; Varone, Antonio; Georgakoudi, Irene

    2015-01-01

    Gene delivery research has gained momentum with the use of lipophilic vectors that mimic viral systems to increase transfection efficiency. However, maintaining cell viability with these systems remains a major challenge. Therefore biocompatible and nontoxic biopolymers that are designed by combining non-immunological viral mimicking components with suitable carriers have been explored to address these limitations. In the present study recombinant DNA technology was used to design a multi-functional gene delivery system for nuclear targeting, while also supporting cell viability. Spider dragline silk recombinant proteins were modified with DNA condensing units and the proton sponge endosomal escape pathway was utilized for enhanced delivery. Short-term transfection efficiency in a COS-7 cell line (adherent kidney cells isolated from African green monkey) was enhanced compared to lipofectamine and polyethyleneimine (PEI), as was cell viability with these recombinant bio-polyplexes. Endosomal escape and consequent nuclear targeting were shown with fluorescence microscopy. PMID:24889658

  9. Proton beam scattering system optimization for clinical and research applications

    SciTech Connect

    Wroe, A. J.; Schulte, R. W.; Slater, J. D.; Barnes, S.; McAuley, G.; Slater, J. M.

    2013-04-15

    Purpose: To develop and test a method for optimizing and constructing a dual scattering system in passively scattered proton therapy. Methods: A beam optics optimization algorithm was developed to optimize the thickness of the first scatterer (S1) and the profile (of both the high-Z material and Lexan) of the second scatterer (S2) to deliver a proton beam matching a given set of parameters, including field diameter, fluence, flatness, and symmetry. A new manufacturing process was also tested that allows the contoured second scattering foil to be created much more economically and quickly using Cerrobend casting. Two application-specific scattering systems were developed and tested using both experimental and Monte Carlo techniques to validate the optimization process described. Results: A scattering system was optimized and constructed to deliver large uniform irradiations of radiobiology samples at low dose rates. This system was successfully built and tested using film and ionization chambers. The system delivered a uniform radiation field of 50 cm diameter (to a dose of {+-}7% of the central axis) while the depth dose profile could be tuned to match the specifications of the particular investigator using modulator wheels and range shifters. A second scattering system for intermediate field size (4 cm < diameter < 10 cm) stereotactic radiosurgery and radiation therapy (SRS and SRT) treatments was also developed and tested using GEANT4. This system improved beam efficiency by over 70% compared with existing scattering systems while maintaining field flatness and depth dose profile. In both cases the proton range uniformity across the radiation field was maintained, further indicating the accuracy of the energy loss formalism in the optimization algorithm. Conclusions: The methods described allow for rapid prototyping of scattering foils to meet the demands of both research and clinical beam delivery applications in proton therapy.

  10. Gantries and dose delivery systems

    NASA Astrophysics Data System (ADS)

    Meer, David; Psoroulas, Serena

    2015-04-01

    Particle therapy is a field in remarkable development, with the goal of increasing the number of indications which could benefit from such treatments and the access to the therapy. The therapeutic usage of a particle beam defines the technical requirements of all the elements of the therapy chain: we summarize the main characteristics of accelerators, the beam line, the treatment room, the integrated therapy and imaging systems used in particle therapy. Aiming at a higher flexibility in the choice of treatments, an increasing number of centers around the world have chosen to equip their treatment rooms with gantries, rotating beam line structures that allow a complete flexibility in the choice of the treatment angle. We review the current designs. A particle therapy gantry though is a quite expensive structure, and future development will increasingly consider reducing the cost and the footprint. Increasing the number of indications also means development in the delivery techniques and solving some of the issues which traditionally affected particle therapy, for example the precision of the delivery in presence of motion and the large penumbras for low depths. We show the current strategies in these fields, focusing on pencil beam scanning (PBS), and give some hints about future developments.

  11. Collagen macromolecular drug delivery systems

    SciTech Connect

    Gilbert, D.L.

    1988-01-01

    The objective of this study was to examine collagen for use as a macromolecular drug delivery system by determining the mechanism of release through a matrix. Collagen membranes varying in porosity, crosslinking density, structure and crosslinker were fabricated. Collagen characterized by infrared spectroscopy and solution viscosity was determined to be pure and native. The collagen membranes were determined to possess native vs. non-native quaternary structure and porous vs. dense aggregate membranes by electron microscopy. Collagen monolithic devices containing a model macromolecule (inulin) were fabricated. In vitro release rates were found to be linear with respect to t{sup {1/2}} and were affected by crosslinking density, crosslinker and structure. The biodegradation of the collagen matrix was also examined. In vivo biocompatibility, degradation and {sup 14}C-inulin release rates were evaluated subcutaneously in rats.

  12. Rapid Data Delivery System (RDDS)

    USGS Publications Warehouse

    Cress, Jill J.; Goplen, Susan E.

    2007-01-01

    Since the start of the active 2000 summer fire season, the U. S. Geological Survey (USGS) Rocky Mountain Geographic Science Center (RMGSC) has been actively engaged in providing crucial and timely support to Federal, State, and local natural hazards monitoring, analysis, response, and recovery activities. As part of this support, RMGSC has developed the Rapid Data Delivery System (RDDS) to provide emergency and incident response teams with timely access to geospatial data. The RDDS meets these needs by combining a simple web-enabled data viewer for the selection and preview of vector and raster geospatial data with an easy to use data ordering form. The RDDS viewer also incorporates geospatial locations for current natural hazard incidents, including wildfires, earthquakes, hurricanes, and volcanoes, allowing incident responders to quickly focus on their area of interest for data selection.

  13. Microfabricated injectable drug delivery system

    DOEpatents

    Krulevitch, Peter A.; Wang, Amy W.

    2002-01-01

    A microfabricated, fully integrated drug delivery system capable of secreting controlled dosages of multiple drugs over long periods of time (up to a year). The device includes a long and narrow shaped implant with a sharp leading edge for implantation under the skin of a human in a manner analogous to a sliver. The implant includes: 1) one or more micromachined, integrated, zero power, high and constant pressure generating osmotic engine; 2) low power addressable one-shot shape memory polymer (SMP) valves for switching on the osmotic engine, and for opening drug outlet ports; 3) microfabricated polymer pistons for isolating the pressure source from drug-filled microchannels; 4) multiple drug/multiple dosage capacity, and 5) anisotropically-etched, atomically-sharp silicon leading edge for penetrating the skin during implantation. The device includes an externally mounted controller for controlling on-board electronics which activates the SMP microvalves, etc. of the implant.

  14. Reducing Dose Uncertainty for Spot-Scanning Proton Beam Therapy of Moving Tumors by Optimizing the Spot Delivery Sequence

    PubMed Central

    Li, Heng; Zhu, X. Ronald; Zhang, Xiaodong

    2016-01-01

    Purpose To develop and validate a novel delivery strategy for reducing the respiratory motion–induced dose uncertainty of spot-scanning proton therapy. Methods and Materials The spot delivery sequence was optimized to reduce dose uncertainty. The effectiveness of the delivery sequence optimization was evaluated using measurements and patient simulation. One hundred ninety-one 2-dimensional measurements using different delivery sequences of a single-layer uniform pattern were obtained with a detector array on a 1-dimensional moving platform. Intensity modulated proton therapy plans were generated for 10 lung cancer patients, and dose uncertainties for different delivery sequences were evaluated by simulation. Results Without delivery sequence optimization, the maximum absolute dose error can be up to 97.2% in a single measurement, whereas the optimized delivery sequence results in a maximum absolute dose error of ≤11.8%. In patient simulation, the optimized delivery sequence reduces the mean of fractional maximum absolute dose error compared with the regular delivery sequence by 3.3% to 10.6% (32.5-68.0% relative reduction) for different patients. Conclusions Optimizing the delivery sequence can reduce dose uncertainty due to respiratory motion in spot-scanning proton therapy, assuming the 4-dimensional CT is a true representation of the patients’ breathing patterns. PMID:26460997

  15. Economical oxygen-delivery system.

    PubMed

    Olson, R M

    1976-04-01

    The conservation of aircraft oxygen supplies is becoming of considerable interest to the Air Force. Onboard oxygen-generating systems are being developed which could support an aircrew if oxygen produced by these systems were used conservatively. These experiments studied the conservation potential of a rebreather bag placed in a vented container near the regulator in an oxygen-delivery system. The bag's volume was close to that of the subject's physiologic dead space. When the subject exhaled, oxygen in the mouth, trachea, and mask dead space went to the rebreather bag, to be rebreathed with the next breath. The CO2-contaminated oxygen from the alveoli was vented to the cabin. The dead-space oxygen could be separated from contaminated oxygen because dead-space air is exhaled first with each breath. When the rebreather-bag volume matched the subject's physiologic dead space so that no CO2 accumulated, a 30% oxygen savings was realized. When the bag was large enough to realize a 50% savings, CO2 accumulation was only 2%.

  16. Fiber coupled optical spark delivery system

    DOEpatents

    Yalin, Azer; Willson, Bryan; Defoort, Morgan

    2008-08-12

    A spark delivery system for generating a spark using a laser beam is provided, the spark delivery system including a laser light source and a laser delivery assembly. The laser delivery assembly includes a hollow fiber and a launch assembly comprising launch focusing optics to input the laser beam in the hollow fiber. In addition, the laser delivery assembly includes exit focusing optics that demagnify an exit beam of laser light from the hollow fiber, thereby increasing the intensity of the laser beam and creating a spark. In accordance with embodiments of the present invention, the assembly may be used to create a spark in a combustion engine. In accordance with other embodiments of the present invention, a method of using the spark delivery system is provided. In addition, a method of choosing an appropriate fiber for creating a spark using a laser beam is also presented.

  17. Physically facilitating drug-delivery systems

    PubMed Central

    Rodriguez-Devora, Jorge I; Ambure, Sunny; Shi, Zhi-Dong; Yuan, Yuyu; Sun, Wei; Xu, Tao

    2012-01-01

    Facilitated/modulated drug-delivery systems have emerged as a possible solution for delivery of drugs of interest to pre-allocated sites at predetermined doses for predefined periods of time. Over the past decade, the use of different physical methods and mechanisms to mediate drug release and delivery has grown significantly. This emerging area of research has important implications for development of new therapeutic drugs for efficient treatments. This review aims to introduce and describe different modalities of physically facilitating drug-delivery systems that are currently in use for cancer and other diseases therapy. In particular, delivery methods based on ultrasound, electrical, magnetic and photo modulations are highlighted. Current uses and areas of improvement for these different physically facilitating drug-delivery systems are discussed. Furthermore, the main advantages and drawbacks of these technologies reviewed are compared. The review ends with a speculative viewpoint of how research is expected to evolve in the upcoming years. PMID:22485192

  18. Radiotherapy systems using proton and carbon beams.

    PubMed

    Jongen, Y

    2008-01-01

    Radiotherapy using proton beams (proton therapy) is rapidly taking an important role among the techniques used in cancer therapy. At the end of 2007, 65.000 patients had been treated for cancer by proton beams in one of the 34 proton therapy facilities operating in the world. When compared to the now classical IMRT, and for a similar dose to the tumor, proton therapy provides a lower integral dose to the healthy organs surrounding the tumor. It is generally accepted that any reduction of the dose to healthy organs reduces the probability of radiation induced complications and of secondary malignancies. Proton therapy equipment can be obtained today from well established medical equipment companies such as Varian, Hitachi or Mitsubishi. But it is a Belgian company, Ion Beam Applications of Louvain-la-Neuve that is the undisputed leader in this market, with more than 55% of the world installed base. In addition to the now classical proton therapy equipments, using synchrotrons or cyclotrons as accelerators, new solutions have been proposed, claiming to be more compact and less expensive. A small startup company from Boston (Still Rivers) is proposing a very high magnetic field, gantry mounted superconducting synchrocyclotron. The us Company Tomotherapy is working to develop a new accelerator concept invented at Lawrence Livermore National Laboratory: the Dielectric Wall Accelerator. Besides proton beam therapy, which is progressively becoming an accepted part of radiation therapy, interest is growing for another form of radiotherapy using ions heavier than protons. Carbon ions have, even to a higher degree, the ballistic selectivity of protons. In addition, carbon ions stopping in the body exhibit a very high Linear Energy Transfer (LET). From this high LET results a very high Relative Biological Efficiency (RBE). This high RBE allows carbon ions to treat efficiently tumors who are radio-resistant and which are difficult to treat with photons or protons. The largest

  19. Tax exemption and integrated delivery systems.

    PubMed

    Aseltyne, W J; Peters, G R

    1994-01-01

    This chapter discusses tax exemption of integrated delivery systems, including the requirements for exemption, the charitable purposes test, the private inurement and private benefit tests, and an application to integrated delivery systems. It also discusses the structure of the Friendly Hills and Facey Nonprofit Medical Foundations, including the analysis of the Internal Revenue Service. Finally, it discusses the process for obtaining tax exemption.

  20. Development of the Choctaw Health Delivery System.

    ERIC Educational Resources Information Center

    Nguyen, Binh N.

    The Choctaw Tribe is the first and only tribe to develop a health delivery system to take over an existing Indian Health Service inpatient facility. The takeover was accomplished in January 1984 under the Indian Self-Determination Act through a contract with the Indian Health Service. The Choctaw Health Delivery System includes a 35-bed general…

  1. Viral and nonviral delivery systems for gene delivery.

    PubMed

    Nayerossadat, Nouri; Maedeh, Talebi; Ali, Palizban Abas

    2012-01-01

    Gene therapy is the process of introducing foreign genomic materials into host cells to elicit a therapeutic benefit. Although initially the main focus of gene therapy was on special genetic disorders, now diverse diseases with different patterns of inheritance and acquired diseases are targets of gene therapy. There are 2 major categories of gene therapy, including germline gene therapy and somatic gene therapy. Although germline gene therapy may have great potential, because it is currently ethically forbidden, it cannot be used; however, to date human gene therapy has been limited to somatic cells. Although numerous viral and nonviral gene delivery systems have been developed in the last 3 decades, no delivery system has been designed that can be applied in gene therapy of all kinds of cell types in vitro and in vivo with no limitation and side effects. In this review we explain about the history of gene therapy, all types of gene delivery systems for germline (nuclei, egg cells, embryonic stem cells, pronuclear, microinjection, sperm cells) and somatic cells by viral [retroviral, adenoviral, adeno association, helper-dependent adenoviral systems, hybrid adenoviral systems, herpes simplex, pox virus, lentivirus, Epstein-Barr virus)] and nonviral systems (physical: Naked DNA, DNA bombardant, electroporation, hydrodynamic, ultrasound, magnetofection) and (chemical: Cationic lipids, different cationic polymers, lipid polymers). In addition to the above-mentioned, advantages, disadvantages, and practical use of each system are discussed. PMID:23210086

  2. Drug delivery systems: An updated review

    PubMed Central

    Tiwari, Gaurav; Tiwari, Ruchi; Sriwastawa, Birendra; Bhati, L; Pandey, S; Pandey, P; Bannerjee, Saurabh K

    2012-01-01

    Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. For the treatment of human diseases, nasal and pulmonary routes of drug delivery are gaining increasing importance. These routes provide promising alternatives to parenteral drug delivery particularly for peptide and protein therapeutics. For this purpose, several drug delivery systems have been formulated and are being investigated for nasal and pulmonary delivery. These include liposomes, proliposomes, microspheres, gels, prodrugs, cyclodextrins, among others. Nanoparticles composed of biodegradable polymers show assurance in fulfilling the stringent requirements placed on these delivery systems, such as ability to be transferred into an aerosol, stability against forces generated during aerosolization, biocompatibility, targeting of specific sites or cell populations in the lung, release of the drug in a predetermined manner, and degradation within an acceptable period of time. PMID:23071954

  3. Starch Applications for Delivery Systems

    NASA Astrophysics Data System (ADS)

    Li, Jason

    2013-03-01

    Starch is one of the most abundant and economical renewable biopolymers in nature. Starch molecules are high molecular weight polymers of D-glucose linked by α-(1,4) and α-(1,6) glycosidic bonds, forming linear (amylose) and branched (amylopectin) structures. Octenyl succinic anhydride modified starches (OSA-starch) are designed by carefully choosing a proper starch source, path and degree of modification. This enables emulsion and micro-encapsulation delivery systems for oil based flavors, micronutrients, fragrance, and pharmaceutical actives. A large percentage of flavors are encapsulated by spray drying in today's industry due to its high throughput. However, spray drying encapsulation faces constant challenges with retention of volatile compounds, oxidation of sensitive compound, and manufacturing yield. Specialty OSA-starches were developed suitable for the complex dynamics in spray drying and to provide high encapsulation efficiency and high microcapsule quality. The OSA starch surface activity, low viscosity and film forming capability contribute to high volatile retention and low active oxidation. OSA starches exhibit superior performance, especially in high solids and high oil load encapsulations compared with other hydrocolloids. The submission is based on research and development of Ingredion

  4. Multi-channel gas-delivery system

    DOEpatents

    Rozenzon, Yan; Trujillo, Robert T.; Beese, Steven C.

    2016-09-13

    One embodiment of the present invention provides a gas-delivery system for delivering reaction gas to a reactor chamber. The gas-delivery system includes a main gas-inlet port for receiving reaction gases and a gas-delivery plate that includes a plurality of gas channels. A gas channel includes a plurality of gas holes for allowing the reaction gases to enter the reactor chamber from the gas channel. The gas-delivery system further includes a plurality of sub-gas lines coupling together the main gas-inlet port and the gas-delivery plate, and a respective sub-gas line is configured to deliver a portion of the received reaction gases to a corresponding gas channel.

  5. Fiber laser coupled optical spark delivery system

    DOEpatents

    Yalin, Azer; Willson, Bryan; Defoort, Morgan; Joshi, Sachin; Reynolds, Adam

    2008-03-04

    A spark delivery system for generating a spark using a laser beam is provided, and includes a laser light source and a laser delivery assembly. The laser delivery assembly includes a hollow fiber and a launch assembly comprising launch focusing optics to input the laser beam in the hollow fiber. The laser delivery assembly further includes exit focusing optics that demagnify an exit beam of laser light from the hollow fiber, thereby increasing the intensity of the laser beam and creating a spark. Other embodiments use a fiber laser to generate a spark. Embodiments of the present invention may be used to create a spark in an engine. Yet other embodiments include collecting light from the spark or a flame resulting from the spark and conveying the light for diagnostics. Methods of using the spark delivery systems and diagnostic systems are provided.

  6. Organized Athletics as a Leisure Delivery System.

    ERIC Educational Resources Information Center

    Kidd, Thomas R.; Mendell, Ron

    1980-01-01

    Athletic programs are leisure time delivery systems for the athletes, spectators, and the local community as long as scholarships and extensive media coverage are not involved. College administration should make sure that sports and athletics do not become a delivery sytem for public relations and finance. (CJ)

  7. Delivery system for laser medical instrument

    NASA Astrophysics Data System (ADS)

    Jelinkova, Helena; Nemec, Michal; Sulc, Jan; Cerny, Pavel; Miyagi, Mitsunobu; Shi, Yi-Wei; Matsuura, Yuji

    2003-10-01

    Investigation of the special constructed hollow glass waveguides was realized. Maximum mean power transmitted via this delivery system was 5.8 W (for alexandrite radiation) or 5.1 W (for mid infrared Er.YAG light). Maximum output intensity 173 GW/cm2 was reached for delivery of 55 psec long Nd:YAG pulses.

  8. Delivery systems for intradermal vaccination.

    PubMed

    Kim, Y C; Jarrahian, C; Zehrung, D; Mitragotri, S; Prausnitz, M R

    2012-01-01

    Intradermal (ID) vaccination can offer improved immunity and simpler logistics of delivery, but its use in medicine is limited by the need for simple, reliable methods of ID delivery. ID injection by the Mantoux technique requires special training and may not reliably target skin, but is nonetheless used currently for BCG and rabies vaccination. Scarification using a bifurcated needle was extensively used for smallpox eradication, but provides variable and inefficient delivery into the skin. Recently, ID vaccination has been simplified by introduction of a simple-to-use hollow microneedle that has been approved for ID injection of influenza vaccine in Europe. Various designs of hollow microneedles have been studied preclinically and in humans. Vaccines can also be injected into skin using needle-free devices, such as jet injection, which is receiving renewed clinical attention for ID vaccination. Projectile delivery using powder and gold particles (i.e., gene gun) have also been used clinically for ID vaccination. Building off the scarification approach, a number of preclinical studies have examined solid microneedle patches for use with vaccine coated onto metal microneedles, encapsulated within dissolving microneedles or added topically to skin after microneedle pretreatment, as well as adapting tattoo guns for ID vaccination. Finally, technologies designed to increase skin permeability in combination with a vaccine patch have been studied through the use of skin abrasion, ultrasound, electroporation, chemical enhancers, and thermal ablation. The prospects for bringing ID vaccination into more widespread clinical practice are encouraging, given the large number of technologies for ID delivery under development.

  9. New delivery systems and propellants.

    PubMed

    Dolovich, M

    1999-01-01

    The removal of chlorofluorocarbon (CFC) propellants from industrial and household products has been agreed to by over 165 countries of which more than 135 are developing countries. The timetable for this process is outlined in the Montreal Protocol on Substances that Deplete the Ozone Layer document and in several subsequent amendments. Pressured metered dose inhalers (pMDIs) for medical use have been granted temporary exemptions until replacement formulations, providing the same medication via the same route, and with the same efficacy and safety profiles, are approved for human use. Hydrofluoroalkanes (HFAs) are the alternative propellants for CFCs-12 and -114. Their potential for damage to the ozone layer is nonexistent, and while they are greenhouse gases, their global warming potential is a fraction (one-tenth) of that of CFCs. Replacement formulations for almost all inhalant respiratory medications have been or are being produced and tested; in Canada, it is anticipated that the transition to these HFA or CFC-free pMDIs will be complete by the year 2005. Initially, an HFA pMDI was to be equivalent to the CFC pMDI being replaced, in terms of aerosol properties and effective clinical dose. However, this will not necessarily be the situation, particularly for some corticosteroid products. Currently, only one CFC-free formulation is available in Canada - Airomir, a HFA salbutamol pMDI. This paper discusses the in vitro aerosol characteristics, in vivo deposition and clinical data for several HFA pMDIs for which there are data available in the literature. Alternative delivery systems to the pMDI, namely, dry powder inhalers and nebulizers, are briefly reviewed.

  10. Heart-targeted nanoscale drug delivery systems.

    PubMed

    Liu, Meifang; Li, Minghui; Wang, Guangtian; Liu, Xiaoying; Liu, Daming; Peng, Haisheng; Wang, Qun

    2014-09-01

    The efficacious delivery of drugs to the heart is an important treatment strategy for various heart diseases. Nanocarriers have shown increasing promise in targeted drug delivery systems. The success of nanocarriers for delivering drugs to therapeutic sites in the heart mainly depends on specific target sites, appropriate drug delivery carriers and effective targeting ligands. Successful targeted drug delivery suggests the specific deposition of a drug in the heart with minimal effects on other organs after administration. This review discusses the pathological manifestations, pathogenesis, therapeutic limitations and new therapeutic advances in various heart diseases. In particular, we summarize the recent advances in heart-targeted nanoscale drug delivery systems, including dendrimers, liposomes, polymer-drug conjugates, microparticles, nanostents, nanoparticles, micelles and microbubbles. Current clinical trials, the commercial market and future perspective are further discussed in the conclusions.

  11. Effect of Intrafraction Prostate Motion on Proton Pencil Beam Scanning Delivery: A Quantitative Assessment

    SciTech Connect

    Tang, Shikui; Deville, Curtiland; McDonough, James; Tochner, Zelig; Wang, Ken Kang-Hsin; Vapiwala, Neha; Both, Stefan

    2013-10-01

    Purpose: To assess the dosimetric impact caused by the interplay between intrafraction prostate motion and the intermittent delivery of proton pencil beam scanning (PBS). Methods and Materials: A cohort of 10 prostate patients was treated with PBS using a bilateral single-field uniform dose (SFUD) modality. Bilateral intensity-modulated proton therapy (IMPT) plans were generated for comparison. Because beam-on time in PBS was intermittent, the actual beam-on time was determined from treatment logs. Prostate motion was generalized according to real-time Calypso tracking data from our previously reported prospective photon trial. We investigated potential dose deviations by considering the interplay effect resulting from the worst-case scenario motion and the PBS delivery sequence. Results: For both bilateral-field SFUD and IMPT plans, clinical target volume (CTV) D{sub 99}% coverage was degraded <2% owing to prostate intrafraction motion when averaged over the course of treatment, but was >10% for the worst fraction. The standard deviation of CTV D{sub 99}% distribution was approximately 1.2%. The CTV coverage of individual fields in SFUD plans degraded as time elapsed after the initial alignment, owing to prostate drift. Intensity-modulated proton therapy and SFUD demonstrated comparable results when bilateral opposed fields were used. Single-field SFUD plans that were repainted twice, which could reduce half of the treatment time, resulted in similar CTV coverage as bilateral-field plans. Conclusions: Intrafraction prostate motion affects the actual delivered dose to CTV; however, when averaged over the course of treatment, CTV D{sub 99}% coverage degraded only approximately 2% even for the worst-case scenario. The IMPT plan results are comparable to those of the SFUD plan, and similar coverage can be achieved if treated by SFUD 1 lateral field per day when rescanning the field twice to shorten the treatment time and mitigate intrafraction motion.

  12. Alternative delivery systems in rural areas.

    PubMed Central

    Christianson, J B

    1989-01-01

    Alternative delivery systems, such as HMOs, PPOs, and primary care case-management programs, have a long history in rural America despite significant impediments to their development. However, little is known about the effect of these systems on rural communities and their medical care delivery systems. Existing studies, which focus on rural HMOs, are qualitative in nature and generally are directed at identifying factors that facilitate or retard HMO development. Despite their limitations, the studies do raise a variety of issues deserving of quantitative analysis. Research is now needed that (1) investigates the effect of rural alternative delivery systems on the cost and quality of care received by rural residents, (2) assesses the effectiveness of different mechanisms used by these systems to contain costs, (3) estimates the effect of alternative delivery systems on rural providers, (4) determines the extent to which the presence or absence of alternative delivery systems influences physician decisions to locate in rural areas, (5) identifies factors that are important in consumer decisions to enroll or not enroll in a rural alternative delivery system, and (6) analyzes the diffusion patterns of these systems in rural areas. PMID:2645250

  13. Hydrogen storage and delivery system development

    SciTech Connect

    Handrock, J.L.; Wally, K.; Raber, T.N.

    1995-09-01

    Hydrogen storage and delivery is an important element in effective hydrogen utilization for energy applications and is an important part of the FY1994-1998 Hydrogen Program Implementation Plan. The purpose of this project is to develop a platform for the engineering evaluation of hydrogen storage and delivery systems with an added focus on lightweight hydride utilization. Hybrid vehicles represent the primary application area of interest, with secondary interests including such items as existing vehicles and stationary uses. The near term goal is the demonstration of an internal combustion engine/storage/delivery subsystem. The long term goal is optimization of storage technologies for both vehicular and industrial stationary uses. In this project an integrated approach is being used to couple system operating characteristics to hardware development. A model has been developed which integrates engine and storage material characteristics into the design of hydride storage and delivery systems. By specifying engine operating parameters, as well as a variety of storage/delivery design features, hydride bed sizing calculations are completed. The model allows engineering trade-off studies to be completed on various hydride material/delivery system configurations. A more generalized model is also being developed to allow the performance characteristics of various hydrogen storage and delivery systems to be compared (liquid, activated carbon, etc.). Many of the features of the hydride storage model are applicable to the development of this more generalized model.

  14. Radiation sterilization of new drug delivery systems

    PubMed Central

    Abuhanoğlu, Gürhan

    2014-01-01

    Radiation sterilization has now become a commonly used method for sterilization of several active ingredients in drugs or drug delivery systems containing these substances. In this context, many applications have been performed on the human products that are required to be sterile, as well as on pharmaceutical products prepared to be developed. The new drug delivery systems designed to deliver the medication to the target tissue or organ, such as microspheres, nanospheres, microemulsion, and liposomal systems, have been sterilized by gamma (γ) and beta (β) rays, and more recently, by e-beam sterilization. In this review, the sterilization of new drug delivery systems was discussed other than conventional drug delivery systems by γ irradiation. PMID:24936306

  15. Development of proton CT imaging system for evaluation of proton range calculation accuracy

    NASA Astrophysics Data System (ADS)

    Tanaka, Sodai; Nishio, Teiji; Matsushita, Keiichiro; Tsuneda, Masato; Aono, Yuki; Kabuki, Shigeto; Sugiura, Akinori; Uesaka, Mitsuru

    2014-09-01

    [Purpose] In treatment planning of proton therapy, X-ray CT image is generally utilized for proton dose and range calculations in a patient body. However, there is an error of the conversion from CT value to WEL (Water Equivalent Length), and it turns into the error of proton range calculation. Therefore, WEL can be directly derived by use of pixel value on proton CT (pCT) image. The purpose of this study is development of a simple and convenient pCT imaging system for evaluation of proton range calculation accuracy. [Method] PCT imaging system was constructed with a plastic scintillator and a cooled CCD camera, which acquires the image of integrated value of the scintillation light toward the beam direction. Experiment for evaluation of this system with 70-MeV protons provided by NIRS cyclotron was performed. The proton beam was irradiated to objects of water and other substances phantom with complicated shape. The pCT image reconstructed from the experimental data was quantitatively evaluated. [Result] Construction of pCT image of various objects was successful. The value of WEL factor of water was 1.0 +/-0.1. [Conclusion] The simple and convenient pCT imaging system for evaluation of proton range calculation accuracy was developed and was evaluated by experiment using proton beam.

  16. WEDDS: The WITS Encrypted Data Delivery System

    NASA Technical Reports Server (NTRS)

    Norris, J.; Backes, P.

    1999-01-01

    WEDDS, the WITS Encrypted Data Delivery System, is a framework for supporting distributed mission operations by automatically transferring sensitive mission data in a secure and efficient manner to and from remote mission participants over the internet.

  17. Small Business Innovation Research Award Success Story: Proton Energy Systems

    SciTech Connect

    2011-04-01

    This success story describes Proton Energy Systems, a small business that designs and manufactures proton exchange membrane (PEM) electrolysis sytems to produce hydrogen from water. The U.S. Department of Energy's Fuel Cell Technologies Program has supported much of Proton's technology development through Small Business Innovation Research (SBIR) Awards and other non-SBIR funding.

  18. Imaging of prompt gamma rays emitted during delivery of clinical proton beams with a Compton camera: feasibility studies for range verification

    NASA Astrophysics Data System (ADS)

    Polf, Jerimy C.; Avery, Stephen; Mackin, Dennis S.; Beddar, Sam

    2015-09-01

    The purpose of this paper is to evaluate the ability of a prototype Compton camera (CC) to measure prompt gamma rays (PG) emitted during delivery of clinical proton pencil beams for prompt gamma imaging (PGI) as a means of providing in vivo verification of the delivered proton radiotherapy beams. A water phantom was irradiated with clinical 114 MeV and 150 MeV proton pencil beams. Up to 500 cGy of dose was delivered per irradiation using clinical beam currents. The prototype CC was placed 15 cm from the beam central axis and PGs from 0.2 MeV up to 6.5 MeV were measured during irradiation. From the measured data (2D) images of the PG emission were reconstructed. (1D) profiles were extracted from the PG images and compared to measured depth dose curves of the delivered proton pencil beams. The CC was able to measure PG emission during delivery of both 114 MeV and 150 MeV proton beams at clinical beam currents. 2D images of the PG emission were reconstructed for single 150 MeV proton pencil beams as well as for a 5   ×   5 cm mono-energetic layer of 114 MeV pencil beams. Shifts in the Bragg peak (BP) range were detectable on the 2D images. 1D profiles extracted from the PG images show that the distal falloff of the PG emission profile lined up well with the distal BP falloff. Shifts as small as 3 mm in the beam range could be detected from the 1D PG profiles with an accuracy of 1.5 mm or better. However, with the current CC prototype, a dose of 400 cGy was required to acquire adequate PG signal for 2D PG image reconstruction. It was possible to measure PG interactions with our prototype CC during delivery of proton pencil beams at clinical dose rates. Images of the PG emission could be reconstructed and shifts in the BP range were detectable. Therefore PGI with a CC for in vivo range verification during proton treatment delivery is feasible. However, improvements in the prototype CC detection efficiency and reconstruction algorithms are necessary

  19. Imaging of prompt gamma rays emitted during delivery of clinical proton beams with a Compton camera: feasibility studies for range verification.

    PubMed

    Polf, Jerimy C; Avery, Stephen; Mackin, Dennis S; Beddar, Sam

    2015-09-21

    The purpose of this paper is to evaluate the ability of a prototype Compton camera (CC) to measure prompt gamma rays (PG) emitted during delivery of clinical proton pencil beams for prompt gamma imaging (PGI) as a means of providing in vivo verification of the delivered proton radiotherapy beams. A water phantom was irradiated with clinical 114 MeV and 150 MeV proton pencil beams. Up to 500 cGy of dose was delivered per irradiation using clinical beam currents. The prototype CC was placed 15 cm from the beam central axis and PGs from 0.2 MeV up to 6.5 MeV were measured during irradiation. From the measured data (2D) images of the PG emission were reconstructed. (1D) profiles were extracted from the PG images and compared to measured depth dose curves of the delivered proton pencil beams. The CC was able to measure PG emission during delivery of both 114 MeV and 150 MeV proton beams at clinical beam currents. 2D images of the PG emission were reconstructed for single 150 MeV proton pencil beams as well as for a 5   ×   5 cm mono-energetic layer of 114 MeV pencil beams. Shifts in the Bragg peak (BP) range were detectable on the 2D images. 1D profiles extracted from the PG images show that the distal falloff of the PG emission profile lined up well with the distal BP falloff. Shifts as small as 3 mm in the beam range could be detected from the 1D PG profiles with an accuracy of 1.5 mm or better. However, with the current CC prototype, a dose of 400 cGy was required to acquire adequate PG signal for 2D PG image reconstruction. It was possible to measure PG interactions with our prototype CC during delivery of proton pencil beams at clinical dose rates. Images of the PG emission could be reconstructed and shifts in the BP range were detectable. Therefore PGI with a CC for in vivo range verification during proton treatment delivery is feasible. However, improvements in the prototype CC detection efficiency and reconstruction algorithms are necessary

  20. Cyclodextrins in delivery systems: Applications

    PubMed Central

    Tiwari, Gaurav; Tiwari, Ruchi; Rai, Awani K.

    2010-01-01

    Cyclodextrins (CDs) are a family of cyclic oligosaccharides with a hydrophilic outer surface and a lipophilic central cavity. CD molecules are relatively large with a number of hydrogen donors and acceptors and, thus in general, they do not permeate lipophilic membranes. In the pharmaceutical industry, CDs have mainly been used as complexing agents to increase aqueous solubility of poorly soluble drugs and to increase their bioavailability and stability. CDs are used in pharmaceutical applications for numerous purposes, including improving the bioavailability of drugs. Current CD-based therapeutics is described and possible future applications are discussed. CD-containing polymers are reviewed and their use in drug delivery is presented. Of specific interest is the use of CD-containing polymers to provide unique capabilities for the delivery of nucleic acids. Studies in both humans and animals have shown that CDs can be used to improve drug delivery from almost any type of drug formulation. Currently, there are approximately 30 different pharmaceutical products worldwide containing drug/CD complexes in the market. PMID:21814436

  1. Planetary Regolith Delivery Systems for ISRU

    NASA Technical Reports Server (NTRS)

    Mantovani, James G.; Townsend, Ivan I., III

    2012-01-01

    The challenges associated with collecting regolith on a planetary surface and delivering it to an in-situ resource utilization system differ significantly from similar activities conducted on Earth. Since system maintenance on a planetary body can be difficult or impossible to do, high reliability and service life are expected of a regolith delivery system. Mission costs impose upper limits on power and mass. The regolith delivery system must provide a leak-tight interface between the near-vacuum planetary surface and the pressurized ISRU system. Regolith delivery in amounts ranging from a few grams to tens of kilograms may be required. Finally, the spent regolith must be removed from the ISRU chamber and returned to the planetary environment via dust tolerant valves capable of operating and sealing over a large temperature range. This paper will describe pneumatic and auger regolith transfer systems that have already been field tested for ISRU, and discuss other systems that await future field testing.

  2. COMPACT PROTON INJECTOR AND FIRST ACCELERATOR SYSTEM TEST FOR COMPACT PROTON DIELECTRIC WALL CANCER THERAPY ACCELERATOR

    SciTech Connect

    Chen, Y; Guethlein, G; Caporaso, G; Sampayan, S; Blackfield, D; Cook, E; Falabella, S; Harris, J; Hawkins, S; Nelson, S; Poole, B; Richardson, R; Watson, J; Weir, J; Pearson, D

    2009-04-23

    A compact proton accelerator for cancer treatment is being developed by using the high-gradient dielectric insulator wall (DWA) technology [1-4]. We are testing all the essential DWA components, including a compact proton source, on the First Article System Test (FAST). The configuration and progress on the injector and FAST will be presented.

  3. Goals for Postsecondary Instructional Delivery Systems.

    ERIC Educational Resources Information Center

    Knapp, Stuart E.; Valentine, Carol A.

    Extrapolating from the trends in postsecondary instructional delivery systems identified by Brown, Lewis and Harcleroad, this report attempts to identify how these trends might be implemented in Oregon. Separating the systems into technology-centered and people-centered, the report proposes future applications of dial access systems, self learning…

  4. Kontrollierte therapeutische Systeme (Controlled drug delivery systems)

    NASA Astrophysics Data System (ADS)

    Ha, Suk-Woo; Wintermantel, Erich

    Es gibt eine grosse Anzahl von Arzneistoffen, die nicht mit der höchsten Effizienz eingesetzt werden können, weil das geeignete therapeutische System (drug delivery system) für die optimale Applikation fehlt. Viele Arzneistoffe setzen eine häufige Anwendung voraus und sind oft mit mehr oder weniger starken Nebenwirkungen oder aber mit Beeinträchtigungen von Arbeits- und Lebensrhythmus der Patienten verbunden. Der therapeutische Erfolg einer medikamentösen Behandlung setzt eine korrekte Diagnose, die Wahl der richtigen Wirksubstanz sowie ihr Vorliegen in geeigneter Darreichungsform voraus. Zudem muss ein genauer Verabreichungsplan erstellt werden, dessen Einhaltung seitens der Patienten eine wesentliche Voraussetzung für die optimale Wirkung des Arzneistoffes ist. Das Mass, mit dem eine Wirksubstanz therapeutisch voll genutzt werden kann, korreliert direkt mit der Darreichungsform, in der sie angewandt wird. Da viele hochwirksame Arzneimittel bereits existieren, hat sich, neben Neuentwicklungen, das Interesse im vergangenen Jahrzehnt der Optimierung von Arzneimittelwirkungen durch neue Darreichungsformen zugewandt.

  5. Modeling and optimization of a time-resolved proton radiographic imaging system for proton cancer treatment

    NASA Astrophysics Data System (ADS)

    Han, Bin

    This dissertation describes a research project to test the clinical utility of a time-resolved proton radiographic (TRPR) imaging system by performing comprehensive Monte Carlo simulations of a physical device coupled with realistic lung cancer patient anatomy defined by 4DCT for proton therapy. A time-resolved proton radiographic imaging system was modeled through Monte Carlo simulations. A particle-tracking feature was employed to evaluate the performance of the proton imaging system, especially in its ability to visualize and quantify proton range variations during respiration. The Most Likely Path (MLP) algorithm was developed to approximate the multiple Coulomb scattering paths of protons for the purpose of image reconstruction. Spatial resolution of ˜ 1 mm and range resolution of 1.3% of the total range were achieved using the MLP algorithm. Time-resolved proton radiographs of five patient cases were reconstructed to track tumor motion and to calculate water equivalent length variations. By comparing with direct 4DCT measurement, the accuracy of tumor tracking was found to be better than 2 mm in five patient cases. Utilizing tumor tracking information to reduce margins to the planning target volume, a gated treatment plan was compared with un-gated treatment plan. The equivalent uniform dose (EUD) and the normal tissue complication probability (NTCP) were used to quantify the gain in the quality of treatments. The EUD of the OARs was found to be reduced up to 11% and the corresponding NTCP of organs at risk (OARs) was found to be reduced up to 16.5%. These results suggest that, with image guidance by proton radiography, dose to OARs can be reduced and the corresponding NTCPs can be significantly reduced. The study concludes that the proton imaging system can accurately track the motion of the tumor and detect the WEL variations, leading to potential gains in using image-guided proton radiography for lung cancer treatments.

  6. Assessing the quality of proton PBS treatment delivery using machine log files: comprehensive analysis of clinical treatments delivered at PSI Gantry 2.

    PubMed

    Scandurra, D; Albertini, F; van der Meer, R; Meier, G; Weber, D C; Bolsi, A; Lomax, A

    2016-02-01

    Pencil beam scanning (PBS) proton therapy requires the delivery of many thousand proton beams, each modulated for position, energy and monitor units, to provide a highly conformal patient treatment. The quality of the treatment is dependent on the delivery accuracy of each beam and at each fraction. In this work we describe the use of treatment log files, which are a record of the machine parameters for a given field delivery on a given fraction, to investigate the integrity of treatment delivery compared to the nominal planned dose. The dosimetry-relevant log file parameters are used to reconstruct the 3D dose distribution on the patient anatomy, using a TPS-independent dose calculation system. The analysis was performed for patients treated at Paul Scherrer Institute on Gantry 2, both for individual fields and per series (or plan), and delivery quality was assessed by determining the percentage of voxels in the log file dose distribution within  +/-  1% of the nominal dose. It was seen that, for all series delivered, the mean pass rate is 96.4%. Furthermore, this work establishes a correlation between the delivery quality of a field and the beam position accuracy. This correlation is evident for all delivered fields regardless of individual patient or plan characteristics. We have also detailed further usefulness of log file analysis within our clinical workflow. In summary, we have highlighted that the integrity of PBS treatment delivery is dependent on daily machine performance and is specifically highly correlated with the accuracy of beam position. We believe this information will be useful for driving machine performance improvements in the PBS field.

  7. Assessing the quality of proton PBS treatment delivery using machine log files: comprehensive analysis of clinical treatments delivered at PSI Gantry 2

    NASA Astrophysics Data System (ADS)

    Scandurra, D.; Albertini, F.; van der Meer, R.; Meier, G.; Weber, D. C.; Bolsi, A.; Lomax, A.

    2016-02-01

    Pencil beam scanning (PBS) proton therapy requires the delivery of many thousand proton beams, each modulated for position, energy and monitor units, to provide a highly conformal patient treatment. The quality of the treatment is dependent on the delivery accuracy of each beam and at each fraction. In this work we describe the use of treatment log files, which are a record of the machine parameters for a given field delivery on a given fraction, to investigate the integrity of treatment delivery compared to the nominal planned dose. The dosimetry-relevant log file parameters are used to reconstruct the 3D dose distribution on the patient anatomy, using a TPS-independent dose calculation system. The analysis was performed for patients treated at Paul Scherrer Institute on Gantry 2, both for individual fields and per series (or plan), and delivery quality was assessed by determining the percentage of voxels in the log file dose distribution within  +/-  1% of the nominal dose. It was seen that, for all series delivered, the mean pass rate is 96.4%. Furthermore, this work establishes a correlation between the delivery quality of a field and the beam position accuracy. This correlation is evident for all delivered fields regardless of individual patient or plan characteristics. We have also detailed further usefulness of log file analysis within our clinical workflow. In summary, we have highlighted that the integrity of PBS treatment delivery is dependent on daily machine performance and is specifically highly correlated with the accuracy of beam position. We believe this information will be useful for driving machine performance improvements in the PBS field.

  8. Assessing the quality of proton PBS treatment delivery using machine log files: comprehensive analysis of clinical treatments delivered at PSI Gantry 2.

    PubMed

    Scandurra, D; Albertini, F; van der Meer, R; Meier, G; Weber, D C; Bolsi, A; Lomax, A

    2016-02-01

    Pencil beam scanning (PBS) proton therapy requires the delivery of many thousand proton beams, each modulated for position, energy and monitor units, to provide a highly conformal patient treatment. The quality of the treatment is dependent on the delivery accuracy of each beam and at each fraction. In this work we describe the use of treatment log files, which are a record of the machine parameters for a given field delivery on a given fraction, to investigate the integrity of treatment delivery compared to the nominal planned dose. The dosimetry-relevant log file parameters are used to reconstruct the 3D dose distribution on the patient anatomy, using a TPS-independent dose calculation system. The analysis was performed for patients treated at Paul Scherrer Institute on Gantry 2, both for individual fields and per series (or plan), and delivery quality was assessed by determining the percentage of voxels in the log file dose distribution within  +/-  1% of the nominal dose. It was seen that, for all series delivered, the mean pass rate is 96.4%. Furthermore, this work establishes a correlation between the delivery quality of a field and the beam position accuracy. This correlation is evident for all delivered fields regardless of individual patient or plan characteristics. We have also detailed further usefulness of log file analysis within our clinical workflow. In summary, we have highlighted that the integrity of PBS treatment delivery is dependent on daily machine performance and is specifically highly correlated with the accuracy of beam position. We believe this information will be useful for driving machine performance improvements in the PBS field. PMID:26767316

  9. Active site proton delivery and the lyase activity of human CYP17A1

    SciTech Connect

    Khatri, Yogan; Gregory, Michael C.; Grinkova, Yelena V.; Denisov, Ilia G.; Sligar, Stephen G.

    2014-01-03

    Highlights: •The disruption of PREG/PROG hydroxylation activity by T306A showed the participation of Cpd I. •T306A supports the involvement of a nucleophilic peroxo-anion during lyase activity. •The presence of cytochrome b{sub 5} augments C–C lyase activity. •Δ5-Steroids are preferred substrates for CYP17 catalysis. -- Abstract: Cytochrome P450 CYP17A1 catalyzes a series of reactions that lie at the intersection of corticoid and androgen biosynthesis and thus occupies an essential role in steroid hormone metabolism. This multifunctional enzyme catalyzes the 17α-hydroxylation of Δ4- and Δ5-steroids progesterone and pregnenolone to form the corresponding 17α-hydroxy products through its hydroxylase activity, and a subsequent 17,20-carbon–carbon scission of pregnene-side chain produce the androgens androstenedione (AD) and dehydroepiandrosterone (DHEA). While the former hydroxylation reaction is believed to proceed through a conventional “Compound I” rebound mechanism, it has been suggested that the latter carbon cleavage is initiated by an iron-peroxy intermediate. We report on the role of Thr306 in CYP17 catalysis. Thr306 is a member of the conserved acid/alcohol pair thought to be essential for the efficient delivery of protons required for hydroperoxoanion heterolysis and formation of Compound I in the cytochromes P450. Wild type and T306A CYP17A1 self-assembled in Nanodiscs were used to quantitate turnover and coupling efficiencies of CYP17’s physiological Δ4- and Δ5-substrates. We observed that T306A co-incorporated in Nanodiscs with its redox partner cytochrome P450 oxidoreductase, coupled NADPH only by 0.9% and 0.7% compared to the wild type (97% and 22%) during the conversion of pregnenolone and progesterone, respectively, to the corresponding 17-OH products. Despite increased oxidation of pyridine nucleotide, hydroxylase activity was drastically diminished in the T306A mutant, suggesting a high degree of uncoupling in which reducing

  10. Nanomedicine-nanoscale drugs and delivery systems.

    PubMed

    Singh, Surya

    2010-12-01

    Significant progress has been made in nanoscale drugs and delivery systems employing diverse chemical formulations to facilitate the rate of drug delivery and release from the human body. The biocompatible nanomaterials have been used in biological markers, contrast agents for biological imaging, healthcare products, pharmaceuticals, drug-delivery systems as well as in detection, diagnosis and treatment of various types of diseases. Nanomedicines offer delivery of potential drugs to human organs which were previously beyond reach of microscale drugs due to specific biological barriers. The nanoscale systems work as nanocarriers for the delivery of drugs. The nanocarriers are made of biocompatible and biodegradable materials such as synthetic proteins, peptides, lipids, polysaccharides, biodegradable polymers and fibers. This review article reports the recent developments in the field of nanomedicine covering biodegradable polymers, nanoparticles, cyclodextrin, dendrimeres, liposomes and lipid-based nanocarriers, nanofibers, nanowires and carbon nanotubes and their chemical functionalization for distribution to different organs, their solubility, surface, chemical and biological properties, stability and release systems. The toxicity and safety of nanomaterials on human health is also briefly discussed.

  11. Educational Power Tools: New Instructional Delivery Systems.

    ERIC Educational Resources Information Center

    Van Horn, Royal

    1991-01-01

    New instructional delivery systems are needed to individualize instruction, relieve the teacher's burden as sole information provider, and meet the challenge of student diversity. Microcomputers, optical memory devices, videodiscs, and hypermedia programs are being combined to create integrated learning systems, multimedia work stations, and other…

  12. New aspects of nanopharmaceutical delivery systems.

    PubMed

    Marcato, Priscyla D; Durán, Nelson

    2008-05-01

    Nanobiotechnology, involving biological systems manufactured at the molecular level, is a multidisciplinary field that has fostered the development of nanoscaled pharmaceutical delivery devices. Micelles, liposomes, solid lipid nanoparticles, polymeric nanoparticles, functionalized nanoparticles, nanocrystals, cyclodextrins, dendrimers, nanotubes and metallic nanoparticles have been used as strategies to deliver conventional pharmaceuticals or substances such as peptides, recombinant proteins, vaccines and nucleotides. Nanoparticles and other colloidal pharmaceutical delivery systems modify many physicochemical properties, thus resulting in changes in the body distribution and other pharmacological processes. These changes can lead to pharmaceutical delivery at specific sites and reduce side effects. Therefore, nanoparticles can improve the therapeutic efficiency, being excellent carriers for biological molecules, including enzymes, recombinant proteins and nucleic acid. This review discusses different pharmaceutical carrier systems, and their potential and limitations in the field of pharmaceutical technology. Products with these technologies which have been approved by the FDA in different clinical phases and which are on the market will be also discussed.

  13. Optimization of Proton CT Detector System and Image Reconstruction Algorithm for On-Line Proton Therapy.

    PubMed

    Lee, Chae Young; Song, Hankyeol; Park, Chan Woo; Chung, Yong Hyun; Kim, Jin Sung; Park, Justin C

    2016-01-01

    The purposes of this study were to optimize a proton computed tomography system (pCT) for proton range verification and to confirm the pCT image reconstruction algorithm based on projection images generated with optimized parameters. For this purpose, we developed a new pCT scanner using the Geometry and Tracking (GEANT) 4.9.6 simulation toolkit. GEANT4 simulations were performed to optimize the geometric parameters representing the detector thickness and the distance between the detectors for pCT. The system consisted of four silicon strip detectors for particle tracking and a calorimeter to measure the residual energies of the individual protons. The optimized pCT system design was then adjusted to ensure that the solution to a CS-based convex optimization problem would converge to yield the desired pCT images after a reasonable number of iterative corrections. In particular, we used a total variation-based formulation that has been useful in exploiting prior knowledge about the minimal variations of proton attenuation characteristics in the human body. Examinations performed using our CS algorithm showed that high-quality pCT images could be reconstructed using sets of 72 projections within 20 iterations and without any streaks or noise, which can be caused by under-sampling and proton starvation. Moreover, the images yielded by this CS algorithm were found to be of higher quality than those obtained using other reconstruction algorithms. The optimized pCT scanner system demonstrated the potential to perform high-quality pCT during on-line image-guided proton therapy, without increasing the imaging dose, by applying our CS based proton CT reconstruction algorithm. Further, we make our optimized detector system and CS-based proton CT reconstruction algorithm potentially useful in on-line proton therapy.

  14. Optimization of Proton CT Detector System and Image Reconstruction Algorithm for On-Line Proton Therapy.

    PubMed

    Lee, Chae Young; Song, Hankyeol; Park, Chan Woo; Chung, Yong Hyun; Kim, Jin Sung; Park, Justin C

    2016-01-01

    The purposes of this study were to optimize a proton computed tomography system (pCT) for proton range verification and to confirm the pCT image reconstruction algorithm based on projection images generated with optimized parameters. For this purpose, we developed a new pCT scanner using the Geometry and Tracking (GEANT) 4.9.6 simulation toolkit. GEANT4 simulations were performed to optimize the geometric parameters representing the detector thickness and the distance between the detectors for pCT. The system consisted of four silicon strip detectors for particle tracking and a calorimeter to measure the residual energies of the individual protons. The optimized pCT system design was then adjusted to ensure that the solution to a CS-based convex optimization problem would converge to yield the desired pCT images after a reasonable number of iterative corrections. In particular, we used a total variation-based formulation that has been useful in exploiting prior knowledge about the minimal variations of proton attenuation characteristics in the human body. Examinations performed using our CS algorithm showed that high-quality pCT images could be reconstructed using sets of 72 projections within 20 iterations and without any streaks or noise, which can be caused by under-sampling and proton starvation. Moreover, the images yielded by this CS algorithm were found to be of higher quality than those obtained using other reconstruction algorithms. The optimized pCT scanner system demonstrated the potential to perform high-quality pCT during on-line image-guided proton therapy, without increasing the imaging dose, by applying our CS based proton CT reconstruction algorithm. Further, we make our optimized detector system and CS-based proton CT reconstruction algorithm potentially useful in on-line proton therapy. PMID:27243822

  15. Nanotechnology-based drug delivery systems

    PubMed Central

    Suri, Sarabjeet Singh; Fenniri, Hicham; Singh, Baljit

    2007-01-01

    Nanoparticles hold tremendous potential as an effective drug delivery system. In this review we discussed recent developments in nanotechnology for drug delivery. To overcome the problems of gene and drug delivery, nanotechnology has gained interest in recent years. Nanosystems with different compositions and biological properties have been extensively investigated for drug and gene delivery applications. To achieve efficient drug delivery it is important to understand the interactions of nanomaterials with the biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signalling involved in pathobiology of the disease under consideration. Several anti-cancer drugs including paclitaxel, doxorubicin, 5-fluorouracil and dexamethasone have been successfully formulated using nanomaterials. Quantom dots, chitosan, Polylactic/glycolic acid (PLGA) and PLGA-based nanoparticles have also been used for in vitro RNAi delivery. Brain cancer is one of the most difficult malignancies to detect and treat mainly because of the difficulty in getting imaging and therapeutic agents past the blood-brain barrier and into the brain. Anti-cancer drugs such as loperamide and doxorubicin bound to nanomaterials have been shown to cross the intact blood-brain barrier and released at therapeutic concentrations in the brain. The use of nanomaterials including peptide-based nanotubes to target the vascular endothelial growth factor (VEGF) receptor and cell adhesion molecules like integrins, cadherins and selectins, is a new approach to control disease progression. PMID:18053152

  16. SU-E-T-470: Beam Performance of the Radiance 330 Proton Therapy System

    SciTech Connect

    Nazaryan, H; Nazaryan, V; Wang, F; Flanz, J; Alexandrov, V

    2014-06-01

    Purpose: The ProTom Radiance 330 proton radiotherapy system is a fully functional, compact proton radiotherapy system that provides advanced proton delivery capabilities. It supports three-dimensional beam scanning with energy and intensity modulation. A series of measurements have been conducted to characterize the beam performance of the first installation of the system at the McLaren Proton Therapy Center in Flint, Michigan. These measurements were part of the technical commissioning of the system. Select measurements and results are presented. Methods: The Radiance 330 proton beam energy range is 70–250 MeV for treatment, and up to 330 MeV for proton tomography and radiography. Its 3-D scanning capability, together with a small beam emittance and momentum spread, provides a highly efficient beam delivery. During the technical commissioning, treatment plans were created to deliver uniform maps at various energies to perform Gamma Index analysis. EBT3 Gafchromic films were irradiated using the Planned irradiation maps. Bragg Peak chamber was used to test the dynamic range during a scan in one layer for high (250 MeV) and Low (70 MeV) energies. The maximum and minimum range, range adjustment and modulation, distal dose falloff (80%–20%), pencil beam spot size, spot placement accuracy were also measured. The accuracy testing included acquiring images, image registration, receiving correction vectors and applying the corrections to the robotic patient positioner. Results: Gamma Index analysis of the Treatment Planning System (TPS) data vs. Measured data showed more than 90% of points within (3%, 3mm) for the maps created by the TPS. At Isocenter Beam Size (One sigma) < 3mm at highest energy (250 MeV) in air. Beam delivery was within 0.6 mm of the intended target at the entrance and the exit of the beam, through the phantom. Conclusion: The Radiance 330 Beam Performance Measurements have confirmed that the system operates as designed with excellent clinical

  17. Renewable energy delivery systems and methods

    DOEpatents

    Walker, Howard Andrew

    2013-12-10

    A system, method and/or apparatus for the delivery of energy at a site, at least a portion of the energy being delivered by at least one or more of a plurality of renewable energy technologies, the system and method including calculating the load required by the site for the period; calculating the amount of renewable energy for the period, including obtaining a capacity and a percentage of the period for the renewable energy to be delivered; comparing the total load to the renewable energy available; and, implementing one or both of additional and alternative renewable energy sources for delivery of energy to the site.

  18. Deep Space Systems Technology Program Future Deliveries

    NASA Technical Reports Server (NTRS)

    Salvo, Christopher G.; Keuneke, Matthew S.

    2000-01-01

    NASA is in a period of frequent launches of low cost deep space missions with challenging performance needs. The modest budgets of these missions make it impossible for each to develop its own technology, therefore, efficient and effective development and insertion of technology for these missions must be approached at a higher level than has been done in the past. The Deep Space Systems Technology Program (DSST), often referred to as X2000, has been formed to address this need. The program is divided into a series of "Deliveries" that develop and demonstrate a set of spacecraft system capabilities with broad applicability for use by multiple missions. The First Delivery Project, to be completed in 2001, will provide a one MRAD-tolerant flight computer, power switching electronics, efficient radioisotope power source, and a transponder with services at 8.4 GHz and 32 GHz bands. Plans call for a Second Delivery in late 2003 to enable complete deep space systems in the 10 to 50 kg class, and a Third Delivery built around Systems on a Chip (extreme levels of electronic and microsystems integration) around 2006. Formulation of Future Deliveries (past the First Delivery) is ongoing and includes plans for such developments as highly miniaturized digital/analog/power electronics, optical communications, multifunctional structures, miniature lightweight propulsion, advanced thermal control techniques, highly efficient radioisotope power sources, and a unified flight ground software architecture to support the needs of future highly intelligent space systems. All developments are targeted at broad applicability and reuse, and will be commercialized within the US.

  19. Tomotherapy and other innovative IMRT delivery systems.

    PubMed

    Fenwick, John D; Tomé, Wolfgang A; Soisson, Emilie T; Mehta, Minesh P; Rock Mackie, T

    2006-10-01

    Fixed-field treatments, delivered using conventional clinical linear accelerators fitted with multileaf collimators, have rapidly become the standard form of intensity-modulated radiotherapy (IMRT). Several innovative nonstandard alternatives also exist, for which delivery and treatment planning systems are now commercially available. Three of these nonstandard IMRT approaches are reviewed here: tomotherapy, robotic linear accelerators (CyberKnife, Accuray Inc., Sunnyvale, CA), and standard linear accelerators modulated by jaws alone or by their jaws acting together with a tertiary beam-masking device. Rationales for the nonstandard IMRT approaches are discussed, and elements of their delivery system designs are briefly described. Differences between fixed-field IMRT dose distributions and the distributions that can be delivered by using the nonstandard technologies are outlined. Because conventional linear accelerators are finely honed machines, innovative design enhancement of one aspect of system performance often limits another facet of machine capability. Consequently the various delivery systems may prove optimal for different types of treatment, with specific machine designs excelling for disease sites with specific target volume and normal structure topologies. However it is likely that the delivery systems will be distinguished not just by the optimality of the dose distributions they deliver, but also by factors such as the efficiency of their treatment process, the integration of their onboard imaging systems into that process, and their ability to measure and minimize or compensate for target movement, including the effects of respiratory motion.

  20. Brain drug delivery systems for neurodegenerative disorders.

    PubMed

    Garbayo, E; Ansorena, E; Blanco-Prieto, M J

    2012-09-01

    Neurodegenerative disorders (NDs) are rapidly increasing as population ages. However, successful treatments for NDs have so far been limited and drug delivery to the brain remains one of the major challenges to overcome. There has recently been growing interest in the development of drug delivery systems (DDS) for local or systemic brain administration. DDS are able to improve the pharmacological and therapeutic properties of conventional drugs and reduce their side effects. The present review provides a concise overview of the recent advances made in the field of brain drug delivery for treating neurodegenerative disorders. Examples include polymeric micro and nanoparticles, lipidic nanoparticles, pegylated liposomes, microemulsions and nanogels that have been tested in experimental models of Parkinson's, Alzheimer's and Huntington's disease. Overall, the results reviewed here show that DDS have great potential for NDs treatment. PMID:23016644

  1. Protonic transport through solitons in hydrogen-bonded systems

    NASA Astrophysics Data System (ADS)

    Kavitha, L.; Jayanthi, S.; Muniyappan, A.; Gopi, D.

    2011-09-01

    We offer an alternative route for investigating soliton solutions in hydrogen-bonded (HB) chains. We invoke the modified extended tangent hyperbolic function method coupled with symbolic computation to solve the governing equation of motion for proton dynamics. We investigate the dynamics of proton transfer in HB chains through bell-shaped soliton excitations, which trigger the bio-energy transport in most biological systems. This solitonic mechanism of proton transfer could play functional roles in muscular contraction, enzymatic activity and oxidative phosphorylation.

  2. Waste Feed Delivery Transfer System Analysis

    SciTech Connect

    JULYK, L.J.

    2000-05-05

    This document provides a documented basis for the required design pressure rating and pump pressure capacity of the Hanford Site waste-transfer system in support of the waste feed delivery to the privatization contractor for vitrification. The scope of the analysis includes the 200 East Area double-shell tank waste transfer pipeline system and the associated transfer system pumps for a11 Phase 1B and Phase 2 waste transfers from AN, AP, AW, AY, and A2 Tank Farms.

  3. Distance Learning Delivery Systems: Instructional Options.

    ERIC Educational Resources Information Center

    Steele, Ray L.

    1993-01-01

    Discusses the availability of satellite and cable programing to provide distance education opportunities in school districts. Various delivery systems are described, including telephones with speakers, personal computers, and satellite dishes; and a sidebar provides a directory of distance learning opportunities, including telecommunications…

  4. Systemic delivery of artemether by dissolving microneedles.

    PubMed

    Qiu, Yuqin; Li, Chun; Zhang, Suohui; Yang, Guozhong; He, Meilin; Gao, Yunhua

    2016-07-11

    Dissolving microneedles (DMNs) based transdermal delivery is an attractive drug delivery approach with minimal invasion. However, it is still challenging to load poorly water-soluble drugs in DMNs for systemic delivery. The aim of the study was to develop DMNs loaded with artemether (ARM) as a model drug, to enable efficient drug penetration through skin for systemic absorption and distribution. The micro-conduits created by microneedles were imaged by confocal laser scanning microscopy (CLSM), and the insertion depth was suggested to be about 270μm. The maximum amount of ARM delivered into skin was 72.67±2.69% of the initial dose loaded on DMNs preparation. Pharmacokinetics study in rats indicated a dose-dependent profile of plasma ARM concentrations, after ARM-loaded DMNs treatment. In contrast to intramuscular injection, DMNs application resulted in lower peak plasma levels, but higher plasma ARM concentration at 8h after administration. There were no significant difference in area under the curve and bioavailability between DMNs group and intramuscular group (P>0.05). Pharmacodynamics studies performed in collagen-induced arthritis (CIA) rats showed that ARM-loaded DMNs could reverse paw edema, similar to ARM intramuscular injection. In conclusion, developed DMNs provided a potential minimally invasive route for systemic delivery of poorly water-soluble drugs. PMID:27150946

  5. Integrated delivery systems focus on service delivery after capitation efforts stall.

    PubMed

    2005-03-01

    Integrated delivery systems focus on service delivery after capitation efforts stall. Integrated delivery systems are going through changes that are focusing the provider organizations more on delivering care than managing risk, says Dean C. Coddington, one of the leading researchers into capitated organizations and a senior consultant with McManis Consulting in Denver.

  6. Integrated delivery systems focus on service delivery after capitation efforts stall.

    PubMed

    2005-03-01

    Integrated delivery systems focus on service delivery after capitation efforts stall. Integrated delivery systems are going through changes that are focusing the provider organizations more on delivering care than managing risk, says Dean C. Coddington, one of the leading researchers into capitated organizations and a senior consultant with McManis Consulting in Denver. PMID:15889632

  7. Chitosan Microspheres in Novel Drug Delivery Systems

    PubMed Central

    Mitra, Analava; Dey, Baishakhi

    2011-01-01

    The main aim in the drug therapy of any disease is to attain the desired therapeutic concentration of the drug in plasma or at the site of action and maintain it for the entire duration of treatment. A drug on being used in conventional dosage forms leads to unavoidable fluctuations in the drug concentration leading to under medication or overmedication and increased frequency of dose administration as well as poor patient compliance. To minimize drug degradation and loss, to prevent harmful side effects and to increase drug bioavailability various drug delivery and drug targeting systems are currently under development. Handling the treatment of severe disease conditions has necessitated the development of innovative ideas to modify drug delivery techniques. Drug targeting means delivery of the drug-loaded system to the site of interest. Drug carrier systems include polymers, micelles, microcapsules, liposomes and lipoproteins to name some. Different polymer carriers exert different effects on drug delivery. Synthetic polymers are usually non-biocompatible, non-biodegradable and expensive. Natural polymers such as chitin and chitosan are devoid of such problems. Chitosan comes from the deacetylation of chitin, a natural biopolymer originating from crustacean shells. Chitosan is a biocompatible, biodegradable, and nontoxic natural polymer with excellent film-forming ability. Being of cationic character, chitosan is able to react with polyanions giving rise to polyelectrolyte complexes. Hence chitosan has become a promising natural polymer for the preparation of microspheres/nanospheres and microcapsules. The techniques employed to microencapsulate with chitosan include ionotropic gelation, spray drying, emulsion phase separation, simple and complex coacervation. This review focuses on the preparation, characterization of chitosan microspheres and their role in novel drug delivery systems. PMID:22707817

  8. Contemporary Proton Therapy Systems Adequately Protect Patients from Exposure to Stray Radiation

    NASA Astrophysics Data System (ADS)

    Newhauser, Wayne D.; Fontenot, Jonas D.; Taddei, Phillip J.; Mirkovic, Dragan; Giebeler, Annelise; Zhang, Rui; Mahajan, Anita; Kornguth, David; Stovall, Marilyn; Yepes, Pablo; Woo, Shiao; Mohan, Radhe

    2009-03-01

    Proton beam therapy has provided safe and effective treatments for a variety of adult cancers. In recent years, there has been increasing interest in utilizing proton therapy for pediatric cancers because it allows better sparing of healthy tissues. Minimizing exposures of normal tissues is especially important in children because they are highly susceptible to consequential late effects, including the development of a radiogenic second cancer, which may occur years or even decades after treatment of the first cancer. While the dosimetric advantage of therapeutic proton beams is well understood, relatively little attention has been paid to the whole-body exposure to stray neutron radiation that is inherent in proton therapy. In this report, we review the physical processes that lead to neutron exposures, discuss the potential for mitigating these exposures using advanced proton beam delivery systems, and present a comparative analysis of predicted second cancer incidence following various external beam therapies. In addition, we discuss uncertainties in the relative biological effectiveness of neutrons for carcinogenesis and the impact that these uncertainties have on second-cancer risk predictions for survivors of adult and childhood cancer who receive proton therapy.

  9. Contemporary Proton Therapy Systems Adequately Protect Patients from Exposure to Stray Radiation

    SciTech Connect

    Newhauser, Wayne D.; Fontenot, Jonas D.; Taddei, Phillip J.; Mirkovic, Dragan; Giebeler, Annelise; Zhang Rui; Mahajan, Anita; Kornguth, David; Stovall, Marilyn; Woo, Shiao; Mohan, Radhe; Yepes, Pablo

    2009-03-10

    Proton beam therapy has provided safe and effective treatments for a variety of adult cancers. In recent years, there has been increasing interest in utilizing proton therapy for pediatric cancers because it allows better sparing of healthy tissues. Minimizing exposures of normal tissues is especially important in children because they are highly susceptible to consequential late effects, including the development of a radiogenic second cancer, which may occur years or even decades after treatment of the first cancer. While the dosimetric advantage of therapeutic proton beams is well understood, relatively little attention has been paid to the whole-body exposure to stray neutron radiation that is inherent in proton therapy. In this report, we review the physical processes that lead to neutron exposures, discuss the potential for mitigating these exposures using advanced proton beam delivery systems, and present a comparative analysis of predicted second cancer incidence following various external beam therapies. In addition, we discuss uncertainties in the relative biological effectiveness of neutrons for carcinogenesis and the impact that these uncertainties have on second-cancer risk predictions for survivors of adult and childhood cancer who receive proton therapy.

  10. Contemporary Proton Therapy Systems Adequately Protect Patients from Exposure to Stray Radiation

    PubMed Central

    Newhauser, Wayne D.; Fontenot, Jonas D.; Taddei, Phillip J.; Mirkovic, Dragan; Giebeler, Annelise; Zhang, Rui; Mahajan, Anita; Kornguth, David; Stovall, Marilyn; Yepes, Pablo; Woo, Shiao; Mohan, Radhe

    2010-01-01

    Proton beam therapy has provided safe and effective treatments for a variety of adult cancers. In recent years, there has been increasing interest in utilizing proton therapy for pediatric cancers because it allows better sparing of healthy tissues. Minimizing exposures of normal tissues is especially important in children because they are highly susceptible to consequential late effects, including the development of a radiogenic second cancer, which may occur years or even decades after treatment of the first cancer. While the dosimetric advantage of therapeutic proton beams is well understood, relatively little attention has been paid to the whole-body exposure to stray neutron radiation that is inherent in proton therapy. In this report, we review the physical processes that lead to neutron exposures, discuss the potential for mitigating these exposures using advanced proton beam delivery systems, and present a comparative analysis of predicted second cancer incidence following various external beam therapies. In addition, we discuss uncertainties in the relative biological effectiveness of neutrons for carcinogenesis and the impact that these uncertainties have on second-cancer risk predictions for survivors of adult and childhood cancer who receive proton therapy. PMID:20844607

  11. A detection system for very low-energy protons from {beta}-delayed proton decay

    SciTech Connect

    Spiridon, A.; Pollacco, E.; Trache, L.; Simmons, E.; McCleskey, M.; Roeder, B. T.; Tribble, R. E.; Pascovici, G.; Riallot, M.; Mols, J. P.; Kebbiri, M.

    2012-11-20

    We have recently developed a gas based detection system called AstroBox, motivated by nuclear astrophysics studies. The goal was to detect very low-energy protons from {beta}-delayed p-decay with reduced beta background and improved energy resolution. The detector was tested using the {beta}-delayed proton-emitter 23Al previously studied with a set-up based on thin double-sided Si strip detectors. The proton spectrum obtained with AstroBox showed no beta background down to {approx}80 keV. The low energy (206 keV, 267 keV) proton peaks were positively identified, well separated, and the resolution was improved.

  12. Biomaterials for Nanoparticle Vaccine Delivery Systems

    PubMed Central

    Sahdev, Preety; Ochyl, Lukasz J.; Moon, James J.

    2014-01-01

    Subunit vaccination benefits from improved safety over attenuated or inactivated vaccines, but their limited capability to elicit long-lasting, concerted cellular and humoral immune responses is a major challenge. Recent studies have demonstrated that antigen delivery via nanoparticle formulations significantly improve immunogenicity of vaccines due to either intrinsic immunostimulatory properties of the materials or by co-entrapment of molecular adjuvants such as Toll-like receptor agonists. These studies have collectively shown that nanoparticles designed to mimic biophysical and biochemical cues of pathogens offer new exciting opportunities to enhance activation of innate immunity and elicit potent cellular and humoral immunity with minimal cytotoxicity. In this review, we present key research advances that were made within the last 5 years in the field of nanoparticle vaccine delivery systems. In particular, we focus on the impact of biomaterials composition, size, and surface charge of nanoparticles on modulation of particle biodistribution, delivery of antigens and immunostimulatory molecules, trafficking and targeting of antigen presenting cells, and overall immune responses in systemic and mucosal tissues. This review describes recent progresses in the design of nanoparticle vaccine delivery carriers, including liposomes, lipid-based particles, micelles and nanostructures composed of natural or synthetic polymers, and lipid-polymer hybrid nanoparticles. PMID:24848341

  13. A wireless actuating drug delivery system

    NASA Astrophysics Data System (ADS)

    Jo, Won-Jun; Baek, Seung-Ki; Park, Jung-Hwan

    2015-04-01

    A wireless actuating drug delivery system was devised. The system is based on induction heating for drug delivery. In this study, thermally generated nitrogen gas produced by induction heating of azobisisobutyronitrile (AIBN) was utilized for pressure-driven release of the drug. The delivery device consists of an actuator chamber, a drug reservoir, and a microchannel. A semicircular copper disc (5 and 6 mm in diameter and 100 µm thick), and thermal conductive tape were integrated as the heating element in the actuator chamber. The final device was 2.7 mm thick. 28 µl of drug solution were placed in the reservoir and the device released the drug quickly at the rate of 6 µl s-1 by induction heating at 160 µT of magnetic intensity. The entire drug solution was released and dispersed after subcutaneous implantation under identical experimental condition. This study demonstrates that the device was simply prepared and drug delivery could be achieved by wireless actuation of a thin, pressure-driven actuator.

  14. Boson representations of fermion systems: Proton-neutron systems

    SciTech Connect

    Sambataro, M.

    1988-05-01

    Applications of a procedure recently proposed to construct boson images of fermion Hamiltonians are shown for proton-neutron systems. First the mapping from SD fermion onto sd boson spaces is discussed and a Q/sub ..pi../xQ/sub ..nu../ interaction investigated. A Hermitian one-body Q boson operator is derived and analytical expressions for its coefficients are obtained. A (Q/sub ..pi../+Q/sub ..nu../)x(Q/sub ..pi../+Q/sub ..nu../) interaction is, then, studied for particle-hole systems and the connections with the SU/sup */(3) dynamical symmetry of the neutron-proton interacting boson model are discussed. Finally, an example of mapping from SDG onto sdg spaces is analyzed. Fermion spectra and E2 matrix elements are well reproduced in the boson spaces.

  15. Hydrogen storage and delivery system development: Fabrication

    SciTech Connect

    Handrock, J.L.; Malinowski, M.E.; Wally, K.

    1996-10-01

    Hydrogen storage and delivery is an important element in effective hydrogen utilization for energy applications and is an important part of the FY1994-1998 Hydrogen Program Implementation Plan. This project is part of the Field Work Proposal entitled Hydrogen Utilization in Internal Combustion Engines (ICE). The goal of the Hydrogen Storage and Delivery System Development Project is to expand the state-of-the-art of hydrogen storage and delivery system design and development. At the foundation of this activity is the development of both analytical and experimental evaluation platforms. These tools provide the basis for an integrated approach for coupling hydrogen storage and delivery technology to the operating characteristics of potential hydrogen energy use applications. Analytical models have been developed for internal combustion engine (ICE) hybrid and fuel cell driven vehicles. The dependence of hydride storage system weight and energy use efficiency on engine brake efficiency and exhaust temperature for ICE hybrid vehicle applications is examined. Results show that while storage system weight decreases with increasing engine brake efficiency energy use efficiency remains relatively unchanged. The development, capability, and use of a newly developed fuel cell vehicle hydride storage system model will also be discussed. As an example of model use power distribution and control for a simulated driving cycle is presented. An experimental test facility, the Hydride Bed Testing Laboratory (HBTL) has been designed and fabricated. The development of this facility and its use in storage system development will be reviewed. These two capabilities (analytical and experimental) form the basis of an integrated approach to storage system design and development. The initial focus of these activities has been on hydride utilization for vehicular applications.

  16. Hydrogen storage and delivery system development: Analysis

    SciTech Connect

    Handrock, J.L.

    1996-10-01

    Hydrogen storage and delivery is an important element in effective hydrogen utilization for energy applications and is an important part of the FY1994-1998 Hydrogen Program Implementation Plan. This project is part of the Field Work Proposal entitled Hydrogen Utilization in Internal Combustion Engines (ICE). The goal of the Hydrogen Storage and Delivery System Development Project is to expand the state-of-the-art of hydrogen storage and delivery system design and development. At the foundation of this activity is the development of both analytical and experimental evaluation platforms. These tools provide the basis for an integrated approach for coupling hydrogen storage and delivery technology to the operating characteristics of potential hydrogen energy use applications. Results of the analytical model development portion of this project will be discussed. Analytical models have been developed for internal combustion engine (ICE) hybrid and fuel cell driven vehicles. The dependence of hydride storage system weight and energy use efficiency on engine brake efficiency and exhaust temperature for ICE hybrid vehicle applications is examined. Results show that while storage system weight decreases with increasing engine brake efficiency energy use efficiency remains relatively unchanged. The development, capability, and use of a recently developed fuel cell vehicle storage system model will also be discussed. As an example of model use, power distribution and control for a simulated driving cycle is presented. Model calibration results of fuel cell fluid inlet and exit temperatures at various fuel cell idle speeds, assumed fuel cell heat capacities, and ambient temperatures are presented. The model predicts general increases in temperature with fuel cell power and differences between inlet and exit temperatures, but under predicts absolute temperature values, especially at higher power levels.

  17. Recent technologies in pulsatile drug delivery systems

    PubMed Central

    Jain, Deepika; Raturi, Richa; Jain, Vikas; Bansal, Praveen; Singh, Ranjit

    2011-01-01

    Pulsatile drug delivery systems (PDDS) have attracted attraction because of their multiple benefits over conventional dosage forms. They deliver the drug at the right time, at the right site of action and in the right amount, which provides more benefit than conventional dosages and increased patient compliance. These systems are designed according to the circadian rhythm of the body, and the drug is released rapidly and completely as a pulse after a lag time. These products follow the sigmoid release profile characterized by a time period. These systems are beneficial for drugs with chronopharmacological behavior, where nocturnal dosing is required, and for drugs that show the first-pass effect. This review covers methods and marketed technologies that have been developed to achieve pulsatile delivery. Marketed technologies, such as PulsincapTM, Diffucaps®, CODAS®, OROS® and PULSYSTM, follow the above mechanism to render a sigmoidal drug release profile. Diseases wherein PDDS are promising include asthma, peptic ulcers, cardiovascular ailments, arthritis and attention deficit syndrome in children and hypercholesterolemia. Pulsatile drug delivery systems have the potential to bring new developments in the therapy of many diseases. PMID:23507727

  18. Moving protons and electrons in biomimetic systems.

    PubMed

    Warren, Jeffrey J; Mayer, James M

    2015-03-17

    An enormous variety of biological redox reactions are accompanied by changes in proton content at enzyme active sites, in their associated cofactors, in substrates and/or products, and between protein interfaces. Understanding this breadth of reactivity is an ongoing chemical challenge. A great many workers have developed and investigated biomimetic model complexes to build new ways of thinking about the mechanistic underpinnings of such complex biological proton-coupled electron transfer (PCET) reactions. Of particular importance are those model reactions that involve transfer of one proton (H(+)) and one electron (e(-)), which is equivalent to transfer of a hydrogen atom (H(•)). In this Current Topic, we review key concepts in PCET reactivity and describe important advances in biomimetic PCET chemistry, with a special emphasis on research that has enhanced efforts to understand biological PCET reactions.

  19. Influence of robust optimization in intensity-modulated proton therapy with different dose delivery techniques

    SciTech Connect

    Liu Wei; Li Yupeng; Li Xiaoqiang; Cao Wenhua; Zhang Xiaodong

    2012-06-15

    Purpose: The distal edge tracking (DET) technique in intensity-modulated proton therapy (IMPT) allows for high energy efficiency, fast and simple delivery, and simple inverse treatment planning; however, it is highly sensitive to uncertainties. In this study, the authors explored the application of DET in IMPT (IMPT-DET) and conducted robust optimization of IMPT-DET to see if the planning technique's sensitivity to uncertainties was reduced. They also compared conventional and robust optimization of IMPT-DET with three-dimensional IMPT (IMPT-3D) to gain understanding about how plan robustness is achieved. Methods: They compared the robustness of IMPT-DET and IMPT-3D plans to uncertainties by analyzing plans created for a typical prostate cancer case and a base of skull (BOS) cancer case (using data for patients who had undergone proton therapy at our institution). Spots with the highest and second highest energy layers were chosen so that the Bragg peak would be at the distal edge of the targets in IMPT-DET using 36 equally spaced angle beams; in IMPT-3D, 3 beams with angles chosen by a beam angle optimization algorithm were planned. Dose contributions for a number of range and setup uncertainties were calculated, and a worst-case robust optimization was performed. A robust quantification technique was used to evaluate the plans' sensitivity to uncertainties. Results: With no uncertainties considered, the DET is less robust to uncertainties than is the 3D method but offers better normal tissue protection. With robust optimization to account for range and setup uncertainties, robust optimization can improve the robustness of IMPT plans to uncertainties; however, our findings show the extent of improvement varies. Conclusions: IMPT's sensitivity to uncertainties can be improved by using robust optimization. They found two possible mechanisms that made improvements possible: (1) a localized single-field uniform dose distribution (LSFUD) mechanism, in which the

  20. Rural medical care: an experimental delivery system.

    PubMed

    Reid, R A; Eberle, B J; Gonzales, L; Quenk, N L; Oseasohn, R

    1975-05-01

    The experimental medical care delivery system has been operational since February, 1969. An average of over 200 patient visits per month were managed at the clinic during the past year. The average visit cost is $23.00, which is competitive with cost rates at neighborhood health centers. The average time per patient visit has been approximately 1 hr and 20 min. Of persons using the clinic, the largest number are women of childbearing age. Elderly patients have visited the clinic most frequently. Illness problems have accounted for the majority of patient visits. The program represents a cooperative effort between a rural community and a university to solve a problem of national interest. The implementation of this program has provided the opportunity to operationalize the family nurse practitioner concept in a system of medical care delivery. The feasibility of providing high quality medical care in a rural community by extending medical resources concentrated in an urban area has been demonstrated. This type of delivery system does provide a viable alternative for extending medical care to rural communities. A clinic manned by paramedical personnel offers the urban medical center along with concerned physicians the opportunity to extend their resources to rural areas which have been unable to attract and retain physicians.

  1. Drug delivery system and breast cancer cells

    NASA Astrophysics Data System (ADS)

    Colone, Marisa; Kaliappan, Subramanian; Calcabrini, Annarica; Tortora, Mariarosaria; Cavalieri, Francesca; Stringaro, Annarita

    2016-06-01

    Recently, nanomedicine has received increasing attention for its ability to improve the efficacy of cancer therapeutics. Nanosized polymer therapeutic agents offer the advantage of prolonged circulation in the blood stream, targeting to specific sites, improved efficacy and reduced side effects. In this way, local, controlled delivery of the drug will be achieved with the advantage of a high concentration of drug release at the target site while keeping the systemic concentration of the drug low, thus reducing side effects due to bioaccumulation. Various drug delivery systems such as nanoparticles, liposomes, microparticles and implants have been demonstrated to significantly enhance the preventive/therapeutic efficacy of many drugs by increasing their bioavailability and targetability. As these carriers significantly increase the therapeutic effect of drugs, their administration would become less cost effective in the near future. The purpose of our research work is to develop a delivery system for breast cancer cells using a microvector of drugs. These results highlight the potential uses of these responsive platforms suited for biomedical and pharmaceutical applications. At the request of all authors of the paper an updated version was published on 12 July 2016. The manuscript was prepared and submitted without Dr. Francesca Cavalieri's contribution and her name was added without her consent. Her name has been removed in the updated and re-published article.

  2. Commissioning and initial experience with the first clinical gantry-mounted proton therapy system.

    PubMed

    Zhao, Tianyu; Sun, Baozhou; Grantham, Kevin; Rankine, Leith; Cai, Bin; Goddu, Sreekrishna M; Santanam, Lakshmi; Knutson, Nels; Zhang, Tiezhi; Reilly, Michael; Bottani, Beth; Bradley, Jeffrey; Mutic, Sasa; Klein, Eric E

    2016-01-01

    The purpose of this study is to describe the comprehensive commissioning process and initial clinical experience of the Mevion S250 proton therapy system, a gantry-mounted, single-room proton therapy platform clinically implemented in the S. Lee Kling Proton Therapy Center at Barnes-Jewish Hospital in St. Louis, MO, USA. The Mevion S250 system integrates a compact synchrocyclotron with a C-inner gantry, an image guidance system and a 6D robotic couch into a beam delivery platform. We present our commissioning process and initial clinical experience, including i) CT calibration; ii) beam data acquisition and machine characteristics; iii) dosimetric commissioning of the treatment planning system; iv) validation through the Imaging and Radiation Oncology Core credentialing process, including irradiations on the spine, prostate, brain, and lung phantoms; v) evaluation of localization accuracy of the image guidance system; and vi) initial clinical experience. Clinically, the system operates well and has provided an excellent platform for the treatment of diseases with protons. PMID:27074470

  3. Assessment of Alternative Student Aid Delivery Systems. A Context Paper.

    ERIC Educational Resources Information Center

    Advanced Technology, Inc., Reston, VA.

    Background questions to support a federally-sponsored assessment of major student aid delivery system options are addressed. Attention is directed to: (1) information needed by the U.S. Secretary of Education to decide about changes to the delivery system; (2) reasons that delivery system redesign is a critical issue; (3) what can be learned from…

  4. Central nervous system effects of whole-body proton irradiation.

    PubMed

    Sweet, Tara Beth; Panda, Nirlipta; Hein, Amy M; Das, Shoshana L; Hurley, Sean D; Olschowka, John A; Williams, Jacqueline P; O'Banion, M Kerry

    2014-07-01

    Space missions beyond the protection of Earth's magnetosphere expose astronauts to an environment that contains ionizing proton radiation. The hazards that proton radiation pose to normal tissues, such as the central nervous system (CNS), are not fully understood, although it has been shown that proton radiation affects the neurogenic environment, killing neural precursors and altering behavior. To determine the time and dose-response characteristics of the CNS to whole-body proton irradiation, C57BL/6J mice were exposed to 1 GeV/n proton radiation at doses of 0-200 cGy and behavioral, physiological and immunohistochemical end points were analyzed over a range of time points (48 h-12 months) postirradiation. These experiments revealed that proton radiation exposure leads to: 1. an acute decrease in cell division within the dentate gyrus of the hippocampus, with significant differences detected at doses as low as 10 cGy; 2. a persistent effect on proliferation in the subgranular zone, at 1 month postirradiation; 3. a decrease in neurogenesis at doses as low as 50 cGy, at 3 months postirradiation; and 4. a decrease in hippocampal ICAM-1 immunoreactivity at doses as low as 10 cGy, at 1 month postirradiation. The data presented contribute to our understanding of biological responses to whole-body proton radiation and may help reduce uncertainty in the assessment of health risks to astronauts. These findings may also be relevant to clinical proton beam therapy. PMID:24937778

  5. Recent Trends of Polymer Mediated Liposomal Gene Delivery System

    PubMed Central

    Lee, Sang-Soo; George Priya Doss, C.; Yagihara, Shin; Kim, Do-Young

    2014-01-01

    Advancement in the gene delivery system have resulted in clinical successes in gene therapy for patients with several genetic diseases, such as immunodeficiency diseases, X-linked adrenoleukodystrophy (X-ALD) blindness, thalassemia, and many more. Among various delivery systems, liposomal mediated gene delivery route is offering great promises for gene therapy. This review is an attempt to depict a portrait about the polymer based liposomal gene delivery systems and their future applications. Herein, we have discussed in detail the characteristics of liposome, importance of polymer for liposome formulation, gene delivery, and future direction of liposome based gene delivery as a whole. PMID:25250340

  6. Hypoxia Responsive Drug Delivery Systems in Tumor Therapy.

    PubMed

    Alimoradi, Houman; Matikonda, Siddharth S; Gamble, Allan B; Giles, Gregory I; Greish, Khaled

    2016-01-01

    Hypoxia is a common characteristic of solid tumors. It is mainly determined by low levels of oxygen resulting from imperfect vascular networks supplying most tumors. In an attempt to improve the present chemotherapeutic treatment and reduce associated side effects, several prodrug strategies have been introduced to achieve hypoxia-specific delivery of cytotoxic anticancer agents. With the advances in nanotechnology, novel delivery systems activated by the consequent outcomes of hypoxia have been developed. However, developing hypoxia responsive drug delivery systems (which only depend on low oxygen levels) is currently naïve. This review discusses four main hypoxia responsive delivery systems: polymeric based drug delivery systems, oxygen delivery systems combined with radiotherapy and chemotherapy, anaerobic bacteria which are used for delivery of genes to express anticancer proteins such as tumor necrosis alpha (TNF-α) and hypoxia-inducible transcription factors 1 alpha (HIF1α) responsive gene delivery systems.

  7. Ultrasound-mediated nail drug delivery system.

    PubMed

    Abadi, Danielle; Zderic, Vesna

    2011-12-01

    A novel ultrasound-mediated drug delivery system has been developed for treatment of a nail fungal disorder (onychomycosis) by improving delivery to the nail bed using ultrasound to increase the permeability of the nail. The slip-in device consists of ultrasound transducers and drug delivery compartments above each toenail. The device is connected to a computer, where a software interface allows users to select their preferred course of treatment. In in vitro testing, canine nails were exposed to 3 energy levels (acoustic power of 1.2 W and exposure durations of 30, 60, and 120 seconds). A stereo -microscope was used to determine how much of a drug-mimicking compound was delivered through the nail layers by measuring brightness on the cross section of each nail tested at each condition, where brightness level decreases coincide with increases in permeability. Each of the 3 energy levels tested showed statistical significance when compared to the control (P < .05) with a permeability factor of 1.3 after 30 seconds of exposure, 1.3 after 60 seconds, and 1.5 after 120 seconds, where a permeability factor of 1 shows no increase in permeability. Current treatments for onychomycosis include systemic, topical, and surgical. Even when used all together, these treatments typically take a long time to result in nail healing, thus making this ultrasound-mediated device a promising alternative. PMID:22124008

  8. Ultrasound-mediated nail drug delivery system.

    PubMed

    Abadi, Danielle; Zderic, Vesna

    2011-12-01

    A novel ultrasound-mediated drug delivery system has been developed for treatment of a nail fungal disorder (onychomycosis) by improving delivery to the nail bed using ultrasound to increase the permeability of the nail. The slip-in device consists of ultrasound transducers and drug delivery compartments above each toenail. The device is connected to a computer, where a software interface allows users to select their preferred course of treatment. In in vitro testing, canine nails were exposed to 3 energy levels (acoustic power of 1.2 W and exposure durations of 30, 60, and 120 seconds). A stereo -microscope was used to determine how much of a drug-mimicking compound was delivered through the nail layers by measuring brightness on the cross section of each nail tested at each condition, where brightness level decreases coincide with increases in permeability. Each of the 3 energy levels tested showed statistical significance when compared to the control (P < .05) with a permeability factor of 1.3 after 30 seconds of exposure, 1.3 after 60 seconds, and 1.5 after 120 seconds, where a permeability factor of 1 shows no increase in permeability. Current treatments for onychomycosis include systemic, topical, and surgical. Even when used all together, these treatments typically take a long time to result in nail healing, thus making this ultrasound-mediated device a promising alternative.

  9. SU-E-T-582: Evaluation of Standard Beam Delivery Devices in Proton Intracranial Radiosurgery

    SciTech Connect

    Wroe, A; Bush, D; Schulte, R; Patyal, B; Slater, J; Webster, J

    2014-06-01

    Purpose: To evaluate the use of standard apertures and range shifters for the treatment of brain metastasis in proton stereotactic radiosurgery. Methods: Five localized brain metastasis patients previously treated using our intracranial proton stereotactic radiosurgery procedure (i.e. with a custom aperture and bolus), were randomly selected from our patient cohort. The custom aperture and bolus treatment plans were used as the standard of care in this case and comparative treatment plans using the standard aperture and range shifter concept were generated. Gantry/table angle and the number of treatment beams were optimized as part of this study to evaluate the ability of the standard aperture/range shifter system to deliver a comparable treatment to the patient. Conformity index, homogeneity index, isodose volumes and integral dose were all evaluated to determine the degree of conformity of the plans created and for comparison to the custom aperture/bolus treatment modality. Results: The generated treatment plans demonstrated that the standard aperture and range shifter combination could be used to produce comparable conformity index and isodose volumes to the custom aperture/bolus case in four out of the five patients studied. In two of the patients a comparative conformity index was achieved by optimizing the angles of the 3 treatment beams, while in two of the cases 1 or 2 additional beams were required. Additionally, this system exhibited efficiency gains of 60-90% over the custom aperture bolus system in reducing the time necessary for treatment planning, device manufacture and QA. Conclusion: This work demonstrated that largely spherical shape of brain metastasis makes this target well suited to an application of standard apertures, while additionally providing efficiency gains in device manufacture and QA for treatment.

  10. Stimuli-Responsive Polymeric Systems for Controlled Protein and Peptide Delivery: Future Implications for Ocular Delivery.

    PubMed

    Mahlumba, Pakama; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Pillay, Viness

    2016-01-01

    Therapeutic proteins and peptides have become notable in the drug delivery arena for their compatibility with the human body as well as their high potency. However, their biocompatibility and high potency does not negate the existence of challenges resulting from physicochemical properties of proteins and peptides, including large size, short half-life, capability to provoke immune responses and susceptibility to degradation. Various delivery routes and delivery systems have been utilized to improve bioavailability, patient acceptability and reduce biodegradation. The ocular route remains of great interest, particularly for responsive delivery of macromolecules due to the anatomy and physiology of the eye that makes it a sensitive and complex environment. Research in this field is slowly gaining attention as this could be the breakthrough in ocular drug delivery of macromolecules. This work reviews stimuli-responsive polymeric delivery systems, their use in the delivery of therapeutic proteins and peptides as well as examples of proteins and peptides used in the treatment of ocular disorders. Stimuli reviewed include pH, temperature, enzymes, light, ultrasound and magnetic field. In addition, it discusses the current progress in responsive ocular drug delivery. Furthermore, it explores future prospects in the use of stimuli-responsive polymers for ocular delivery of proteins and peptides. Stimuli-responsive polymers offer great potential in improving the delivery of ocular therapeutics, therefore there is a need to consider them in order to guarantee a local, sustained and ideal delivery of ocular proteins and peptides, evading tissue invasion and systemic side-effects. PMID:27483234

  11. Microemulsions based transdermal drug delivery systems.

    PubMed

    Vadlamudi, Harini C; Narendran, Hyndavi; Nagaswaram, Tejeswari; Yaga, Gowri; Thanniru, Jyotsna; Yalavarthi, Prasanna R

    2014-01-01

    Since the discovery of microemulsions by Jack H Schulman, there has been huge progress made in applying microemulsion systems in plethora of research and industrial process. Microemulsions are optically isotropic systems consisting of water, oil and amphiphile. These systems are beneficial due to their thermodynamic stability, optical clarity, ease of preparation, higher diffusion and absorption rates. Moreover, it has been reported that the ingredients of microemulsion can effectively overcome the diffusion barrier and penetrate through the stratum corneum of the skin. Hence it becomes promising for both transdermal and dermal drug delivery. However, low viscosity of microemulsion restrains its applicability in pharmaceutical industry. To overcome the above drawback, the low viscous microemulsions were added to viscous gel bases to potentiate its applications as topical drug delivery systems so that various drug related toxic effects and erratic drug absorption can be avoided. The present review deals with the microemulsions, various techniques involved in the development of organic nanoparticles. The review emphasized on microemulsion based systems such as hydrogels and organogels. The physicochemical characteristics, mechanical properties, rheological and stability principles involved in microemulsion based viscous gels were also explored. PMID:25466399

  12. Making the health care delivery system accountable.

    PubMed

    Wilen, S B; Stone, B M

    1998-01-01

    Accountability has become the fact of life for the health care provider and the delivery system. Until recently, accountability has been viewed primarily through the judicial process as issues of fraud and liability, or by managed care entities through evaluation of the financial bottom line. It is this second consideration and its ramifications that will be explored in this article. Appropriate measurement tools are needed to evaluate services, delivery, performance, customer satisfaction, and outcomes assessment. Measurement tools will be considered in light of the industry's unique considerations and realities. All participants, including insurers, employers, management, and health care providers and recipients, bear responsibilities which necessitate assessment and analysis. However, until the basic question, "Who is the customer?" is resolved, accountability issues remain complex and obscured. Accountability costs and impacts must be evaluated over time. They go way beyond bottom line cost containment and reduction. Accountability will be accomplished when the health care industry implements quality and measurement concepts that yield the highest levels of validity and appropriateness for health care delivery.

  13. Modeling the Delivery Physiology of Distributed Learning Systems.

    ERIC Educational Resources Information Center

    Paquette, Gilbert; Rosca, Ioan

    2003-01-01

    Discusses instructional delivery models and their physiology in distributed learning systems. Highlights include building delivery models; types of delivery models, including distributed classroom, self-training on the Web, online training, communities of practice, and performance support systems; and actors (users) involved, including experts,…

  14. Protons and Hydroxide Ions in Aqueous Systems.

    PubMed

    Agmon, Noam; Bakker, Huib J; Campen, R Kramer; Henchman, Richard H; Pohl, Peter; Roke, Sylvie; Thämer, Martin; Hassanali, Ali

    2016-07-13

    Understanding the structure and dynamics of water's constituent ions, proton and hydroxide, has been a subject of numerous experimental and theoretical studies over the last century. Besides their obvious importance in acid-base chemistry, these ions play an important role in numerous applications ranging from enzyme catalysis to environmental chemistry. Despite a long history of research, many fundamental issues regarding their properties continue to be an active area of research. Here, we provide a review of the experimental and theoretical advances made in the last several decades in understanding the structure, dynamics, and transport of the proton and hydroxide ions in different aqueous environments, ranging from water clusters to the bulk liquid and its interfaces with hydrophobic surfaces. The propensity of these ions to accumulate at hydrophobic surfaces has been a subject of intense debate, and we highlight the open issues and challenges in this area. Biological applications reviewed include proton transport along the hydration layer of various membranes and through channel proteins, problems that are at the core of cellular bioenergetics. PMID:27314430

  15. Protons and Hydroxide Ions in Aqueous Systems.

    PubMed

    Agmon, Noam; Bakker, Huib J; Campen, R Kramer; Henchman, Richard H; Pohl, Peter; Roke, Sylvie; Thämer, Martin; Hassanali, Ali

    2016-07-13

    Understanding the structure and dynamics of water's constituent ions, proton and hydroxide, has been a subject of numerous experimental and theoretical studies over the last century. Besides their obvious importance in acid-base chemistry, these ions play an important role in numerous applications ranging from enzyme catalysis to environmental chemistry. Despite a long history of research, many fundamental issues regarding their properties continue to be an active area of research. Here, we provide a review of the experimental and theoretical advances made in the last several decades in understanding the structure, dynamics, and transport of the proton and hydroxide ions in different aqueous environments, ranging from water clusters to the bulk liquid and its interfaces with hydrophobic surfaces. The propensity of these ions to accumulate at hydrophobic surfaces has been a subject of intense debate, and we highlight the open issues and challenges in this area. Biological applications reviewed include proton transport along the hydration layer of various membranes and through channel proteins, problems that are at the core of cellular bioenergetics.

  16. Clinical characterization of a proton beam continuous uniform scanning system with dose layer stacking

    PubMed Central

    Farr, J. B.; Mascia, A. E.; Hsi, W.-C.; Allgower, C. E.; Jesseph, F.; Schreuder, A. N.; Wolanski, M.; Nichiporov, D. F.; Anferov, V.

    2008-01-01

    A proton beam delivery system on a gantry with continuous uniform scanning and dose layer stacking at the Midwest Proton Radiotherapy Institute has been commissioned and accepted for clinical use. This paper was motivated by a lack of guidance on the testing and characterization for clinical uniform scanning systems. As such, it describes how these tasks were performed with a uniform scanning beam delivery system. This paper reports the methods used and important dosimetric characteristics of radiation fields produced by the system. The commissioning data include the transverse and longitudinal dose distributions, penumbra, and absolute dose values. Using a 208 MeV cyclotron’s proton beam, the system provides field sizes up to 20 and 30 cm in diameter for proton ranges in water up to 27 and 20 cm, respectively. The dose layer stacking method allows for the flexible construction of spread-out Bragg peaks with uniform modulation of up to 15 cm in water, at typical dose rates of 1–3 Gy∕min. For measuring relative dose distributions, multielement ion chamber arrays, small-volume ion chambers, and radiographic films were employed. Measurements during the clinical commissioning of the system have shown that the lateral and longitudinal dose uniformity of 2.5% or better can be achieved for all clinically important field sizes and ranges. The measured transverse penumbra widths offer a slight improvement in comparison to those achieved with a double scattering beam spreading technique at the facility. Absolute dose measurements were done using calibrated ion chambers, thermoluminescent and alanine detectors. Dose intercomparisons conducted using various types of detectors traceable to a national standards laboratory indicate that the measured dosimetry data agree with each other within 5%. PMID:19070228

  17. Multifunctional non-viral delivery systems based on conjugated polymers.

    PubMed

    Yang, Gaomai; Lv, Fengting; Wang, Bing; Liu, Libing; Yang, Qiong; Wang, Shu

    2012-12-01

    Multifunctional nanomaterials with simultaneous therapeutic and imaging functions explore new strategies for the treatment of various diseases. Conjugated polymers (CPs) are considered as novel candidates to serve as multifunctional delivery systems due to their high fluorescence quantum yield, good photostability, and low cytotoxicity. Highly sensitive sensing and imaging properties of CPs are well reviewed, while the applications of CPs as delivery systems are rarely covered. This feature article mainly focuses on CP-based multifunctional non-viral delivery systems for drug, protein, gene, and cell delivery. Promising directions for the further development of CP-based delivery systems are also discussed.

  18. Fuel delivery system including heat exchanger means

    NASA Technical Reports Server (NTRS)

    Coffinberry, G. A. (Inventor)

    1978-01-01

    A fuel delivery system is presented wherein first and second heat exchanger means are each adapted to provide the transfer of heat between the fuel and a second fluid such as lubricating oil associated with the gas turbine engine. Valve means are included which are operative in a first mode to provide for flow of the second fluid through both first and second heat exchange means and further operative in a second mode for bypassing the second fluid around the second heat exchanger means.

  19. Provesicles as novel drug delivery systems.

    PubMed

    Bayindir, Zerrin S; Yuksel, Nilufer

    2015-01-01

    Vesicular systems exhibit many attractive properties such as controlled drug release, ability to carry both hydrophilic and hydrophobic drugs, targetability and good biocompatibility. With these unique properties they can provide improved drug bioavailability and reduced side effects. Until now, many vesicular formulations have been studied in clinical and preclinical stages. Nevertheless, the major concern about these systems is their low physicochemical stability and high manufacturing expenses. The stability problems (fusion, aggregation, sedimentation, swelling, and drug leakage during storage) associated with the aqueous nature of vesicular systems hinders their effective usage. The advances on improving the stability of vesicular systems led to the emergence of provesicular systems, which are commonly described as dry, free flowing preformulations of vesicular drug delivery systems. Provesicles form vesicular systems upon hydratation with water and exhibit the advantages of vesicular systems with improved stability. The present article briefly reviews vesicular systems (particularly liposomes and niosomes) and enlightens about the innovations in the field. Overall investigations are reviewed and the provesicle approach is explained by giving detailed information on the composition, preparation, administration and characterization methods of provesicular systems (proliposomes and proniosomes). The scope of this article is expected to give insight to the researchers and industrialists to perform further research in this area. PMID:25658383

  20. Transcutaneous immunization with Intercell's vaccine delivery system.

    PubMed

    Seid, Robert C; Look, Jee Loon; Ruiz, Christian; Frolov, Vladimir; Flyer, David; Schafer, Jason; Ellingsworth, Larry

    2012-06-19

    Transcutaneous immunization (TCI) has become an attractive alternate route of immunization due to increase understanding of the skin immune system and to recent technical innovations in skin patch delivery systems. Basic principles of TCI have been demonstrated in animal and human studies, covering a variety of bacterial, viral, and cancer diseases. At Intercell, we have advanced two major platforms of TCI: 1) a needle-free vaccine delivery patch (VDP) and 2) a vaccine enhancement patch (VEP). Simplified, the VDP contains an antigen with or without an adjuvant that is administered on the skin; while the VEP contains only the adjuvant and is used in combination with an injected vaccine. In many of our TCI studies, the VDP or VEP is routinely applied on pretreated skin, in which the stratum corneum has been partially removed by mild abrasion. Recently, we have achieved technical breakthroughs in formulating and stabilizing vaccines in a dry patch format. For instance, a microplate-based screening process has been implemented to rapidly identify excipients, singularly or in combination, to stabilize biological macromolecules in patch blend formulations. A second technical innovation is our nonwoven (patch) disc matrix-supported drying technology, which allows efficient drying of our patch formulation blend to produce dry stable dosage forms of VDP or VEP. The low cost and the facileness in the manufacturing of VDP (or VEP) combined with the development of thermostable dry patches should improve the supply chain efficiency and reduce the dependence on cold chain.

  1. Silk Electrogel Based Gastroretentive Drug Delivery System

    NASA Astrophysics Data System (ADS)

    Wang, Qianrui

    Gastric cancer has become a global pandemic and there is imperative to develop efficient therapies. Oral dosing strategy is the preferred route to deliver drugs for treating the disease. Recent studies suggested silk electro hydrogel, which is pH sensitive and reversible, has potential as a vehicle to deliver the drug in the stomach environment. The aim of this study is to establish in vitro electrogelation e-gel based silk gel as a gastroretentive drug delivery system. We successfully extended the duration of silk e-gel in artificial gastric juice by mixing silk solution with glycerol at different ratios before the electrogelation. Structural analysis indicated the extended duration was due to the change of beta sheet content. The glycerol mixed silk e-gel had good doxorubicin loading capability and could release doxorubicin in a sustained-release profile. Doxorubicin loaded silk e-gels were applied to human gastric cancer cells. Significant cell viability decrease was observed. We believe that with further characterization as well as functional analysis, the silk e-gel system has the potential to become an effective vehicle for gastric drug delivery applications.

  2. A telemedicine health care delivery system

    NASA Technical Reports Server (NTRS)

    Sanders, Jay H.

    1991-01-01

    The Interactive Telemedicine Systems (ITS) system was specifically developed to address the ever widening gap between our medical care expertise and our medical care delivery system. The frustrating reality is that as our knowledge of how to diagnose and treat medical conditions has continued to advance, the system to deliver that care has remained in an embryonic stage. This has resulted in millions of people being denied their most basic health care needs. Telemedicine utilizes an interactive video system integrated with biomedical telemetry that allows a physician at a base station specialty medical complex or teaching hospital to examine and treat a patient at multiple satellite locations, such as rural hospitals, ambulatory health centers, correctional institutions, facilities caring for the elderly, community hospital emergency departments, or international health facilities. Based on the interactive nature of the system design, the consulting physician at the base station can do a complete history and physical examination, as if the patient at the satellite site was sitting in the physician's office. This system is described.

  3. Fluid Delivery System For Capillary Electrophoretic Applications.

    DOEpatents

    Li, Qingbo; Liu, Changsheng; Kane, Thomas E.; Kernan, John R.; Sonnenschein, Bernard; Sharer, Michael V.

    2002-04-23

    An automated electrophoretic system is disclosed. The system employs a capillary cartridge having a plurality of capillary tubes. The cartridge has a first array of capillary ends projecting from one side of a plate. The first array of capillary ends are spaced apart in substantially the same manner as the wells of a microtitre tray of standard size. This allows one to simultaneously perform capillary electrophoresis on samples present in each of the wells of the tray. The system includes a stacked, dual carrousel arrangement to eliminate cross-contamination resulting from reuse of the same buffer tray on consecutive executions from electrophoresis. The system also has a gel delivery module containing a gel syringe/a stepper motor or a high pressure chamber with a pump to quickly and uniformly deliver gel through the capillary tubes. The system further includes a multi-wavelength beam generator to generate a laser beam which produces a beam with a wide range of wavelengths. An off-line capillary reconditioner thoroughly cleans a capillary cartridge to enable simultaneous execution of electrophoresis with another capillary cartridge. The streamlined nature of the off-line capillary reconditioner offers the advantage of increased system throughput with a minimal increase in system cost.

  4. Phospholipid nanodisc engineering for drug delivery systems.

    PubMed

    Murakami, Tatsuya

    2012-06-01

    Biocompatible mesoscale nanoparticles (5-100 nm in diameter) are attractive tools for drug delivery. Among them are several types of liposomes and polymer micelles already in clinical trial or use. Generally, biocompatibility of such particles is achieved by coating them with polyethylene glycol (PEG). Without PEG coating, particles are quickly trapped in the reticuloendothelial system when intravenously administered. However, recent studies have revealed several potential problems with PEG coating, including antigenicity and restriction of cellular uptake. This has motivated the development of alternative drug and gene delivery vehicles, including chemically and genetically engineered high-density lipoprotein (HDL)-like nanodiscs or "bicelles". HDL is a naturally occurring mesoscale nanoparticle that normally ferries cholesterol around in the body. Its initial "nascent" form is thought to be a simple 10 nm disc of phospholipids in a bilayer, and can be easily synthesized in vitro by mixing recombinant apoA-I proteins with various phospholipids. In this review, the use of synthetic HDL-like phospholipid nanodiscs as biocompatible drug carriers is summarized, focussing on manufacturing, size-control, drug loading and cell targeting.

  5. Oral Dispersible System: A New Approach in Drug Delivery System

    PubMed Central

    Hannan, P. A.; Khan, J. A.; Khan, A.; Safiullah, S.

    2016-01-01

    Dosage form is a mean used for the delivery of drug to a living body. In order to get the desired effect the drug should be delivered to its site of action at such rate and concentration to achieve the maximum therapeutic effect and minimum adverse effect. Since oral route is still widely accepted route but having a common drawback of difficulty in swallowing of tablets and capsules. Therefore a lot of research has been done on novel drug delivery systems. This review is about oral dispersible tablets a novel approach in drug delivery systems that are now a day's more focused in formulation world, and laid a new path that, helped the patients to build their compliance level with the therapy, also reduced the cost and ease the administration especially in case of pediatrics and geriatrics. Quick absorption, rapid onset of action and reduction in drug loss properties are the basic advantages of this dosage form. PMID:27168675

  6. Oral Dispersible System: A New Approach in Drug Delivery System.

    PubMed

    Hannan, P A; Khan, J A; Khan, A; Safiullah, S

    2016-01-01

    Dosage form is a mean used for the delivery of drug to a living body. In order to get the desired effect the drug should be delivered to its site of action at such rate and concentration to achieve the maximum therapeutic effect and minimum adverse effect. Since oral route is still widely accepted route but having a common drawback of difficulty in swallowing of tablets and capsules. Therefore a lot of research has been done on novel drug delivery systems. This review is about oral dispersible tablets a novel approach in drug delivery systems that are now a day's more focused in formulation world, and laid a new path that, helped the patients to build their compliance level with the therapy, also reduced the cost and ease the administration especially in case of pediatrics and geriatrics. Quick absorption, rapid onset of action and reduction in drug loss properties are the basic advantages of this dosage form.

  7. Leadership Dynamics Promoting Systemic Reform for Inclusive Service Delivery

    ERIC Educational Resources Information Center

    Scanlan, Martin

    2009-01-01

    This article presents a multicase study of two systems of schools striving to reform service delivery systems for students with special needs. Considering these systems as institutional actors, the study examines what promotes the understanding and implementation of special education service delivery within a system of schools in a manner that…

  8. Characterization of conformation and interaction of gene delivery vector polyethylenimine with phospholipid bilayer at different protonation state.

    PubMed

    Choudhury, Chandan Kumar; Kumar, Abhinaw; Roy, Sudip

    2013-10-14

    Polyethylenimine (PEI) is a pH sensitive polymer possessing stretched and coiled conformation at low and high pH, respectively. It is an efficient gene delivery agent. Thus, the interaction of PEI with the biomembrane is very crucial to understand the gene delivery mechanism. In this report, we have investigated the structural properties of PEI and bilayer due to the interaction of PEI with lipid molecules. PEI has coil structure at high pH while at low pH it is elongated. The neutral PEI chain predominately settles itself at the bilayer water interface. We do not find any disruption or pore formation on the bilayer due to interaction of neutral PEI chain. PEI at low pH gets elongated due to electrostatic interaction between charges of the protonated sites. This protonated PEI chain interacts with bilayer membrane, which leads to formation of water/ion channel through the membrane. We have analyzed the structure of the channel and water dynamics along the channel.

  9. Biomedical Imaging in Implantable Drug Delivery Systems

    PubMed Central

    Zhou, Haoyan; Hernandez, Christopher; Goss, Monika; Gawlik, Anna; Exner, Agata A.

    2015-01-01

    Implantable drug delivery systems (DDS) provide a platform for sustained release of therapeutic agents over a period of weeks to months and sometimes years. Such strategies are typically used clinically to increase patient compliance by replacing frequent administration of drugs such as contraceptives and hormones to maintain plasma concentration within the therapeutic window. Implantable or injectable systems have also been investigated as a means of local drug administration which favors high drug concentration at a site of interest, such as a tumor, while reducing systemic drug exposure to minimize unwanted side effects. Significant advances in the field of local DDS have led to increasingly sophisticated technology with new challenges including quantification of local and systemic pharmacokinetics and implant-body interactions. Because many of these sought-after parameters are highly dependent on the tissue properties at the implantation site, and rarely represented adequately with in vitro models, new nondestructive techniques that can be used to study implants in situ are highly desirable. Versatile imaging tools can meet this need and provide quantitative data on morphological and functional aspects of implantable systems. The focus of this review article is an overview of current biomedical imaging techniques, including magnetic resonance imaging (MRI), ultrasound imaging, optical imaging, X-ray and computed tomography (CT), and their application in evaluation of implantable DDS. PMID:25418857

  10. Direct absorbed dose to water determination based on water calorimetry in scanning proton beam delivery

    SciTech Connect

    Sarfehnia, A.; Clasie, B.; Chung, E.; Lu, H. M.; Flanz, J.; Cascio, E.; Engelsman, M.; Paganetti, H.; Seuntjens, J.

    2010-07-15

    Purpose: The aim of this manuscript is to describe the direct measurement of absolute absorbed dose to water in a scanned proton radiotherapy beam using a water calorimeter primary standard. Methods: The McGill water calorimeter, which has been validated in photon and electron beams as well as in HDR {sup 192}Ir brachytherapy, was used to measure the absorbed dose to water in double scattering and scanning proton irradiations. The measurements were made at the Massachusetts General Hospital proton radiotherapy facility. The correction factors in water calorimetry were numerically calculated and various parameters affecting their magnitude and uncertainty were studied. The absorbed dose to water was compared to that obtained using an Exradin T1 Chamber based on the IAEA TRS-398 protocol. Results: The overall 1-sigma uncertainty on absorbed dose to water amounts to 0.4% and 0.6% in scattered and scanned proton water calorimetry, respectively. This compares to an overall uncertainty of 1.9% for currently accepted IAEA TRS-398 reference absorbed dose measurement protocol. The absorbed dose from water calorimetry agrees with the results from TRS-398 well to within 1-sigma uncertainty. Conclusions: This work demonstrates that a primary absorbed dose standard based on water calorimetry is feasible in scattered and scanned proton beams.

  11. Eye tracking and gating system for proton therapy of orbital tumors

    SciTech Connect

    Shin, Dongho; Yoo, Seung Hoon; Moon, Sung Ho; Yoon, Myonggeun; Lee, Se Byeong; Park, Sung Yong

    2012-07-15

    Purpose: A new motion-based gated proton therapy for the treatment of orbital tumors using real-time eye-tracking system was designed and evaluated. Methods: We developed our system by image-pattern matching, using a normalized cross-correlation technique with LabVIEW 8.6 and Vision Assistant 8.6 (National Instruments, Austin, TX). To measure the pixel spacing of an image consistently, four different calibration modes such as the point-detection, the edge-detection, the line-measurement, and the manual measurement mode were suggested and used. After these methods were applied to proton therapy, gating was performed, and radiation dose distributions were evaluated. Results: Moving phantom verification measurements resulted in errors of less than 0.1 mm for given ranges of translation. Dosimetric evaluation of the beam-gating system versus nongated treatment delivery with a moving phantom shows that while there was only 0.83 mm growth in lateral penumbra for gated radiotherapy, there was 4.95 mm growth in lateral penumbra in case of nongated exposure. The analysis from clinical results suggests that the average of eye movements depends distinctively on each patient by showing 0.44 mm, 0.45 mm, and 0.86 mm for three patients, respectively. Conclusions: The developed automatic eye-tracking based beam-gating system enabled us to perform high-precision proton radiotherapy of orbital tumors.

  12. Implantable microchip: the futuristic controlled drug delivery system.

    PubMed

    Sutradhar, Kumar Bishwajit; Sumi, Chandra Datta

    2016-01-01

    There is no doubt that controlled and pulsatile drug delivery system is an important challenge in medicine over the conventional drug delivery system in case of therapeutic efficacy. However, the conventional drug delivery systems often offer a limited by their inability to drug delivery which consists of systemic toxicity, narrow therapeutic window, complex dosing schedule for long term treatment etc. Therefore, there has been a search for the drug delivery system that exhibit broad enhancing activity for more drugs with less complication. More recently, some elegant study has noted that, a new type of micro-electrochemical system or MEMS-based drug delivery systems called microchip has been improved to overcome the problems related to conventional drug delivery. Moreover, micro-fabrication technology has enabled to develop the implantable controlled released microchip devices with improved drug administration and patient compliance. In this article, we have presented an overview of the investigations on the feasibility and application of microchip as an advanced drug delivery system. Commercial manufacturing materials and methods, related other research works and current advancement of the microchips for controlled drug delivery have also been summarized.

  13. Ocular drug delivery systems: An overview

    PubMed Central

    Patel, Ashaben; Cholkar, Kishore; Agrahari, Vibhuti; Mitra, Ashim K

    2014-01-01

    The major challenge faced by today’s pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreoretinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments

  14. Description and Documentation of the Dental School Dental Delivery System.

    ERIC Educational Resources Information Center

    Chase, Rosen and Wallace, Inc., Alexandria, VA.

    A study was undertaken to describe and document the dental school dental delivery system using an integrated systems approach. In late 1976 and early 1977, a team of systems analysts and dental consultants visited three dental schools to observe the delivery of dental services and patient flow and to interview administrative staff and faculty.…

  15. Artificial synapse network on inorganic proton conductor for neuromorphic systems

    NASA Astrophysics Data System (ADS)

    Zhu, Li Qiang; Wan, Chang Jin; Guo, Li Qiang; Shi, Yi; Wan, Qing

    2014-01-01

    The basic units in our brain are neurons, and each neuron has more than 1,000 synapse connections. Synapse is the basic structure for information transfer in an ever-changing manner, and short-term plasticity allows synapses to perform critical computational functions in neural circuits. Therefore, the major challenge for the hardware implementation of neuromorphic computation is to develop artificial synapse network. Here in-plane lateral-coupled oxide-based artificial synapse network coupled by proton neurotransmitters are self-assembled on glass substrates at room-temperature. A strong lateral modulation is observed due to the proton-related electrical-double-layer effect. Short-term plasticity behaviours, including paired-pulse facilitation, dynamic filtering and spatiotemporally correlated signal processing are mimicked. Such laterally coupled oxide-based protonic/electronic hybrid artificial synapse network proposed here is interesting for building future neuromorphic systems.

  16. Isotopic anomalies and proton irradiation in the early solar system

    NASA Technical Reports Server (NTRS)

    Clayton, D. D.; Dwek, E.; Woosley, S. E.

    1977-01-01

    Nuclear cross sections relevant to the various isotopic-abundance anomalies found in solar-system objects are evaluated in an attempt to set constraints on the hypothesized mechanism of irradiation of forming planetesimals by energetic protons from the young sun. A power-law proton spectrum is adopted, attention is restricted to proton energies less than about 20 MeV, and average cross sections are calculated for several reactions that might be expected to lead to the observed anomalies. The following specific anomalies are examined in detail: Al-26, Na-22, Xe-126, I-129, Kr-80, V-50, Nb-92, La-138, Ta-180, Hg-196, K-40, Ar-36, O-17, O-18, N-15, C-13, Li, Be, and B. It is suggested that the picture of presolar-grain carriers accounts for the facts more naturally than do irradiation models.

  17. Relative biological effectiveness (RBE) and out-of-field cell survival responses to passive scattering and pencil beam scanning proton beam deliveries

    NASA Astrophysics Data System (ADS)

    Butterworth, Karl T.; McGarry, Conor K.; Clasie, Ben; Carabe-Fernandez, Alejandro; Schuemann, Jan; Depauw, Nicolas; Tang, Shikui; McMahon, Stephen J.; Schettino, Giuseppe; O'Sullivan, Joe M.; Lu, Hsaio-Ming; Kooy, Hanne; Paganetti, Harald; Hounsell, Alan R.; Held, Kathryn D.; Prise, Kevin M.

    2012-10-01

    The relative biological effectiveness (RBE) of passive scattered (PS) and pencil beam scanned (PBS) proton beam delivery techniques for uniform beam configurations was determined by clonogenic survival. The radiobiological impact of modulated beam configurations on cell survival occurring in- or out-of-field for both delivery techniques was determined with intercellular communication intact or physically inhibited. Cell survival responses were compared to those observed using a 6 MV photon beam produced with a linear accelerator. DU-145 cells showed no significant difference in survival response to proton beams delivered by PS and PBS or 6 MV photons taking into account a RBE of 1.1 for protons at the centre of the spread out Bragg peak. Significant out-of-field effects similar to those observed for 6 MV photons were observed for both PS and PBS proton deliveries with cell survival decreasing to 50-60% survival for scattered doses of 0.05 and 0.03 Gy for passive scattered and pencil beam scanned beams respectively. The observed out-of-field responses were shown to be dependent on intercellular communication between the in- and out-of-field cell populations. These data demonstrate, for the first time, a similar RBE between passive and actively scanned proton beams and confirm that out-of-field effects may be important determinants of cell survival following exposure to modulated photon and proton fields

  18. Relative biological effectiveness (RBE) and out-of-field cell survival responses to passive scattering and pencil beam scanning proton beam deliveries.

    PubMed

    Butterworth, Karl T; McGarry, Conor K; Clasie, Ben; Carabe-Fernandez, Alejandro; Schuemann, Jan; Depauw, Nicolas; Tang, Shikui; McMahon, Stephen J; Schettino, Giuseppe; O'Sullivan, Joe M; Lu, Hsaio-Ming; Kooy, Hanne; Paganetti, Harald; Hounsell, Alan R; Held, Kathryn D; Prise, Kevin M

    2012-10-21

    The relative biological effectiveness (RBE) of passive scattered (PS) and pencil beam scanned (PBS) proton beam delivery techniques for uniform beam configurations was determined by clonogenic survival. The radiobiological impact of modulated beam configurations on cell survival occurring in- or out-of-field for both delivery techniques was determined with intercellular communication intact or physically inhibited. Cell survival responses were compared to those observed using a 6 MV photon beam produced with a linear accelerator. DU-145 cells showed no significant difference in survival response to proton beams delivered by PS and PBS or 6 MV photons taking into account a RBE of 1.1 for protons at the centre of the spread out Bragg peak. Significant out-of-field effects similar to those observed for 6 MV photons were observed for both PS and PBS proton deliveries with cell survival decreasing to 50-60% survival for scattered doses of 0.05 and 0.03 Gy for passive scattered and pencil beam scanned beams respectively. The observed out-of-field responses were shown to be dependent on intercellular communication between the in- and out-of-field cell populations. These data demonstrate, for the first time, a similar RBE between passive and actively scanned proton beams and confirm that out-of-field effects may be important determinants of cell survival following exposure to modulated photon and proton fields.

  19. Micro injector sample delivery system for charged molecules

    DOEpatents

    Davidson, James C.; Balch, Joseph W.

    1999-11-09

    A micro injector sample delivery system for charged molecules. The injector is used for collecting and delivering controlled amounts of charged molecule samples for subsequent analysis. The injector delivery system can be scaled to large numbers (>96) for sample delivery to massively parallel high throughput analysis systems. The essence of the injector system is an electric field controllable loading tip including a section of porous material. By applying the appropriate polarity bias potential to the injector tip, charged molecules will migrate into porous material, and by reversing the polarity bias potential the molecules are ejected or forced away from the tip. The invention has application for uptake of charged biological molecules (e.g. proteins, nucleic acids, polymers, etc.) for delivery to analytical systems, and can be used in automated sample delivery systems.

  20. Reservoir-Based Drug Delivery Systems Utilizing Microtechnology

    PubMed Central

    Stevenson, Cynthia L.; Santini, John T.; Langer, Robert

    2012-01-01

    This review covers reservoir-based drug delivery systems that incorporate microtechnology, with an emphasis on oral, dermal, and implantable systems. Key features of each technology are highlighted such as working principles, fabrication methods, dimensional constraints, and performance criteria. Reservoir-based systems include a subset of microfabricated drug delivery systems and provide unique advantages. Reservoirs, whether external to the body or implanted, provide a well-controlled environment for a drug formulation, allowing increased drug stability and prolonged delivery times. Reservoir systems have the flexibility to accommodate various delivery schemes, including zero order, pulsatile, and on demand dosing, as opposed to a standard sustained release profile. Furthermore, the development of reservoir-based systems for targeted delivery for difficult to treat applications (e.g., ocular) has resulted in potential platforms for patient therapy. PMID:22465783

  1. Development of a proton Computed Tomography detector system

    NASA Astrophysics Data System (ADS)

    Naimuddin, Md.; Coutrakon, G.; Blazey, G.; Boi, S.; Dyshkant, A.; Erdelyi, B.; Hedin, D.; Johnson, E.; Krider, J.; Rukalin, V.; Uzunyan, S. A.; Zutshi, V.; Fordt, R.; Sellberg, G.; Rauch, J. E.; Roman, M.; Rubinov, P.; Wilson, P.

    2016-02-01

    Computer tomography is one of the most promising new methods to image abnormal tissues inside the human body. Tomography is also used to position the patient accurately before radiation therapy. Hadron therapy for treating cancer has become one of the most advantegeous and safe options. In order to fully utilize the advantages of hadron therapy, there is a necessity of performing radiography with hadrons as well. In this paper we present the development of a proton computed tomography system. Our second-generation proton tomography system consists of two upstream and two downstream trackers made up of fibers as active material and a range detector consisting of plastic scintillators. We present details of the detector system, readout electronics, and data acquisition system as well as the commissioning of the entire system. We also present preliminary results from the test beam of the range detector.

  2. Targeting of Synthetic Gene Delivery Systems

    PubMed Central

    2003-01-01

    Safe, efficient, and specific delivery of therapeutic genes remains an important bottleneck for the development of gene therapy. Synthetic, nonviral systems have a unique pharmaceutical profile with potential advantages for certain applications. Targeting of the synthetic vector improves the specificity of gene medicines through a modulation of the carriers' biodistribution, thus creating a dose differential between healthy tissue and the target site. The biodistribution of current carrier systems is being influenced to a large extent by intrinsic physicochemical characteristics, such as charge and size. Consequently, such nonspecific interactions can interfere with specific targeting, for example, by ligands. Therefore, a carrier complex should ideally be inert, that is, free from intrinsic properties that would bias its distribution away from the target site. Strategies such as coating of DNA carrier complexes with hydrophilic polymers have been used to mask some of these intrinsic targeting effects and avoid nonspecific interactions. Preexisting endogenous ligand-receptor interactions have frequently been used for targeting to certain cell types or tumours. Recently exogenous ligands have been derived from microorganisms or, like antibodies or phage-derived peptides, developed de novo. In animal models, such synthetic vectors have targeted remote sites such as a tumour. Furthermore, the therapeutic proof of the concept has been demonstrated for fitting combinations of synthetic vectors and therapeutic gene. PMID:12721518

  3. Guidelines for Psychological Practice in Health Care Delivery Systems

    ERIC Educational Resources Information Center

    American Psychologist, 2013

    2013-01-01

    Psychologists practice in an increasingly diverse range of health care delivery systems. The following guidelines are intended to assist psychologists, other health care providers, administrators in health care delivery systems, and the public to conceptualize the roles and responsibilities of psychologists in these diverse contexts. These…

  4. New Delivery Systems for the 21st Century.

    ERIC Educational Resources Information Center

    Van Patten, James J.

    This paper presents an historical perspective on the development of educational delivery systems, and then turns to the challenges of the information age and the issues of developing new delivery systems in this challenging environment. The paper discusses the fragility of power sources and of the networked world; technological weaknesses; freedom…

  5. Nanosized particulate systems for dermal and transdermal delivery.

    PubMed

    Hassan, Amany O Kamel; Elshafeey, Ahmed H

    2010-12-01

    Nanosized particles have received much attention in industry, biology, and medicine. Today nanotechnology is finding growing applications in pharmaceutical formulation for skin delivery. This review surveys some of the approaches in the field of nanosized particulate systems for both dermal and transdermal delivery, highlighting the nanosized microemulsion, vesicular systems, solid lipid nanoaprticles (SLN), nanostructured lipid carriers (NLC) and polymeric nanoparticles. PMID:21361126

  6. 7 CFR 246.12 - Food delivery systems.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 4 2011-01-01 2011-01-01 false Food delivery systems. 246.12 Section 246.12 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF... State Agency Provisions § 246.12 Food delivery systems. (a) General. This section sets forth design...

  7. 7 CFR 246.12 - Food delivery systems.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Food delivery systems. 246.12 Section 246.12 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF... State Agency Provisions § 246.12 Food delivery systems. (a) General. This section sets forth design...

  8. 7 CFR 246.12 - Food delivery systems.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 4 2013-01-01 2013-01-01 false Food delivery systems. 246.12 Section 246.12 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF... State Agency Provisions § 246.12 Food delivery systems. (a) General. This section sets forth design...

  9. 7 CFR 246.12 - Food delivery systems.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 4 2014-01-01 2014-01-01 false Food delivery systems. 246.12 Section 246.12 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF... State Agency Provisions § 246.12 Food delivery systems. (a) General. This section sets forth design...

  10. 7 CFR 246.12 - Food delivery systems.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 4 2012-01-01 2012-01-01 false Food delivery systems. 246.12 Section 246.12 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF... State Agency Provisions § 246.12 Food delivery systems. (a) General. This section sets forth design...

  11. Vesicular system: Versatile carrier for transdermal delivery of bioactives.

    PubMed

    Singh, Deependra; Pradhan, Madhulika; Nag, Mukesh; Singh, Manju Rawat

    2015-01-01

    The transdermal route of drug delivery has gained immense interest for pharmaceutical researchers. The major hurdle for diffusion of drugs and bioactives through transdermal route is the stratum corneum, the outermost layer of the skin. Currently, various approaches such as physical approach, chemical approach, and delivery carriers have been used to augment the transdermal delivery of bioactives. This review provides a brief overview of mechanism of drug transport across skin, different lipid vesicular systems, with special emphasis on lipid vesicular systems including transfersomes, liposomes, niosomes, ethosomes, virosomes, and pharmacosomes and their application for the delivery of different bioactives. PMID:24564350

  12. Bioavailability of phytochemicals and its enhancement by drug delivery systems

    PubMed Central

    Aqil, Farrukh; Munagala, Radha; Jeyabalan, Jeyaprakash; Vadhanam, Manicka V.

    2013-01-01

    Issues of poor oral bioavailability of cancer chemopreventives have hindered progress in cancer prevention. Novel delivery systems that modulate the pharmacokinetics of existing drugs, such as nanoparticles, cyclodextrins, niosomes, liposomes and implants, could be used to enhance the delivery of chemopreventive agents to target sites. The development of new approaches in prevention and treatment of cancer could encompass new delivery systems for approved and newly investigated compounds. In this review, we discuss some of the delivery approaches that have already made an impact by either delivering a drug to target tissue or increasing its bioavailability by many fold. PMID:23435377

  13. Photoresponsive molecular switch for regulating transmembrane proton-transfer kinetics.

    PubMed

    Li, Ying; Tse, Edmund C M; Barile, Christopher J; Gewirth, Andrew A; Zimmerman, Steven C

    2015-11-11

    To control proton delivery across biological membranes, we synthesized a photoresponsive molecular switch and incorporated it in a lipid layer. This proton gate was reversibly activated with 390 nm light (Z-isomer) and then deactivated by 360 nm irradiation (E-isomer). In a lipid layer this stimuli responsive proton gate allowed the regulation of proton flux with irradiation to a lipid-buried O2 reduction electrocatalyst. Thus, the catalyst was turned on and off with the E-to-Z interconversion. This light-induced membrane proton delivery system may be useful in developing any functional device that performs proton-coupled electron-transfer reactions.

  14. Shielding design for a laser-accelerated proton therapy system.

    PubMed

    Fan, J; Luo, W; Fourkal, E; Lin, T; Li, J; Veltchev, I; Ma, C-M

    2007-07-01

    In this paper, we present the shielding analysis to determine the necessary neutron and photon shielding for a laser-accelerated proton therapy system. Laser-accelerated protons coming out of a solid high-density target have broad energy and angular spectra leading to dose distributions that cannot be directly used for therapeutic applications. A special particle selection and collimation device is needed to generate desired proton beams for energy- and intensity-modulated proton therapy. A great number of unwanted protons and even more electrons as a side-product of laser acceleration have to be stopped by collimation devices and shielding walls, posing a challenge in radiation shielding. Parameters of primary particles resulting from the laser-target interaction have been investigated by particle-in-cell simulations, which predicted energy spectra with 300 MeV maximum energy for protons and 270 MeV for electrons at a laser intensity of 2 x 10(21) W cm(-2). Monte Carlo simulations using FLUKA have been performed to design the collimators and shielding walls inside the treatment gantry, which consist of stainless steel, tungsten, polyethylene and lead. A composite primary collimator was designed to effectively reduce high-energy neutron production since their highly penetrating nature makes shielding very difficult. The necessary shielding for the treatment gantry was carefully studied to meet the criteria of head leakage <0.1% of therapeutic absorbed dose. A layer of polyethylene enclosing the whole particle selection and collimation device was used to shield neutrons and an outer layer of lead was used to reduce photon dose from neutron capture and electron bremsstrahlung. It is shown that the two-layer shielding design with 10-12 cm thick polyethylene and 4 cm thick lead can effectively absorb the unwanted particles to meet the shielding requirements. PMID:17664585

  15. Delivery system reform tracking: a framework for understanding change.

    PubMed

    Tollen, Laura; Enthoven, Alain; Crosson, Francis J; Taylor, Nancy; Audet, Anne-Marie; Schoen, Cathy; Ross, Murray

    2011-06-01

    The health care delivery system is changing rapidly, with providers forming patient-centered medical homes and exploring the creation of accountable care organizations. Enactment of the Affordable Care Act will likely accelerate these changes. Significant delivery system reforms will simultaneously affect the structures, capabilities, incentives, and outcomes of the delivery system. With so many changes taking place at once, there is a need for a new tool to track progress at the community level. Many of the necessary data elements for a delivery system reform tracking tool are already being collected in various places and by different stakeholders. The authors propose that all elements be brought together in a unified whole to create a detailed picture of delivery system change. This brief provides a rationale for creating such a tool and presents a framework for doing so. PMID:21638935

  16. Controlled drug delivery systems: past forward and future back.

    PubMed

    Park, Kinam

    2014-09-28

    Controlled drug delivery technology has progressed over the last six decades. This progression began in 1952 with the introduction of the first sustained release formulation. The 1st generation of drug delivery (1950-1980) focused on developing oral and transdermal sustained release systems and establishing controlled drug release mechanisms. The 2nd generation (1980-2010) was dedicated to the development of zero-order release systems, self-regulated drug delivery systems, long-term depot formulations, and nanotechnology-based delivery systems. The latter part of the 2nd generation was largely focused on studying nanoparticle formulations. The Journal of Controlled Release (JCR) has played a pivotal role in the 2nd generation of drug delivery technologies, and it will continue playing a leading role in the next generation. The best path towards a productive 3rd generation of drug delivery technology requires an honest, open dialog without any preconceived ideas of the past. The drug delivery field needs to take a bold approach to designing future drug delivery formulations primarily based on today's necessities, to produce the necessary innovations. The JCR provides a forum for sharing the new ideas that will shape the 3rd generation of drug delivery technology.

  17. Superparamagnetic Iron Oxide Nanoparticle-Based Delivery Systems for Biotherapeutics

    PubMed Central

    Mok, Hyejung; Zhang, Miqin

    2014-01-01

    Introduction Superparamagnetic iron oxide nanoparticle (SPION)-based carrier systems have many advantages over other nanoparticle-based systems. They are biocompatible, biodegradable, facilely tunable, and superparamagnetic and thus controllable by an external magnetic field. These attributes enable their broad biomedical applications. In particular, magnetically-driven carriers are drawing considerable interest as an emerging therapeutic delivery system because of their superior delivery efficiency. Area covered This article reviews the recent advances in use of SPION-based carrier systems to improve the delivery efficiency and target specificity of biotherapeutics. We examine various formulations of SPION-based delivery systems, including SPION micelles, clusters, hydrogels, liposomes, and micro/nanospheres, as well as their specific applications in delivery of biotherapeutics. Expert opinion Recently, biotherapeutics including therapeutic cells, proteins and genes have been studied as alternative treatments to various diseases. Despite the advantages of high target specificity and low adverse effects, clinical translation of biotherapeutics has been hindered by the poor stability and low delivery efficiency compared to chemical drugs. Accordingly, biotherapeutic delivery systems that can overcome these limitations are actively pursued. SPION-based materials can be ideal candidates for developing such delivery systems because of their excellent biocompatibility and superparamagnetism that enables long-term accumulation/retention at target sites by utilization of a suitable magnet. In addition, synthesis technologies for production of finely-tuned, homogeneous SPIONs have been well developed, which may promise their rapid clinical translation. PMID:23199200

  18. Marine Origin Polysaccharides in Drug Delivery Systems

    PubMed Central

    Cardoso, Matias J.; Costa, Rui R.; Mano, João F.

    2016-01-01

    Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine. PMID:26861358

  19. SU-E-T-303: Spot Scanning Dose Delivery with Rapid Cycling Proton Beams From RCMS

    SciTech Connect

    Cheng, C; Liu, H; Lee, S

    2014-06-01

    Purpose: A rapid cycling proton beam has several distinct characteristics superior to a slow extraction synchrotron: The beam energy and energy spread, beam intensity and spot size can be varied spot by spot. The feasibility of using a spot scanning beam from a rapidc-ycling-medical-synchrotron (RCMS) at 10 Hz repetition frequency is investigated in this study for its application in proton therapy. Methods: The versatility of the beam is illustrated by two examples in water phantoms: (1) a cylindrical PTV irradiated by a single field and (2) a spherical PTV irradiated by two parallel opposed fields. A uniform dose distribution is to be delivered to the volumes. Geant4 Monte Carlo code is used to validate the dose distributions in each example. Results: Transverse algorithms are developed to produce uniform distributions in each transverseplane in the two examples with a cylindrical and a spherical PTV respectively. Longitudinally, different proton energies are used in successive transverse planes toproduce the SOBP required to cover the PTVs. In general, uniformity of dosedistribution within 3% is obtained for the cylinder and 3.5% for the sphere. The transversealgorithms requires only few hundred beam spots for each plane The algorithms may beapplied to larger volumes by increasing the intensity spot by spot for the same deliverytime of the same dose. The treatment time can be shorter than 1 minute for any fieldconfiguration and tumor shape. Conclusion: The unique beam characteristics of a spot scanning beam from a RCMS at 10 Hz repetitionfrequency are used to design transverse and longitudinal algorithms to produce uniformdistribution for any arbitrary shape and size of targets. The proposed spot scanning beam ismore versatile than existing spot scanning beams in proton therapy with better beamcontrol and lower neutron dose. This work is supported in part by grants from the US Department of Energy under contract; DE-FG02-12ER41800 and the National Science

  20. Recent advancements in erythrocytes, platelets, and albumin as delivery systems

    PubMed Central

    Xu, Peipei; Wang, Ruju; Wang, Xiaohui; Ouyang, Jian

    2016-01-01

    In the past few years, nanomaterial-based drug delivery systems have been applied to enhance the efficacy of therapeutics and to alleviate negative effects through the controlled delivery of targeting and releasing agents. However, few drug carriers can achieve high targeting efficacy, even when targeting modalities and surface markers are introduced. Immunological problems have also limited their wide applications. Biological drug delivery systems, such as erythrocytes, platelets, and albumin, have been extensively investigated because of their unique properties. In this review, erythrocytes, platelets, and albumin are described as efficient drug delivery systems. Their properties, applications, advantages, and limitations in disease treatment are explained. This review confirms that these systems can be used to facilitate a specific, biocompatible, and smart drug delivery. PMID:27274282

  1. Recent advancements in erythrocytes, platelets, and albumin as delivery systems.

    PubMed

    Xu, Peipei; Wang, Ruju; Wang, Xiaohui; Ouyang, Jian

    2016-01-01

    In the past few years, nanomaterial-based drug delivery systems have been applied to enhance the efficacy of therapeutics and to alleviate negative effects through the controlled delivery of targeting and releasing agents. However, few drug carriers can achieve high targeting efficacy, even when targeting modalities and surface markers are introduced. Immunological problems have also limited their wide applications. Biological drug delivery systems, such as erythrocytes, platelets, and albumin, have been extensively investigated because of their unique properties. In this review, erythrocytes, platelets, and albumin are described as efficient drug delivery systems. Their properties, applications, advantages, and limitations in disease treatment are explained. This review confirms that these systems can be used to facilitate a specific, biocompatible, and smart drug delivery.

  2. A respiratory-gated treatment system for proton therapy

    SciTech Connect

    Lu, H.-M.; Brett, Robert; Sharp, Gregory; Safai, Soiros; Jiang, Steve; Flanz, Jay; Kooy, Hanne

    2007-08-15

    Proton therapy offers the potential for excellent dose conformity and reduction in integral dose. The superior dose distribution is, however, much more sensitive to changes in radiological depths along the beam path than for photon fields. Respiratory motion can cause such changes for treatments sites like lung, liver, and mediastinum and thus affect the proton dose distribution significantly. We have implemented and commissioned a respiratory-gated system for range-modulated treatment fields. The gating system was designed to ensure that each gate always contains complete modulation cycles so that for any beam segment the delivered dose has the planned depth-dose distribution. Measurements have been made to estimate the time delays for the various components of the system. The total delay between the actual motion and the beam on/off control is in the range of 65-195 ms. Time-resolved dose measurements and film tests were also conducted to examine the overall gating effect.

  3. A dynamic collimation system for penumbra reduction in spot-scanning proton therapy: Proof of concept

    SciTech Connect

    Hyer, Daniel E. Hill, Patrick M.; Wang, Dongxu; Smith, Blake R.; Flynn, Ryan T.

    2014-09-15

    lateral penumbra of low-energy SS proton treatments may be greatly reduced with the use of this system at the cost of only a small penalty in delivery time.

  4. Mucoadhesive and thermogelling systems for vaginal drug delivery.

    PubMed

    Caramella, Carla M; Rossi, Silvia; Ferrari, Franca; Bonferoni, Maria Cristina; Sandri, Giuseppina

    2015-09-15

    This review focuses on two formulation approaches, mucoadhesion and thermogelling, intended for prolonging residence time on vaginal mucosa of medical devices or drug delivery systems, thus improving their efficacy. The review, after a brief description of the vaginal environment and, in particular, of the vaginal secretions that strongly affect in vivo performance of vaginal formulations, deals with the above delivery systems. As for mucoadhesive systems, conventional formulations (gels, tablets, suppositories and emulsions) and novel drug delivery systems (micro-, nano-particles) intended for vaginal administration to achieve either local or systemic effect are reviewed. As for thermogelling systems, poly(ethylene oxide-propylene oxide-ethylene oxide) copolymer-based and chitosan-based formulations are discussed as thermogelling systems. The methods employed for functional characterization of both mucoadhesive and thermogelling drug delivery systems are also briefly described.

  5. Formulation and Application of Biodegradable Nanoparticles Based Biopharmaceutical Delivery - An Efficient Delivery System.

    PubMed

    Bhattacharjee, Surajit; Sarkar, Biplab; Sharma, Ashish Ranjan; Gupta, Priya; Sharma, Garima; Lee, Sang-Soo; Chakraborty, Chiranjib

    2016-01-01

    Biodegradable polymer based drug delivery has emerged as a promising and successful clinical tool for specific targeting and controlled drug release delivery system. Various other unique advantages associated with this delivery system include prolonged circulation, biocompatibility, degradation in nontoxic by-products etc. Till date, various biopharmaceutical agents have been successfully encapsulated within biodegradable polymers and used in clinics. However, before the clinical implementation of such nanocarriers different parameters have to be considered which influence the success of these nanocarriers such as drug release profile, size of nanocarrier, degradation mechanism, toxicity profile, type of polymer used, appropriate synthesis method, selection of mode of delivery etc. The following review focuses on such considerations to explore the area of designing and development of biodegradable polymeric nanosystems which when encapsulated with biopharmaceutical agents can be efficient for clinical application. PMID:26951099

  6. The LITA Drill and Sample Delivery System

    NASA Astrophysics Data System (ADS)

    Paulsen, G.; Yoon, S.; Zacny, K.; Wettergreeng, D.; Cabrol, N. A.

    2013-12-01

    The Life in the Atacama (LITA) project has a goal of demonstrating autonomous roving, sample acquisition, delivery and analysis operations in Atacama, Chile. To enable the sample handling requirement, Honeybee Robotics developed a rover-deployed, rotary-percussive, autonomous drill, called the LITA Drill, capable of penetrating to ~80 cm in various formations, capturing and delivering subsurface samples to a 20 cup carousel. The carousel has a built-in capability to press the samples within each cup, and position target cups underneath instruments for analysis. The drill and sample delivery system had to have mass and power requirements consistent with a flight system. The drill weighs 12 kg and uses less than 100 watt of power to penetrate ~80 cm. The LITA Drill auger has been designed with two distinct stages. The lower part has deep and gently sloping flutes for retaining powdered sample, while the upper section has shallow and steep flutes for preventing borehole collapse and for efficient movement of cuttings and fall back material out of the hole. The drill uses the so called 'bite-sampling' approach that is samples are taken in short, 5-10 cm bites. To take the first bite, the drill is lowered onto the ground and upon drilling of the first bite it is then retracted into an auger tube. The auger with the auger tube are then lifted off the ground and positioned next to the carousel. To deposit the sample, the auger is rotated and retracted above the auger tube. The cuttings retained on the flutes are either gravity fed or are brushed off by a passive side brush into the cup. After the sample from the first bite has been deposited, the drill is lowered back into the same hole to take the next bite. This process is repeated until a target depth is reached. The bite sampling is analogous to peck drilling in the machining process where a bit is periodically retracted to clear chips. If there is some fall back into the hole once the auger has cleared the hole, this

  7. Optical diagnostics integrated with laser spark delivery system

    DOEpatents

    Yalin, Azer; Willson, Bryan; Defoort, Morgan; Joshi, Sachin; Reynolds, Adam

    2008-09-02

    A spark delivery system for generating a spark using a laser beam is provided, and includes a laser light source and a laser delivery assembly. The laser delivery assembly includes a hollow fiber and a launch assembly comprising launch focusing optics to input the laser beam in the hollow fiber. The laser delivery assembly further includes exit focusing optics that demagnify an exit beam of laser light from the hollow fiber, thereby increasing the intensity of the laser beam and creating a spark. Other embodiments use a fiber laser to generate a spark. Embodiments of the present invention may be used to create a spark in an engine. Yet other embodiments include collecting light from the spark or a flame resulting from the spark and conveying the light for diagnostics. Methods of using the spark delivery systems and diagnostic systems are provided.

  8. Designing and assessing a sustainable networked delivery (SND) system: hybrid business-to-consumer book delivery case study.

    PubMed

    Kim, Junbeum; Xu, Ming; Kahhat, Ramzy; Allenby, Braden; Williams, Eric

    2009-01-01

    We attempted to design and assess an example of a sustainable networked delivery (SND) system: a hybrid business-to-consumer book delivery system. This system is intended to reduce costs, achieve significant reductions in energy consumption, and reduce environmental emissions of critical local pollutants and greenhouse gases. The energy consumption and concomitant emissions of this delivery system compared with existing alternative delivery systems were estimated. We found that regarding energy consumption, an emerging hybrid delivery system which is a sustainable networked delivery system (SND) would consume 47 and 7 times less than the traditional networked delivery system (TND) and e-commerce networked delivery system (END). Regarding concomitant emissions, in the case of CO2, the SND system produced 32 and 7 times fewer emissions than the TND and END systems. Also the SND system offer meaningful economic benefit such as the costs of delivery and packaging, to the online retailer, grocery, and consumer. Our research results show that the SND system has a lot of possibilities to save local transportation energy consumption and delivery costs, and reduce environmental emissions in delivery system.

  9. Designing and assessing a sustainable networked delivery (SND) system: hybrid business-to-consumer book delivery case study.

    PubMed

    Kim, Junbeum; Xu, Ming; Kahhat, Ramzy; Allenby, Braden; Williams, Eric

    2009-01-01

    We attempted to design and assess an example of a sustainable networked delivery (SND) system: a hybrid business-to-consumer book delivery system. This system is intended to reduce costs, achieve significant reductions in energy consumption, and reduce environmental emissions of critical local pollutants and greenhouse gases. The energy consumption and concomitant emissions of this delivery system compared with existing alternative delivery systems were estimated. We found that regarding energy consumption, an emerging hybrid delivery system which is a sustainable networked delivery system (SND) would consume 47 and 7 times less than the traditional networked delivery system (TND) and e-commerce networked delivery system (END). Regarding concomitant emissions, in the case of CO2, the SND system produced 32 and 7 times fewer emissions than the TND and END systems. Also the SND system offer meaningful economic benefit such as the costs of delivery and packaging, to the online retailer, grocery, and consumer. Our research results show that the SND system has a lot of possibilities to save local transportation energy consumption and delivery costs, and reduce environmental emissions in delivery system. PMID:19209604

  10. Improvement of different vaccine delivery systems for cancer therapy

    PubMed Central

    2011-01-01

    Cancer vaccines are the promising tools in the hands of the clinical oncologist. Many tumor-associated antigens are excellent targets for immune therapy and vaccine design. Optimally designed cancer vaccines should combine the best tumor antigens with the most effective immunotherapy agents and/or delivery strategies to achieve positive clinical results. Various vaccine delivery systems such as different routes of immunization and physical/chemical delivery methods have been used in cancer therapy with the goal to induce immunity against tumor-associated antigens. Two basic delivery approaches including physical delivery to achieve higher levels of antigen production and formulation with microparticles to target antigen-presenting cells (APCs) have demonstrated to be effective in animal models. New developments in vaccine delivery systems will improve the efficiency of clinical trials in the near future. Among them, nanoparticles (NPs) such as dendrimers, polymeric NPs, metallic NPs, magnetic NPs and quantum dots have emerged as effective vaccine adjuvants for infectious diseases and cancer therapy. Furthermore, cell-penetrating peptides (CPP) have been known as attractive carrier having applications in drug delivery, gene transfer and DNA vaccination. This review will focus on the utilization of different vaccine delivery systems for prevention or treatment of cancer. We will discuss their clinical applications and the future prospects for cancer vaccine development. PMID:21211062

  11. Delivery system for molten salt oxidation of solid waste

    DOEpatents

    Brummond, William A.; Squire, Dwight V.; Robinson, Jeffrey A.; House, Palmer A.

    2002-01-01

    The present invention is a delivery system for safety injecting solid waste particles, including mixed wastes, into a molten salt bath for destruction by the process of molten salt oxidation. The delivery system includes a feeder system and an injector that allow the solid waste stream to be accurately metered, evenly dispersed in the oxidant gas, and maintained at a temperature below incineration temperature while entering the molten salt reactor.

  12. Convection-enhanced delivery to the central nervous system.

    PubMed

    Lonser, Russell R; Sarntinoranont, Malisa; Morrison, Paul F; Oldfield, Edward H

    2015-03-01

    Convection-enhanced delivery (CED) is a bulk flow-driven process. Its properties permit direct, homogeneous, targeted perfusion of CNS regions with putative therapeutics while bypassing the blood-brain barrier. Development of surrogate imaging tracers that are co-infused during drug delivery now permit accurate, noninvasive real-time tracking of convective infusate flow in nervous system tissues. The potential advantages of CED in the CNS over other currently available drug delivery techniques, including systemic delivery, intrathecal and/or intraventricular distribution, and polymer implantation, have led to its application in research studies and clinical trials. The authors review the biophysical principles of convective flow and the technology, properties, and clinical applications of convective delivery in the CNS.

  13. Novel delivery systems for improving the clinical use of peptides.

    PubMed

    Kovalainen, Miia; Mönkäre, Juha; Riikonen, Joakim; Pesonen, Ullamari; Vlasova, Maria; Salonen, Jarno; Lehto, Vesa-Pekka; Järvinen, Kristiina; Herzig, Karl-Heinz

    2015-07-01

    Peptides have long been recognized as a promising group of therapeutic substances to treat various diseases. Delivery systems for peptides have been under development since the discovery of insulin for the treatment of diabetes. The challenge of using peptides as drugs arises from their poor bioavailability resulting from the low permeability of biological membranes and their instability. Currently, subcutaneous injection is clinically the most common administration route for peptides. This route is cost-effective and suitable for self-administration, and the development of appropriate dosing equipment has made performing the repeated injections relatively easy; however, only few clinical subcutaneous peptide delivery systems provide sustained peptide release. As a result, frequent injections are needed, which may cause discomfort and additional risks resulting from a poor administration technique. Controlled peptide delivery systems, able to provide required therapeutic plasma concentrations over an extended period, are needed to increase peptide safety and patient compliancy. In this review, we summarize the current peptidergic drugs, future developments, and parenteral peptide delivery systems. Special emphasis is given to porous silicon, a novel material in peptide delivery. Biodegradable and biocompatible porous silicon possesses some unique properties, such as the ability to carry exceptional high peptide payloads and to modify peptide release extensively. We have successfully developed porous silicon as a carrier material for improved parenteral peptide delivery. Nanotechnology, with its different delivery systems, will enable better use of peptides in several therapeutic applications in the near future. PMID:26023145

  14. Information Delivery Systems: The Future Is Here.

    ERIC Educational Resources Information Center

    O'Malley, Penelope Grenoble

    1993-01-01

    Looks at developments in information delivery (including new interactive media formats, vastly increased channel capacity for standard cable television, and the development of wireless cable and other distribution technologies) that are revolutionizing the communications industry. Raises questions about the role technical communicators are being…

  15. Trends in Health Care Systems Delivery.

    ERIC Educational Resources Information Center

    Hughes, Edward F. X.

    1989-01-01

    The trend now driving American health care is that the payors are refusing to pay the true economic costs. Health care technology and the public's demand for it, the growth of managed care (Health Maintenance Organizations), and the need to increase the effectiveness of health care are affecting health care delivery. (MLW)

  16. Microneedles As a Delivery System for Gene Therapy

    PubMed Central

    Chen, Wei; Li, Hui; Shi, De; Liu, Zhenguo; Yuan, Weien

    2016-01-01

    Gene delivery systems can be divided to two major types: vector-based (either viral vector or non-viral vector) and physical delivery technologies. Many physical carriers, such as electroporation, gene gun, ultrasound start to be proved to have the potential to enable gene therapy. A relatively new physical delivery technology for gene delivery consists of microneedles (MNs), which has been studied in many fields and for many molecule types and indications. Microneedles can penetrate the stratum corneum, which is the main barrier for drug delivery through the skin with ease of administration and without significant pain. Many different kinds of MNs, such as metal MNs, coated MNs, dissolving MNs have turned out to be promising in gene delivery. In this review, we discussed the potential as well as the challenges of utilizing MNs to deliver nucleic acids for gene therapy. We also proposed that a combination of MNs and other gene delivery approaches may lead to a better delivery system for gene therapy. PMID:27303298

  17. Iontophoresis: A Potential Emergence of a Transdermal Drug Delivery System

    PubMed Central

    Dhote, Vinod; Bhatnagar, Punit; Mishra, Pradyumna K.; Mahajan, Suresh C.; Mishra, Dinesh K.

    2012-01-01

    The delivery of drugs into systemic circulation via skin has generated much attention during the last decade. Transdermal therapeutic systems propound controlled release of active ingredients through the skin and into the systemic circulation in a predictive manner. Drugs administered through these systems escape first-pass metabolism and maintain a steady state scenario similar to a continuous intravenous infusion for up to several days. However, the excellent impervious nature of the skin offers the greatest challenge for successful delivery of drug molecules by utilizing the concepts of iontophoresis. The present review deals with the principles and the recent innovations in the field of iontophoretic drug delivery system together with factors affecting the system. This delivery system utilizes electric current as a driving force for permeation of ionic and non-ionic medications. The rationale behind using this technique is to reversibly alter the barrier properties of skin, which could possibly improve the penetration of drugs such as proteins, peptides and other macromolecules to increase the systemic delivery of high molecular weight compounds with controlled input kinetics and minimum inter-subject variability. Although iontophoresis seems to be an ideal candidate to overcome the limitations associated with the delivery of ionic drugs, further extrapolation of this technique is imperative for translational utility and mass human application. PMID:22396901

  18. Variable Delivery Systems for Peer Associated Token Reinforcement

    ERIC Educational Resources Information Center

    Edwards, Clifford H.

    1975-01-01

    This study focused on normal junior high school students in the natural school environment. Its purpose was to determine if different token delivery systems would differentially affect the disruptive behavior patterns of students in the normal classroom. (Author/RK)

  19. Micro- and nano-fabricated implantable drug-delivery systems

    PubMed Central

    Meng, Ellis; Hoang, Tuan

    2013-01-01

    Implantable drug-delivery systems provide new means for achieving therapeutic drug concentrations over entire treatment durations in order to optimize drug action. This article focuses on new drug administration modalities achieved using implantable drug-delivery systems that are enabled by micro- and nano-fabrication technologies, and microfluidics. Recent advances in drug administration technologies are discussed and remaining challenges are highlighted. PMID:23323562

  20. Lactic acid bacteria as oral delivery systems for biomolecules.

    PubMed

    Berlec, A; Ravnikar, M; Strukelj, B

    2012-11-01

    Lactic acid bacteria (LAB) have become increasingly studied over the last two decades as potential delivery systems for various biological molecules to the gastrointestinal tract. This article presents an overview of characteristics of LAB as delivery systems and of the applications which have already been developed. The majority of LAB strains are able to survive the intestinal passage and some are also able to persist and colonize the intestine. Several strains were in fact described as members of the human commensal flora. They can interact with their host and are able to deliver large molecular weight biomolecules across the epithelium via M-cells or dendritic cells. The most widely applied LAB species has been Lactococcus lactis; however species from genus Lactobacillus are gaining popularity and the first examples from genus Bifidobacterium are starting to emerge. Bacteria are mostly applied live and enable continuous delivery of the biomolecules. However, killed bacteria (e.g. gram-positive enhancer matrix), with bound biomolecules or as adjuvants, are also being developed. The techniques for genetic modification of LAB are well known. This review focuses on the delivery of recombinant proteins and DNA, which can cause either local or systemic effects. We divide recombinant proteins into antigens and therapeutic proteins. Delivery of antigens for the purpose of vaccination represents the most abundant application with numerous successful demonstrations of the efficacy on the animal model. Therapeutic proteins have mostly been developed for the treatment of the inflammatory bowel disease, by the delivery of anti-inflammatory cytokines, or downregulation of proinflammatory cytokines. Delivery of allergens for the modulation of allergic disorders represents the second most popular application of therapeutic proteins. The delivery of DNA by LAB was demonstrated and offers exciting opportunities, especially as a vaccine. New discoveries may eventually lead to the

  1. Silk-based delivery systems of bioactive molecules

    PubMed Central

    Numata, Keiji; Kaplan, David L

    2010-01-01

    Silks are biodegradable, biocompatible, self-assemblying proteins that can also be tailored via genetic engineering to contain specific chemical features, offering utility for drug and gene delivery. Silkworm silk has been used in biomedical sutures for decades and has recently achieved Food and Drug Administration approval for expanded biomaterials device utility. With the diversity and control of size, structure and chemistry, modified or recombinant silk proteins can be designed and utilized in various biomedical application, such as for the delivery of bioactive molecules. This review focuses on the biosynthesis and applications of silk-based multi-block copolymer systems and related silk protein drug delivery systems. The utility of these systems for the delivery of small molecule drugs, proteins and genes are reviewed. PMID:20298729

  2. Development of Small RNA Delivery Systems for Lung Cancer Therapy

    PubMed Central

    Fujita, Yu; Kuwano, Kazuyoshi; Ochiya, Takahiro

    2015-01-01

    RNA interference (RNAi) has emerged as a powerful tool for studying target identification and holds promise for the development of therapeutic gene silencing. Recent advances in RNAi delivery and target selection provide remarkable opportunities for translational medical research. The induction of RNAi relies on small silencing RNAs, which affect specific messenger RNA (mRNA) degradation. Two types of small RNA molecules, small interfering RNAs (siRNAs) and microRNAs (miRNAs), have a central function in RNAi technology. The success of RNAi-based therapeutic delivery may be dependent upon uncovering a delivery route, sophisticated delivery carriers, and nucleic acid modifications. Lung cancer is still the leading cause of cancer death worldwide, for which novel therapeutic strategies are critically needed. Recently, we have reported a novel platform (PnkRNA™ and nkRNA®) to promote naked RNAi approaches through inhalation without delivery vehicles in lung cancer xenograft models. We suggest that a new class of RNAi therapeutic agent and local drug delivery system could also offer a promising RNAi-based strategy for clinical applications in cancer therapy. In this article, we show recent strategies for an RNAi delivery system and suggest the possible clinical usefulness of RNAi-based therapeutics for lung cancer treatment. PMID:25756380

  3. SU-E-T-73: Commissioning of a Treatment Planning System for Proton Spot Scanning

    SciTech Connect

    Saini, J; Kang, Y; Schultz, L; Nicewonger, D; Herrera, M; Wong, T; Bowen, S; Bloch, C

    2014-06-01

    Purpose: A treatment planning system (TPS) was commissioned for clinical use with a fixed beam line proton delivery system. An outline of the data collection, modeling, and verification is provided. Methods: Beam data modeling for proton spot scanning in CMS Xio TPS requires the following measurements: (i) integral depth dose curves (IDDCs); (ii) absolute dose calibration; and (iii) beam spot characteristics. The IDDCs for 18 proton energies were measured using an integrating detector in a single spot field in a water phantom. Absolute scaling of the IDDCs were performed based on ion chamber measurements in mono-energetic 10×10 cm{sup 2} fields in water. Beam spot shapes were measured in air using a flat panel scintillator detector at multiple planes. For beam model verification, more than 45 uniform dose phantom and patient plans were generated. These plans were used to measure range, point dose, and longitudinal and lateral profiles. Tolerances employed for verification are: point dose and longitudinal profiles, ±2%; range, ±1 mm; FWHM for lateral profiles, ±2 mm; and patient plan dose distribution, gamma index of >90% at 3%/3 mm criteria. Results: More than 97% of the point dose measurements out of 115 were within +/-2% with maximum deviation of 3%. 98% of the ranges measured were within 1 mm with maximum deviation of 1.4mm. The normalized depth doses were within 2% at all depths. The maximum error in FWHM of lateral profiles was found to be less than 2mm. For 5 patient plans representing different anatomic sites, a total of 38 planes for 12 beams were analyzed for gamma index with average value of 99% and minimum of 94%. Conclusions: The planning system is successfully commissioned and can be safely deployed for clinical use. Measurements of IDDCs on user beam are highly recommended instead of using standard beam IDDCs.

  4. Promoting Quality of Program Delivery via an Internet Message Delivery System

    ERIC Educational Resources Information Center

    Bishop, Dana C.; Dusenbury, Linda; Pankratz, Melinda M.; Hansen, William B.

    2013-01-01

    This article presents results from a study that evaluated an online message system designed to improve the delivery of prevention programs. We conducted a quasi-experimental study with 32 agencies and schools that implemented substance use prevention programs and examined differences between the comparison and intervention groups. We also examined…

  5. Colloidal drug delivery systems: current status and future directions.

    PubMed

    Garg, Tarun; Rath, Goutam; Goyal, Amit Kumar

    2015-01-01

    In this paper, we provide an overview an extensive range of colloidal drug delivery systems with special focus on vesicular and particulates systems that are being used in research or might be potentially useful as carriers systems for drug or active biomolecules or as cell carriers with application in the therapeutic field. We present some important examples of commercially available drug delivery systems with applications in research or in clinical fields. This class of systems is widely used due to excellent drug targeting, sustained and controlled release behavior, higher entrapment efficiency of drug molecules, prevention of drug hydrolysis or enzymatic degradation, and improvement of therapeutic efficacy. These characteristics help in the selection of suitable carrier systems for drug, cell, and gene delivery in different fields.

  6. Hydrogel-Based Controlled Delivery Systems for Articular Cartilage Repair

    PubMed Central

    Madry, Henning

    2016-01-01

    Delivery of bioactive factors is a very valuable strategy for articular cartilage repair. Nevertheless, the direct supply of such biomolecules is limited by several factors including rapid degradation, the need for supraphysiological doses, the occurrence of immune and inflammatory responses, and the possibility of dissemination to nontarget sites that may impair their therapeutic action and raise undesired effects. The use of controlled delivery systems has the potential of overcoming these hurdles by promoting the temporal and spatial presentation of such factors in a defined target. Hydrogels are promising materials to develop delivery systems for cartilage repair as they can be easily loaded with bioactive molecules controlling their release only where required. This review exposes the most recent technologies on the design of hydrogels as controlled delivery platforms of bioactive molecules for cartilage repair. PMID:27642587

  7. Hydrogel-Based Controlled Delivery Systems for Articular Cartilage Repair.

    PubMed

    Rey-Rico, Ana; Madry, Henning; Cucchiarini, Magali

    2016-01-01

    Delivery of bioactive factors is a very valuable strategy for articular cartilage repair. Nevertheless, the direct supply of such biomolecules is limited by several factors including rapid degradation, the need for supraphysiological doses, the occurrence of immune and inflammatory responses, and the possibility of dissemination to nontarget sites that may impair their therapeutic action and raise undesired effects. The use of controlled delivery systems has the potential of overcoming these hurdles by promoting the temporal and spatial presentation of such factors in a defined target. Hydrogels are promising materials to develop delivery systems for cartilage repair as they can be easily loaded with bioactive molecules controlling their release only where required. This review exposes the most recent technologies on the design of hydrogels as controlled delivery platforms of bioactive molecules for cartilage repair. PMID:27642587

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

    PubMed

    Amler, Evžen; Filová, Eva; Buzgo, Matej; Prosecká, Eva; Rampichová, Michala; Nečas, Alois; Nooeaid, Patcharakamon; Boccaccini, Aldo R

    2014-05-01

    A wide range of drug-delivery systems are currently attracting the attention of researchers. Nanofibers are very interesting carriers for drug delivery. This is because nanofibers are versatile, flexible, nanobiomimetic and similar to extracellular matrix components, possible to be functionalized both on their surface as well as in their core, and also because they can be produced easily and cost effectively. There have been increasing attempts to use nanofibers in the construction of a range of tissues, including cartilage and bone. Nanofibers have also been favorably engaged as a drug-delivery system in cell-free scaffolds. This short overview is devoted to current applications and to further perspectives of nanofibers as drug-delivery devices in the field of cartilage and bone regeneration, and also in osteochondral reconstruction. PMID:24978465

  9. Medical applications of 3 μm delivery waveguide system

    NASA Astrophysics Data System (ADS)

    Němec, Michal; Jelínkova, Helena; Koranda, Petr; Miyagi, Mitsunobu; Iwai, Katsumasa; Shi, Yi-Wei; Matsuura, Yuji

    2006-02-01

    Hollow glass waveguide is one from a few instruments favored in industrial and medical fields for the delivery of mid-infrared laser light. The article summarizes delivery of the Er:YAG laser radiation (λ = 2.94 μm) by the cyclic olefin polymer coated silver hollow glass waveguides with various inner diameters - 320 μm, 700 μm, and 1 mm, and with length of 0.1 - 1 m. For medical applications, the so called "contact mode" in which the end of the waveguide is in contact with the soft or hard tissues is discussed. For this treatment the special sealed caps were used for preventing the waveguide system damage. Delivery of long (free-running) and short (Q-switched) mid-infrared pulses was investigated. The delivery systems were investigated for the ophthalmic, urologic, and dental tissue treatments. The comparison of interaction effects caused by the laser pulses with various lengths was made.

  10. Self-assembled and nanostructured siRNA delivery systems.

    PubMed

    Jeong, Ji Hoon; Park, Tae Gwan; Kim, Sun Hwa

    2011-09-01

    A wide range of organic and inorganic materials have been used in the development of nano-scale self-assembling gene delivery systems to improve the therapeutic efficacy of nucleic acid drugs. Small interfering RNA (siRNA) has recently been recognized as a promising and potent nucleic acid medicine for the treatment of incurable genetic disorders including cancer; however, siRNA-based therapeutics suffer from the same delivery problems as conventional nucleic acid drugs such as plasmid DNA and antisense oligonucleotides. Many of the delivery strategies developed for nucleic acid drugs have been applied to siRNA therapeutics, but they have not produced satisfactory in vivo gene silencing efficiencies to warrant clinical trials. This review discusses recent progress in the development of self-assembled and nanostructured delivery systems for efficient siRNA-induced gene silencing and their potential application in clinical settings. PMID:21424157

  11. Targeted Delivery Systems for Molecular Therapy in Skeletal Disorders

    PubMed Central

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

    2016-01-01

    Abnormalities in the integral components of bone, including bone matrix, bone mineral and bone cells, give rise to complex disturbances of skeletal development, growth and homeostasis. Non-specific drug delivery using high-dose systemic administration may decrease therapeutic efficacy of drugs and increase the risk of toxic effects in non-skeletal tissues, which remain clinical challenges in the treatment of skeletal disorders. Thus, targeted delivery systems are urgently needed to achieve higher drug delivery efficiency, improve therapeutic efficacy in the targeted cells/tissues, and minimize toxicities in non-targeted cells/tissues. In this review, we summarize recent progress in the application of different targeting moieties and nanoparticles for targeted drug delivery in skeletal disorders, and also discuss the advantages, challenges and perspectives in their clinical translation. PMID:27011176

  12. Hydrogel-Based Controlled Delivery Systems for Articular Cartilage Repair

    PubMed Central

    Madry, Henning

    2016-01-01

    Delivery of bioactive factors is a very valuable strategy for articular cartilage repair. Nevertheless, the direct supply of such biomolecules is limited by several factors including rapid degradation, the need for supraphysiological doses, the occurrence of immune and inflammatory responses, and the possibility of dissemination to nontarget sites that may impair their therapeutic action and raise undesired effects. The use of controlled delivery systems has the potential of overcoming these hurdles by promoting the temporal and spatial presentation of such factors in a defined target. Hydrogels are promising materials to develop delivery systems for cartilage repair as they can be easily loaded with bioactive molecules controlling their release only where required. This review exposes the most recent technologies on the design of hydrogels as controlled delivery platforms of bioactive molecules for cartilage repair.

  13. 'Smart' non-viral delivery systems for targeted delivery of RNAi to the lungs.

    PubMed

    Ramsey, Joanne M; Hibbitts, Alan; Barlow, James; Kelly, Ciara; Sivadas, Neeraj; Cryan, Sally-Ann

    2013-01-01

    The emergence of RNAi offers a potentially exciting new therapeutic paradigm for respiratory diseases. However, effective delivery remains a key requirement for their translation into the clinic and has been a major factor in the limited clinical success seen to date. Inhalation offers tissue-specific targeting of the RNAi to treat respiratory diseases and a diminished risk of off-target effects. In order to deliver RNAi directly to the respiratory tract via inhalation, 'smart' non-viral carriers are required to protect the RNAi during delivery/aerosolization and enhance cell-specific uptake to target cells. Here, we review the state-of-the-art in therapeutic aerosol bioengineering, and specifically non-viral siRNA delivery platforms, for delivery via inhalation. This includes developments in inhaler device engineering and particle engineering, including manufacturing methods and excipients used in therapeutic aerosol bioengineering that underpin the development of smart, cell type-specific delivery systems to target siRNA to respiratory epithelial cells and/or alveolar macrophages. PMID:23323781

  14. Beam characteristics in two different proton uniform scanning systems: A side-by-side comparison

    PubMed Central

    Nichiporov, Dmitri; Hsi, Wen; Farr, Jonathan

    2012-01-01

    Purpose: To compare clinically relevant dosimetric characteristics of proton therapy fields produced by two uniform scanning systems that have a number of similar hardware components but employ different techniques of beam spreading. Methods: This work compares two technologically distinct systems implementing a method of uniform scanning and layer stacking that has been developed independently at Indiana University (IU) and by Ion Beam Applications, S. A. (IBA). Clinically relevant dosimetric characteristics of fields produced by these systems are studied, such as beam range control, peak-to-entrance ratio (PER), lateral penumbra, field flatness, effective source position, precision of dose delivery at different gantry angles, etc. Results: Under comparable conditions, both systems controlled beam range with an accuracy of 0.5 mm and a precision of 0.1 mm. Compared to IBA, the IU system produced pristine peaks with a slightly higher PER (3.23 and 3.45, respectively) and smaller, symmetrical, lateral in-air penumbra of 1 mm compared to about 1.9/2.4 mm in the inplane/crossplane (IP/CP) directions for IBA. Large field flatness results in the IP/CP directions were similar: 3.0/2.4% for IU and 2.9/2.4% for IBA. The IU system featured a longer virtual source-to-isocenter position, which was the same for the IP and CP directions (237 cm), as opposed to 212/192 cm (IP/CP) for IBA. Dose delivery precision at different gantry angles was higher in the IBA system (0.5%) than in the IU system (1%). Conclusions: Each of the two uniform scanning systems considered in this work shows some attractive performance characteristics while having other features that can be further improved. Overall, radiation field characteristics of both systems meet their clinical specifications and show comparable results. Most of the differences observed between the two systems are clinically insignificant. PMID:22559626

  15. Beam characteristics in two different proton uniform scanning systems: A side-by-side comparison

    SciTech Connect

    Nichiporov, Dmitri; Hsi Wen; Farr, Jonathan

    2012-05-15

    Purpose: To compare clinically relevant dosimetric characteristics of proton therapy fields produced by two uniform scanning systems that have a number of similar hardware components but employ different techniques of beam spreading. Methods: This work compares two technologically distinct systems implementing a method of uniform scanning and layer stacking that has been developed independently at Indiana University (IU) and by Ion Beam Applications, S. A. (IBA). Clinically relevant dosimetric characteristics of fields produced by these systems are studied, such as beam range control, peak-to-entrance ratio (PER), lateral penumbra, field flatness, effective source position, precision of dose delivery at different gantry angles, etc. Results: Under comparable conditions, both systems controlled beam range with an accuracy of 0.5 mm and a precision of 0.1 mm. Compared to IBA, the IU system produced pristine peaks with a slightly higher PER (3.23 and 3.45, respectively) and smaller, symmetrical, lateral in-air penumbra of 1 mm compared to about 1.9/2.4 mm in the inplane/crossplane (IP/CP) directions for IBA. Large field flatness results in the IP/CP directions were similar: 3.0/2.4% for IU and 2.9/2.4% for IBA. The IU system featured a longer virtual source-to-isocenter position, which was the same for the IP and CP directions (237 cm), as opposed to 212/192 cm (IP/CP) for IBA. Dose delivery precision at different gantry angles was higher in the IBA system (0.5%) than in the IU system (1%). Conclusions: Each of the two uniform scanning systems considered in this work shows some attractive performance characteristics while having other features that can be further improved. Overall, radiation field characteristics of both systems meet their clinical specifications and show comparable results. Most of the differences observed between the two systems are clinically insignificant.

  16. Neutron-proton pairing correlations in odd mass systems

    SciTech Connect

    Fellah, M. Allal, N. H.; Oudih, M. R.

    2015-03-30

    An expression of the ground-state which describes odd mass systems within the BCS approach in the isovector neutron-proton pairing case is proposed using the blocked level technique. The gap equations as well as the energy expression are then derived. It is shown that they exactly generalize the expressions obtained in the pairing between like-particles case. The various gap parameters and the energy are then numerically studied as a function of the pairing-strength within the schematic one-level model.

  17. Gastroretentive drug delivery systems for the treatment of Helicobacter pylori

    PubMed Central

    Zhao, Shan; Lv, Yan; Zhang, Jian-Bin; Wang, Bing; Lv, Guo-Jun; Ma, Xiao-Jun

    2014-01-01

    Helicobacter pylori (H. pylori) is one of the most common pathogenic bacterial infections and is found in the stomachs of approximately half of the world’s population. It is the primary known cause of gastritis, gastroduodenal ulcer disease and gastric cancer. However, combined drug therapy as the general treatment in the clinic, the rise of antibiotic-resistant bacteria, adverse reactions and poor patient compliance are major obstacles to the eradication of H. pylori. Oral site-specific drug delivery systems that could increase the longevity of the treatment agent at the target site might improve the therapeutic effect and avoid side effects. Gastroretentive drug delivery systems potentially prolong the gastric retention time and controlled/sustained release of a drug, thereby increasing the concentration of the drug at the application site, potentially improving its bioavailability and reducing the necessary dosage. Recommended gastroretentive drug delivery systems for enhancing local drug delivery include floating systems, bioadhesive systems and expandable systems. In this review, we summarize the important physiological parameters of the gastrointestinal tract that affect the gastric residence time. We then focus on various aspects useful in the development of gastroretentive drug delivery systems, including current trends and the progress of novel forms, especially with respect to their application for the treatment of H. pylori infections. PMID:25071326

  18. Albumin-based nanocomposite spheres for advanced drug delivery systems.

    PubMed

    Misak, Heath E; Asmatulu, Ramazan; Gopu, Janani S; Man, Ka-Poh; Zacharias, Nora M; Wooley, Paul H; Yang, Shang-You

    2014-01-01

    A novel drug delivery system incorporating human serum albumin, poly(lactic-co-glycolic acid, magnetite nanoparticles, and therapeutic agent(s) was developed for potential application in the treatment of diseases such as rheumatoid arthritis and skin cancer. An oil-in-oil emulsion/solvent evaporation (O/OSE) method was modified to produce a drug delivery system with a diameter of 0.5–2 μm. The diameter was mainly controlled by adjusting the viscosity of albumin in the discontinuous phase of the O/OSE method. The drug-release study showed that the release of drug and albumin was mostly dependent on the albumin content of the drug delivery system, which is very similar to the drug occlusion-mesopore model. Cytotoxicity tests indicated that increasing the albumin content in the drug delivery system increased cell viability, possibly due to the improved biocompatibility of the system. Overall, these studies show that the proposed system could be a viable option as a drug delivery system in the treatment of many illnesses, such as rheumatoid arthritis, and skin and breast cancers. PMID:24106002

  19. Pulmonary drug delivery systems: recent developments and prospects.

    PubMed

    Courrier, H M; Butz, N; Vandamme, Th F

    2002-01-01

    Targeting drug delivery into the lungs has become one of the most important aspects of systemic or local drug delivery systems. Consequently, in the last few years, techniques and new drug delivery devices intended to deliver drugs into the lungs have been widely developed. Currently, the main drug targeting regimens include direct application of a drug into the lungs, mostly by inhalation therapy using either pressurized metered dose inhalers (pMDI) or dry powder inhalers (DPI). Intratracheal administration is commonly used as a first approach in lung drug delivery in vivo. To convey a sufficient dose of drug to the lungs, suitable drug carriers are required. These can be either solid, liquid, or gaseous excipients. Liposomes, nano- and microparticles, cyclodextrins, microemulsions, micelles, suspensions, or solutions are all examples of this type of pharmaceutical carrier that have been successfully used to target drugs into the lungs. The use of microreservoir-type systems offers clear advantages, such as high loading capacity and the possibility of controlling size and permeability, and thus of controlling the release kinetics of the drugs from the carrier systems. These systems make it possible to use relatively small numbers of vector molecules to deliver substantial amounts of a drug to the target. This review discusses the drug carriers administered or intended to be administered into the lungs. The transition to CFC-free inhalers and drug delivery systems formulated with new propellants are also discussed. Finally, in addition to the various advances made in the field of pulmonary-route administration, we describe new systems based on perfluorooctyl bromide, which guarantee oxygen delivery in the event of respiratory distress and drug delivery into the lungs.

  20. Characterizing a proton beam scanning system for Monte Carlo dose calculation in patients.

    PubMed

    Grassberger, C; Lomax, Anthony; Paganetti, H

    2015-01-21

    The presented work has two goals. First, to demonstrate the feasibility of accurately characterizing a proton radiation field at treatment head exit for Monte Carlo dose calculation of active scanning patient treatments. Second, to show that this characterization can be done based on measured depth dose curves and spot size alone, without consideration of the exact treatment head delivery system. This is demonstrated through calibration of a Monte Carlo code to the specific beam lines of two institutions, Massachusetts General Hospital (MGH) and Paul Scherrer Institute (PSI). Comparison of simulations modeling the full treatment head at MGH to ones employing a parameterized phase space of protons at treatment head exit reveals the adequacy of the method for patient simulations. The secondary particle production in the treatment head is typically below 0.2% of primary fluence, except for low-energy electrons (<0.6 MeV for 230 MeV protons), whose contribution to skin dose is negligible. However, there is significant difference between the two methods in the low-dose penumbra, making full treatment head simulations necessary to study out-of-field effects such as secondary cancer induction. To calibrate the Monte Carlo code to measurements in a water phantom, we use an analytical Bragg peak model to extract the range-dependent energy spread at the two institutions, as this quantity is usually not available through measurements. Comparison of the measured with the simulated depth dose curves demonstrates agreement within 0.5 mm over the entire energy range. Subsequently, we simulate three patient treatments with varying anatomical complexity (liver, head and neck and lung) to give an example how this approach can be employed to investigate site-specific discrepancies between treatment planning system and Monte Carlo simulations.

  1. Characterizing a proton beam scanning system for Monte Carlo dose calculation in patients

    NASA Astrophysics Data System (ADS)

    Grassberger, C.; Lomax, Anthony; Paganetti, H.

    2015-01-01

    The presented work has two goals. First, to demonstrate the feasibility of accurately characterizing a proton radiation field at treatment head exit for Monte Carlo dose calculation of active scanning patient treatments. Second, to show that this characterization can be done based on measured depth dose curves and spot size alone, without consideration of the exact treatment head delivery system. This is demonstrated through calibration of a Monte Carlo code to the specific beam lines of two institutions, Massachusetts General Hospital (MGH) and Paul Scherrer Institute (PSI). Comparison of simulations modeling the full treatment head at MGH to ones employing a parameterized phase space of protons at treatment head exit reveals the adequacy of the method for patient simulations. The secondary particle production in the treatment head is typically below 0.2% of primary fluence, except for low-energy electrons (<0.6 MeV for 230 MeV protons), whose contribution to skin dose is negligible. However, there is significant difference between the two methods in the low-dose penumbra, making full treatment head simulations necessary to study out-of-field effects such as secondary cancer induction. To calibrate the Monte Carlo code to measurements in a water phantom, we use an analytical Bragg peak model to extract the range-dependent energy spread at the two institutions, as this quantity is usually not available through measurements. Comparison of the measured with the simulated depth dose curves demonstrates agreement within 0.5 mm over the entire energy range. Subsequently, we simulate three patient treatments with varying anatomical complexity (liver, head and neck and lung) to give an example how this approach can be employed to investigate site-specific discrepancies between treatment planning system and Monte Carlo simulations.

  2. Characterizing a Proton Beam Scanning System for Monte Carlo Dose Calculation in Patients

    PubMed Central

    Grassberger, C; Lomax, Tony; Paganetti, H

    2015-01-01

    The presented work has two goals. First, to demonstrate the feasibility of accurately characterizing a proton radiation field at treatment head exit for Monte Carlo dose calculation of active scanning patient treatments. Second, to show that this characterization can be done based on measured depth dose curves and spot size alone, without consideration of the exact treatment head delivery system. This is demonstrated through calibration of a Monte Carlo code to the specific beam lines of two institutions, Massachusetts General Hospital (MGH) and Paul Scherrer Institute (PSI). Comparison of simulations modeling the full treatment head at MGH to ones employing a parameterized phase space of protons at treatment head exit reveals the adequacy of the method for patient simulations. The secondary particle production in the treatment head is typically below 0.2% of primary fluence, except for low–energy electrons (<0.6MeV for 230MeV protons), whose contribution to skin dose is negligible. However, there is significant difference between the two methods in the low-dose penumbra, making full treatment head simulations necessary to study out-of field effects such as secondary cancer induction. To calibrate the Monte Carlo code to measurements in a water phantom, we use an analytical Bragg peak model to extract the range-dependent energy spread at the two institutions, as this quantity is usually not available through measurements. Comparison of the measured with the simulated depth dose curves demonstrates agreement within 0.5mm over the entire energy range. Subsequently, we simulate three patient treatments with varying anatomical complexity (liver, head and neck and lung) to give an example how this approach can be employed to investigate site-specific discrepancies between treatment planning system and Monte Carlo simulations. PMID:25549079

  3. Formulation and Stability Aspects of Nanosized Solid Drug Delivery Systems.

    PubMed

    Szabo, Peter; Zelko, Romana

    2015-01-01

    Nano drug delivery systems are considered as useful means to remedy the problems of drugs of poor solubility, permeability and bioavailability, which became one of the most troublesome questions of the pharmaceutical industry. Different types of nanosized drug delivery systems have been developed and investigated for oral administration, providing auspicious solutions for drug development. In this paper nanosized drug delivery systems intended for oral administration are discussed based on the chemical nature of the carrier of drug molecules. Lipid nanoparticles comprising solid lipid nanoparticles, improved nanostructured lipid carriers and nanostructured silica- lipid hybrid particles have become popular in the formulation of lipophilic drugs of poor oral bioavailability. Polymeric nanoparticles including nanospheres and nanocapsules and polymeric fibrous systems have also emerged as potential drug delivery systems owing to their unique structure. The feasibility of surface functionalization of mesoporous materials and gold nanoparticles enables high level of control over particle characteristics making inorganic nanoparticles an exceptional formulation approach. The authors paid particular attention to the functionality-related stability of the reviewed delivery systems. PMID:26027571

  4. Formulation and Stability Aspects of Nanosized Solid Drug Delivery Systems.

    PubMed

    Szabo, Peter; Zelko, Romana

    2015-01-01

    Nano drug delivery systems are considered as useful means to remedy the problems of drugs of poor solubility, permeability and bioavailability, which became one of the most troublesome questions of the pharmaceutical industry. Different types of nanosized drug delivery systems have been developed and investigated for oral administration, providing auspicious solutions for drug development. In this paper nanosized drug delivery systems intended for oral administration are discussed based on the chemical nature of the carrier of drug molecules. Lipid nanoparticles comprising solid lipid nanoparticles, improved nanostructured lipid carriers and nanostructured silica- lipid hybrid particles have become popular in the formulation of lipophilic drugs of poor oral bioavailability. Polymeric nanoparticles including nanospheres and nanocapsules and polymeric fibrous systems have also emerged as potential drug delivery systems owing to their unique structure. The feasibility of surface functionalization of mesoporous materials and gold nanoparticles enables high level of control over particle characteristics making inorganic nanoparticles an exceptional formulation approach. The authors paid particular attention to the functionality-related stability of the reviewed delivery systems.

  5. Hydrocolloid-based nutraceutical delivery systems

    SciTech Connect

    Janaswamy, Srinivas; Youngren, Susanne R.

    2012-07-11

    Nutraceuticals are important due to their inherent health benefits. However, utilization and consumption are limited by their poor water solubility and instability at normal processing and storage conditions. Herein, we propose an elegant and novel approach for the delivery of nutraceuticals in their active form using hydrocolloid matrices that are inexpensive and non-toxic with generally recognized as safe (GRAS) status. Iota-carrageenan and curcumin have been chosen as models of hydrocolloid and nutraceutical compounds, respectively. The iota-carrageenan network maintains a stable organization after encapsulating curcumin molecules, protects them from melting and then releases them in a sustained manner. These findings lay a strong foundation for developing value-added functional and medicinal foods.

  6. Cyclodextrin-based gene delivery systems.

    PubMed

    Ortiz Mellet, Carmen; García Fernández, José M; Benito, Juan M

    2011-03-01

    Cyclodextrin (CD) history has been largely dominated by their unique ability to form inclusion complexes with guests fitting in their hydrophobic cavity. Chemical funcionalization was soon recognized as a powerful mean for improving CD applications in a wide range of fields, including drug delivery, sensing or enzyme mimicking. However, 100 years after their discovery, CDs are still perceived as novel nanoobjects of undeveloped potential. This critical review provides an overview of different strategies to promote interactions between CD conjugates and genetic material by fully exploiting the inside-outside/upper-lower face anisotropy of the CD nanometric platform. Covalent modification, self-assembling and supramolecular ligation can be put forward with the ultimate goal to build artificial viruses for programmed and efficient gene therapy (222 references).

  7. Improving vaccine delivery using novel adjuvant systems.

    PubMed

    Pichichero, Michael E

    2008-01-01

    Adjuvants have been common additions to vaccines to help facilitate vaccine delivery. With advancements in vaccine technology, several adjuvants which activate immune specific responses have emerged. Available data show these adjuvants elicit important immune responses in both healthy and immunocompromised populations, as well as the elderly. Guidelines for the use and licensure of vaccine adjuvants remain under discussion. However, there is a greater understanding of the innate and adaptive immune response, and the realization of the need for immune specific adjuvants appears to be growing. This is a focused review of four adjuvants currently in clinical trial development: ASO4, ASO2A, CPG 7907, and GM-CSF. The vaccines including these adjuvants are highly relevant today, and are expected to reduce the disease burden of cervical cancer, hepatitis B and malaria. PMID:18398303

  8. MAST Propellant and Delivery System Design Methods

    NASA Technical Reports Server (NTRS)

    Nadeem, Uzair; Mc Cleskey, Carey M.

    2015-01-01

    A Mars Aerospace Taxi (MAST) concept and propellant storage and delivery case study is undergoing investigation by NASA's Element Design and Architectural Impact (EDAI) design and analysis forum. The MAST lander concept envisions landing with its ascent propellant storage tanks empty and supplying these reusable Mars landers with propellant that is generated and transferred while on the Mars surface. The report provides an overview of the data derived from modeling between different methods of propellant line routing (or "lining") and differentiate the resulting design and operations complexity of fluid and gaseous paths based on a given set of fluid sources and destinations. The EDAI team desires a rough-order-magnitude algorithm for estimating the lining characteristics (i.e., the plumbing mass and complexity) associated different numbers of vehicle propellant sources and destinations. This paper explored the feasibility of preparing a mathematically sound algorithm for this purpose, and offers a method for the EDAI team to implement.

  9. Coacervate delivery systems for proteins and small molecule drugs

    PubMed Central

    Johnson, Noah R; Wang, Yadong

    2015-01-01

    Coacervates represent an exciting new class of drug delivery vehicles, developed in the past decade as carriers of small molecule drugs and proteins. This review summarizes several well-described coacervate systems, including Elastin-like peptides for delivery of anti-cancer therapeutics,Heparin-based coacervates with synthetic polycations for controlled growth factor delivery,Carboxymethyl chitosan aggregates for oral drug delivery,Mussel adhesive protein and hyaluronic acid coacervates. Coacervates present advantages in their simple assembly and easy incorporation into tissue engineering scaffolds or as adjuncts to cell therapies. They are also amenable to functionalization such as for targeting or for enhancing the bioactivity of their cargo. These new drug carriers are anticipated to have broad applications and noteworthy impact in the near future. PMID:25138695

  10. Coacervate delivery systems for proteins and small molecule drugs.

    PubMed

    Johnson, Noah R; Wang, Yadong

    2014-12-01

    Coacervates represent an exciting new class of drug delivery vehicles, developed in the past decade as carriers of small molecule drugs and proteins. This review summarizes several well-described coacervate systems, including: i) elastin-like peptides for delivery of anticancer therapeutics; ii) heparin-based coacervates with synthetic polycations for controlled growth factor delivery; iii) carboxymethyl chitosan aggregates for oral drug delivery; iv) Mussel adhesive protein and hyaluronic acid coacervates. Coacervates present advantages in their simple assembly and easy incorporation into tissue engineering scaffolds or as adjuncts to cell therapies. They are also amenable to functionalization such as for targeting or for enhancing the bioactivity of their cargo. These new drug carriers are anticipated to have broad applications and noteworthy impact in the near future.

  11. Recent advances of cocktail chemotherapy by combination drug delivery systems.

    PubMed

    Hu, Quanyin; Sun, Wujin; Wang, Chao; Gu, Zhen

    2016-03-01

    Combination chemotherapy is widely exploited for enhanced cancer treatment in the clinic. However, the traditional cocktail administration of combination regimens often suffers from varying pharmacokinetics among different drugs. The emergence of nanotechnology offers an unparalleled opportunity for developing advanced combination drug delivery strategies with the ability to encapsulate various drugs simultaneously and unify the pharmacokinetics of each drug. This review surveys the most recent advances in combination delivery of multiple small molecule chemotherapeutics using nanocarriers. The mechanisms underlying combination chemotherapy, including the synergistic, additive and potentiation effects, are also discussed with typical examples. We further highlight the sequential and site-specific co-delivery strategies, which provide new guidelines for development of programmable combination drug delivery systems. Clinical outlook and challenges are also discussed in the end.

  12. Dendrimeric systems and their applications in ocular drug delivery.

    PubMed

    Yavuz, Burçin; Pehlivan, Sibel Bozdağ; Unlü, Nurşen

    2013-01-01

    Ophthalmic drug delivery is one of the most attractive and challenging research area for pharmaceutical scientists and ophthalmologists. Absorption of an ophthalmic drug in conventional dosage forms is seriously limited by physiological conditions. The use of nonionic or ionic biodegradable polymers in aqueous solutions and colloidal dosage forms such as liposomes, nanoparticles, nanocapsules, microspheres, microcapsules, microemulsions, and dendrimers has been studied to overcome the problems mentioned above. Dendrimers are a new class of polymeric materials. The unique nanostructured architecture of dendrimers has been studied to examine their role in delivery of therapeutics and imaging agents. Dendrimers can enhance drug's water solubility, bioavailability, and biocompatibility and can be applied for different routes of drug administration successfully. Permeability enhancer properties of dendrimers were also reported. The use of dendrimers can also reduce toxicity versus activity and following an appropriate application route they allow the delivery of the drug to the targeted site and provide desired pharmacokinetic parameters. Therefore, dendrimeric drug delivery systems are of interest in ocular drug delivery. In this review, the limitations related to eye's unique structure, the advantages of dendrimers, and the potential applications of dendrimeric systems to ophthalmology including imaging, drug, peptide, and gene delivery will be discussed. PMID:24396306

  13. Dendrimeric Systems and Their Applications in Ocular Drug Delivery

    PubMed Central

    Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Ünlü, Nurşen

    2013-01-01

    Ophthalmic drug delivery is one of the most attractive and challenging research area for pharmaceutical scientists and ophthalmologists. Absorption of an ophthalmic drug in conventional dosage forms is seriously limited by physiological conditions. The use of nonionic or ionic biodegradable polymers in aqueous solutions and colloidal dosage forms such as liposomes, nanoparticles, nanocapsules, microspheres, microcapsules, microemulsions, and dendrimers has been studied to overcome the problems mentioned above. Dendrimers are a new class of polymeric materials. The unique nanostructured architecture of dendrimers has been studied to examine their role in delivery of therapeutics and imaging agents. Dendrimers can enhance drug's water solubility, bioavailability, and biocompatibility and can be applied for different routes of drug administration successfully. Permeability enhancer properties of dendrimers were also reported. The use of dendrimers can also reduce toxicity versus activity and following an appropriate application route they allow the delivery of the drug to the targeted site and provide desired pharmacokinetic parameters. Therefore, dendrimeric drug delivery systems are of interest in ocular drug delivery. In this review, the limitations related to eye's unique structure, the advantages of dendrimers, and the potential applications of dendrimeric systems to ophthalmology including imaging, drug, peptide, and gene delivery will be discussed. PMID:24396306

  14. Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease

    PubMed Central

    Gunay, Mine Silindir; Ozer, A. Yekta; Chalon, Sylvie

    2016-01-01

    Background: Although a variety of therapeutic approaches are available for the treatment of Parkinson’s disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. Methods: This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. Results: It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson’s disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α-synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Conclusion: Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson’s disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson’s Disease therapy and reduce its side effects. PMID:26714584

  15. Development of the compact proton beam therapy system dedicated to spot scanning with real-time tumor-tracking technology

    NASA Astrophysics Data System (ADS)

    Umezawa, Masumi; Fujimoto, Rintaro; Umekawa, Tooru; Fujii, Yuusuke; Takayanagi, Taisuke; Ebina, Futaro; Aoki, Takamichi; Nagamine, Yoshihiko; Matsuda, Koji; Hiramoto, Kazuo; Matsuura, Taeko; Miyamoto, Naoki; Nihongi, Hideaki; Umegaki, Kikuo; Shirato, Hiroki

    2013-04-01

    Hokkaido University and Hitachi Ltd. have started joint development of the Gated Spot Scanning Proton Therapy with Real-Time Tumor-Tracking System by integrating real-time tumor tracking technology (RTRT) and the proton therapy system dedicated to discrete spot scanning techniques under the "Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program)". In this development, we have designed the synchrotron-based accelerator system by using the advantages of the spot scanning technique in order to realize a more compact and lower cost proton therapy system than the conventional system. In the gated irradiation, we have focused on the issues to maximize irradiation efficiency and minimize the dose errors caused by organ motion. In order to understand the interplay effect between scanning beam delivery and target motion, we conducted a simulation study. The newly designed system consists of the synchrotron, beam transport system, one compact rotating gantry treatment room with robotic couch, and one experimental room for future research. To improve the irradiation efficiency, the new control function which enables multiple gated irradiations per synchrotron cycle has been applied and its efficacy was confirmed by the irradiation time estimation. As for the interplay effect, we confirmed that the selection of a strict gating width and scan direction enables formation of the uniform dose distribution.

  16. Note: Proton microbeam formation with continuously variable kinetic energy using a compact system for three-dimensional proton beam writing

    SciTech Connect

    Ohkubo, T. Ishii, Y.

    2015-03-15

    A compact focused gaseous ion beam system has been developed to form proton microbeams of a few hundreds of keV with a penetration depth of micrometer range in 3-dimensional proton beam writing. Proton microbeams with kinetic energies of 100-140 keV were experimentally formed on the same point at a constant ratio of the kinetic energy of the object side to that of the image side. The experimental results indicate that the beam diameters were measured to be almost constant at approximately 6 μm at the same point with the kinetic energy range. These characteristics of the system were experimentally and numerically demonstrated to be maintained as long as the ratio was constant.

  17. Systemic delivery to central nervous system by engineered PLGA nanoparticles

    PubMed Central

    Cai, Qiang; Wang, Long; Deng, Gang; Liu, Junhui; Chen, Qianxue; Chen, Zhibiao

    2016-01-01

    Neurological disorders are an important global public health problem, but pharmaceutical treatments are limited due to drug access to the central nervous system being restricted by the blood-brain barrier (BBB). Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are one of the most promising drug and gene delivery systems for crossing the BBB. While these systems offer great promise, PLGA NPs also have some intrinsic drawbacks and require further engineering for clinical and research applications. Multiple strategies have been developed for using PLGA NPs to deliver compounds across the BBB. We classify these strategies into three categories according to the adaptations made to the PLGA NPs (1) to facilitate travel from the injection site (pre-transcytosis strategies); (2) to enhance passage across the brain endothelial cells (BBB transcytosis strategies) and (3) to achieve targeting of the impaired nervous system cells (post-transcytosis strategies). PLGA NPs modified according to these three strategies are denoted first, second, and third generation NPs, respectively. We believe that fusing these three strategies to engineer multifunctional PLGA NPs is the only way to achieve translational applications. PMID:27158367

  18. Local arterial wall drug delivery using balloon catheter system.

    PubMed

    Tesfamariam, Belay

    2016-09-28

    Balloon-based drug delivery systems allow localized application of drugs to a vascular segment to reduce neointimal hyperplasia and restenosis. Drugs are coated onto balloons using excipients as drug carriers to facilitate adherence and release of drug during balloon inflation. Drug-coated balloon delivery system is characterized by a rapid drug transfer that achieves high drug concentration along the vessel wall surface, intended to correspond to the balloon dilation-induced vascular injury and healing processes. The balloon catheter system allows homogenous drug delivery to the vessel wall, such that the drug release per unit surface area is kept constant along balloons of different lengths. Optimization of the balloon coating matrix is essential for efficient drug transfer and tissue retention until the artery remodels to a normal set point. Challenges in the development of balloon-based drug delivery to the arterial wall include finding suitable excipients for drug formulation to enable drug release to a targeted lesion site effectively, maintain coating integrity during transit, prolong tissue retention and reduce particulate generation. This review highlights various factors involved in the successful design of balloon-based delivery systems, including drug release kinetics, matrix coating transfer, transmural drug partitioning, dissolution rate and release of unbound active drug. PMID:27473765

  19. Quality assurance of proton beams using a multilayer ionization chamber system

    SciTech Connect

    Dhanesar, Sandeep; Sahoo, Narayan; Kerr, Matthew; Taylor, M. Brad; Summers, Paige; Zhu, X. Ronald; Poenisch, Falk; Gillin, Michael

    2013-09-15

    Purpose: The measurement of percentage depth-dose (PDD) distributions for the quality assurance of clinical proton beams is most commonly performed with a computerized water tank dosimetry system with ionization chamber, commonly referred to as water tank. Although the accuracy and reproducibility of this method is well established, it can be time-consuming if a large number of measurements are required. In this work the authors evaluate the linearity, reproducibility, sensitivity to field size, accuracy, and time-savings of another system: the Zebra, a multilayer ionization chamber system.Methods: The Zebra, consisting of 180 parallel-plate ionization chambers with 2 mm resolution, was used to measure depth-dose distributions. The measurements were performed for scattered and scanned proton pencil beams of multiple energies delivered by the Hitachi PROBEAT synchrotron-based delivery system. For scattered beams, the Zebra-measured depth-dose distributions were compared with those measured with the water tank. The principal descriptors extracted for comparisons were: range, the depth of the distal 90% dose; spread-out Bragg peak (SOBP) length, the region between the proximal 95% and distal 90% dose; and distal-dose fall off (DDF), the region between the distal 80% and 20% dose. For scanned beams, the Zebra-measured ranges were compared with those acquired using a Bragg peak chamber during commissioning.Results: The Zebra demonstrated better than 1% reproducibility and monitor unit linearity. The response of the Zebra was found to be sensitive to radiation field sizes greater than 12.5 × 12.5 cm; hence, the measurements used to determine accuracy were performed using a field size of 10 × 10 cm. For the scattered proton beams, PDD distributions showed 1.5% agreement within the SOBP, and 3.8% outside. Range values agreed within −0.1 ± 0.4 mm, with a maximum deviation of 1.2 mm. SOBP length values agreed within 0 ± 2 mm, with a maximum deviation of 6 mm. DDF

  20. Futures of Service Delivery Systems for Handicapped Individuals. No. 12.

    ERIC Educational Resources Information Center

    Stedman, Donald J.; Wiegerink, Ronald

    Seventeen issues relating to service delivery systems for the handicapped are discussed, including the following: integration of human service systems; meshinq of planning, service, research, and training; installing a monitoring, evaluation, and feedback activity into the planning process; evaluating public education programs; coordinating…

  1. RNAi delivery-whole plant systems reducing psyllids and leafhoppers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We developed a system for delivery of dsRNA constructs in whole-plant systems (herbaceous plants, woody grapevine and citrus seedlings and trees) which is currently being evaluated. Successful feeding of dsRNA in sucrose solutions to psyllids was followed by using flush shoots excised from trees. ...

  2. Engaging Faculty in Telecommunications-Based Instructional Delivery Systems.

    ERIC Educational Resources Information Center

    Swalec, John J.

    In the design and development of telecommunications-based instructional delivery systems, attention to faculty involvement and training is often overlooked until the system is operational. The Waubonsee Telecommunications Instructional Consortium (TIC), in Illinois, is one network that benefited from early faculty input. Even before the first…

  3. Carrier-Based Drug Delivery System for Treatment of Acne

    PubMed Central

    Vyas, Amber; Kumar Sonker, Avinesh

    2014-01-01

    Approximately 95% of the population suffers at some point in their lifetime from acne vulgaris. Acne is a multifactorial disease of the pilosebaceous unit. This inflammatory skin disorder is most common in adolescents but also affects neonates, prepubescent children, and adults. Topical conventional systems are associated with various side effects. Novel drug delivery systems have been used to reduce the side effect of drugs commonly used in the topical treatment of acne. Topical treatment of acne with active pharmaceutical ingredients (API) makes direct contact with the target site before entering the systemic circulation which reduces the systemic side effect of the parenteral or oral administration of drug. The objective of the present review is to discuss the conventional delivery systems available for acne, their drawbacks, and limitations. The advantages, disadvantages, and outcome of using various carrier-based delivery systems like liposomes, niosomes, solid lipid nanoparticles, and so forth, are explained. This paper emphasizes approaches to overcome the drawbacks and limitations associated with the conventional system and the advances and application that are poised to further enhance the efficacy of topical acne formulations, offering the possibility of simplified dosing regimen that may improve treatment outcomes using novel delivery system. PMID:24688376

  4. Charting the information technology direction for an integrated delivery system.

    PubMed

    Scott, H H

    1998-01-01

    Automating the healthcare integrated delivery system requires a special set of skills, talent, and communication that goes beyond the capability of the i.t. manager alone. Bringing together all elements of the integrated delivery system and forming a well-integrated information environment will require a level of teamwork rarely seen in any industry. Today's IT manager is like an orchestra conductor. He or she should look ahead in the musical composition, manage the tempo, and bring all the sounds of the eclectic set of instruments together in harmony and achievement of the melody. Following the key success factor outlined here may not guarantee success in automating the integrated delivery system, but following them should keep the process harmonious.

  5. A clinical perspective on mucoadhesive buccal drug delivery systems

    PubMed Central

    Gilhotra, Ritu M; Ikram, Mohd; Srivastava, Sunny; Gilhotra, Neeraj

    2014-01-01

    Mucoadhesion can be defined as a state in which two components, of which one is of biological origin, are held together for extended periods of time by the help of interfacial forces. Among the various transmucosal routes, buccal mucosa has excellent accessibility and relatively immobile mucosa, hence suitable for administration of retentive dosage form. The objective of this paper is to review the works done so far in the field of mucoadhesive buccal drug delivery systems (MBDDS), with a clinical perspective. Starting with a brief introduction of the mucoadhesive drug delivery systems, oral mucosa, and the theories of mucoadhesion, this article then proceeds to cover the works done so far in the field of MBDDS, categorizing them on the basis of ailments they are meant to cure. Additionally, we focus on the various patents, recent advancements, and challenges as well as the future prospects for mucoadhesive buccal drug delivery systems. PMID:24683406

  6. Biologically erodable microspheres as potential oral drug delivery systems

    NASA Astrophysics Data System (ADS)

    Mathiowitz, Edith; Jacob, Jules S.; Jong, Yong S.; Carino, Gerardo P.; Chickering, Donald E.; Chaturvedi, Pravin; Santos, Camilla A.; Vijayaraghavan, Kavita; Montgomery, Sean; Bassett, Michael; Morrell, Craig

    1997-03-01

    Biologically adhesive delivery systems offer important advantages1-5 over conventional drug delivery systems6. Here we show that engineered polymer microspheres made of biologically erodable polymers, which display strong adhesive interactions with gastrointestinal mucus and cellular linings, can traverse both the mucosal absorptive epithelium and the follicle-associated epithelium covering the lymphoid tissue of Peyer's patches. The polymers maintain contact with intestinal epithelium for extended periods of time and actually penetrate it, through and between cells. Thus, once loaded with compounds of pharmacological interest, the microspheres could be developed as delivery systems to transfer biologically active molecules to the circulation. We show that these microspheres increase the absorption of three model substances of widely different molecular size: dicumarol, insulin and plasmid DNA.

  7. Physical and chemical stimuli-responsive drug delivery systems: targeted delivery and main routes of administration.

    PubMed

    Lopes, Joana R; Santos, Gory; Barata, Pedro; Oliveira, Rita; Lopes, Carla M

    2013-01-01

    In the area of drug delivery, novel tools and technological approaches have captured the attention of researchers in order to improve the performance of conventional therapeutics and patient compliance to pharmacological therapy. Stimuli-responsive drug delivery systems (DDS) appear as a promising approach to control and target drug delivery. When these DDS are administered, the drug release is activated and then modulated through some action or external input and facilitated by the energy supplied externally. The stimuli responsible to activate the drug release can be classified into three types according to their nature or the type of energy applied: physical (e.g. magnetic field, electric field, ultrasound, temperature and osmotic pressure); chemical (e.g. pH, ionic strength and glucose); and biological (enzymes and endogenous receptors). The present review gives an overview of the most significant physical and chemical stimuliresponsive DDS and elucidates about their current and relevant applications in controlled and targeted drug delivery attending different routes of administration.

  8. Engineering Stent Based Delivery System for Esophageal Cancer Using Docetaxel.

    PubMed

    Shaikh, Mohsin; Choudhury, Namita Roy; Knott, Robert; Garg, Sanjay

    2015-07-01

    Esophageal cancer patients are often diagnosed as "advanced" cases. These patients are subjected to palliative stenting using self-expanding metallic stents (SEMS) to maintain oral alimentation. Unfortunately, SEMS get reoccluded due to tumor growth, in and over the stent struts. To investigate potential solutions to this problem, docetaxel (DTX) delivery films were prepared using PurSil AL 20 (PUS), which can be used as a covering material for the SEMS. Drug-polymer miscibility and interactions were studied. Bilayer films were prepared by adhering the blank film to the DTX loaded film in order to maintain the unidirectional delivery to the esophagus. In vitro release and the local DTX delivery were studied using in vitro permeation experiments. It was found that DTX and PUS were physically and chemically compatible. The bilayer films exhibited sustained release (>30 days) and minimal DTX permeation through esophageal tissues in vitro. The rate-determining step for the DTX delivery was calculated. It was found that >0.9 fraction of rate control lies with the esophageal tissues, suggesting that DTX delivery can be sustained for longer periods compared to the in vitro release observed. Thus, the bilayer films can be developed as a localized sustained delivery system in combination with the stent.

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

    PubMed Central

    Moodley, Kovanya; Pillay, Viness; Choonara, Yahya E.; du Toit, Lisa C.; Ndesendo, Valence M. K.; Kumar, Pradeep; Cooppan, Shivaan; Bawa, Priya

    2012-01-01

    Recent pharmaceutical research has focused on controlled drug delivery having an advantage over conventional methods. Adequate controlled plasma drug levels, reduced side effects as well as improved patient compliance are some of the benefits that these systems may offer. Controlled delivery systems that can provide zero-order drug delivery have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Thus, zero-order drug release is ideal in a large area of drug delivery which has therefore led to the development of various technologies with such drug release patterns. Systems such as multilayered tablets and other geometrically altered devices have been created to perform this function. One of the principles of multilayered tablets involves creating a constant surface area for release. Polymeric materials play an important role in the functioning of these systems. Technologies developed to date include among others: Geomatrix® multilayered tablets, which utilizes specific polymers that may act as barriers to control drug release; Procise®, which has a core with an aperture that can be modified to achieve various types of drug release; core-in-cup tablets, where the core matrix is coated on one surface while the circumference forms a cup around it; donut-shaped devices, which possess a centrally-placed aperture hole and Dome Matrix® as well as “release modules assemblage”, which can offer alternating drug release patterns. This review discusses the novel altered geometric system technologies that have been developed to provide controlled drug release, also focusing on polymers that have been employed in such developments. PMID:22312236

  10. [Development of drug delivery systems for targeting to macrophages].

    PubMed

    Chono, Sumio

    2007-09-01

    Drug delivery systems (DDS) using liposomes as drug carriers for targeting to macrophages have been developed for the treatment of diseases that macrophages are related to their progress. Initially, DDS for the treatment of atherosclerosis are described. The influence of particle size on the drug delivery to atherosclerotic lesions that macrophages are richly present and antiatherosclerotic effects following intravenous administration of liposomes containing dexamethasone (DXM-liposomes) was investigated in atherogenic mice. Both the drug delivery efficacy of DXM-liposomes (particle size, 200 nm) to atherosclerotic lesions and their antiatherosclerotic effects were greater than those of 70 and 500 nm. These results indicate that there is an optimal particle size for drug delivery to atherosclerotic lesions. DDS for the treatment of respiratory infections are then described. The influence of particle size and surface mannosylation on the drug delivery to alveolar macrophages (AMs) and antibacterial effects following pulmonary administration of liposomes containing ciprofloxacin (CPFX-liposomes) was investigated in rats. The drug delivery efficacy of CPFX-liposomes to AMs was particle size-dependent over the range 100-1000 nm and then became constant at over 1000 nm. These results indicate that the most effective size is 1000 nm. Both the drug delivery efficacy of mannosylated CPFX-liposomes (particle size, 1000 nm) to AMs and their antibacterial effects were significantly greater than those of unmodified CPFX-liposomes. These results indicate that the surface mannosylation is useful method for drug delivery to AMs. This review provides useful information to help in the development of novel pharmaceutical formulations aimed at drug targeting to macrophages.

  11. Bioengineered Silk Protein-Based Gene Delivery Systems

    PubMed Central

    Numata, Keiji; Subramanian, Balajikarthick; Currie, Heather A.; Kaplan, David L.

    2009-01-01

    Silk proteins self-assemble into mechanically robust material structures that are also biodegradable and non-cytotoxic, suggesting utility for gene delivery. Since silk proteins can also be tailored in terms of chemistry, molecular weight and other design features via genetic engineering, further control of this system for gene delivery can be considered. In the present study, silk-based block copolymers were bioengineered with poly(l-lysine) domains for gene delivery. Ionic complexes of these silk-polylysine based block copolymers with plasmid DNA (pDNA) were prepared for gene delivery to human embryonic kidney (HEK) cells. The material systems were characterized by agarose gel electrophoresis, atomic force microscopy, and dynamic light scattering. The polymers self-assembled in solution and complexed plasmid DNA through ionic interactions. The pDNA complexes with 30-lysine residues prepared at a polymer/nucleotide ratio of 10 and with a solution diameter of 380 nm, showed the highest efficiency for transfection. The pDNA complexes were also immobilized on silk films and demonstrated direct cell transfection from these surfaces. The results demonstrate the potential of bioengineered silk proteins as a new family of highly tailored gene delivery systems. PMID:19577803

  12. Programmable nanomedicine: synergistic and sequential drug delivery systems

    NASA Astrophysics Data System (ADS)

    Pacardo, Dennis B.; Ligler, Frances S.; Gu, Zhen

    2015-02-01

    Recent developments in nanomedicine for the cancer therapy have enabled programmable delivery of therapeutics by exploiting the stimuli-responsive properties of nanocarriers. These therapeutic systems were designed with the relevant chemical and physical properties that respond to different triggers for enhanced anticancer efficacy, including the reduced development of drug-resistance, lower therapeutic dose, site-specific transport, and spatiotemporally controlled release. This minireview discusses the current advances in programmable nanocarriers for cancer therapy with particular emphasis on synergistic and sequential drug delivery systems.

  13. Cyclosporine Amicellar delivery system for dry eyes

    PubMed Central

    Kang, Han; Cha, Kwang-Ho; Cho, Wonkyung; Park, Junsung; Park, Hee Jun; Sun, Bo Kyung; Hyun, Sang-Min; Hwang, Sung-Joo

    2016-01-01

    Background The objectives of this study were to develop stable cyclosporine A (CsA) ophthalmic micelle solutions for dry-eye syndrome and evaluate their physicochemical properties and therapeutic efficacy. Materials and methods CsA-micelle solutions (MS-CsA) were created by a simple method with Cremophor EL, ethanol, and phosphate buffer. We investigated the particle size, pH, and osmolarity. In addition, long-term physical and chemical stability for MS-CsA was observed. To confirm the therapeutic efficacy, tear production in dry eye-induced rabbits was evaluated using the Schirmer tear test (STT). When compared to a commercial product, Restasis, MS-CsA demonstrated improvement in goblet-cell density and conjunctival epithelial morphology, as demonstrated in histological hematoxylin and eosin staining. Results MS-CsA had a smaller particle size (average diameter 14–18 nm) and a narrow size distribution. Physicochemical parameters, such as particle size, pH, osmolarity, and remaining CsA concentration were all within the expected range of 60 days. STT scores significantly improved in MS-CsA treated groups (P<0.05) in comparison to those of the Restasis-treated group. The number of goblet cells for rabbit conjunctivas after the administration of MS-CsA was 94.83±8.38, a significantly higher result than the 65.17±11.51 seen with Restasis. The conjunctival epithelial morphology of dry eye-induced rabbits thinned with loss of goblet cells. However, after 5 days of treatment with drug formulations, rabbit conjunctivas recovered epithelia and showed a relative increase in the number of goblet cells. Conclusion The results of this study indicate the potential use of a novel MS for the ophthalmic delivery of CsA in treating dry eyes. PMID:27382280

  14. Limited Efficiency of Drug Delivery to Specific Intracellular Organelles Using Subcellularly "Targeted" Drug Delivery Systems.

    PubMed

    Maity, Amit Ranjan; Stepensky, David

    2016-01-01

    Many drugs have been designed to act on intracellular targets and to affect intracellular processes inside target cells. For the desired effects to be exerted, these drugs should permeate target cells and reach specific intracellular organelles. This subcellular drug targeting approach has been proposed for enhancement of accumulation of these drugs in target organelles and improved efficiency. This approach is based on drug encapsulation in drug delivery systems (DDSs) and/or their decoration with specific targeting moieties that are intended to enhance the drug/DDS accumulation in the intracellular organelle of interest. During recent years, there has been a constant increase in interest in DDSs targeted to specific intracellular organelles, and many different approaches have been proposed for attaining efficient drug delivery to specific organelles of interest. However, it appears that in many studies insufficient efforts have been devoted to quantitative analysis of the major formulation parameters of the DDSs disposition (efficiency of DDS endocytosis and endosomal escape, intracellular trafficking, and efficiency of DDS delivery to the target organelle) and of the resulting pharmacological effects. Thus, in many cases, claims regarding efficient delivery of drug/DDS to a specific organelle and efficient subcellular targeting appear to be exaggerated. On the basis of the available experimental data, it appears that drugs/DDS decoration with specific targeting residues can affect their intracellular fate and result in preferential drug accumulation within an organelle of interest. However, it is not clear whether these approaches will be efficient in in vivo settings and be translated into preclinical and clinical applications. Studies that quantitatively assess the mechanisms, barriers, and efficiencies of subcellular drug delivery and of the associated toxic effects are required to determine the therapeutic potential of subcellular DDS targeting.

  15. Bicellar systems as a new colloidal delivery strategy for skin.

    PubMed

    Rubio, L; Rodríguez, G; Barbosa-Barros, L; Alonso, C; Cócera, M; de la Maza, A; Parra, J L; López, O

    2012-04-01

    The presented work evaluates the use of bicellar systems as new delivery vectors for controlled release of compounds through the skin. Two different active principles were introduced into the bicellar systems: diclofenac diethylamine (DDEA) and flufenamic acid (Ffa). Bicellar systems are discoidal aggregates formed by long and short alkyl chain phospholipids. Characterization of the bicellar systems by dynamic light scattering (DLS) and cryogenic transmission electron microscopy (Cryo-TEM) showed that particle size decreased when DDEA was encapsulated and increased when Ffa was included in the bicellar systems. Percutaneous absorption studies demonstrated a lower penetration of DDEA and Ffa through the skin when the drugs were included in the bicellar systems than when the drugs were applied in an aqueous solution (DDEA) and in an ethanolic solution (Ffa); the reduction in penetration was more pronounced with Ffa. These bicellar systems may have retardant effects on percutaneous absorption, which result in a promising strategy for future drug or cosmetic delivery applications.

  16. Drug delivery systems improve pharmaceutical profile and facilitate medication adherence.

    PubMed

    Wertheimer, Albert I; Santella, Thomas M; Finestone, Albert J; Levy, Richard A

    2005-01-01

    Innovations in dosage forms and dose delivery systems across a wide range of medications offer substantial clinical advantages, including reduced dosing frequency and improved patient adherence; minimized fluctuation of drug concentrations and maintenance of blood levels within a desired range; localized drug delivery; and the potential for reduced adverse effects and increased safety. The advent of new large-molecule drugs for previously untreatable or only partially treatable diseases is stimulating the development of suitable delivery systems for these agents. Although advanced formulations may be more expensive than conventional dosage forms, they often have a more favorable pharmacologic profile and can be cost-effective. Inclusion of these dosage forms on drug formulary lists may help patients remain on therapy and reduce the economic and social burden of care.

  17. Micro and Nanoparticle Drug Delivery Systems for Preventing Allotransplant Rejection

    PubMed Central

    Fisher, James D.; Acharya, Abhinav P.; Little, Steven R.

    2015-01-01

    Despite decades of advances in transplant immunology, tissue damage caused by acute allograft rejection remains the primary cause of morbidity and mortality in the transplant recipient. Moreover, the long-term sequelae of lifelong immunosuppression leaves patients at risk for developing a host of other deleterious conditions. Controlled drug delivery using micro- and nanoparticles (MNPs) is an effective way to deliver higher local doses of a given drug to specific tissues and cells while mitigating systemic effects. Herein, we review several descriptions of MNP immunotherapies aimed at prolonging allograft survival. We also discuss developments in the field of biomimetic drug delivery that use MNP constructs to induce and recruit our bodies' own suppressive immune cells. Finally, we comment on the regulatory pathway associated with these drug delivery systems. Collectively, it is our hope the studies described in this review will help to usher in a new era of immunotherapy in organ transplantation. PMID:25937032

  18. A framework for describing health care delivery organizations and systems.

    PubMed

    Piña, Ileana L; Cohen, Perry D; Larson, David B; Marion, Lucy N; Sills, Marion R; Solberg, Leif I; Zerzan, Judy

    2015-04-01

    Describing, evaluating, and conducting research on the questions raised by comparative effectiveness research and characterizing care delivery organizations of all kinds, from independent individual provider units to large integrated health systems, has become imperative. Recognizing this challenge, the Delivery Systems Committee, a subgroup of the Agency for Healthcare Research and Quality's Effective Health Care Stakeholders Group, which represents a wide diversity of perspectives on health care, created a draft framework with domains and elements that may be useful in characterizing various sizes and types of care delivery organizations and may contribute to key outcomes of interest. The framework may serve as the door to further studies in areas in which clear definitions and descriptions are lacking.

  19. Smart surface-enhanced Raman scattering traceable drug delivery systems.

    PubMed

    Liu, Lei; Tang, Yonghong; Dai, Sheng; Kleitz, Freddy; Qiao, Shi Zhang

    2016-07-01

    A novel smart nanoparticle-based system has been developed for tracking intracellular drug delivery through surface-enhanced Raman scattering (SERS). This new drug delivery system (DDS) shows targeted cytotoxicity towards cancer cells via pH-cleavable covalent carboxylic hydrazone links and the SERS tracing capability based on gold@silica nanocarriers. Doxorubicin, as a model anticancer drug, was employed to compare SERS with conventional fluorescence tracing approaches. It is evident that SERS demonstrates higher sensitivity and resolution, revealing intracellular details, as the strengths of the original Raman signals can be amplified by SERS. Importantly, non-destructive SERS will provide the designed DDS with great autonomy and potential to study the dynamic procedures of non-fluorescent drug delivery into living cells. PMID:27297745

  20. Medicated chewing gum, a novel drug delivery system.

    PubMed

    Aslani, Abolfazl; Rostami, Farnaz

    2015-04-01

    New formulations and technologies have been developed through oral drug delivery systems' researches. Such researches display significance of oral route amongst patients. We've reviewed all the features associated with medicated chewing gum as a modern drug delivery by introducing the history, advantages and disadvantages, methods of manufacturing, composition differences, evaluation tests and examples of varieties of medicated chewing gums. Acceptance of medicated chewing gum has been augmented through years. The advantages and therapeutic benefits of chewing gum support its development as we can see new formulations with new drugs contained have been produced from past and are going to find a place in market by formulation of new medicated chewing gums. Potential applications of medicated chewing gums are highly widespread as they will be recognized in future. Nowadays standards for qualifying chewing gums are the same as tablets. Patient-centered studies include medicated chewing gums as a delivery system too which creates compliance for patients. PMID:26109999

  1. Smart surface-enhanced Raman scattering traceable drug delivery systems

    NASA Astrophysics Data System (ADS)

    Liu, Lei; Tang, Yonghong; Dai, Sheng; Kleitz, Freddy; Qiao, Shi Zhang

    2016-06-01

    A novel smart nanoparticle-based system has been developed for tracking intracellular drug delivery through surface-enhanced Raman scattering (SERS). This new drug delivery system (DDS) shows targeted cytotoxicity towards cancer cells via pH-cleavable covalent carboxylic hydrazone links and the SERS tracing capability based on gold@silica nanocarriers. Doxorubicin, as a model anticancer drug, was employed to compare SERS with conventional fluorescence tracing approaches. It is evident that SERS demonstrates higher sensitivity and resolution, revealing intracellular details, as the strengths of the original Raman signals can be amplified by SERS. Importantly, non-destructive SERS will provide the designed DDS with great autonomy and potential to study the dynamic procedures of non-fluorescent drug delivery into living cells.A novel smart nanoparticle-based system has been developed for tracking intracellular drug delivery through surface-enhanced Raman scattering (SERS). This new drug delivery system (DDS) shows targeted cytotoxicity towards cancer cells via pH-cleavable covalent carboxylic hydrazone links and the SERS tracing capability based on gold@silica nanocarriers. Doxorubicin, as a model anticancer drug, was employed to compare SERS with conventional fluorescence tracing approaches. It is evident that SERS demonstrates higher sensitivity and resolution, revealing intracellular details, as the strengths of the original Raman signals can be amplified by SERS. Importantly, non-destructive SERS will provide the designed DDS with great autonomy and potential to study the dynamic procedures of non-fluorescent drug delivery into living cells. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr03869g

  2. Proton Therapy

    NASA Astrophysics Data System (ADS)

    Oelfke, Uwe

    Proton therapy is one of the most rapidly developing new treatment technologies in radiation oncology. This treatment approach has — after roughly 40 years of technical developments — reached a mature state that allows a widespread clinical application. We therefore review the basic physical and radio-biological properties of proton beams. The main physical aspect is the elemental dose distribution arising from an infinitely narrow proton pencil beam. This includes the physics of proton stopping powers and the concept of CSDA range. Furthermore, the process of multiple Coulomb scattering is discussed for the lateral dose distribution. Next, the basic terms for the description of radio-biological properties of proton beams like LET and RBE are briefly introduced. Finally, the main concepts of modern proton dose delivery concepts are introduced before the standard method of inverse treatment planning for hadron therapy is presented.

  3. Proton magnetic resonance spectroscopy of leech muscle and nervous system.

    PubMed

    Petroff, O A; Hogan, E; Johansen, J; Kleinhaus, A L

    1987-01-01

    1. Proton nuclear magnetic resonance spectroscopy (1H NMR) was used to measure the major intracellular metabolites in perchloric acid extracts of the Macrobdella decora muscle and nervous systems and the Oryctolagus cuniculus cerebrum. 2. Acetate, alanine, choline, glutamate, inositol, and lactate were assigned in the spectrum of leech ventral cord, leech muscle, and rabbit cerebrum. 3. Hirudonine and propionate were clearly observed only in the spectrum of leech muscle. 4. Creatine, N-acetyl aspartate, gamma aminobutyric acid, aspartate, and taurine, distinctive components of spectra of the mammalian cerebrum, were not seen in the invertebrate spectra. 5. 1H NMR spectroscopy provides a simple and rapid means of characterizing the major organic metabolites found in leech muscle and nervous tissues.

  4. A low energy beam transport system for proton beam

    SciTech Connect

    Yang, Y.; Zhang, Z. M.; Wu, Q.; Zhang, W. H.; Ma, H. Y.; Sun, L. T.; Zhang, X. Z.; Liu, Z. W.; He, Y.; Zhao, H. W.; Xie, D. Z.

    2013-03-15

    A low energy beam transport (LEBT) system has been built for a compact pulsed hadron source (CPHS) at Tsinghua University in China. The LEBT, consisting of two solenoids and three short-drift sections, transports a pulsed proton beam of 60 mA of energy of 50 keV to the entrance of a radio frequency quadrupole (RFQ). Measurement has shown a normalized RMS beam emittance less than 0.2 {pi} mm mrad at the end of the LEBT. Beam simulations were carried out to compare with the measurement and are in good agreement. Based on the successful CPHS LEBT development, a new LEBT for a China ADS projector has been designed. The features of the new design, including a beam chopper and beam simulations of the LEBT are presented and discussed along with CPHS LEBT development in this article.

  5. Transferosomes - A vesicular transdermal delivery system for enhanced drug permeation

    PubMed Central

    Rajan, Reshmy; Jose, Shoma; Mukund, V. P. Biju; Vasudevan, Deepa T.

    2011-01-01

    Transdermal administration of drugs is generally limited by the barrier function of the skin. Vesicular systems are one of the most controversial methods for transdermal delivery of active substances. The interest in designing transdermal delivery systems was relaunched after the discovery of elastic vesicles like transferosomes, ethosomes, cubosomes, phytosomes, etc. This paper presents the composition, mechanisms of penetration, manufacturing and characterization methods of transferosomes as transdermal delivery systems of active substances. For a drug to be absorbed and distributed into organs and tissues and eliminated from the body, it must pass through one or more biological membranes/barriers at various locations. Such a movement of drug across the membrane is called as drug transport. For the drugs to be delivered to the body, they should cross the membranous barrier. The concept of these delivery systems was designed in an attempt to concentrate the drug in the tissues of interest, while reducing the amount of drug in the remaining tissues. Hence, surrounding tissues are not affected by the drug. In addition, loss of drug does not happen due to localization of drug, leading to get maximum efficacy of the medication. Therefore, the phospholipid based carrier systems are of considerable interest in this era. PMID:22171309

  6. Nanostructured lipid carriers system: recent advances in drug delivery.

    PubMed

    Iqbal, Md Asif; Md, Shadab; Sahni, Jasjeet Kaur; Baboota, Sanjula; Dang, Shweta; Ali, Javed

    2012-12-01

    Nanostructured lipid carrier (NLC) is second generation smarter drug carrier system having solid matrix at room temperature. This carrier system is made up of physiological, biodegradable and biocompatible lipid materials and surfactants and is accepted by regulatory authorities for application in different drug delivery systems. The availability of many products in the market in short span of time reveals the success story of this delivery system. Since the introduction of the first product, around 30 NLC preparations are commercially available. NLC exhibit superior advantages over other colloidal carriers viz., nanoemulsions, polymeric nanoparticles, liposomes, SLN etc. and thus, have been explored to more extent in pharmaceutical technology. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes NLC versatile delivery system for various routes of administration. The present review gives insights on the definitions and characterization of NLC as colloidal carriers including the production techniques and suitable formulations. This review paper also highlights the importance of NLC in pharmaceutical applications for the various routes of drug delivery viz., topical, oral, pulmonary, ocular and parenteral administration and its future perspective as a pharmaceutical carrier. PMID:22931500

  7. The Targeted-liposome Delivery System of Antitumor Drugs.

    PubMed

    Wu, Wei-dang; Yi, Xiu-lin; Jiang, Li-xin; Li, Ya-zhuo; Gao, Jing; Zeng, Yong; Yi, Rong-da; Dai, Li-peng; Li, Wei; Ci, Xiao-yan; Si, Duan-yun; Liu, Chang-xiao

    2015-01-01

    The liposome delivery system has been intensively explored as novel drug delivery system (DDS) for antitumor drugs, due to its safety, selective cytotoxicity, long circulation and slow elimination in blood, which is favorable for cancer therapy. The liposome-based chemotherapeutics are used to treat a variety of cancers to enhance the therapeutic index of antitumor drugs. Here, the author reviewed the important targets for cancer therapy and the pharmacokinetic behavior of liposomal drugs in vivo, as well as the application of the targeting liposomal system in cancer therapy. Considering further application for clinical use, the great challenges of the liposome-based delivery system were also proposed as follows: 1) prepare stealth liposome with steric stabilization and further enhance the therapeutic effects and safety; 2) explore more safe clinical targets and complementary or different types of targeting liposome; 3) thirdly, more investment is needed on the research of pharmacokinetics of the elements such as the ligands (antibody), PEG and lipids of liposome delivery system as well as safety evaluation. Considering the complex process of the liposomal encapsulation drugs in vivo, the author inferred that there are maybe different forms of the encapsulation drug to be internalized by the tumor tissues at the same time and space, although there are little reports on it. PMID:26652257

  8. Nanostructured Delivery Systems: Augmenting the Delivery of Antiretroviral Drugs for Better Management of HIV/AIDS.

    PubMed

    Singh, Gurinder; Pai, Roopa S; Mustafa, Sanaul

    2015-01-01

    In the last two decades, HIV-1, the retrovirus associated with acquired immunodeficiency syndrome (AIDS), is globally one of the primary causes of morbidity and mortality. Unfortunately, existing approaches for interventions are not able to suppress the progression of infection due to this virus. Of the many obstacles, viral entry into the mono-nuclear phagocyte system encompassing monocytes/macrophages and dendritic cells is a major concern. Viral infection is also responsible for the subsequent distribution of the virus into various tissues throughout the organism. Tremendous progress has been made during the past few years to diagnose and treat patients with HIV/AIDS infection, yet much remains to be done. Recommended treatment involves long-term and multiple drug therapy that causes severe side effects. With almost 12% of the world population suffering from HIV/AIDS, better management of this global threat is highly desired. Nanostructured delivery systems hold promise for improving the situation. Such systems can facilitate the uptake of antiretroviral drugs, causing a considerable improvement in HIV/AIDS therapy. Nanoscale systems have intriguing potential to drastically improve existing HIV/AIDS diagnosis and treatment platforms. Nanosystems constitute a wide range of systems varying from polymeric nanoparticles, to solid-lipid nanoparticles, liposomes, micro- and nanoemulsions, dendrimers, and self-nanoemulsifying systems. Improved bioavailability, solubility, stability, and biocompatibility make them an ideal choice for delivery of antiretroviral drugs. The present review initially describes an updated bird's-eye view account of the literature. Then, we provide a relatively sententious overview on updated patents of recent nanostructured delivery systems for antiretroviral drugs. Finally, we discuss low-cost therapy (such as antioxidants and immune modulators) for the treatment and prevention of HIV/AIDS. PMID:26559551

  9. WE-D-17A-01: A Dynamic Collimation System for Spot Scanned Proton Therapy: Conceptual Overview

    SciTech Connect

    Hyer, D; Hill, P; Wang, D; Smith, B; Flynn, R

    2014-06-15

    Purpose: In the absence of a collimation system, the lateral penumbra in pencil beam scanning (PBS) proton therapy delivered at low energies is highly dependent on the spot size. This dependence, coupled with the fact that spot sizes increase with decreasing energy, reduces the benefit of the PBS technique for treating shallow tumors such as those found in the head and neck region. In order to overcome this limitation, a dynamic collimation system (DCS) was developed for sharpening the lateral penumbra of low energy proton therapy dose distributions delivered by PBS. Methods: The proposed DCS consists of two pairs of orthogonal trimmer blades which intercept the edges of the proton beam near the target edge in the beam's eye view. Each trimmer blade is capable of rapid motion in the direction perpendicular to the central beam axis by means of a linear motor, with maximum velocity and acceleration of 2.5 m/s and 19.6 m/s{sup 2}, respectively. Two-dimensional treatment plans were created both with and without the DCS for in-air spot sizes (σ-air) of 3, 5, 7, and 9 mm, representing a wide array of clinically available equipment. Results: In its current configuration, the snout of the DCS has outer dimensions of 22.6 × 22.6 cm{sup 2} and is capable of delivering a minimum treatment field size of 15 × 15 cm{sup 2}. Using off the shelf components, the constructed system would weigh less than 20 kg. The treatment plans created with the DCS yielded a reduction in the mean dose to normal tissue surrounding the target of 26.2–40.6% for spot sizes of 3–9 mm, respectively. Conclusion: The DCS can be integrated with current or future proton therapy equipment and we believe it will serve as a useful tool to further improve the next generation of proton therapy delivery.

  10. NANOPARTICLE DELIVERY SYSTEMS IN CANCER VACCINES

    PubMed Central

    Krishnamachari, Yogita; Geary, Sean M.; Lemke, Caitlin D.; Salem, Aliasger K.

    2013-01-01

    Therapeutic strategies that involve the manipulation of the host’s immune system are gaining momentum in cancer research. Antigen-loaded nanocarriers are capable of being actively taken up by antigen presenting cells (APCs) and have shown promising potential in cancer immunotherapy by initiating a strong immunostimulatory cascade that results in potent antigen-specific immune responses against the cancer. Such carrier systems offer versatility in that they can simultaneously co-deliver adjuvants with the antigens to enhance APC activation and maturation. Furthermore, modifying the surface properties of these nanocarriers affords active targeting properties to APCs and/or enhanced accumulation in solid tumors. Here we review some recent advances in these colloidal and particulate nanoscale systems designed for cancer immunotherapy and the potential for these systems to translate into clinical cancer vaccines. PMID:20721603

  11. Mercury sorbent delivery system for flue gas

    DOEpatents

    Klunder; ,Edgar B.

    2009-02-24

    The invention presents a device for the removal of elemental mercury from flue gas streams utilizing a layer of activated carbon particles contained within the filter fabric of a filter bag for use in a flue gas scrubbing system.

  12. Coordination polymer particles as potential drug delivery systems.

    PubMed

    Imaz, Inhar; Rubio-Martínez, Marta; García-Fernández, Lorena; García, Francisca; Ruiz-Molina, Daniel; Hernando, Jordi; Puntes, Victor; Maspoch, Daniel

    2010-07-14

    Micro- and nanoscale coordination polymer particles can be used for encapsulating and delivering drugs. In vitro cancer cell cytotoxicity assays showed that these capsules readily release doxorubicin, which shows anticancer efficacy. The results from this work open up new avenues for metal-organic capsules to be used as potential drug delivery systems.

  13. Nanoparticulate Adjuvants and Delivery Systems for Allergen Immunotherapy

    PubMed Central

    De Souza Rebouças, Juliana; Esparza, Irene; Ferrer, Marta; Sanz, María Luisa; Irache, Juan Manuel; Gamazo, Carlos

    2012-01-01

    In the last decades, significant progress in research and clinics has been made to offer possible innovative therapeutics for the management of allergic diseases. However, current allergen immunotherapy shows limitations concerning the long-term efficacy and safety due to local side effects and risk of anaphylaxis. Thus, effective and safe vaccines with reduced dose of allergen have been developed using adjuvants. Nevertheless, the use of adjuvants still has several disadvantages, which limits its use in human vaccines. In this context, several novel adjuvants for allergen immunotherapy are currently being investigated and developed. Currently, nanoparticles-based allergen-delivery systems have received much interest as potential adjuvants for allergen immunotherapy. It has been demonstrated that the incorporation of allergens into a delivery system plays an important role in the efficacy of allergy vaccines. Several nanoparticles-based delivery systems have been described, including biodegradable and nondegradable polymeric carriers. Therefore, this paper provides an overview of the current adjuvants used for allergen immunotherapy. Furthermore, nanoparticles-based allergen-delivery systems are focused as a novel and promising strategy for allergy vaccines. PMID:22496608

  14. Nanoparticulate adjuvants and delivery systems for allergen immunotherapy.

    PubMed

    De Souza Rebouças, Juliana; Esparza, Irene; Ferrer, Marta; Sanz, María Luisa; Irache, Juan Manuel; Gamazo, Carlos

    2012-01-01

    In the last decades, significant progress in research and clinics has been made to offer possible innovative therapeutics for the management of allergic diseases. However, current allergen immunotherapy shows limitations concerning the long-term efficacy and safety due to local side effects and risk of anaphylaxis. Thus, effective and safe vaccines with reduced dose of allergen have been developed using adjuvants. Nevertheless, the use of adjuvants still has several disadvantages, which limits its use in human vaccines. In this context, several novel adjuvants for allergen immunotherapy are currently being investigated and developed. Currently, nanoparticles-based allergen-delivery systems have received much interest as potential adjuvants for allergen immunotherapy. It has been demonstrated that the incorporation of allergens into a delivery system plays an important role in the efficacy of allergy vaccines. Several nanoparticles-based delivery systems have been described, including biodegradable and nondegradable polymeric carriers. Therefore, this paper provides an overview of the current adjuvants used for allergen immunotherapy. Furthermore, nanoparticles-based allergen-delivery systems are focused as a novel and promising strategy for allergy vaccines.

  15. [Synthesis of nanoparticles for dental drug delivery systems].

    PubMed

    Bakó, József; Szepesi, Márta; Márton, Ildikó; Borbély, János; Hegedûs, Csaba

    2007-06-01

    Modern drug delivery systems are designed for targeted controlled slow drug release. Up to now polymer based hydrogels have been applied in dentistry, which systems can affect the rate of the release due to their structure. Recently, intensive research for other methods is performed all over the world in order to improve the effectiveness of delivery systems. Nanotechnology is one of the most dynamically developing disciplines and is a powerful tool to increase the bioavailability of drugs. The aim of this work is to synthesise biocompatible nanoparticles by free radical initiated copolymerization of the monomers, 2-hydroxyethyl methacrylate (HEMA) and polyethyleneglycol dimethacrylate (PEGDMA) in aqueous solution, which can support the formation of nanoparticles that can be used as a drug delivery system for dental applications. The polymer-based nanoparticles were prepared via micellar polymerisation, which resulted a well dispersible white powder material. The size of particles was determined by Dynamic Laser Light Scattering (DLS) and Scanning Electron Microscopy (SEM). The size of particles is in range of 50-180 nm, measured by SEM. These values are commensurable with the results obtained by DLS experiments, where two size ranges were observed, as 40 +/- 15 nm and 180 +/- 30 nm. The nanoparticles are suitable for incorporation into a hydrogel matrix and to design new drug delivery devices for dental applications.

  16. NimbleTools: A Universally Designed Test Delivery System

    ERIC Educational Resources Information Center

    Russell, Michael; Hoffmann, Thomas; Higgins, Jennifer

    2009-01-01

    Students with disabilities and special needs have faced challenges in accessing educational content, and in taking traditional pen-and-paper tests. How might technology improve the process, while making statewide tests truly accessible to all students? NimbleTools is the first computer-based test delivery system that incorporates principles of…

  17. Coordination polymer particles as potential drug delivery systems.

    PubMed

    Imaz, Inhar; Rubio-Martínez, Marta; García-Fernández, Lorena; García, Francisca; Ruiz-Molina, Daniel; Hernando, Jordi; Puntes, Victor; Maspoch, Daniel

    2010-07-14

    Micro- and nanoscale coordination polymer particles can be used for encapsulating and delivering drugs. In vitro cancer cell cytotoxicity assays showed that these capsules readily release doxorubicin, which shows anticancer efficacy. The results from this work open up new avenues for metal-organic capsules to be used as potential drug delivery systems. PMID:20485835

  18. Assessment of Alternative Student Aid Delivery Systems: Analytic Agenda for the Current System.

    ERIC Educational Resources Information Center

    Advanced Technology, Inc., Reston, VA.

    A guide for analyzing the effects of the current student aid delivery system and for estimating the effects of system alternatives is presented. Attention is directed to measures, data sources, and analysis methods needed to evaluate the effects of each delivery system activity on the various participants (e.g., lenders, financial aid applicants,…

  19. Drug Delivery Systems and Combination Therapy by Using Vinca Alkaloids

    PubMed Central

    Lee, Chun-Ting; Huang, Yen-Wei; Yang, Chih-Hui; Huang, Keng-Shiang

    2015-01-01

    Developing new methods for chemotherapy drug delivery has become a topic of great concern. Vinca alkaloids are among the most widely used chemotherapy reagents for tumor therapy; however, their side effects are particularly problematic for many medical doctors. To reduce the toxicity and enhance the therapeutic efficiency of vinca alkaloids, many researchers have developed strategies such as using liposome-entrapped drugs, chemical- or peptide-modified drugs, polymeric packaging drugs, and chemotherapy drug combinations. This review mainly focuses on the development of a vinca alkaloid drug delivery system and the combination therapy. Five vinca alkaloids (eg, vincristine, vinblastine, vinorelbine, vindesine, and vinflunine) are reviewed. PMID:25877096

  20. Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier

    PubMed Central

    Upadhyay, Ravi Kant

    2014-01-01

    Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods. PMID:25136634

  1. Drug delivery systems, CNS protection, and the blood brain barrier.

    PubMed

    Upadhyay, Ravi Kant

    2014-01-01

    Present review highlights various drug delivery systems used for delivery of pharmaceutical agents mainly antibiotics, antineoplastic agents, neuropeptides, and other therapeutic substances through the endothelial capillaries (BBB) for CNS therapeutics. In addition, the use of ultrasound in delivery of therapeutic agents/biomolecules such as proline rich peptides, prodrugs, radiopharmaceuticals, proteins, immunoglobulins, and chimeric peptides to the target sites in deep tissue locations inside tumor sites of brain has been explained. In addition, therapeutic applications of various types of nanoparticles such as chitosan based nanomers, dendrimers, carbon nanotubes, niosomes, beta cyclodextrin carriers, cholesterol mediated cationic solid lipid nanoparticles, colloidal drug carriers, liposomes, and micelles have been discussed with their recent advancements. Emphasis has been given on the need of physiological and therapeutic optimization of existing drug delivery methods and their carriers to deliver therapeutic amount of drug into the brain for treatment of various neurological diseases and disorders. Further, strong recommendations are being made to develop nanosized drug carriers/vehicles and noninvasive therapeutic alternatives of conventional methods for better therapeutics of CNS related diseases. Hence, there is an urgent need to design nontoxic biocompatible drugs and develop noninvasive delivery methods to check posttreatment clinical fatalities in neuropatients which occur due to existing highly toxic invasive drugs and treatment methods.

  2. Medicated chewing gum, a novel drug delivery system

    PubMed Central

    Aslani, Abolfazl; Rostami, Farnaz

    2015-01-01

    New formulations and technologies have been developed through oral drug delivery systems’ researches. Such researches display significance of oral route amongst patients. We’ve reviewed all the features associated with medicated chewing gum as a modern drug delivery by introducing the history, advantages and disadvantages, methods of manufacturing, composition differences, evaluation tests and examples of varieties of medicated chewing gums. Acceptance of medicated chewing gum has been augmented through years. The advantages and therapeutic benefits of chewing gum support its development as we can see new formulations with new drugs contained have been produced from past and are going to find a place in market by formulation of new medicated chewing gums. Potential applications of medicated chewing gums are highly widespread as they will be recognized in future. Nowadays standards for qualifying chewing gums are the same as tablets. Patient-centered studies include medicated chewing gums as a delivery system too which creates compliance for patients. PMID:26109999

  3. Unsteady jet in designing innovative drug delivery system

    NASA Astrophysics Data System (ADS)

    Wang, Cong; Mazur, Paul; Cosse, Julia; Rider, Stephanie; Gharib, Morteza

    2014-11-01

    Micro-needle injections, a promising pain-free drug delivery method, is constrained by its limited penetration depth. This deficiency can be overcome by implementing fast unsteady jet that can penetrate sub-dermally. The development of a faster liquid jet would increase the penetration depth and delivery volume of micro-needles. In this preliminary work, the nonlinear transient behavior of an elastic tube balloon in providing fast discharge is analyzed. A physical model that combines the Mooney Rivlin Material model and Young-Lapalce's Law was developed and used to investigate the fast discharging dynamic phenomenon. A proof of concept prototype was constructed to demonstrate the feasibility of a simple thumb-sized delivery system to generate liquid jet with desired speed in the range of 5-10 m/s. This work is supported by ZCUBE Corporation.

  4. Electrohydrodynamics: A facile technique to fabricate drug delivery systems

    PubMed Central

    Chakraborty, Syandan; Liao, I-Chien; Adler, Andrew; Leong, Kam W.

    2009-01-01

    Electrospinning and electrospraying are facile electrohydrodynamic fabrication methods that can generate drug delivery systems (DDS) through a one-step process. The nano-structured fiber and particle morphologies produced by these techniques offer tunable release kinetics applicable to diverse biomedical applications. Coaxial-electrospinning/electrospraying, a relatively new technique of fabricating core-shell fibers/particles have added to the versatility of these DDS by affording a near zero-order drug release kinetics, dampening of burst release, and applicability to a wider range of bioactive agents. Controllable electrospinning/spraying of fibers and particles and subsequent drug release from these chiefly polymeric vehicles depends on well-defined solution and process parameters. The additional drug delivery capability from electrospun fibers can further enhance the material’s functionality in tissue engineering applications. This review discusses the state-of-the-art of using electrohydrodynamic technique to generate nano-fiber/particles as drug delivery devices. PMID:19651167

  5. Crystallization Methods for Preparation of Nanocrystals for Drug Delivery System.

    PubMed

    Gao, Yuan; Wang, Jingkang; Wang, Yongli; Yin, Qiuxiang; Glennon, Brian; Zhong, Jian; Ouyang, Jinbo; Huang, Xin; Hao, Hongxun

    2015-01-01

    Low water solubility of drug products causes delivery problems such as low bioavailability. The reduced particle size and increased surface area of nanocrystals lead to the increasing of the dissolution rate. The formulation of drug nanocrystals is a robust approach and has been widely applied to drug delivery system (DDS) due to the significant development of nanoscience and nanotechnology. It can be used to improve drug efficacy, provide targeted delivery and minimize side-effects. Crystallization is the main and efficient unit operation to produce nanocrystals. Both traditional crystallization methods such as reactive crystallization, anti-solvent crystallization and new crystallization methods such as supercritical fluid crystallization, high-gravity controlled precipitation can be used to produce nanocrystals. The current mini-review outlines the main crystallization methods addressed in literature. The advantages and disadvantages of each method were summarized and compared.

  6. Dendrimer Advances for the Central Nervous System Delivery of Therapeutics

    PubMed Central

    2013-01-01

    The effectiveness of noninvasive treatment for central nervous system (CNS) diseases is generally limited by the poor access of therapeutic agents into the CNS. Most CNS drugs cannot permeate into the brain parenchyma because of the blood-brain barrier (BBB), and overcoming this has become one of the most significant challenges in the development of CNS therapeutics. Rapid advances in nanotechnology have provided promising solutions to this challenge. This review discusses the latest applications of dendrimers in the treatment of CNS diseases with an emphasis on brain tumors. Dendrimer-mediated drug delivery, imaging, and diagnosis are also reviewed. The toxicity, biodistribution, and transport mechanisms in dendrimer-mediated delivery of CNS therapeutic agents bypassing or crossing the BBB are also discussed. Future directions and major challenges of dendrimer-mediated delivery of CNS therapeutic agents are included. PMID:24274162

  7. [Systems for the delivery of health care].

    PubMed

    Kérouac, S; Duquette, A; Sandhu, B K

    1990-06-01

    Re-examining the role of the nurse, the authors remind us of the importance of understanding how our system of health care has evolved, as well as what it holds for the future. Presenting an historical overview of the past 50 years, they discuss concepts related to moving the profession forward and suggest the decade ahead offers key opportunities.

  8. Creating physician-driven integrated delivery systems.

    PubMed

    Wagner, L

    1995-03-01

    Put doctors in control of key strategic and clinical decisions? Make them part owners or give them financial performance incentives? Yes, say many experts, that's the road to success for integrated systems. Read how they're doing it and evaluate your physician integration initiatives on HSL's 10-question self-assessment.

  9. Interpenetrating Polymer Networks as Innovative Drug Delivery Systems

    PubMed Central

    Lohani, Alka; Singh, Garima; Bhattacharya, Shiv Sankar; Verma, Anurag

    2014-01-01

    Polymers have always been valuable excipients in conventional dosage forms, also have shown excellent performance into the parenteral arena, and are now capable of offering advanced and sophisticated functions such as controlled drug release and drug targeting. Advances in polymer science have led to the development of several novel drug delivery systems. Interpenetrating polymer networks (IPNs) have shown superior performances over the conventional individual polymers and, consequently, the ranges of applications have grown rapidly for such class of materials. The advanced properties of IPNs like swelling capacity, stability, biocompatibility, nontoxicity and biodegradability have attracted considerable attention in pharmaceutical field especially in delivering bioactive molecules to the target site. In the past few years various research reports on the IPN based delivery systems showed that these carriers have emerged as a novel carrier in controlled drug delivery. The present review encompasses IPNs, their types, method of synthesis, factors which affects the morphology of IPNs, extensively studied IPN based drug delivery systems, and some natural polymers widely used for IPNs. PMID:24949205

  10. Interpenetrating polymer networks as innovative drug delivery systems.

    PubMed

    Lohani, Alka; Singh, Garima; Bhattacharya, Shiv Sankar; Verma, Anurag

    2014-01-01

    Polymers have always been valuable excipients in conventional dosage forms, also have shown excellent performance into the parenteral arena, and are now capable of offering advanced and sophisticated functions such as controlled drug release and drug targeting. Advances in polymer science have led to the development of several novel drug delivery systems. Interpenetrating polymer networks (IPNs) have shown superior performances over the conventional individual polymers and, consequently, the ranges of applications have grown rapidly for such class of materials. The advanced properties of IPNs like swelling capacity, stability, biocompatibility, nontoxicity and biodegradability have attracted considerable attention in pharmaceutical field especially in delivering bioactive molecules to the target site. In the past few years various research reports on the IPN based delivery systems showed that these carriers have emerged as a novel carrier in controlled drug delivery. The present review encompasses IPNs, their types, method of synthesis, factors which affects the morphology of IPNs, extensively studied IPN based drug delivery systems, and some natural polymers widely used for IPNs.

  11. Chitosan nanoparticle based delivery systems for sustainable agriculture.

    PubMed

    Kashyap, Prem Lal; Xiang, Xu; Heiden, Patricia

    2015-01-01

    Development of technologies that improve food productivity without any adverse impact on the ecosystem is the need of hour. In this context, development of controlled delivery systems for slow and sustained release of agrochemicals or genetic materials is crucial. Chitosan has emerged as a valuable carrier for controlled delivery of agrochemicals and genetic materials because of its proven biocompatibility, biodegradability, non-toxicity, and adsorption abilities. The major advantages of encapsulating agrochemicals and genetic material in a chitosan matrix include its ability to function as a protective reservoir for the active ingredients, protecting the ingredients from the surrounding environment while they are in the chitosan domain, and then controlling their release, allowing them to serve as efficient gene delivery systems for plant transformation or controlled release of pesticides. Despite the great progress in the use of chitosan in the area of medical and pharmaceutical sciences, there is still a wide knowledge gap regarding the potential application of chitosan for encapsulation of active ingredients in agriculture. Hence, the present article describes the current status of chitosan nanoparticle-based delivery systems in agriculture, and to highlight challenges that need to be overcome.

  12. Direct current power delivery system and method

    DOEpatents

    Zhang, Di; Garces, Luis Jose; Dai, Jian; Lai, Rixin

    2016-09-06

    A power transmission system includes a first unit for carrying out the steps of receiving high voltage direct current (HVDC) power from an HVDC power line, generating an alternating current (AC) component indicative of a status of the first unit, and adding the AC component to the HVDC power line. Further, the power transmission system includes a second unit for carrying out the steps of generating a direct current (DC) voltage to transfer the HVDC power on the HVDC power line, wherein the HVDC power line is coupled between the first unit and the second unit, detecting a presence or an absence of the added AC component in the HVDC power line, and determining the status of the first unit based on the added AC component.

  13. System modeling speeds clamshell unloader delivery

    SciTech Connect

    Schuster, J.W.; Zirkler, A.H.; Duke, G.

    1995-04-01

    This article describes how enhanced dust control concepts and design studies found best method to ensure quick, safe clamshell unloader transport and assembly. A new facility, US Generating Co.`s Logan Generating Station, was built in New Jersey, along the Delaware River and four miles from Chester, Pa. At the outset, concerns arose over possible unusual regulatory issues because the plant`s coal barge unloading system extends into the river where it falls under the jurisdiction of the State of Delaware. However, the project contract with the equipment supplier avoided complications by calling for a turnkey project, including erection, start-up, commissioning and training. The supplier responded by using a modeling technique to ensure environmental compatibility. The contract called for one stationary-clamshell bucket grab unloader, complete with a dust control system, barge haul and barge breasting systems, and auxiliary cranes for handling the barge haul lines. Bucket coal capacity is 10 tons at 50 pounds per cubic foot density. When operating on a 40-second duty cycle, the unloader is rated at 910 tons per hour free digging capacity. Under dry, high dust conditions, the duty cycle is extended to 50 seconds to allow for pause time after the bucket closes and while over the hopper prior to bucket discharge.

  14. Verification of proton range, position, and intensity in IMPT with a 3D liquid scintillator detector system

    SciTech Connect

    Archambault, L.; Poenisch, F.; Sahoo, N.; Robertson, D.; Lee, A.; Gillin, M. T.; Mohan, R.; Beddar, S.

    2012-03-15

    Purpose: Intensity-modulated proton therapy (IMPT) using spot scanned proton beams relies on the delivery of a large number of beamlets to shape the dose distribution in a highly conformal manner. The authors have developed a 3D system based on liquid scintillator to measure the spatial location, intensity, and depth of penetration (energy) of the proton beamlets in near real-time. Methods: The detector system consists of a 20 x 20 x 20 cc liquid scintillator (LS) material in a light tight enclosure connected to a CCD camera. This camera has a field of view of 25.7 by 19.3 cm and a pixel size of 0.4 mm. While the LS is irradiated, the camera continuously acquires images of the light distribution produced inside the LS. Irradiations were made with proton pencil beams produced with a spot-scanning nozzle. Pencil beams with nominal ranges in water between 9.5 and 17.6 cm were scanned to irradiate an area of 10 x 10 cm square on the surface of the LS phantom. Image frames were acquired at 50 ms per frame. Results: The signal to noise ratio of a typical Bragg peak was about 170. Proton range measured from the light distribution produced in the LS was accurate to within 0.3 mm on average. The largest deviation seen between the nominal and measured range was 0.6 mm. Lateral position of the measured pencil beam was accurate to within 0.4 mm on average. The largest deviation seen between the nominal and measured lateral position was 0.8 mm; however, the accuracy of this measurement could be improved by correcting light scattering artifacts. Intensity of single proton spots were measured with precision ranging from 3 % for the smallest spot intensity (0.005 MU) to 0.5 % for the largest spot (0.04 MU). Conclusions: Our LS detector system has been shown to be capable of fast, submillimeter spatial localization of proton spots delivered in a 3D volume. This system could be used for beam range, intensity and position verification in IMPT.

  15. Synthetic Microbes As Drug Delivery Systems

    PubMed Central

    2015-01-01

    Synthetic cell therapy is a field that has broad potential for future applications in human disease treatment. Next generation therapies will consist of engineered bacterial strains capable of diagnosing disease, producing and delivering therapeutics, and controlling their numbers to meet containment and safety concerns. A thorough understanding of the microbial ecology of the human body and the interaction of the microbes with the immune system will benefit the choice of an appropriate chassis that engrafts stably and interacts productively with the resident community in specific body niches. PMID:25079685

  16. Brain-specific delivery of naproxen using different carrier systems.

    PubMed

    Mahmoud, Sheha; Mohammad, Alhawi

    2010-11-01

    Naproxen is one of the most potent NSAIDs and plays an important role in the treatment of neurodegenerative diseases. Poor brain delivery of naproxen at therapeutic doses, in addition to its serious gastrointestinal side effects, has prompted research into the development of a specific carrier system that is capable of delivering naproxen to the brain at smaller doses. The purpose of this study was to evaluate two brain-specific carrier systems of naproxen. The first was the dihydropyridine/pyridinium redox system that utilized a lipophilic chemical delivery system coupled to the carboxylic acid group of naproxen through an ethanolamine linker. Secondly, an ascorbic acid system, which has reducing properties and acts as a biological carrier through sodium-dependent vitamin-C transporter, was used for brain-specific delivery of naproxen. The prepared prodrugs were stable in aqueous buffers (pH 1.2 and 7.4) and rapidly hydrolyzed in biological fluids. Bioavailability studies revealed that both prodrugs 10 and 17 were rapidly cleared from blood with half lives of about 1 h, which will likely decrease systemic adverse effects. The rapid clearance from the blood was accompanied by an increase in the prodrug concentration in the brain, which occurred as a result of the prodrug being more locked in compared to the parent drug naproxen.

  17. Using DNA nanotechnology to produce a drug delivery system

    NASA Astrophysics Data System (ADS)

    Huyen La, Thi; Thu Thuy Nguyen, Thi; Phuc Pham, Van; Huyen Nguyen, Thi Minh; Huan Le, Quang

    2013-03-01

    Drug delivery to cancer cells in chemotherapy is one of the most advanced research topics. The effectiveness of the current cancer treatment drugs is limited because they are not capable of distinguishing between cancer cells and normal cells so that they kill not only cancer cells but also normal ones. To overcome this disadvantage by profiting from the differences in physical and chemical properties between cancer and normal cells, nanoparticles (NPs) delivering a drug are designed in a specific manner such that they can distinguish the cancer cells from the normal ones and are targeted only to the cancer cells. Currently, there are various drug delivery systems with many advantages, but sharing some common disadvantages such as difficulty with controlling the size, low encapsulation capacity and low stability. With the development and success of DNA nanotechnology, DNA strands are used to create effective drug delivery NPs with precisely controlled size and structure, safety and high stability. This article presents our study on drug encapsulation in DNA nanostructure which loaded docetaxel and curcumin in a desire to create a new and effective drug delivery system with high biological compatibility. Invited talk at the 6th International Workshop on Advanced Materials Science and Nanotechnology, 30 October-2 November, 2012, Ha Long, Vietnam.

  18. Exosome mimetics: a novel class of drug delivery systems

    PubMed Central

    Kooijmans, Sander AA; Vader, Pieter; van Dommelen, Susan M; van Solinge, Wouter W; Schiffelers, Raymond M

    2012-01-01

    The identification of extracellular phospholipid vesicles as conveyors of cellular information has created excitement in the field of drug delivery. Biological therapeutics, including short interfering RNA and recombinant proteins, are prone to degradation, have limited ability to cross biological membranes, and may elicit immune responses. Therefore, delivery systems for such drugs are under intensive investigation. Exploiting extracellular vesicles as carriers for biological therapeutics is a promising strategy to overcome these issues and to achieve efficient delivery to the cytosol of target cells. Exosomes are a well studied class of extracellular vesicles known to carry proteins and nucleic acids, making them especially suitable for such strategies. However, the considerable complexity and the related high chance of off-target effects of these carriers are major barriers for translation to the clinic. Given that it is well possible that not all components of exosomes are required for their proper functioning, an alternative strategy would be to mimic these vesicles synthetically. By assembly of liposomes harboring only crucial components of natural exosomes, functional exosome mimetics may be created. The low complexity and use of well characterized components strongly increase the pharmaceutical acceptability of such systems. However, exosomal components that would be required for the assembly of functional exosome mimetics remain to be identified. This review provides insights into the composition and functional properties of exosomes, and focuses on components which could be used to enhance the drug delivery properties of exosome mimetics. PMID:22619510

  19. Health care delivery system reform: accountable care organizations.

    PubMed

    Dove, James T; Weaver, W Douglas; Lewin, Jack

    2009-09-01

    Health care reform is moving forward at a frantic pace. There have been 3 documents released from the Senate Finance Committee and proposed legislation from the Senate HELP Committee and the House of Representatives Tri-Committee on Health Reform. The push for legislative action has not been sidetracked by the economic conditions. Integrated health care delivery is the current favored approach to aligning resource use and cost. Accountable care organizations (ACOs), a concept included in health care reform legislation before both the House and Senate, propose to translate the efficiencies and lessons learned from large integrated systems and apply them to nonintegrated practices. The ACO design could be real or virtual integration of local delivery providers. This new structure is complicated, and clinicians, patients, and payers should have input regarding the design and function of it. Because most of health care is delivered in the ambulatory setting, it remains to be determined whether the ACOs are best developed in parallel among physician practices and hospitals or as partnerships between hospitals and physicians. Many are concerned that hospital-led ACOs will force physician employment by hospitals with possible unintended negative consequences for physicians, hospitals, and patients. Patients, physicians, other providers, and payers are in a better position to guide the redesign of the health care delivery system than government agencies, policy organizations, or elected officials, no matter how well intended. We strongly believe-and ACC has proclaimed-that change in health care delivery must be accomplished with patients and physicians at the table.

  20. An emerging platform for drug delivery: aerogel based systems.

    PubMed

    Ulker, Zeynep; Erkey, Can

    2014-03-10

    Over the past few decades, advances in "aerogel science" have provoked an increasing interest for these materials in pharmaceutical sciences for drug delivery applications. Because of their high surface areas, high porosities and open pore structures which can be tuned and controlled by manipulation of synthesis conditions, nanostructured aerogels represent a promising class of materials for delivery of various drugs as well as enzymes and proteins. Along with biocompatible inorganic aerogels and biodegradable organic aerogels, more complex systems such as surface functionalized aerogels, composite aerogels and layered aerogels have also been under development and possess huge potential. Emphasis is given to the details of the aerogel synthesis and drug loading methods as well as the influence of synthesis parameters and loading methods on the adsorption and release of the drugs. Owing to their ability to increase the bioavailability of low solubility drugs, to improve both their stability and their release kinetics, there are an increasing number of research articles concerning aerogels in different drug delivery applications. This review presents an up to date overview of the advances in all kinds of aerogel based drug delivery systems which are currently under investigation.

  1. Aerosol delivery of programmed cell death protein 4 using polysorbitol-based gene delivery system for lung cancer therapy.

    PubMed

    Kim, You-Kyoung; Xing, Lei; Chen, Bao-An; Xu, Fengguo; Jiang, Hu-Lin; Zhang, Can

    2014-11-01

    The development of a safe and effective gene delivery system is the most challenging obstacle to the broad application of gene therapy in the clinic. In this study, we report the development of a polysorbitol-based gene delivery system as an alternative gene carrier for lung cancer therapy. The copolymer was prepared by a Michael addition reaction between sorbitol diacrylate (SD) and spermine (SPE); the SD-SPE copolymer effectively condenses with DNA on the nanoscale and protects it from nucleases. SD-SPE/DNA complexes showed excellent transfection with low toxicity both in vitro and in vivo, and aerosol delivery of SD-SPE complexes with programmed cell death protein 4 DNA significantly suppressed lung tumorigenesis in K-ras(LA1) lung cancer model mice. These results demonstrate that SD-SPE has great potential as a gene delivery system based on its excellent biocompatibility and high gene delivery efficiency for lung cancer gene therapy. PMID:24983766

  2. Fault tolerance control for proton exchange membrane fuel cell systems

    NASA Astrophysics Data System (ADS)

    Wu, Xiaojuan; Zhou, Boyang

    2016-08-01

    Fault diagnosis and controller design are two important aspects to improve proton exchange membrane fuel cell (PEMFC) system durability. However, the two tasks are often separately performed. For example, many pressure and voltage controllers have been successfully built. However, these controllers are designed based on the normal operation of PEMFC. When PEMFC faces problems such as flooding or membrane drying, a controller with a specific design must be used. This paper proposes a unique scheme that simultaneously performs fault diagnosis and tolerance control for the PEMFC system. The proposed control strategy consists of a fault diagnosis, a reconfiguration mechanism and adjustable controllers. Using a back-propagation neural network, a model-based fault detection method is employed to detect the PEMFC current fault type (flooding, membrane drying or normal). According to the diagnosis results, the reconfiguration mechanism determines which backup controllers to be selected. Three nonlinear controllers based on feedback linearization approaches are respectively built to adjust the voltage and pressure difference in the case of normal, membrane drying and flooding conditions. The simulation results illustrate that the proposed fault tolerance control strategy can track the voltage and keep the pressure difference at desired levels in faulty conditions.

  3. Advancing polymeric delivery systems amidst a nucleic acid therapy renaissance

    PubMed Central

    Burke, Paul A.; Pun, Suzie H.; Reineke, Theresa M.

    2013-01-01

    Nucleic acid therapeutics are attracting renewed interest due to recent clinical advances and product approvals. Most leading programs use chemical conjugates, or viral vectors in the case of gene therapy, while several use no delivery system at all. Polymer systems, which have been at the periphery of this renaissance, often involve greater molecular complexity than competing approaches, which must be justified by their advantages. Advanced analytical methods, along with biological tools for characterizing biotransformation and intracellular trafficking, are increasingly being applied to nucleic acid delivery systems including those based on polymers. These frontiers of investigation create the opportunity for an era where highly defined polymer compositions are optimized based on mechanistic insights in a way that has not been previously possible, offering the prospect of greater differentiation from alternatives. This will require integrated collaboration between polymer scientists and those from other disciplines. PMID:24683504

  4. Advancing polymeric delivery systems amidst a nucleic acid therapy renaissance.

    PubMed

    Burke, Paul A; Pun, Suzie H; Reineke, Theresa M

    2013-10-15

    Nucleic acid therapeutics are attracting renewed interest due to recent clinical advances and product approvals. Most leading programs use chemical conjugates, or viral vectors in the case of gene therapy, while several use no delivery system at all. Polymer systems, which have been at the periphery of this renaissance, often involve greater molecular complexity than competing approaches, which must be justified by their advantages. Advanced analytical methods, along with biological tools for characterizing biotransformation and intracellular trafficking, are increasingly being applied to nucleic acid delivery systems including those based on polymers. These frontiers of investigation create the opportunity for an era where highly defined polymer compositions are optimized based on mechanistic insights in a way that has not been previously possible, offering the prospect of greater differentiation from alternatives. This will require integrated collaboration between polymer scientists and those from other disciplines.

  5. Advancing polymeric delivery systems amidst a nucleic acid therapy renaissance.

    PubMed

    Burke, Paul A; Pun, Suzie H; Reineke, Theresa M

    2013-10-15

    Nucleic acid therapeutics are attracting renewed interest due to recent clinical advances and product approvals. Most leading programs use chemical conjugates, or viral vectors in the case of gene therapy, while several use no delivery system at all. Polymer systems, which have been at the periphery of this renaissance, often involve greater molecular complexity than competing approaches, which must be justified by their advantages. Advanced analytical methods, along with biological tools for characterizing biotransformation and intracellular trafficking, are increasingly being applied to nucleic acid delivery systems including those based on polymers. These frontiers of investigation create the opportunity for an era where highly defined polymer compositions are optimized based on mechanistic insights in a way that has not been previously possible, offering the prospect of greater differentiation from alternatives. This will require integrated collaboration between polymer scientists and those from other disciplines. PMID:24683504

  6. A new technique for making bright proton bunches using barrier RF systems

    SciTech Connect

    Bhat, C.M.; /Fermilab

    2005-05-01

    I describe here a very promising scheme for producing bright proton bunches for proton-antiproton and proton-proton colliders. The method is based on the use of wide-band barrier rf systems. First, I explain the principle of the method. The beam dynamics simulations applied to the Fermilab Main Injector (MI) suggest that the scheme allows a wide range of bunch intensities and emittances for ppbar collider. This method has the potential to increase the instantaneous luminosity by {ge}30% at the Tevatron.

  7. Chronopharmaceutical Drug Delivery Systems: Hurdles, Hype or Hope?⊗

    PubMed Central

    Youan, Bi-Botti C.

    2010-01-01

    The current advances in chronobiology and the knowledge gained from chronotherapy of selected diseases strongly suggest that “the one size fits all at all times” approach to drug delivery is no longer substantiated, at least for selected bioactive agents and disease therapy or prevention. Thus, there is a critical and urgent need for chronopharmaceutical research (e.g., design and evaluation of robust, spatially and temporally controlled drug delivery systems that would be clinically intended for chronotherapy by different routes of administration). This review provides a brief overview of current delivery system intended for chronotherapy. In theory, such an ideal “magic pill” preferably with affordable cost, would improve the safety, efficacy and patient compliance of old and new drugs. However, currently, there are three major hurdles for the successful transition of such system from laboratory to patient bedside. These include the challenges to identify adequate (i) rhythmic biomaterials and systems, (ii) rhythm engineering modeling, perhaps using system biology and (iii) regulatory guidance. PMID:20438781

  8. Quality measurement and system change of cancer care delivery.

    PubMed

    Haggstrom, David A; Doebbeling, Bradley N

    2011-12-01

    Cancer care quality measurement and system change may serve as a case example for larger possibilities in the health care system related to other diseases. Cancer care quality gaps and variation exist across both technical and patient-centered cancer quality measures, especially among vulnerable populations. There is a need to develop measures that address the following dimensions of quality and its context: disparities, overuse, patient-centeredness, and uncertainty. Developments that may promote system change in cancer care delivery include changes in the information market, organizational accountability, and consumer empowerment. Information market changes include public cancer care quality reporting, enabled by health information exchange, and incentivized by pay-for-performance. Moving organizational accountability, reimbursement, and quality measurement from individual episodes of care to multiple providers providing coordinated cancer care may address quality gaps associated with the fragmentation of care delivery. Consumer empowerment through new technologies, such as personal health records, may lead to the collection of patient-centered quality measures and promote patient self-management. Across all of these developments, leadership and ongoing research to guide informed system changes will be necessary to transform the cancer care delivery system.

  9. Nanoscale drug delivery systems and the blood-brain barrier.

    PubMed

    Alyautdin, Renad; Khalin, Igor; Nafeeza, Mohd Ismail; Haron, Muhammad Huzaimi; Kuznetsov, Dmitry

    2014-01-01

    The protective properties of the blood-brain barrier (BBB) are conferred by the intricate architecture of its endothelium coupled with multiple specific transport systems expressed on the surface of endothelial cells (ECs) in the brain's vasculature. When the stringent control of the BBB is disrupted, such as following EC damage, substances that are safe for peripheral tissues but toxic to neurons have easier access to the central nervous system (CNS). As a consequence, CNS disorders, including degenerative diseases, can occur independently of an individual's age. Although the BBB is crucial in regulating the biochemical environment that is essential for maintaining neuronal integrity, it limits drug delivery to the CNS. This makes it difficult to deliver beneficial drugs across the BBB while preventing the passage of potential neurotoxins. Available options include transport of drugs across the ECs through traversing occludins and claudins in the tight junctions or by attaching drugs to one of the existing transport systems. Either way, access must specifically allow only the passage of a particular drug. In general, the BBB allows small molecules to enter the CNS; however, most drugs with the potential to treat neurological disorders other than infections have large structures. Several mechanisms, such as modifications of the built-in pumping-out system of drugs and utilization of nanocarriers and liposomes, are among the drug-delivery systems that have been tested; however, each has its limitations and constraints. This review comprehensively discusses the functional morphology of the BBB and the challenges that must be overcome by drug-delivery systems and elaborates on the potential targets, mechanisms, and formulations to improve drug delivery to the CNS.

  10. Nanoscale drug delivery systems and the blood–brain barrier

    PubMed Central

    Alyautdin, Renad; Khalin, Igor; Nafeeza, Mohd Ismail; Haron, Muhammad Huzaimi; Kuznetsov, Dmitry

    2014-01-01

    The protective properties of the blood–brain barrier (BBB) are conferred by the intricate architecture of its endothelium coupled with multiple specific transport systems expressed on the surface of endothelial cells (ECs) in the brain’s vasculature. When the stringent control of the BBB is disrupted, such as following EC damage, substances that are safe for peripheral tissues but toxic to neurons have easier access to the central nervous system (CNS). As a consequence, CNS disorders, including degenerative diseases, can occur independently of an individual’s age. Although the BBB is crucial in regulating the biochemical environment that is essential for maintaining neuronal integrity, it limits drug delivery to the CNS. This makes it difficult to deliver beneficial drugs across the BBB while preventing the passage of potential neurotoxins. Available options include transport of drugs across the ECs through traversing occludins and claudins in the tight junctions or by attaching drugs to one of the existing transport systems. Either way, access must specifically allow only the passage of a particular drug. In general, the BBB allows small molecules to enter the CNS; however, most drugs with the potential to treat neurological disorders other than infections have large structures. Several mechanisms, such as modifications of the built-in pumping-out system of drugs and utilization of nanocarriers and liposomes, are among the drug-delivery systems that have been tested; however, each has its limitations and constraints. This review comprehensively discusses the functional morphology of the BBB and the challenges that must be overcome by drug-delivery systems and elaborates on the potential targets, mechanisms, and formulations to improve drug delivery to the CNS. PMID:24550672

  11. Delivery.

    PubMed

    Miller, Thomas A

    2013-11-01

    Enthusiasm greeted the development of synthetic organic insecticides in the mid-twentieth century, only to see this give way to dismay and eventually scepticism and outright opposition by some. Regardless of how anyone feels about this issue, insecticides and other pesticides have become indispensable, which creates something of a dilemma. Possibly as a result of the shift in public attitude towards insecticides, genetic engineering of microbes was first met with scepticism and caution among scientists. Later, the development of genetically modified crop plants was met with an attitude that hardened into both acceptance and hard-core resistance. Transgenic insects, which came along at the dawn of the twenty-first century, encountered an entrenched opposition. Those of us responsible for studying the protection of crops have been affected more or less by these protagonist and antagonistic positions, and the experiences have often left one thoughtfully mystified as decisions are made by non-participants. Most of the issues boil down to concerns over delivery mechanisms.

  12. Delivery

    PubMed Central

    Miller, Thomas A

    2013-01-01

    Enthusiasm greeted the development of synthetic organic insecticides in the mid-twentieth century, only to see this give way to dismay and eventually scepticism and outright opposition by some. Regardless of how anyone feels about this issue, insecticides and other pesticides have become indispensable, which creates something of a dilemma. Possibly as a result of the shift in public attitude towards insecticides, genetic engineering of microbes was first met with scepticism and caution among scientists. Later, the development of genetically modified crop plants was met with an attitude that hardened into both acceptance and hard-core resistance. Transgenic insects, which came along at the dawn of the twenty-first century, encountered an entrenched opposition. Those of us responsible for studying the protection of crops have been affected more or less by these protagonist and antagonistic positions, and the experiences have often left one thoughtfully mystified as decisions are made by non-participants. Most of the issues boil down to concerns over delivery mechanisms. © 2013 Society of Chemical Industry PMID:23852646

  13. 20 CFR 662.100 - What is the One-Stop delivery system?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 4 2013-04-01 2013-04-01 false What is the One-Stop delivery system? 662.100...) DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT General Description of the One-Stop Delivery System § 662.100 What is the One-Stop delivery system? (a) In general, the...

  14. 20 CFR 662.100 - What is the One-Stop delivery system?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 4 2014-04-01 2014-04-01 false What is the One-Stop delivery system? 662.100...) DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT General Description of the One-Stop Delivery System § 662.100 What is the One-Stop delivery system? (a) In general, the...

  15. 20 CFR 662.100 - What is the One-Stop delivery system?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false What is the One-Stop delivery system? 662.100... DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT General Description of the One-Stop Delivery System § 662.100 What is the One-Stop delivery system? (a) In general, the...

  16. 20 CFR 662.100 - What is the One-Stop delivery system?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 4 2012-04-01 2012-04-01 false What is the One-Stop delivery system? 662.100...) DESCRIPTION OF THE ONE-STOP SYSTEM UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT General Description of the One-Stop Delivery System § 662.100 What is the One-Stop delivery system? (a) In general, the...

  17. Porous tube plant nutrient delivery system development: A device for nutrient delivery in microgravity

    NASA Technical Reports Server (NTRS)

    Dreschel, T. W.; Brown, C. S.; Piastuch, W. C.; Hinkle, C. R.; Knott, W. M.

    1994-01-01

    The Porous Tube Plant Nutrient Delivery Systems or PTPNDS (U.S. Patent #4,926,585) has been under development for the past six years with the goal of providing a means for culturing plants in microgravity, specifically providing water and nutrients to the roots. Direct applications of the PTPNDS include plant space biology investigations on the Space Shuttle and plant research for life support in the Space Station Freedom. In the past, we investigated various configurations, the suitability of different porous materials, and the effects of pressure and pore size on plant growth. Current work is focused on characterizing the physical operation of the system, examining the effects of solution aeration, and developing prototype configurations for the Plant Growth Unit (PGU), the flight system for the Shuttle mid-deck. Future developments will involve testing on KC-135 parabolic flights, the design of flight hardware and testing aboard the Space Shuttle.

  18. Intracellular Delivery System for Antibody–Peptide Drug Conjugates

    PubMed Central

    Berguig, Geoffrey Y; Convertine, Anthony J; Frayo, Shani; Kern, Hanna B; Procko, Erik; Roy, Debashish; Srinivasan, Selvi; Margineantu, Daciana H; Booth, Garrett; Palanca-Wessels, Maria Corinna; Baker, David; Hockenbery, David; Press, Oliver W; Stayton, Patrick S

    2015-01-01

    Antibodies armed with biologic drugs could greatly expand the therapeutic potential of antibody–drug conjugates for cancer therapy, broadening their application to disease targets currently limited by intracellular delivery barriers. Additional selectivity and new therapeutic approaches could be realized with intracellular protein drugs that more specifically target dysregulated pathways in hematologic cancers and other malignancies. A multifunctional polymeric delivery system for enhanced cytosolic delivery of protein drugs has been developed that incorporates endosomal-releasing activity, antibody targeting, and a biocompatible long-chain ethylene glycol component for optimized safety, pharmacokinetics, and tumor biodistribution. The pH-responsive polymeric micelle carrier, with an internalizing anti-CD22 monoclonal targeting antibody, effectively delivered a proapoptotic Bcl-2 interacting mediator (BIM) peptide drug that suppressed tumor growth for the duration of treatment and prolonged survival in a xenograft mouse model of human B-cell lymphoma. Antitumor drug activity was correlated with a mechanistic induction of the Bcl-2 pathway biomarker cleaved caspase-3 and a marked decrease in the Ki-67 proliferation biomarker. Broadening the intracellular target space by more effective delivery of protein/peptide drugs could expand the repertoire of antibody–drug conjugates to currently undruggable disease-specific targets and permit tailored drug strategies to stratified subpopulations and personalized medicines. PMID:25669432

  19. Development and characterization of chronomodulated drug delivery system of captopril

    PubMed Central

    Patil, Archana S; Dandagi, Panchaxari M; Masthiholimath, Vinayak S; Gadad, Anand P; Najwade, Basavaraj K

    2011-01-01

    Background: Hypertension shows circadian rhythm that there is a rise in pressure from the time of waking or before (about 4 to 8 a.m.), in most people. Conventional drug delivery system of captopril is inappropriate for the delivery of drug, as they cannot be administered just before the symptoms are worsened, because during this time the patients are asleep, bedtime dosing of captopril will not provide a therapeutic plasma drug concentration at the early hours of morning because of poor pharmacokinetic profile and shorter half-life of 1.9 hours. Thus, this study attempts to design and evaluate a chronomodulated pulsatile drug delivery system of captopril which was aimed to release the drug after a lag time of 6 hours. Materials and Methods: Present delivery system was prepared by rupturable coating method. The core containing captopril as a bioactive compound were prepared by direct compression method and then coated sequentially with an inner swelling layer containing hydrocolloid HPMC E5 and an outer rupturable layer consisted of Eudragit RL/RS (1 : 1). Total 12 formulations with different levels of inner swelling layer and outer polymeric layer were prepared and subjected to various processing and formulative parameters like the effect of core composition, level of swelling layer, and rupturable coating on lag time was investigated. In vitro drug release and rupture tests were performed using United States Pharmacopoeia paddle method at 50 rpm in 0.1N HCl and phosphate buffer of pH 6.8. Results: The results showed that as the amount of inner swelling layer increases, the lag time decreases and as the Eudragit coating level increases, the lag time increases and percent water uptake of time-dependent pulsatile release system decreases. The presence of an osmotic agent and effervescent agent helped in shortening of lag time. Conclusion: The system was found to be satisfactory in terms of release of the drug after the lag time of 6 hours. PMID:23071948

  20. Nanoengineered drug delivery systems for enhancing antibiotic therapy.

    PubMed

    Kalhapure, Rahul S; Suleman, Nadia; Mocktar, Chunderika; Seedat, Nasreen; Govender, Thirumala

    2015-03-01

    Formulation scientists are recognizing nanoengineered drug delivery systems as an effective strategy to overcome limitations associated with antibiotic drug therapy. Antibiotics encapsulated into nanodelivery systems will contribute to improved management of patients with various infectious diseases and to overcoming the serious global burden of antibiotic resistance. An extensive review of several antibiotic-loaded nanocarriers that have been formulated to target drugs to infectious sites, achieve controlled drug release profiles, and address formulation challenges, such as low-drug entrapment efficiencies, poor solubility and stability is presented in this paper. The physicochemical properties and the in vitro/in vivo performances of various antibiotic-loaded delivery systems, such as polymeric nanoparticles, micelles, dendrimers, liposomes, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanohybirds, nanofibers/scaffolds, nanosheets, nanoplexes, and nanotubes/horn/rods and nanoemulsions, are highlighted and evaluated. Future studies that will be essential to optimize formulation and commercialization of these antibiotic-loaded nanosystems are also identified. The review presented emphasizes the significant formulation progress achieved and potential that novel nanoengineered antibiotic drug delivery systems have for enhancing the treatment of patients with a range of infections.

  1. MO-A-18C-01: Proton Therapy I: Basics of Proton Therapy

    SciTech Connect

    Arjomandy, B; Sahoo, N; Pankuch, M

    2014-06-15

    The goal of this session is to introduce the audience to the physics, dosimetry and treatment planning procedures used in proton therapy. The course material covers the basic physics of proton interaction with matter and physical characteristics of clinical proton beams. It will provide information on proton delivery systems and beam delivery techniques for scattered and scanning proton beams. It will include the requirements for dosimetry measurements and present the equipment needed for commissioning of proton beams for clinical use and quality assurance checks as well as methods used for proton beam calibration and dose verification of patient treatment fields. The session covers the treatment planning strategies for various anatomical sites, methods to address uncertainties in proton therapy and uncertainty mitigation to generate robust treatment plans. Challenges involved in the motion management in proton therapy will also be discussed. Learning Objectives: Gain knowledge on physics, dosimetry, treatment planning and quality assurance for proton therapy. Understand the uncertainties associated with proton therapy and currently used strategies for their mitigation in treatment planning.

  2. The Delivery System of Environmental Education at the Tertiary Level in the Asia-Pacific Region.

    ERIC Educational Resources Information Center

    Sato, Masahisa; Bhandari, Bishnu; Abe, Osamu

    2001-01-01

    Analyzes the delivery system of environmental education at the tertiary level in relation to higher education attendance rate. Describes the characteristics of the delivery system in countries such as China, India, Australia, Japan, South Korea, and Indonesia. (Author/MM)

  3. Experimental validation of the TOPAS Monte Carlo system for passive scattering proton therapy

    SciTech Connect

    Testa, M.; Schümann, J.; Lu, H.-M.; Paganetti, H.; Shin, J.; Faddegon, B.; Perl, J.

    2013-12-15

    Purpose: TOPAS (TOol for PArticle Simulation) is a particle simulation code recently developed with the specific aim of making Monte Carlo simulations user-friendly for research and clinical physicists in the particle therapy community. The authors present a thorough and extensive experimental validation of Monte Carlo simulations performed with TOPAS in a variety of setups relevant for proton therapy applications. The set of validation measurements performed in this work represents an overall end-to-end testing strategy recommended for all clinical centers planning to rely on TOPAS for quality assurance or patient dose calculation and, more generally, for all the institutions using passive-scattering proton therapy systems. Methods: The authors systematically compared TOPAS simulations with measurements that are performed routinely within the quality assurance (QA) program in our institution as well as experiments specifically designed for this validation study. First, the authors compared TOPAS simulations with measurements of depth-dose curves for spread-out Bragg peak (SOBP) fields. Second, absolute dosimetry simulations were benchmarked against measured machine output factors (OFs). Third, the authors simulated and measured 2D dose profiles and analyzed the differences in terms of field flatness and symmetry and usable field size. Fourth, the authors designed a simple experiment using a half-beam shifter to assess the effects of multiple Coulomb scattering, beam divergence, and inverse square attenuation on lateral and longitudinal dose profiles measured and simulated in a water phantom. Fifth, TOPAS’ capabilities to simulate time dependent beam delivery was benchmarked against dose rate functions (i.e., dose per unit time vs time) measured at different depths inside an SOBP field. Sixth, simulations of the charge deposited by protons fully stopping in two different types of multilayer Faraday cups (MLFCs) were compared with measurements to benchmark the

  4. Experimental validation of the TOPAS Monte Carlo system for passive scattering proton therapy

    PubMed Central

    Testa, M.; Schümann, J.; Lu, H.-M.; Shin, J.; Faddegon, B.; Perl, J.; Paganetti, H.

    2013-01-01

    Purpose: TOPAS (TOol for PArticle Simulation) is a particle simulation code recently developed with the specific aim of making Monte Carlo simulations user-friendly for research and clinical physicists in the particle therapy community. The authors present a thorough and extensive experimental validation of Monte Carlo simulations performed with TOPAS in a variety of setups relevant for proton therapy applications. The set of validation measurements performed in this work represents an overall end-to-end testing strategy recommended for all clinical centers planning to rely on TOPAS for quality assurance or patient dose calculation and, more generally, for all the institutions using passive-scattering proton therapy systems. Methods: The authors systematically compared TOPAS simulations with measurements that are performed routinely within the quality assurance (QA) program in our institution as well as experiments specifically designed for this validation study. First, the authors compared TOPAS simulations with measurements of depth-dose curves for spread-out Bragg peak (SOBP) fields. Second, absolute dosimetry simulations were benchmarked against measured machine output factors (OFs). Third, the authors simulated and measured 2D dose profiles and analyzed the differences in terms of field flatness and symmetry and usable field size. Fourth, the authors designed a simple experiment using a half-beam shifter to assess the effects of multiple Coulomb scattering, beam divergence, and inverse square attenuation on lateral and longitudinal dose profiles measured and simulated in a water phantom. Fifth, TOPAS’ capabilities to simulate time dependent beam delivery was benchmarked against dose rate functions (i.e., dose per unit time vs time) measured at different depths inside an SOBP field. Sixth, simulations of the charge deposited by protons fully stopping in two different types of multilayer Faraday cups (MLFCs) were compared with measurements to benchmark the

  5. Clinical proton MR spectroscopy in central nervous system disorders.

    PubMed

    Oz, Gülin; Alger, Jeffry R; Barker, Peter B; Bartha, Robert; Bizzi, Alberto; Boesch, Chris; Bolan, Patrick J; Brindle, Kevin M; Cudalbu, Cristina; Dinçer, Alp; Dydak, Ulrike; Emir, Uzay E; Frahm, Jens; González, Ramón Gilberto; Gruber, Stephan; Gruetter, Rolf; Gupta, Rakesh K; Heerschap, Arend; Henning, Anke; Hetherington, Hoby P; Howe, Franklyn A; Hüppi, Petra S; Hurd, Ralph E; Kantarci, Kantarci; Klomp, Dennis W J; Kreis, Roland; Kruiskamp, Marijn J; Leach, Martin O; Lin, Alexander P; Luijten, Peter R; Marjańska, Malgorzata; Maudsley, Andrew A; Meyerhoff, Dieter J; Mountford, Carolyn E; Nelson, Sarah J; Pamir, M Necmettin; Pan, Jullie W; Peet, Andrew C; Poptani, Harish; Posse, Stefan; Pouwels, Petra J W; Ratai, Eva-Maria; Ross, Brian D; Scheenen, Tom W; Schuster, Christian; Smith, Ian C P; Soher, Brian J; Tkáč, Ivan; Vigneron, Daniel B; Kauppinen, Risto A

    2014-03-01

    A large body of published work shows that proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of (1)H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of (1)H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which (1)H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units.

  6. Biopolymer-Based Delivery Systems: Challenges and Opportunities.

    PubMed

    Joye, Iris J; McClements, D Julian

    2016-01-01

    Biopolymer-based nanostructures or microstructures can be fabricated with different compositions, structures, and properties so that colloidal delivery systems can be tailored for specific applications. These structures can be assembled using various approaches, including electrospinning, coacervation, nanoprecipitation, injection, layer-by-layer deposition, and/or gelation. A major application of biopolymer-based particles is to encapsulate, protect, and release active molecules in the agricultural, food, supplements, personal care, and pharmaceutical sectors. The inherent variability and complexity of biopolymers (proteins and polysaccharides) often makes it challenging to produce particles with well-defined physicochemical and functional attributes. In this review, we discuss the properties of biopolymers, common particle fabrication methods, and some of the major challenges and opportunities associated with developing biopolymer-based particles for application as food-grade delivery systems.

  7. Magnetic nanoparticle drug delivery systems for targeting tumor

    NASA Astrophysics Data System (ADS)

    Mody, Vicky V.; Cox, Arthur; Shah, Samit; Singh, Ajay; Bevins, Wesley; Parihar, Harish

    2014-04-01

    Tumor hypoxia, or low oxygen concentration, is a result of disordered vasculature that lead to distinctive hypoxic microenvironments not found in normal tissues. Many traditional anti-cancer agents are not able to penetrate into these hypoxic zones, whereas, conventional cancer therapies that work by blocking cell division are not effective to treat tumors within hypoxic zones. Under these circumstances the use of magnetic nanoparticles as a drug delivering agent system under the influence of external magnetic field has received much attention, based on their simplicity, ease of preparation, and ability to tailor their properties for specific biological applications. Hence in this review article we have reviewed current magnetic drug delivery systems, along with their application and clinical status in the field of magnetic drug delivery.

  8. Low-cost health delivery systems: lessons from Nicaragua.

    PubMed Central

    Heiby, J R

    1981-01-01

    In 1976 the Ministry of Health of Nicaragua began a low cost program to deliver simple health services in rural areas through trained traditional birth attendants or "parteras." After two years the program had prepared 768 parteras in a five-day training course. Parteras were equipped with a kit that included oral rehydration salts, an antihelminthic, multi-vitamins with iron, aspirin, contraceptives, and obstetrical equipment. The difficulties encountered in implementing this limited set of simple health services illustrate a number of potential obstacles to the achievement of universal, comprehensive primary health care in less developed countries. The most prominent difficulties involved elements of the health service delivery system itself: supervision, the collection and use of management information, training, partera selection, and logistics. The experience also provided examples of issues in the design of delivery systems that require specific applied research. PMID:7212140

  9. Systemic delivery of recombinant proteins by genetically modified myoblasts

    SciTech Connect

    Barr, E.; Leiden, J.M. )

    1991-12-06

    The ability to stably deliver recombinant proteins to the systemic circulation would facilitate the treatment of a variety of acquired and inherited diseases. To explore the feasibility of the use of genetically engineered myoblasts as a recombinant protein delivery system, stable transfectants of the murine C2C12 myoblast cell line were produced that synthesize and secrete high levels of human growth hormone (hGH) in vitro. Mice injected with hGH-transfected myoblasts had significant levels of hGH in both muscle and serum that were stable for at least 3 weeks after injection. Histological examination of muscles injected with {beta}-galactosidase-expressing C2C12 myoblasts demonstrated that many of the injected cells had fused to form multinucleated myotubes. Thus, genetically engineered myoblasts can be used for the stable delivery of recombinant proteins into the circulation.

  10. Inhaled formulations and pulmonary drug delivery systems for respiratory infections.

    PubMed

    Zhou, Qi Tony; Leung, Sharon Shui Yee; Tang, Patricia; Parumasivam, Thaigarajan; Loh, Zhi Hui; Chan, Hak-Kim

    2015-05-01

    Respiratory infections represent a major global health problem. They are often treated by parenteral administrations of antimicrobials. Unfortunately, systemic therapies of high-dose antimicrobials can lead to severe adverse effects and this calls for a need to develop inhaled formulations that enable targeted drug delivery to the airways with minimal systemic drug exposure. Recent technological advances facilitate the development of inhaled anti-microbial therapies. The newer mesh nebulisers have achieved minimal drug residue, higher aerosolisation efficiencies and rapid administration compared to traditional jet nebulisers. Novel particle engineering and intelligent device design also make dry powder inhalers appealing for the delivery of high-dose antibiotics. In view of the fact that no new antibiotic entities against multi-drug resistant bacteria have come close to commercialisation, advanced formulation strategies are in high demand for combating respiratory 'super bugs'.

  11. The CNAO dose delivery system for modulated scanning ion beam radiotherapy

    SciTech Connect

    Giordanengo, S.; Marchetto, F.; Garella, M. A.; Donetti, M.; Bourhaleb, F.; Monaco, V.; Hosseini, M. A.; Peroni, C.; Sacchi, R.; Cirio, R.; Ciocca, M.; Mirandola, A.

    2015-01-15

    Purpose: This paper describes the system for the dose delivery currently used at the Centro Nazionale di Adroterapia Oncologica (CNAO) for ion beam modulated scanning radiotherapy. Methods: CNAO Foundation, Istituto Nazionale di Fisica Nucleare and University of Torino have designed, built, and commissioned a dose delivery system (DDS) to monitor and guide ion beams accelerated by a dedicated synchrotron and to distribute the dose with a full 3D scanning technique. Protons and carbon ions are provided for a wide range of energies in order to cover a sizable span of treatment depths. The target volume, segmented in several layers orthogonally to the beam direction, is irradiated by thousands of pencil beams which must be steered and held to the prescribed positions until the prescribed number of particles has been delivered. For the CNAO beam lines, these operations are performed by the DDS. The main components of this system are two independent beam monitoring detectors, called BOX1 and BOX2, interfaced with two control systems performing the tasks of real-time fast and slow control, and connected to the scanning magnets and the beam chopper. As a reaction to any condition leading to a potential hazard, a DDS interlock signal is sent to the patient interlock system which immediately stops the irradiation. The essential tasks and operations performed by the DDS are described following the data flow from the treatment planning system through the end of the treatment delivery. Results: The ability of the DDS to guarantee a safe and accurate treatment was validated during the commissioning phase by means of checks of the charge collection efficiency, gain uniformity of the chambers, and 2D dose distribution homogeneity and stability. A high level of reliability and robustness has been proven by three years of system activity needing rarely more than regular maintenance and working with 100% uptime. Four identical and independent DDS devices have been tested showing

  12. The rate of second electron transfer to QB(-) in bacterial reaction center of impaired proton delivery shows hydrogen-isotope effect.

    PubMed

    Maróti, Ágnes; Wraight, Colin A; Maróti, Péter

    2015-02-01

    The 2nd electron transfer in reaction center of photosynthetic bacterium Rhodobacter sphaeroides is a two step process in which protonation of QB(-) precedes interquinone electron transfer. The thermal activation and pH dependence of the overall rate constants of different RC variants were measured and compared in solvents of water (H2O) and heavy water (D2O). The electron transfer variants where the electron transfer is rate limiting (wild type and M17DN, L210DN and H173EQ mutants) do not show solvent isotope effect and the significant decrease of the rate constant of the second electron transfer in these mutants is due to lowering the operational pKa of QB(-)/QBH: 4.5 (native), 3.9 (L210DN), 3.7 (M17DN) and 3.1 (H173EQ) at pH7. On the other hand, the proton transfer variants where the proton transfer is rate limiting demonstrate solvent isotope effect of pH-independent moderate magnitude (2.11±0.26 (WT+Ni(2+)), 2.16±0.35 (WT+Cd(2+)) and 2.34±0.44 (L210DN/M17DN)) or pH-dependent large magnitude (5.7 at pH4 (L213DN)). Upon deuteration, the free energy and the enthalpy of activation increase in all proton transfer variants by about 1 kcal/mol and the entropy of activation becomes negligible in L210DN/M17DN mutant. The results are interpreted as manifestation of equilibrium and kinetic solvent isotope effects and the structural, energetic and kinetic possibility of alternate proton delivery pathways are discussed.

  13. Feasibility Study: Ductless Hydronic Distribution Systems with Fan Coil Delivery

    SciTech Connect

    Springer, D.; Dakin, B.; Backman, C.

    2012-07-01

    The primary objectives of this study are to estimate potential energy savings relative to conventional ducted air distribution, and to identify equipment requirements, costs, and barriers with a focus on ductless hydronic delivery systems that utilize water-to-air terminal units in each zone. Results indicate that annual heating and cooling energy use can be reduced by up to 27% assuming replacement of the conventional 13 SEER heat pump and coil with a similarly rated air-to-water heat pump.

  14. Governance of integrated delivery systems/networks: a stakeholder approach.

    PubMed

    Savage, G T; Taylor, R L; Rotarius, T M; Buesseler, J A

    1997-01-01

    The health care environment is complex and turbulent, and traditional governance forms face many challenges. As integrated delivery systems/networks are formed, governance structures must be responsive to both internal and external stakeholders. Both internal efficiencies and socially responsible actions are required of these relatively new organizational forms. To meet these needs, a two-tier governance structure is presented that consists of overarching and facilitating boards. PMID:9058084

  15. A look at emerging delivery systems for topical drug products.

    PubMed

    Fireman, Sharon; Toledano, Ofer; Neimann, Karine; Loboda, Natalia; Dayan, Nava

    2011-01-01

    The introduction of new topical drugs based on new chemical entities has become a rare event. Instead, pharmaceutical companies have been focused on reformulating existing drugs resulting in an ever-growing number of topical drug products for every approved drug substance. In light of this trend, soon reformulations may not be as rewarding to their sponsors as they are today unless they offer a substantial improvement over other formulations of the same drug substance and the same indication, namely improved efficacy over existing drugs, reduced side effects, unique drug combinations, or applicability for new indications. This article reviews and compares topical drug delivery systems currently under active research that are designed to offer such advantages in the coming years. The reviewed delivery systems are: liposomes, niosomes, transferosomes, ethosomes, solid lipid nanoparticles, nanostructured lipid carriers, cyclodextrin, and sol-gel microcapsules. Among all the topical drug delivery systems currently undergoing active research, only the sol-gel microencapsulation is at clinical stages. PMID:22353154

  16. Paclitaxel Nano-Delivery Systems: A Comprehensive Review.

    PubMed

    Ma, Ping; Mumper, Russell J

    2013-02-18

    Paclitaxel is one of the most effective chemotherapeutic drugs ever developed and is active against a broad range of cancers, such as lung, ovarian, and breast cancers. Due to its low water solubility, paclitaxel is formulated in a mixture of Cremophor EL and dehydrated ethanol (50:50, v/v) a combination known as Taxol. However, Taxol has some severe side effects related to Cremophor EL and ethanol. Therefore, there is an urgent need for the development of alternative Taxol formulations. The encapsulation of paclitaxel in biodegradable and non-toxic nano-delivery systems can protect the drug from degradation during circulation and in-turn protect the body from toxic side effects of the drug thereby lowering its toxicity, increasing its circulation half-life, exhibiting improved pharmacokinetic profiles, and demonstrating better patient compliance. Also, nanoparticle-based delivery systems can take advantage of the enhanced permeability and retention (EPR) effect for passive tumor targeting, therefore, they are promising carriers to improve the therapeutic index and decrease the side effects of paclitaxel. To date, paclitaxel albumin-bound nanoparticles (Abraxane®) have been approved by the FDA for the treatment of metastatic breast cancer and non-small cell lung cancer (NSCLC). In addition, there are a number of novel paclitaxel nanoparticle formulations in clinical trials. In this comprehensive review, several types of developed paclitaxel nano-delivery systems will be covered and discussed, such as polymeric nanoparticles, lipid-based formulations, polymer conjugates, inorganic nanoparticles, carbon nanotubes, nanocrystals, and cyclodextrin nanoparticles.

  17. Novel targeted bladder drug-delivery systems: a review

    PubMed Central

    Zacchè, Martino Maria; Srikrishna, Sushma; Cardozo, Linda

    2015-01-01

    The objective of pharmaceutics is the development of drugs with increased efficacy and reduced side effects. Prolonged exposure of the diseased tissue to the drug is of crucial importance. Drug-delivery systems (DDSs) have been introduced to control rate, time, and place of release. Drugs can easily reach the bladder through a catheter, while systemically administered agents may undergo extensive metabolism. Continuous urine filling and subsequent washout hinder intravesical drug delivery (IDD). Moreover, the low permeability of the urothelium, also described as the bladder permeability barrier, poses a major challenge in the development of the IDD. DDSs increase bioavailability of drugs, therefore improving therapeutic effect and patient compliance. This review focuses on novel DDSs to treat bladder conditions such as overactive bladder, interstitial cystitis, bladder cancer, and recurrent urinary tract infections. The rationale and strategies for both systemic and local delivery methods are discussed, with emphasis on new formulations of well-known drugs (oxybutynin), nanocarriers, polymeric hydrogels, intravesical devices, encapsulated DDSs, and gene therapy. We give an overview of current and future prospects of DDSs for bladder disorders, including nanotechnology and gene therapy. PMID:26649286

  18. Protamine-based nanoparticles as new antigen delivery systems.

    PubMed

    González-Aramundiz, José Vicente; Peleteiro Olmedo, Mercedes; González-Fernández, África; Alonso Fernández, María José; Csaba, Noemi Stefánia

    2015-11-01

    The use of biodegradable nanoparticles as antigen delivery vehicles is an attractive approach to overcome the problems associated with the use of Alum-based classical adjuvants. Herein we report, the design and development of protamine-based nanoparticles as novel antigen delivery systems, using recombinant hepatitis B surface antigen as a model viral antigen. The nanoparticles, composed of protamine and a polysaccharide (hyaluronic acid or alginate), were obtained using a mild ionic cross-linking technique. The size and surface charge of the nanoparticles could be modulated by adjusting the ratio of the components. Prototypes with optimal physicochemical characteristics and satisfactory colloidal stability were selected for the assessment of their antigen loading capacity, antigen stability during storage and in vitro and in vivo proof-of-concept studies. In vitro studies showed that antigen-loaded nanoparticles induced the secretion of cytokines by macrophages more efficiently than the antigen in solution, thus indicating a potential adjuvant effect of the nanoparticles. Finally, in vivo studies showed the capacity of these systems to trigger efficient immune responses against the hepatitis B antigen following intramuscular administration, suggesting the potential interest of protamine-polysaccharide nanoparticles as antigen delivery systems.

  19. Peptide/protein vaccine delivery system based on PLGA particles

    PubMed Central

    Allahyari, Mojgan; Mohit, Elham

    2016-01-01

    abstract Due to the excellent safety profile of poly (D,L-lactide-co-glycolide) (PLGA) particles in human, and their biodegradability, many studies have focused on the application of PLGA particles as a controlled-release vaccine delivery system. Antigenic proteins/peptides can be encapsulated into or adsorbed to the surface of PLGA particles. The gradual release of loaded antigens from PLGA particles is necessary for the induction of efficient immunity. Various factors can influence protein release rates from PLGA particles, which can be defined intrinsic features of the polymer, particle characteristics as well as protein and environmental related factors. The use of PLGA particles encapsulating antigens of different diseases such as hepatitis B, tuberculosis, chlamydia, malaria, leishmania, toxoplasma and allergy antigens will be described herein. The co-delivery of antigens and immunostimulants (IS) with PLGA particles can prevent the systemic adverse effects of immunopotentiators and activate both dendritic cells (DCs) and natural killer (NKs) cells, consequently enhancing the therapeutic efficacy of antigen-loaded PLGA particles. We will review co-delivery of different TLR ligands with antigens in various models, highlighting the specific strengths and weaknesses of the system. Strategies to enhance the immunotherapeutic effect of DC-based vaccine using PLGA particles can be designed to target DCs by functionalized PLGA particle encapsulating siRNAs of suppressive gene, and disease specific antigens. Finally, specific examples of cellular targeting where decorating the surface of PLGA particles target orally administrated vaccine to M-cells will be highlighted. PMID:26513024

  20. Advancing drug delivery systems for the treatment of multiple sclerosis.

    PubMed

    Tabansky, Inna; Messina, Mark D; Bangeranye, Catherine; Goldstein, Jeffrey; Blitz-Shabbir, Karen M; Machado, Suly; Jeganathan, Venkatesh; Wright, Paul; Najjar, Souhel; Cao, Yonghao; Sands, Warren; Keskin, Derin B; Stern, Joel N H

    2015-12-01

    Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. It is characterized by demyelination of neurons and loss of neuronal axons and oligodendrocytes. In MS, auto-reactive T cells and B cells cross the blood-brain barrier (BBB), causing perivenous demyelinating lesions that form multiple discrete inflammatory demyelinated plaques located primarily in the white matter. In chronic MS, cortical demyelination and progressive axonal transections develop. Treatment for MS can be stratified into disease-modifying therapies (DMTs) and symptomatic therapy. DMTs aim to decrease circulating immune cells or to prevent these cells from crossing the BBB and reduce the inflammatory response. There are currently 10 DMTs approved for the relapsing forms of MS; these vary with regard to their efficacy, route and frequency of administration, adverse effects, and toxicity profile. Better drug delivery systems are being developed in order to decrease adverse effects, increase drug efficacy, and increase patient compliance through the direct targeting of pathologic cells. Here, we address the uses and benefits of advanced drug delivery systems, including nanoparticles, microparticles, fusion antibodies, and liposomal formulations. By altering the properties of therapeutic particles and enhancing targeting, breakthrough drug delivery technologies potentially applicable to multiple disease treatments may rapidly emerge.

  1. Leishmaniasis: focus on the design of nanoparticulate vaccine delivery systems.

    PubMed

    Doroud, Delaram; Rafati, Sima

    2012-01-01

    Although mass vaccination of the entire population of an endemic area would be the most cost-effective tool to diminish Leishmania burden, an effective vaccine is not yet commercially available. Practically, vaccines have failed to achieve the required level of protection, possibly owing to the lack of an appropriate adjuvant and/or delivery system. Therefore, there is still an imperative demand for an improved, safe and efficient delivery system to enhance the immunogenicity of available vaccine candidates. Nanoparticles are proficient in boosting the quality and magnitude of immune responses in a predictable fashion. Herein, we discuss how nanoparticulate vaccine delivery systems can be used to induce appropriate immune responses against leishmaniasis by controlling physicochemical properties of the vaccine. Stability, production reproducibility, low cost per dose and low risk-benefit ratios are desirable characteristics of an ideal vaccine formulation and solid lipid nanoparticles may serve as one of the most promising practical strategies to help to achieve such a leishmanial vaccine, at least in canine species in the developing world.

  2. The Development and Clinical Use of a Beam ON-LINE PET System Mounted on a Rotating Gantry Port in Proton Therapy

    SciTech Connect

    Nishio, Teiji; Miyatake, Aya; Ogino, Takashi; Nakagawa, Keiichi; Saijo, Nagahiro; Esumi, Hiroyasu

    2010-01-15

    Purpose: To verify the usefulness of our developed beam ON-LINE positron emission tomography (PET) system mounted on a rotating gantry port (BOLPs-RGp) for dose-volume delivery-guided proton therapy (DGPT). Methods and Materials: In the proton treatment room at our facility, a BOLPs-RGp was constructed so that a planar PET apparatus could be mounted with its field of view covering the iso-center of the beam irradiation system. Activity measurements were performed in 48 patients with tumors of the head and neck, liver, lungs, prostate, and brain. The position and intensity of the activity were measured using the BOLPs-RGp during the 200 s immediately after the proton irradiation. Results: The daily measured activity images acquired by the BOLPs-RGp showed the proton irradiation volume in each patient. Changes in the proton-irradiated volume were indicated by differences between a reference activity image (taken at the first treatment) and the daily activity-images. In the case of head-and-neck treatment, the activity distribution changed in the areas where partial tumor reduction was observed. In the case of liver treatment, it was observed that the washout effect in necrotic tumor cells was slower than in non-necrotic tumor cells. Conclusions: The BOLPs-RGp was developed for the DGPT. The accuracy of proton treatment was evaluated by measuring changes of daily measured activity. Information about the positron-emitting nuclei generated during proton irradiation can be used as a basis for ensuring the high accuracy of irradiation in proton treatment.

  3. Data delivery system for MAPPER using image compression

    NASA Astrophysics Data System (ADS)

    Yang, Jeehong; Savari, Serap A.

    2013-03-01

    The data delivery throughput of electron beam lithography systems can be improved by applying lossless image compression to the layout image and using an electron beam writer that can decode the compressed image on-the-fly. In earlier research we introduced the lossless layout image compression algorithm Corner2, which assumes a somewhat idealized writing strategy, namely row-by-row with a raster order. The MAPPER system has electron beam writers positioned in a lattice formation and each electron beam writer writes a designated block in a zig-zag order. We introduce Corner2-MEB, which redesigns Corner2 for MAPPER systems.

  4. Overview on gastroretentive drug delivery systems for improving drug bioavailability.

    PubMed

    Lopes, Carla M; Bettencourt, Catarina; Rossi, Alessandra; Buttini, Francesca; Barata, Pedro

    2016-08-20

    In recent decades, many efforts have been made in order to improve drug bioavailability after oral administration. Gastroretentive drug delivery systems are a good example; they emerged to enhance the bioavailability and effectiveness of drugs with a narrow absorption window in the upper gastrointestinal tract and/or to promote local activity in the stomach and duodenum. Several strategies are used to increase the gastric residence time, namely bioadhesive or mucoadhesive systems, expandable systems, high-density systems, floating systems, superporous hydrogels and magnetic systems. The present review highlights some of the drugs that can benefit from gastroretentive strategies, such as the factors that influence gastric retention time and the mechanism of action of gastroretentive systems, as well as their classification into single and multiple unit systems.

  5. A mucoadhesive in situ gel delivery system for paclitaxel.

    PubMed

    Jauhari, Saurabh; Dash, Alekha K

    2006-01-01

    MUC1 gene encodes a transmembrane mucin glycoprotein that is overexpressed in human breast cancer and colon cancer. The objective of this study was to develop an in situ gel delivery system containing paclitaxel (PTX) and mucoadhesives for sustained and targeted delivery of anticancer drugs. The delivery system consisted of chitosan and glyceryl monooleate (GMO) in 0.33M citric acid containing PTX. The in vitro release of PTX from the gel was performed in presence and absence of Tween 80 at drug loads of 0.18%, 0.30%, and 0.54% (wt/wt), in Sorensen's phosphate buffer (pH 7.4) at 37 degrees C. Different mucin-producing cell lines (Calu-3>Caco-2) were selected for PTX transport studies. Transport of PTX from solution and gel delivery system was performed in side by side diffusion chambers from apical to basal (A-B) and basal to apical (B-A) directions. In vitro release studies revealed that within 4 hours, only 7.61% +/- 0.19%, 12.0% +/- 0.98%, 31.7% +/- 0.40% of PTX were released from 0.18%, 0.30%, and 0.54% drug-loaded gel formulation, respectively, in absence of Tween 80. However, in presence of surfactant (0.05% wt/vol) in the dissolution medium, percentages of PTX released were 28.1% +/- 4.35%, 44.2% +/- 6.35%, and 97.1% +/- 1.22%, respectively. Paclitaxel has shown a polarized transport in all the cell monolayers with B-A transport 2 to 4 times higher than in the A-B direction. The highest mucin-producing cell line (Calu-3) has shown the lowest percentage of PTX transport from gels as compared with Caco-2 cells. Transport of PTX from mucoadhesive gels was shown to be influenced by the mucin-producing capability of cell.

  6. Near-barrier fusion of proton- and neutron-halo systems

    NASA Astrophysics Data System (ADS)

    Aguilera, E. F.

    2016-07-01

    It is shown that the behaviour of the fusion excitation functions for proton-halo and neutron-halo systems presents important differences, especially in the energy region slightly above the barrier. Measurements for 6He, 11Li and 11Be projectiles are discussed to exemplify the behaviour of neutron-halo systems, while experiments with 8B beams illustrate the situation for proton-halo nuclei. With respect to a standard benchmark, neutron- (proton-) halo systems show a fusion suppression (enhancement) above the barrier.

  7. Self-nanoemulsifying drug delivery systems (SNEDDS) for oral delivery of protein drugs: I. Formulation development.

    PubMed

    Rao, Sripriya Venkata Ramana; Shao, Jun

    2008-10-01

    The global aim of this research project was to develop a self-nanoemulsifying drug delivery system (SNEDDS) for non-invasive delivery of protein drugs. The specific aim of this study was to develop SNEDDS formulations. An experimental design was adopted to develop SNEDDS. Fluorescent labeled beta-lactamase (FITC-BLM), a model protein, was loaded into SNEDDS through solid dispersion technique. The experimental design provided 720 compositions of different oil, surfactant, and co-surfactant at various ratios, of which 33 SNEDDS prototypes were obtained. Solid dispersion of FITC-BLM in SoyPC prepared was able to dissolve in 16 SNEDDS prototypes (approximately 2200 mU BLM in 1g SNEDDS). SNEDDS NE-12-7 (composition: Lauroglycol FCC, Cremophor EL and Transcutol; ratio: 5:4:3) formed O/W nanoemulsion with mean droplet size in the range of 22-50 nm when diluted with various pH media and different dilution factor with PBS (pH 7.4). The phase diagram of NE-12-7 indicated a broad region of nanoemulsion. BLM-loaded SNEDDS (NE-12-7) stored at 4 degrees C for 12 weeks indicated 10% loss of BLM activity. A SNEDDS was developed to load FITC-BLM into the oil phase which can spontaneously form O/W nanoemulsion upon the addition of water.

  8. A 400G optical wireless integration delivery system.

    PubMed

    Li, Xinying; Yu, Jianjun; Zhang, Junwen; Dong, Ze; Li, Fan; Chi, Nan

    2013-08-12

    We experimentally demonstrate a record 400G optical wireless integration system simultaneously delivering 2 × 112 Gb/s two-channel polarization-division-multiplexing 16-ary quadrature amplitude modulation (PDM-16QAM) signal at 37.5 GHz wireless carrier and 2 × 108 Gb/s two-channel PDM quadrature phase shift keying (PDM-QPSK) signal at 100 GHz wireless carrier, adopting two millimeter-wave (mm-wave) frequency bands, two orthogonal antenna polarizations, multiple-input multiple-output (MIMO), photonic mm-wave generation and advanced digital signal processing (DSP). In the case of no fiber transmission, the bit error ratios (BERs) for both the 112 Gb/s PDM-16QAM signal after 1.5 m wireless delivery at 37.5 GHz and the 108 Gb/s PDM-QPSK signal after 0.7 m wireless delivery at 100 GHz are below the pre-forward-error-correction (pre-FEC) threshold of 3.8 × 10(-3). To our knowledge, this is the first demonstration of a 400G optical wireless integration system in mm-wave frequency bands and also a capacity record of wireless delivery.

  9. An implantable thermoresponsive drug delivery system based on Peltier device.

    PubMed

    Yang, Rongbing; Gorelov, Alexander V; Aldabbagh, Fawaz; Carroll, William M; Rochev, Yury

    2013-04-15

    Locally dropping the temperature in vivo is the main obstacle to the clinical use of a thermoresponsive drug delivery system. In this paper, a Peltier electronic element is incorporated with a thermoresponsive thin film based drug delivery system to form a new drug delivery device which can regulate the release of rhodamine B in a water environment at 37 °C. Various current signals are used to control the temperature of the cold side of the Peltier device and the volume of water on top of the Peltier device affects the change in temperature. The pulsatile on-demand release profile of the model drug is obtained by turning the current signal on and off. The work has shown that the 2600 mAh power source is enough to power this device for 1.3 h. Furthermore, the excessive heat will not cause thermal damage in the body as it will be dissipated by the thermoregulation of the human body. Therefore, this simple novel device can be implanted and should work well in vivo.

  10. [Development of topical drug delivery systems utilizing polymeric materials].

    PubMed

    Machida, Y

    1993-05-01

    Topical drug delivery is important from the view points of improvement of therapeutic effect and reduction of systemic side effects. Utilization of polymeric materials seemed to be as a key for the development of new topical dosage forms including targeting drug delivery systems. Adriamycin ointment for local chemotherapy to breast cancer prepared using polyethylene glycol, ammonium polyacrylate and hydroxypropyl cellulose (HPC) according to an optimum formulation showed an excellent clinical effect in spite of a decreased drug content. Double-layered mucoadhesive sticks for the treatment of uterine cervix cancer were prepared by direct compression of powder mixture of bleomycin, HPC and carboxyvinyl polymer (CP). Drug release property of the sticks could be controlled by the weight of outer layer, drug combining ratio to each layer and coating of core layer. The results suggested a possibility of a "once-a-week" treatment that is preferable for the patients. Magnetic granules for the treatment of esophageal cancer were prepared using ferrite, HPC and CP. Magnetic guidance and retainment of the granules on esophageal mucosa were confirmed using rabbits in vivo. Buoyant sustained release preparations were prepared using chitosan, soybean protein, HPC and other polymers. Usefulness of the buoyant preparations was suggested from the results in vitro and in vivo. Insulin microspheres (IMS) for targeting delivery to the small intestine were prepared by the newly developed method. Employment of enteric coating material (Eudragit) and combination of protease inhibitor protected insulin from enzymatic attack and gave decreased levels of blood glucose by oral administration.

  11. An overview of adjuvant formulations and delivery systems.

    PubMed

    García, Alexis; De Sanctis, Juan B

    2014-04-01

    Adjuvants may promote immune responses: by recruiting professional antigen-presenting cells (APCs) to the vaccination site, increasing the delivery of antigens to APCs, or by activating APCs to produce cytokines and by triggering T cell responses. Aluminium salts have been effective at promoting protective humoral immunity; however, they are not effective in generating cell-mediated immunity. A number of different approaches have been developed to potentiate immune response and they have been partially successful. Research has been conducted into vaccine delivery systems (VDS); enhancing cross-presentation by targeting antigens to (APCs). Antigen discovery has increased over the past decade, and consequently, it has accelerated vaccine development demanding a new generation of VDS that combines different types of adjuvants into specific formulations with greater activity. The new approaches offer a wide spectrum of opportunities in vaccine research with direct applications in the near future. PMID:23919674

  12. Bacterial vectors and delivery systems in cancer therapy.

    PubMed

    Gardlik, Roman; Fruehauf, Johannes H

    2010-10-01

    Live bacterial vectors may be useful tools for the development of novel cancer therapies that can be added to the repertoire of existing drugs. Several bacterial strains effectively colonize solid tumors and act as antitumor therapeutics. The naturally occurring tumor-colonizing characteristics of bacterial species such as Salmonella sp, Clostridium sp and Escherichia coli can be further modified by genetic manipulations, making these bacterial systems excellent vehicles for the production and targeted delivery of therapeutic molecules into cancer cells. This feature review summarizes recent research on cancer therapy using genetically modified bacteria. Different approaches - bactofection, DNA vaccination, and bacterially mediated protein and RNAi delivery - in which modified bacteria are used as anticancer therapeutics, are discussed.

  13. Development of a Production Ready Automated Wire Delivery System

    NASA Technical Reports Server (NTRS)

    1997-01-01

    The current development effort is a Phase 3 research study entitled "A Production Ready Automated Wire Delivery System", contract number NAS8-39933, awarded to Nichols Research Corporation (NRC). The goals of this research study were to production harden the existing Automated Wire Delivery (AWDS) motion and sensor hardware and test the modified AWDS in a range of welding applications. In addition, the prototype AWDS controller would be moved to the VME bus platform by designing, fabricating and testing a single board VME bus AWDS controller. This effort was to provide an AWDS that could transition from the laboratory environment to production operations. The project was performed in two development steps. Step 1 modified and tested an improved MWG. Step 2 developed and tested the AWDS single board VME bus controller. Step 3 installed the Wire Pilot in a Weld Controller with the imbedded VME bus controller.

  14. Multifunctional, stimuli-sensitive nanoparticulate systems for drug delivery

    PubMed Central

    Torchilin, Vladimir P.

    2015-01-01

    The use of nanoparticulate pharmaceutical drug delivery systems (NDDSs) to enhance the in vivo effectiveness of drugs is now well established. The development of multifunctional and stimulus-sensitive NDDSs is an active area of current research. Such NDDSs can have long circulation times, target the site of the disease and enhance the intracellular delivery of a drug. This type of NDDS can also respond to local stimuli that are characteristic of the pathological site by, for example, releasing an entrapped drug or shedding a protective coating, thus facilitating the interaction between drug-loaded nanocarriers and target cells or tissues. In addition, imaging contrast moieties can be attached to these carriers to track their real-time biodistribution and accumulation in target cells or tissues. Here, I highlight recent developments with multifunctional and stimuli-sensitive NDDSs and their therapeutic potential for diseases including cancer, cardiovascular diseases and infectious diseases. PMID:25287120

  15. Advances in nanotechnology-based delivery systems for curcumin.

    PubMed

    Sun, Min; Su, Xun; Ding, Buyun; He, Xiuli; Liu, Xiuju; Yu, Aihua; Lou, Hongxiang; Zhai, Guangxi

    2012-07-01

    Curcumin (CUR), a bioactive component of turmeric, which is a commonly used spice and nutritional supplement, is isolated from the rhizomes of Curcuma longa Linn. (Zingiberaceae). In recent years, the potential pharmacological actions of CUR in inflammatory disorders, cardiovascular disease, cancer, Alzheimer's disease and neurological disorders have been shown. However, the clinical application of CUR is severely limited by its main drawbacks such as instability, low solubility, poor bioavailability and rapid metabolism. Multifarious nanotechnology-based delivery approaches have been used to enhance the oral bioavailability, biological activity or tissue-targeting ability of CUR. This article reviews potential novel drug delivery systems for CUR including liposomes, polymeric nanoparticles, solid lipid nanoparticles, micelles, nanogels, nanosuspensions, nanoemulsions, complexes and dendrimer/dimer, which provide promising results for CUR to improve its biological activities. PMID:22846093

  16. Mesostructured silica and aluminosilicate carriers for oxytetracycline delivery systems.

    PubMed

    Berger, D; Nastase, S; Mitran, R A; Petrescu, M; Vasile, E; Matei, C; Negreanu-Pirjol, T

    2016-08-30

    Oxytetracycline delivery systems containing various MCM-type silica and aluminosilicate with different antibiotic content were developed in order to establish the influence of the support structural and textural properties and aluminum content on the drug release profile. The antibiotic molecules were loaded into the support mesochannels by incipient wetness impregnation method using a drug concentrated aqueous solution. The carriers and drug-loaded materials were investigated by small- and wide-angle XRD, FTIR spectroscopy, TEM and N2 adsorption-desorption isotherms. Faster release kinetics of oxytetracycline from uncalcined silica and aluminosilicate supports was observed, whereas higher drug content led to lower delivery rate. The presence of aluminum into the silica network also slowed down the release rate. The antimicrobial assays performed on Staphylococcus aureus clinical isolates showed that the oxytetracycline-loaded materials containing MCM-41-type mesoporous silica or aluminosilicate carriers inhibited the bacterial development. PMID:26861688

  17. Multifunctional, stimuli-sensitive nanoparticulate systems for drug delivery.

    PubMed

    Torchilin, Vladimir P

    2014-11-01

    The use of nanoparticulate pharmaceutical drug delivery systems (NDDSs) to enhance the in vivo effectiveness of drugs is now well established. The development of multifunctional and stimulus-sensitive NDDSs is an active area of current research. Such NDDSs can have long circulation times, target the site of the disease and enhance the intracellular delivery of a drug. This type of NDDS can also respond to local stimuli that are characteristic of the pathological site by, for example, releasing an entrapped drug or shedding a protective coating, thus facilitating the interaction between drug-loaded nanocarriers and target cells or tissues. In addition, imaging contrast moieties can be attached to these carriers to track their real-time biodistribution and accumulation in target cells or tissues. Here, I highlight recent developments with multifunctional and stimuli-sensitive NDDSs and their therapeutic potential for diseases including cancer, cardiovascular diseases and infectious diseases. PMID:25287120

  18. [Liposomal boron delivery system for neutron capture therapy].

    PubMed

    Nakamura, Hiroyuki

    2008-02-01

    Boron neutron capture therapy (BNCT) is a binary cancer treatment based on the nuclear reaction of two essentially nontoxic species, (10)B and thermal neutrons. High accumulation and selective delivery of boron into tumor tissue are the most important requirements to achieve efficient neutron capture therapy of cancers. This review focuses on the liposomal boron delivery system (BDS) as a recent promising approach that meets these requirements for BNCT. BDS involves two strategies: (1) encapsulation of boron in the aqueous core of liposomes and (2) accumulation of boron in the liposomal bilayer. Various boronated liposomes have been developed and significant boron accumulation into tumor tissue with high tumor/blood boron ratios has been achieved by BDS.

  19. Applications of novel drug delivery system for herbal formulations.

    PubMed

    Ajazuddin; Saraf, S

    2010-10-01

    Over the past several years, great advances have been made on development of novel drug delivery systems (NDDS) for plant actives and extracts. The variety of novel herbal formulations like polymeric nanoparticles, nanocapsules, liposomes, phytosomes, nanoemulsions, microsphere, transferosomes, and ethosomes has been reported using bioactive and plant extracts. The novel formulations are reported to have remarkable advantages over conventional formulations of plant actives and extracts which include enhancement of solubility, bioavailability, protection from toxicity, enhancement of pharmacological activity, enhancement of stability, improved tissue macrophages distribution, sustained delivery, and protection from physical and chemical degradation. The present review highlights the current status of the development of novel herbal formulations and summarizes their method of preparation, type of active ingredients, size, entrapment efficiency, route of administration, biological activity and applications of novel formulations. PMID:20471457

  20. Mesostructured silica and aluminosilicate carriers for oxytetracycline delivery systems.

    PubMed

    Berger, D; Nastase, S; Mitran, R A; Petrescu, M; Vasile, E; Matei, C; Negreanu-Pirjol, T

    2016-08-30

    Oxytetracycline delivery systems containing various MCM-type silica and aluminosilicate with different antibiotic content were developed in order to establish the influence of the support structural and textural properties and aluminum content on the drug release profile. The antibiotic molecules were loaded into the support mesochannels by incipient wetness impregnation method using a drug concentrated aqueous solution. The carriers and drug-loaded materials were investigated by small- and wide-angle XRD, FTIR spectroscopy, TEM and N2 adsorption-desorption isotherms. Faster release kinetics of oxytetracycline from uncalcined silica and aluminosilicate supports was observed, whereas higher drug content led to lower delivery rate. The presence of aluminum into the silica network also slowed down the release rate. The antimicrobial assays performed on Staphylococcus aureus clinical isolates showed that the oxytetracycline-loaded materials containing MCM-41-type mesoporous silica or aluminosilicate carriers inhibited the bacterial development.

  1. Dual thermo- and pH-responsive zwitterionic sulfobataine copolymers for oral delivery system.

    PubMed

    Chen, Ching-Yi; Wang, Hsiang-Ling

    2014-09-01

    A novel oral delivery system consisting of thermoresponsive zwitterionic poly(sulfobetaine methacrylate) (PSBMA) and pH-responsive poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) is synthesized via free radical polymerization. This copolymer can self-aggregate into nanoparticles via electrostatic attraction between ammonium cation and sulfo-anion of PSBMA and successfully encapsulate anticancer drug, curcumin (CUR), with highest loading content of 2.6% in the P(SBMA-co-DPA) nanoparticles. The stimuli-responsive phase transition behaviors of P(SBMA-co-DPA) copolymers at different pH buffer solution show pH-dependent upper critical solution temperature (UCST) attributed to the influence of protonation/deprotonation of the pH-responsive DPA segments. Through the delicate adjustment of the PSBMA/PDPA molar ratios, the stimuli-responsive phase transition could be suitable for physiological environment. The kinetic drug release profiles demonstrate that P(SBMA-co-DPA) nanoparticles have the potential as oral delivery carriers due to their effective release of entrapped drugs in the stimulated intestinal fluid and preventing the deterioration of drug in stimulated gastric fluid. PMID:25042406

  2. Carbon relaxation analysis in proton coupled spin systems

    NASA Astrophysics Data System (ADS)

    Rossi, Claudio; Marchettini, Nadia; Bastianoni, Simone; Dongti, Alessandro

    1995-07-01

    Selective, non-selective and biselective carbon spin-lattice relaxation measurements were determined in methyl-salicylate DMSO-d 6 solution. The frequency dependence of biselective relaxation measurements of protonated aromatic carbons showed the effects of J-scalar modulation. The dipolar contribution induced by asymmetric selective proton inversion of the spin population of a single satellite peak could be useful for investigating of the Shimizu-Fujiwara-Mackor-Maclean relaxation rate. Analysis of the ratios is also proposed for the calculation of dipolar relaxation mechanism efficiency.

  3. Recent trends in vaccine delivery systems: A review

    PubMed Central

    Saroja, CH; Lakshmi, PK; Bhaskaran, Shyamala

    2011-01-01

    Vaccines are the preparations given to patients to evoke immune responses leading to the production of antibodies (humoral) or cell-mediated responses that will combat infectious agents or noninfectious conditions such as malignancies. Alarming safety profile of live vaccines, weak immunogenicity of sub-unit vaccines and immunization, failure due to poor patient compliance to booster doses which should potentiate prime doses are few strong reasons, which necessitated the development of new generation of prophylactic and therapeutic vaccines to promote effective immunization. Attempts are being made to deliver vaccines through carriers as they control the spatial and temporal presentation of antigens to immune system thus leading to their sustained release and targeting. Hence, lower doses of weak immunogens can be effectively directed to stimulate immune responses and eliminate the need for the administration of prime and booster doses as a part of conventional vaccination regimen. This paper reviews carrier systems such as liposomes, microspheres, nanoparticles, dendrimers, micellar systems, ISCOMs, plant-derived viruses which are now being investigated and developed as vaccine delivery systems. This paper also describes various aspects of “needle-free technologies” used to administer the vaccine delivery systems through different routes into the human body. PMID:23071924

  4. New Delivery Systems for Local Anaesthetics—Part 2

    PubMed Central

    Shipton, Edward A.

    2012-01-01

    Part 2 of this paper deals with the techniques for drug delivery of topical and injectable local anaesthetics. The various routes of local anaesthetic delivery (epidural, peripheral, wound catheters, intra-nasal, intra-vesical, intra-articular, intra-osseous) are explored. To enhance transdermal local anaesthetic permeation, additional methods to the use of an eutectic mixture of local anaesthetics and the use of controlled heat can be used. These methods include iontophoresis, electroporation, sonophoresis, and magnetophoresis. The potential clinical uses of topical local anaesthetics are elucidated. Iontophoresis, the active transportation of a drug into the skin using a constant low-voltage direct current is discussed. It is desirable to prolong local anaesthetic blockade by extending its sensory component only. The optimal release and safety of the encapsulated local anaesthetic agents still need to be determined. The use of different delivery systems should provide the clinician with both an extended range and choice in the degree of prolongation of action of each agent. PMID:22190921

  5. Applications of Magnetic Nanoparticles in Targeted Drug Delivery System.

    PubMed

    Mou, Xianbo; Ali, Zeeshan; Li, Song; He, Nongyue

    2015-01-01

    Magnetic nanoparticles (MNPs) are a special kind of nanomaterials and widely used in biomedical technology applications. Currently they are popularly customized for disease detection and treatment, particularly as drug carriers in drug targeted delivery systems, as a therapeutic in hyperthermia (treating tumors with heat), and as contrast agents in magnetic resonance imaging (MRI). Due to their biocompatibility and superparamagnetic properties, MNPs as next generation drug carriers have great attraction. Although the potential benefits of MNPs are considerable, any potential toxicity associated with these MNPs should be identified distinctly. The drug loading capability and the biomedical properties of MNPs generated by different surface coatings are the most sensitive parameters in toxicity. A lot of organic and inorganic materials are utilized as coating materials for surface functionalization and reducing toxicity of MNPs. pH or temperature sensitivity materials are widely used to manage drug loading and targeted release. In addition, MNPs can be controlled and directed to the desired pathological region by using external magnetic files (EMF). The realization of targeted drug delivery has decreased the dosage and improved the efficiency of drugs, which results in reduced side effects to normal tissues. This review discussed the possible organ toxicities of MNPs and their current advances as a drug delivery vehicle. PMID:26328305

  6. New serine-derived gemini surfactants as gene delivery systems.

    PubMed

    Cardoso, Ana M; Morais, Catarina M; Cruz, A Rita; Silva, Sandra G; do Vale, M Luísa; Marques, Eduardo F; de Lima, Maria C Pedroso; Jurado, Amália S

    2015-01-01

    Gemini surfactants have been extensively used for in vitro gene delivery. Amino acid-derived gemini surfactants combine the special aggregation properties characteristic of the gemini surfactants with high biocompatibility and biodegradability. In this work, novel serine-derived gemini surfactants, differing in alkyl chain lengths and in the linker group bridging the spacer to the headgroups (amine, amide and ester), were evaluated for their ability to mediate gene delivery either per se or in combination with helper lipids. Gemini surfactant-based DNA complexes were characterized in terms of hydrodynamic diameter, surface charge, stability in aqueous buffer and ability to protect DNA. Efficient formulations, able to transfect up to 50% of the cells without causing toxicity, were found at very low surfactant/DNA charge ratios (1/1-2/1). The most efficient complexes presented sizes suitable for intravenous administration and negative surface charge, a feature known to preclude potentially adverse interactions with serum components. This work brings forward a new family of gemini surfactants with great potential as gene delivery systems.

  7. Proton energy optimization and reduction for intensity-modulated proton therapy

    PubMed Central

    Cao, Wenhua; Lim, Gino; Liao, Li; Li, Yupeng; Jiang, Shengpeng; Li, Xiaoqiang; Li, Heng; Suzuki, Kazumichi; Zhu, X. Ronald; Gomez, Daniel; Zhang, Xiaodong

    2015-01-01

    Intensity-modulated proton therapy (IMPT) is commonly delivered via the spot-scanning technique. To “scan” the target volume, the proton beam is controlled by varying its energy to penetrate the patient’s body at different depths. Although scanning the proton beamlets or spots with the same energy can be as fast as 10–20 m/s, changing from one proton energy to another requires approximately two additional seconds. The total IMPT delivery time thus depends mainly on the number of proton energies used in a treatment. Current treatment planning systems typically use all proton energies that are required for the proton beam to penetrate in a range from the distal edge to the proximal edge of the target. The optimal selection of proton energies has not been well studied. In this study, we sought to determine the feasibility of optimizing and reducing the number of proton energies in IMPT planning. We proposed an iterative mixed-integer programming optimization method to select a subset of all available proton energies while satisfying dosimetric criteria. We applied our proposed method to six patient datasets: four cases of prostate cancer, one case of lung cancer, and one case of mesothelioma. The numbers of energies were reduced by 14.3%–18.9% for the prostate cancer cases, 11.0% for the lung cancer cases, and 26.5% for the mesothelioma case. The results indicate that the number of proton energies used in conventionally designed IMPT plans can be reduced without degrading dosimetric performance. The IMPT delivery efficiency could be improved by energy layer optimization leading to increased throughput for a busy proton center in which a delivery system with slow energy switch is employed. PMID:25295881

  8. Formulation of microemulsion systems for dermal delivery of silymarin.

    PubMed

    Panapisal, Vipaporn; Charoensri, Sawitree; Tantituvanont, Angkana

    2012-06-01

    Silymarin is a standardized extract from Silybum marianum seeds, known for its many skin benefits such as antioxidant, anti-inflammatory, and immunomodulatory properties. In this study, the potential of several microemulsion formulations for dermal delivery of silymarin was evaluated. The pseudo-ternary phase diagrams were constructed for the various microemulsion formulations which were prepared using glyceryl monooleate, oleic acid, ethyl oleate, or isopropyl myristate as the oily phase; a mixture of Tween 20®, Labrasol®, or Span 20® with HCO-40® (1:1 ratio) as surfactants; and Transcutol® as a cosurfactant. Oil-in-water microemulsions were selected to incorporate 2% w/w silymarin. After six heating-cooling cycles, physical appearances of all microemulsions were unchanged and no drug precipitation occurred. Chemical stability studies showed that microemulsion containing Labrasol® and isopropyl myristate stored at 40°C for 6 months showed the highest silybin remaining among others. The silybin remainings depended on the type of surfactant and were sequenced in the order of: Labrasol® > Tween 20® > Span 20®. In vitro release studies showed prolonged release for microemulsions when compared to silymarin solution. All release profiles showed the best fits with Higuchi kinetics. Non-occlusive in vitro skin permeation studies showed absence of transdermal delivery of silybin. The percentages of silybin in skin extracts were not significantly different among the different formulations (p > 0.05). Nevertheless, some silybin was detected in the receiver fluid when performing occlusive experiments. Microemulsions containing Labrasol® also were found to enhance silymarin solubility. Other drug delivery systems with occlusive effect could be further developed for dermal delivery of silymarin.

  9. A multi-drug delivery system with sequential release using titania nanotube arrays.

    PubMed

    Aw, Moom Sinn; Addai-Mensah, Jonas; Losic, Dusan

    2012-04-01

    A multi-drug delivery system with sequential release based on titania nanotube arrays and polymer micelles as drug carriers is presented. Delivery of multiple water insoluble and soluble drugs required for combined local therapy is demonstrated.

  10. Hybrid quantum/classical approaches for proton transfer in condensed phase systems

    NASA Astrophysics Data System (ADS)

    Kim, Soo Young

    Nuclear quantum effects such as tunneling and zero point energy play an important role in proton transfer reactions. Since a fully quantum mechanical treatment of condensed phase systems is not practical, mixed quantum/classical methods have been developed to simulate proton transfer reactions in solution. In this work the molecular dynamics with quantum transitions (MDQT) method, which incorporates nonadiabatic transitions among the vibrational states, was extended to treat the donor-acceptor vibrational motion as well as the hydrogen motion quantum mechanically for proton transfer reactions. This approach was applied to a model system representing intramolecular proton transfer within a phenol-amine complex in liquid methyl chloride. In addition, a hybrid quantum/classical molecular dynamics approach was applied to a proton transfer reaction represented by a symmetric double well system coupled to a dissipative bath. The hybrid quantum/classical results agree well with numerically exact results in the spatial-diffusion-limited regime, which is most relevant for proton transfer in proteins. In these two studies, the fundamental issues such as the nuclear quantum effects of the proton and donor-acceptor motions and the dissipation effects in the hybrid quantum/classical approach were explored. These results have important implications for applications to hydrogen transfer reactions in solution and proteins.

  11. Supersaturating drug delivery systems: fast is not necessarily good enough.

    PubMed

    Augustijns, Patrick; Brewster, Marcus E

    2012-01-01

    An emerging technology subtype that has been adopted by formulators to address low-solubility issues is the supersaturating drug delivery system; this system is based on the "spring" and "parachute" design elements, which have been applied to lipid-based formulations, S(M)EDDS, solid dispersions, nano-based systems, and many others. This broad formulation approach attempts to delicately balance the need of creating intraluminal drug concentrations in excess of its thermodynamic solubility while at the same time providing for sufficient solution stability to allow for useful drug absorption. The conundrum created is that the higher the extent of supersaturation, the lower the physical stability of the metastable solution based on an increased tendency for a solubilized drug to precipitate. Traditional dissolution testing is a touchstone of formulation development based on the need for useful dissolution rates and drug availability. Dissolution testing is likewise important in the development and characterization of enabling and supersaturating drug delivery systems; however, their execution and interpretation are distinct from that associated with conventional dosage forms. The nature of the dissolution assay (sink versus nonsink, apparatus type, and rate and extent of supersaturation) can impact the ability to efficiently use the dissolution data in the configuration of these enabling formulations.

  12. Moxifloxacin in situ gelling microparticles–bioadhesive delivery system

    PubMed Central

    Guo, Qiongyu; Aly, Ahmed; Schein, Oliver; Trexler, Morgana M.; Elisseeff, Jennifer H.

    2012-01-01

    Antibiotic use for ocular treatments has been largely limited by poor local bioavailability with conventional eyedrops formulations. Here, we developed a controlled delivery system composed of moxifloxacin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulated in a chondroitin sulfate-based, two-component bioadhesive hydrogel. Using a simple and fast electrohydrodynamic spray drying (electrospraying) technique, surfactant-free moxifloxacin-loaded microparticles were fabricated with diameters on the order of 1 μm. A mixed solvent system of methanol/dichloromethane (MeOH/DCM) was employed to prepare the microparticles for the electrospraying processing. Extended release of moxifloxacin using a series of MeOH/DCM mixed solvents was accomplished over 10 days with release concentrations higher than the minimum inhibitory concentration (MIC). In contrast, moxifloxacin loaded directly in hydrogels was released rapidly within 24 h. We observed a decrease of the drug release rate from the microparticles when using an increased percentage of methanol in the mixed solvent from 10% to 30% (v/v), which can be explained by the mixed solvent system providing a driving force to form a gradient of the drug concentrations inside the microparticles. In addition, the delivery system developed in this study, which incorporates a bioadhesive to localize drug release by in situ gelling, may potentially integrate antibiotic prophylaxis and wound healing in the eye. PMID:25755996

  13. Targeted electrohydrodynamic printing for micro-reservoir drug delivery systems

    NASA Astrophysics Data System (ADS)

    Hwang, Tae Heon; Kim, Jin Bum; Som Yang, Da; Park, Yong-il; Ryu, WonHyoung

    2013-03-01

    Microfluidic drug delivery systems consisting of a drug reservoir and microfluidic channels have shown the possibility of simple and robust modulation of drug release rate. However, the difficulty of loading a small quantity of drug into drug reservoirs at a micro-scale limited further development of such systems. Electrohydrodynamic (EHD) printing was employed to fill micro-reservoirs with controlled amount of drugs in the range of a few hundreds of picograms to tens of micrograms with spatial resolution of as small as 20 µm. Unlike most EHD systems, this system was configured in combination with an inverted microscope that allows in situ targeting of drug loading at micrometer scale accuracy. Methylene blue and rhodamine B were used as model drugs in distilled water, isopropanol and a polymer solution of a biodegradable polymer and dimethyl sulfoxide (DMSO). Also tetracycline-HCl/DI water was used as actual drug ink. The optimal parameters of EHD printing to load an extremely small quantity of drug into microscale drug reservoirs were investigated by changing pumping rates, the strength of an electric field and drug concentration. This targeted EHD technique was used to load drugs into the microreservoirs of PDMS microfluidic drug delivery devices and their drug release performance was demonstrated in vitro.

  14. Moxifloxacin in situ gelling microparticles-bioadhesive delivery system.

    PubMed

    Guo, Qiongyu; Aly, Ahmed; Schein, Oliver; Trexler, Morgana M; Elisseeff, Jennifer H

    2012-01-01

    Antibiotic use for ocular treatments has been largely limited by poor local bioavailability with conventional eyedrops formulations. Here, we developed a controlled delivery system composed of moxifloxacin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulated in a chondroitin sulfate-based, two-component bioadhesive hydrogel. Using a simple and fast electrohydrodynamic spray drying (electrospraying) technique, surfactant-free moxifloxacin-loaded microparticles were fabricated with diameters on the order of 1 μm. A mixed solvent system of methanol/dichloromethane (MeOH/DCM) was employed to prepare the microparticles for the electrospraying processing. Extended release of moxifloxacin using a series of MeOH/DCM mixed solvents was accomplished over 10 days with release concentrations higher than the minimum inhibitory concentration (MIC). In contrast, moxifloxacin loaded directly in hydrogels was released rapidly within 24 h. We observed a decrease of the drug release rate from the microparticles when using an increased percentage of methanol in the mixed solvent from 10% to 30% (v/v), which can be explained by the mixed solvent system providing a driving force to form a gradient of the drug concentrations inside the microparticles. In addition, the delivery system developed in this study, which incorporates a bioadhesive to localize drug release by in situ gelling, may potentially integrate antibiotic prophylaxis and wound healing in the eye. PMID:25755996

  15. G2 Autonomous Control for Cryogenic Delivery Systems

    NASA Technical Reports Server (NTRS)

    Dito, Scott J.

    2014-01-01

    The Independent System Health Management-Autonomous Control (ISHM-AC) application development for cryogenic delivery systems is intended to create an expert system that will require minimal operator involvement and ultimately allow for complete autonomy when fueling a space vehicle in the time prior to launch. The G2-Autonomous Control project is the development of a model, simulation, and ultimately a working application that will control and monitor the cryogenic fluid delivery to a rocket for testing purposes. To develop this application, the project is using the programming language/environment Gensym G2. The environment is an all-inclusive application that allows development, testing, modeling, and finally operation of the unique application through graphical and programmatic methods. We have learned G2 through training classes and subsequent application development, and are now in the process of building the application that will soon be used to test on cryogenic loading equipment here at the Kennedy Space Center Cryogenics Test Laboratory (CTL). The G2 ISHM-AC application will bring with it a safer and more efficient propellant loading system for the future launches at Kennedy Space Center and eventually mobile launches from all over the world.

  16. Proton exchange membrane fuel cell conductivity and system analysis

    NASA Astrophysics Data System (ADS)

    Han, Qian

    A fuel cell converts chemical energy to electrical energy. It is a device that uses the electrochemical reaction of hydrogen and an oxidant, to produce electrical energy silently, without combustion. The role of the electrolyte in a PEM fuel cell is played by a proton exchange membrane. NafionRTM and its derivatives are the most widely used and studied polymers. Percolation theory holds a key to understanding the behavior of these polymers. In this dissertation, the percolation phenomenon was first simulated for the thermal conductivity of a representative polymer material. The simulation program was based on the finite element method, using Ansys software, which not only simplifies the method of calculation, but also increases the accuracy of the result. Ansys programs were developed to study the effects of matrix thickness, filler particle volume percentage, and various conductivities of the base material and filler particles. Comparison with existing experimental results and other models showed that the results from the finite element method were more accurate than the other models, especially the three-dimensional model. A similar Ansys program was utilized to predict the percolation threshold for the polymer electric conductivity, and its relationship with extra water content over the studied temperature range. The result showed that the percolation threshold varied with temperature and is in the range of 22% to 26% at room temperature, and matches the experimental data within 10% error margin. A natural gas fuel cell (NGFC) is a direct-energy conversion system which uses natural gas as the hydrogen carrier. A parametric model was developed to predict the overall system performance of a natural-gas-fueled PEM fuel cell system sized for a residential or small commercial building. The model accounts for interactions between various operating parameters: fuel consumption, air and water requirements, power produced, and heat and waste water discharge. For example

  17. Paclitaxel Nano-Delivery Systems: A Comprehensive Review

    PubMed Central

    Ma, Ping; Mumper, Russell J.

    2013-01-01

    Paclitaxel is one of the most effective chemotherapeutic drugs ever developed and is active against a broad range of cancers, such as lung, ovarian, and breast cancers. Due to its low water solubility, paclitaxel is formulated in a mixture of Cremophor EL and dehydrated ethanol (50:50, v/v) a combination known as Taxol. However, Taxol has some severe side effects related to Cremophor EL and ethanol. Therefore, there is an urgent need for the development of alternative Taxol formulations. The encapsulation of paclitaxel in biodegradable and non-toxic nano-delivery systems can protect the drug from degradation during circulation and in-turn protect the body from toxic side effects of the drug thereby lowering its toxicity, increasing its circulation half-life, exhibiting improved pharmacokinetic profiles, and demonstrating better patient compliance. Also, nanoparticle-based delivery systems can take advantage of the enhanced permeability and retention (EPR) effect for passive tumor targeting, therefore, they are promising carriers to improve the therapeutic index and decrease the side effects of paclitaxel. To date, paclitaxel albumin-bound nanoparticles (Abraxane®) have been approved by the FDA for the treatment of metastatic breast cancer and non-small cell lung cancer (NSCLC). In addition, there are a number of novel paclitaxel nanoparticle formulations in clinical trials. In this comprehensive review, several types of developed paclitaxel nano-delivery systems will be covered and discussed, such as polymeric nanoparticles, lipid-based formulations, polymer conjugates, inorganic nanoparticles, carbon nanotubes, nanocrystals, and cyclodextrin nanoparticles. PMID:24163786

  18. Reliability review of the remote tool delivery system locomotor

    SciTech Connect

    Chesser, J.B.

    1999-04-01

    The locomotor being built by RedZone Robotics is designed to serve as a remote tool delivery (RID) system for waste retrieval, tank cleaning, viewing, and inspection inside the high-level waste tanks 8D-1 and 8D-2 at West Valley Nuclear Services (WVNS). The RTD systm is to be deployed through a tank riser. The locomotor portion of the RTD system is designed to be inserted into the tank and is to be capable of moving around the tank by supporting itself and moving on the tank internal structural columns. The locomotor will serve as a mounting platform for a dexterous manipulator arm. The complete RTD system consists of the locomotor, dexterous manipulator arm, cameras, lights, cables, hoses, cable/hose management system, power supply, and operator control station.

  19. THE SUPERCONDUCTION MAGNETS OF THE ILC BEAM DELIVERY SYSTEM.

    SciTech Connect

    PARKER,B.; ANEREELA, M.; ESCALLIE, J.; HE, P.; JAIN, A.; MARONE, A.; NOSOCHKOV, Y.; SERYI, A.

    2007-06-25

    The ILC Reference Design Report was completed early in February 2007. The Magnet Systems Group was formed to translate magnetic field requirements into magnet designs and cost estimates for the Reference Design. As presently configured, the ILC will have more than 13,000 magnetic elements of which more than 2300 will be based on superconducting technology. This paper will describe the major superconducting magnet needs for the ILC as presently determined by the Area Systems Groups, responsible for beam line design, working with the Magnet Systems Group. The superconducting magnet components include Main Linac quadrupoles, Positron Source undulators, Damping Ring wigglers, a complex array of Final Focus superconducting elements in the Beam Delivery System, and large superconducting solenoids in the e{sup +} and e{sup -} Sources, and the Ring to Main Linac lines.

  20. Nanotechnology: a focus on nanoparticles as a drug delivery system.

    PubMed

    Kingsley, Jeffrey D; Dou, Huanyu; Morehead, Justin; Rabinow, Barrett; Gendelman, Howard E; Destache, Christopher J

    2006-09-01

    This review will provide an in-depth discussion on the previous development of nanoparticle-based drug delivery systems (DDS) and discuss original research data that includes the therapeutic enhancement of antiretroviral therapy. The use of nanoparticle DDS will allow practitioners to use drugs to target specific areas of the body. In the treatment of malignancies, the use of nanoparticles as a DDS is making measurable treatment impact. Medical imaging will also utilize DDS to illuminate tumors, the brain, or other cellular functions in the body. The utility of nanoparticle DDS to improve human health is potentially enormous.

  1. Activity-based costing for integrated delivery systems.

    PubMed

    Baker, J J

    1995-01-01

    The paradigm shift toward managed care is fueling new cost-finding demands. More sophisticated methods are emerging to meet these demands. Foremost among the new methods is activity-based costing (ABC). ABC is designed to eliminate cross-subsidies between products or services. Because costs are traced by activities across departments and cost centers, costs can also be traced by activities across integrated delivery systems (IDSs). The methodology makes ABC very applicable to combinations of providers including chains, affiliated groups, and IDS participants. PMID:8820298

  2. Power Delivery from an Actual Thermoelectric Generation System

    NASA Astrophysics Data System (ADS)

    Kaibe, Hiromasa; Kajihara, Takeshi; Nagano, Kouji; Makino, Kazuya; Hachiuma, Hirokuni; Natsuume, Daisuke

    2014-06-01

    Similar to photovoltaic (PV) and fuel cells, thermoelectric generators (TEGs) supply direct-current (DC) power, essentially requiring DC/alternating current (AC) conversion for delivery as electricity into the grid network. Use of PVs is already well established through power conditioning systems (PCSs) that enable DC/AC conversion with maximum-power-point tracking, which enables commercial use by customers. From the economic, legal, and regulatory perspectives, a commercial PCS for PVs should also be available for TEGs, preferably as is or with just simple adjustment. Herein, we report use of a PV PCS with an actual TEG. The results are analyzed, and proper application for TEGs is proposed.

  3. [Studies on transdermal delivery system of dihydroetorphine hydrochloride].

    PubMed

    Chen, X P; Guo, Q D; Shi, T S

    1996-01-01

    A transdermal delivery system of dihydroetorphine hydrochloride (DHE-TDS) was developed. The DHE-TDS mainly composed of polyvinyl alcohol, polyvinyl pyrrolidone and lactose. Tests on rabbits showed only slight skin irritation according to federal hazardous substances act. By giving DHE-TDS to rabbits, DHE release was shown to be governed by first-order mechanism. When DHE-TDS was given to Wistar rats, a relatively stable blood drug concentration was observed from 4-32 h after drug administration. Writhing tests showed that one dose of DHE-TDS would maintain the narcotic action on rats for at least 48 h.

  4. Demonstrations of alternative delivery systems under Medicare and Medicaid.

    PubMed

    Galblum, T W; Trieger, S

    1982-03-01

    The current Administration supports competition as one method of helping to contain escalating costs. Proponents of competition claim many advantages to its implementation, but their claims have yet to be widely tested. Over the past several years, however, the Health Care Financing Administration has supported a number of Medicare and Medicaid demonstrations to yield information on plan participation, marketing, and reimbursement under alternative delivery systems. Much of these data are applicable to the competitive plans being considered by the Administration and Congress. This paper discusses recent findings from these projects.

  5. Activity-based costing for integrated delivery systems.

    PubMed

    Baker, J J

    1995-01-01

    The paradigm shift toward managed care is fueling new cost-finding demands. More sophisticated methods are emerging to meet these demands. Foremost among the new methods is activity-based costing (ABC). ABC is designed to eliminate cross-subsidies between products or services. Because costs are traced by activities across departments and cost centers, costs can also be traced by activities across integrated delivery systems (IDSs). The methodology makes ABC very applicable to combinations of providers including chains, affiliated groups, and IDS participants.

  6. The Superconducting Magnets of the ILC Beam Delivery System

    SciTech Connect

    Parker, B.; Anerella, M.; Escallier, J.; He, P.; Jain, A.; Marone, A.; Nosochkov, Y.; Seryi, Andrei; /SLAC

    2007-09-28

    The ILC Beam Delivery System (BDS) uses a variety of superconducting magnets to maximize luminosity and minimize background. Compact final focus quadrupoles with multifunction correction coils focus incoming beams to few nanometer spot sizes while focusing outgoing disrupted beams into a separate extraction beam line. Anti-solenoids mitigate effects from overlapping focusing and the detector solenoid field. Far from the interaction point (IP) strong octupoles help minimize IP backgrounds. A low-field but very large aperture dipole is integrated with the detector solenoid to reduce backgrounds from beamstrahlung pairs generated at the IP. Physics requirements and magnetic design solutions for the BDS superconducting magnets are reviewed in this paper.

  7. Proton-linked sugar transport systems in bacteria.

    PubMed

    Henderson, P J

    1990-08-01

    The cell membranes of various bacteria contain proton-linked transport systems for D-xylose, L-arabinose, D-galactose, D-glucose, L-rhamnose, L-fucose, lactose, and melibiose. The melibiose transporter of E. coli is linked to both Na+ and H+ translocation. The substrate and inhibitor specificities of the monosaccharide transporters are described. By locating, cloning, and sequencing the genes encoding the sugar/H+ transporters in E. coli, the primary sequences of the transport proteins have been deduced. Those for xylose/H+, arabinose/H+, and galactose/H+ transport are homologous to each other. Furthermore, they are just as similar to the primary sequences of the following: glucose transport proteins found in a Cyanobacterium, yeast, alga, rat, mouse, and man; proteins for transport of galactose, lactose, or maltose in species of yeast; and to a developmentally regulated protein of Leishmania for which a function is not yet established. Some of these proteins catalyze facilitated diffusion of the sugar without cation transport. From the alignments of the homologous amino acid sequences, predictions of common structural features can be made: there are likely to be twelve membrane-spanning alpha-helices, possibly in two groups of six; there is a central hydrophilic region, probably comprised largely of alpha-helix; the highly conserved amino acid residues (40-50 out of 472-522 total) form discrete patterns or motifs throughout the proteins that are presumably critical for substrate recognition and the molecular mechanism of transport. Some of these features are found also in other transport proteins for citrate, tetracycline, lactose, or melibiose, the primary sequences of which are not similar to each other or to the homologous series of transporters. The glucose/Na+ transporter of rabbit and man is different in primary sequence to all the other sugar transporters characterized, but it is homologous to the proline/Na+ transporter of E. coli, and there is evidence

  8. Bionanocomposites containing magnetic graphite as potential systems for drug delivery.

    PubMed

    Ribeiro, Lígia N M; Alcântara, Ana C S; Darder, Margarita; Aranda, Pilar; Herrmann, Paulo S P; Araújo-Moreira, Fernando M; García-Hernández, Mar; Ruiz-Hitzky, Eduardo

    2014-12-30

    New magnetic bio-hybrid matrices for potential application in drug delivery are developed from the assembly of the biopolymer alginate and magnetic graphite nanoparticles. Ibuprofen (IBU) intercalated in a Mg-Al layered double hydroxide (LDH) was chosen as a model drug delivery system (DDS) to be incorporated as third component of the magnetic bionanocomposite DDS. For comparative purposes DDS based on the incorporation of pure IBU in the magnetic bio-hybrid matrices were also studied. All the resulting magnetic bionanocomposites were processed as beads and films and characterized by different techniques with the aim to elucidate the role of the magnetic graphite on the systems, as well as that of the inorganic brucite-like layers in the drug-loaded LDH. In this way, the influence of both inorganic components on the mechanical properties, the water uptake ability, and the kinetics of the drug release from these magnetic systems were determined. In addition, the possibility of modulating the levels of IBU release by stimulating the bionanocomposites with an external magnetic field was also evaluated in in vitro assays.

  9. Bionanocomposites containing magnetic graphite as potential systems for drug delivery.

    PubMed

    Ribeiro, Lígia N M; Alcântara, Ana C S; Darder, Margarita; Aranda, Pilar; Herrmann, Paulo S P; Araújo-Moreira, Fernando M; García-Hernández, Mar; Ruiz-Hitzky, Eduardo

    2014-12-30

    New magnetic bio-hybrid matrices for potential application in drug delivery are developed from the assembly of the biopolymer alginate and magnetic graphite nanoparticles. Ibuprofen (IBU) intercalated in a Mg-Al layered double hydroxide (LDH) was chosen as a model drug delivery system (DDS) to be incorporated as third component of the magnetic bionanocomposite DDS. For comparative purposes DDS based on the incorporation of pure IBU in the magnetic bio-hybrid matrices were also studied. All the resulting magnetic bionanocomposites were processed as beads and films and characterized by different techniques with the aim to elucidate the role of the magnetic graphite on the systems, as well as that of the inorganic brucite-like layers in the drug-loaded LDH. In this way, the influence of both inorganic components on the mechanical properties, the water uptake ability, and the kinetics of the drug release from these magnetic systems were determined. In addition, the possibility of modulating the levels of IBU release by stimulating the bionanocomposites with an external magnetic field was also evaluated in in vitro assays. PMID:25455784

  10. Delivery of Probiotics in the Space Food System

    NASA Technical Reports Server (NTRS)

    Castro, S. L.; Ott, C. M.; Douglas, G. L.

    2014-01-01

    The addition of probiotic bacteria to the space food system is expected to confer immunostimulatory benefits on crewmembers during spaceflight, counteracting the immune dysregulation that has been documented in spaceflight [1]. Specifically, the probiotic Lactobacillus acidophilus has been shown to promote health benefits including antagonism towards and inhibition of virulence related gene expression in pathogens, mucosal stimulation of immune cells, and a reduction in the occurrence and duration of cold and flu-like symptoms [2-5]. The optimum delivery system for probiotics has not been determined for spaceflight, where the food system is shelf stable and the lack of refrigeration prevents the use of traditional dairy delivery methods. This work proposes to determine whether L. acidophilus is more viable, and therefore more likely to confer immune benefit, when delivered in a capsule form or when delivered in nonfat dry milk powder with a resuscitation opportunity upon rehydration, following 0, 4, and 8 months of storage at -80degC, 4degC, and 22degC, and both prior to and after challenge with simulated gastric and intestinal juices. We hypothesize that the low moisture neutral dairy matrix provided by the nonfat dry milk, and the rehydration step prior to consumption, will extend probiotic viability and stress tolerance compared to a capsule during potential storage conditions in spaceflight and in simulated digestion conditions.

  11. Delivery of Probiotics in the Space Food System

    NASA Technical Reports Server (NTRS)

    Castro, S. L.; Ott, C. M.; Douglas, G. L.

    2014-01-01

    The addition of probiotic bacteria to the space food system is expected to confer immunostimulatory benefits on crewmembers during spaceflight, counteracting the immune dysregulation that has been documented in spaceflight. Specifically, the probiotic Lactobacillus acidophilus has been shown to promote health benefits including antagonism towards and inhibition of virulence related gene expression in pathogens, mucosal stimulation of immune cells, and a reduction in the occurrence and duration of cold and flu-like symptoms. The optimum delivery system for probiotics has not been determined for spaceflight, where the food system is shelf stable and the lack of refrigeration prevents the use of traditional dairy delivery methods. This work proposes to determine whether L. acidophilus is more viable, and therefore more likely to confer immune benefit, when delivered in a capsule form or when delivered in nonfat dry milk powder with a resuscitation opportunity upon rehydration, following 0, 4, and 8 months of storage at -80degC, 4degC, and 22degC, and both prior to and after challenge with simulated gastric and intestinal juices. We hypothesize that the low moisture neutral dairy matrix provided by the nonfat dry milk, and the rehydration step prior to consumption, will extend probiotic viability and stress tolerance compared to a capsule during potential storage conditions in spaceflight and in simulated digestion conditions.

  12. A Universal Delivery System for Percutaneous Heart Valve Implantation.

    PubMed

    Bartosch, Marco; Peters, Heiner; Spriestersbach, Hendrik; O H-Ici, Darach; Berger, Felix; Schmitt, Boris

    2016-09-01

    Transcatheter heart valve implantation is an emerging technology and an alternative to surgical valve replacement. Most existing systems consist of valves sewn into balloon-expandable stents with a delivery catheter functioning with the specific valve only. The aim of this study was to develop a universally applicable delivery system (DS) for plane stents, valves sewn into both balloon-expandable and self-expandable stents and feasible for use with different access routes. A DS was designed and manufactured in five different diameters. The requirements were derived from the implants, the implantation technique and the cardiovascular geometry of the experimental sheep. The combination of a self-expandable Nitinol stent and a jugular access point represented the major challenge as both flexibility and rigidity of the DS were required. To fulfill these contradicting mechanical properties the sheaths were comprised of a soft outer polymer tube with a stainless steel coiled spring inside. Tissue-engineered and pericardial pulmonary valves were implanted. Also polymeric and balloon-expandable stents were delivered to various positions in the vascular system. The initial success rate was 70.5%. After refinement of the DS, a success rate of 83.3% was achieved with the remaining failed implantations resulting from inadequate sizes of the prostheses. PMID:26864537

  13. Developing system for delivery of optical radiation in medicobiological researches

    NASA Astrophysics Data System (ADS)

    Loschenov, Victor B.; Taraz, Majid

    2004-06-01

    Methods of optical diagnostics and methods of photodynamic therapy are actively used in medico-biological researches. The system for delivery of optical radiation is one of the key methods in these researches. Usually these systems use flexible optical fibers with diameters from 200 to 1000 micron. Two types of systems for delivery are subdivided, first for diagnostic researches, second for therapeutic procedures. Existing diagnostic catheters, which have most widely applied in medicine, have bifurcated with diameter of the tip equal 1.8 mm. These devices, which are called fiber-optical catheters, satisfy the majority endoscopes researches. However, till now the problem of optical-diagnostics inside tissue is not soled. Especially it is important at diagnostics of a mammary gland, livers, thyroid glands tumor, tumor of a brain and some other studies connected with punctures. In these cases, it is necessary that diameter of fiber-optical catheters be less than one millimeter. This work is devoted to the development of these catheters. Also in clinical procedures such as photodynamic therapy (PDT) and interstitial laser photocoagulation (ILP), cylindrical light diffusing tips are rapidly becoming a popular device for the administration of the desired light dose for the illumination of hollow organs, such as bronchus, trachea and oesophagus. This work is devoted to the development of these catheters.

  14. Demonstrated delivery/employment systems for unattended ground sensors

    NASA Astrophysics Data System (ADS)

    Taylor, Robert R.; Bendowski, Michael A.; McFeaters, Ryan C.

    1997-07-01

    This paper describes the payload delivery system developed and proven to deploy an electronic warfare device to specific, predetermined locations on the battlefield. Initially called the Artillery Delivered Expendable Jammer (AD/EXJAM), it is now designated the Air Delivered-Ground (Deployed) Expendable Jammer (AD-G/EXJAM). The initial units were demonstrated from 155 MM artillery; the later units, from UAV's, helicopters and slow moving, fixed wing aircraft. While these two delivery systems were originally designed specifically for the EXJAM system, the concept is directly applicable to unattended ground sensors that require unmanned remote emplacement. Keys to the success of the jammer included design, development and field testing of power supplies, antennas, deployment systems and packaging to allow payloads to withstand high-g impact and other severe environments typically encountered. The artillery deployed systems were designed to be `wooden' rounds needing no special handling and storing. These systems treat the payload as independent elements which are self-ejected from a fired M483A1 or M864 round and are completely automatic upon hitting the ground. The more recent payloads can be delivered from UAV's and include remote control capabilities, increased operating life and increased power output. The present payload is packaged into a cylindrical shape, approximately six inches in diameter and 6.5 inches long and are contained within a carrier, attached to an Unmanned Air Vehicle (UAV) or any other air vehicle. Upon reaching the dispensing point, the release command can be issue by either the UAV or a separate ground control unit in RF contact with the carrier. The carrier then begins a timed dispensing sequence that has been selected for optimum payload emplacement in the target area. New developments include a design and subsystem demonstration of a tactical munitions dispenser variant of the deployment system. Operational characteristics of any specific

  15. Non-coding RNAs: Therapeutic Strategies and Delivery Systems.

    PubMed

    Ling, Hui

    2016-01-01

    The vast majority of the human genome is transcribed into RNA molecules that do not code for proteins, which could be small ones approximately 20 nucleotide in length, known as microRNAs, or transcripts longer than 200 bp, defined as long noncoding RNAs. The prevalent deregulation of microRNAs in human cancers prompted immediate interest on the therapeutic value of microRNAs as drugs and drug targets. Many features of microRNAs such as well-defined mechanisms, and straightforward oligonucleotide design further make them attractive candidates for therapeutic development. The intensive efforts of exploring microRNA therapeutics are reflected by the large body of preclinical studies using oligonucleotide-based mimicking and blocking, culminated by the recent entry of microRNA therapeutics in clinical trial for several human diseases including cancer. Meanwhile, microRNA therapeutics faces the challenge of effective and safe delivery of nucleic acid therapeutics into the target site. Various chemical modifications of nucleic acids and delivery systems have been developed to increase targeting specificity and efficacy, and reduce the associated side effects including activation of immune response. Recently, long noncoding RNAs become attractive targets for therapeutic intervention because of their association with complex and delicate phenotypes, and their unconventional pharmaceutical activities such as capacity of increasing output of proteins. Here I discuss the general therapeutic strategies targeting noncoding RNAs, review delivery systems developed to maximize noncoding RNA therapeutic efficacy, and offer perspectives on the future development of noncoding RNA targeting agents for colorectal cancer. PMID:27573903

  16. Versatile RNA Interference Nanoplatform for Systemic Delivery of RNAs

    PubMed Central

    2015-01-01

    Development of nontoxic, tumor-targetable, and potent in vivo RNA delivery systems remains an arduous challenge for clinical application of RNAi therapeutics. Herein, we report a versatile RNAi nanoplatform based on tumor-targeted and pH-responsive nanoformulas (NFs). The NF was engineered by combination of an artificial RNA receptor, Zn(II)-DPA, with a tumor-targetable and drug-loadable hyaluronic acid nanoparticle, which was further modified with a calcium phosphate (CaP) coating by in situ mineralization. The NF can encapsulate small-molecule drugs within its hydrophobic inner core and strongly secure various RNA molecules (siRNAs, miRNAs, and oligonucleotides) by utilizing Zn(II)-DPA and a robust CaP coating. We substantiated the versatility of the RNAi nanoplatform by demonstrating effective delivery of siRNA and miRNA for gene silencing or miRNA replacement into different human types of cancer cells in vitro and into tumor-bearing mice in vivo by intravenous administration. The therapeutic potential of NFs coloaded with an anticancer drug doxorubicin (Dox) and multidrug resistance 1 gene target siRNA (siMDR) was also demonstrated in this study. NFs loaded with Dox and siMDR could successfully sensitize drug-resistant OVCAR8/ADR cells to Dox and suppress OVCAR8/ADR tumor cell proliferation in vitro and tumor growth in vivo. This gene/drug delivery system appears to be a highly effective nonviral method to deliver chemo- and RNAi therapeutics into host cells. PMID:24779637

  17. Ammonium as a sustainable proton shuttle in bioelectrochemical systems.

    PubMed

    Cord-Ruwisch, Ralf; Law, Yingyu; Cheng, Ka Yu

    2011-10-01

    This work examines a pH control method using ammonium (NH(4)(+)) as a sustainable proton shuttle in a CEM-equipped BES. Current generation was sustained by adding NH(3) or ammonium hydroxide (NH(4)OH) to the anolyte, controlling its pH at 7. Ammonium ion migration maintained the catholyte pH at approximately 9.25. Such NH(4)(+)/NH(3) migration accounted for 90±10% of the ionic flux in the BES. Reintroducing the volatilized NH(3) from the cathode into the anolyte maintained a suitable anolyte pH for sustained microbial-driven current generation. Hence, NH(4)(+)/NH(3) acted as a proton shuttle that is not consumed in the process.

  18. Evaluation of bioadhesive polymers as delivery systems for nose to brain delivery: in vitro characterisation studies.

    PubMed

    Charlton, S T; Davis, S S; Illum, L

    2007-04-01

    There is an increasing need for nasal drug delivery systems that could improve the efficiency of the direct nose to brain pathway especially for drugs for treatment of central nervous system disorders. Novel approaches that are able to combine active targeting of a formulation to the olfactory region with controlled release bioadhesive characteristics, for maintaining the drug on the absorption site are suggested. If necessary an absorption enhancer could be incorporated. Low methylated pectins have been shown to gel and be retained in the nasal cavity after deposition. Chitosan is known to be bioadhesive and also to work as an absorption enhancer. Consequently, two types of pectins, LM-5 and LM-12, together with chitosan G210, were selected for characterisation in terms of molecular weight, gelling ability and viscosity. Furthermore, studies on the in vitro release of model drugs from candidate formulations and the transport of drugs across MDCK1 cell monolayers in the presence of pectin and chitosan were also performed. Bioadhesive formulations providing controlled release with increased or decreased epithelial transport were developed. Due to their promising characteristics 3% LM-5, 1% LM-12 pectin and 1% chitosan G210 formulations were selected for further biological evaluation in animal models.

  19. Systemic delivery of blood-brain barrier-targeted polymeric nanoparticles enhances delivery to brain tissue.

    PubMed

    Saucier-Sawyer, Jennifer K; Deng, Yang; Seo, Young-Eun; Cheng, Christopher J; Zhang, Junwei; Quijano, Elias; Saltzman, W Mark

    2015-01-01

    Delivery of therapeutic agents to the central nervous system is a significant challenge, hindering progress in the treatment of diseases such as glioblastoma. Due to the presence of the blood-brain barrier (BBB), therapeutic agents do not readily transverse the brain endothelium to enter the parenchyma. Previous reports suggest that surface modification of polymer nanoparticles (NPs) can improve their ability to cross the BBB, but it is unclear whether the observed enhancements in transport are large enough to enhance therapy. In this study, we synthesized two degradable polymer NP systems surface-modified with ligands previously suggested to improve BBB transport, and tested their ability to cross the BBB after intravenous injection in mice. All the NP preparations were able to cross the BBB, although generally in low amounts (<0.5% of the injected dose), which was consistent with prior reports. One NP produced significantly higher brain uptake (∼0.8% of the injected dose): a block copolymer of polylactic acid and hyperbranched polyglycerol, surface modified with adenosine (PLA-HPG-Ad). PLA-HPG-Ad NPs provided controlled release of camptothecin, killing U87 glioma cells in culture. When administered intravenously in mice with intracranial U87 tumors, they failed to increase survival. These results suggest that enhancing NP transport across the BBB does not necessarily yield proportional pharmacological effects.

  20. A novel liquid effervescent floating delivery system for sustained drug delivery.

    PubMed

    Ibrahim, H K

    2009-08-01

    An effervescent floating liquid formulation with in situ gelling properties has been assessed for its potential for sustaining drug delivery and targeting. The formulation consisted of sodium alginate and glyceryl monooleate (GMO). The developed formulation met all pre-requisites to become an in situ gelling floating system and it gelled and floated instantaneously in the pH conditions of the stomach. Moreover, the gels formed in situ remained intact for more than 48 h to facilitate sustained release of drugs. Increasing the mannuronic acid ratio of sodium alginate and the GMO concentration significantly retarded the release rate and extent. The in vitro release of both hydrophilic and hydrophobic drugs from the prepared formulations followed root-time kinetics during the sustained release period. Replacing the free drug with drug encapsulated microspheres enabled tailoring of the release profile and achieved zero-order release kinetics. The system retained its appearance and rheological properties for 12 months at ambient conditions. The values of the similarity factor Sd proved the absence of any significant difference in the release profile upon storage.

  1. Diagnosing delivery problems in the White House Information Distribution System

    SciTech Connect

    Nahabedian, M.; Shrobe, H.

    1996-12-31

    As part of a collaboration with the White House Office of Media Affairs, members of the MIT Artificial Intelligence Laboratory designed a system, called COMLINK, which distributes a daily stream of documents released by the Office of Media Affairs. Approximately 4000 direct subscribers receive information from this service but more than 100,000 people receive the information through redistribution channels. The information is distributed via Email and the World Wide Web. In such a large scale distribution scheme, there is a constant problem of subscriptions becoming invalid because the user`s Email account has terminated. This causes a backwash of hundreds of {open_quotes}bounced mail{close_quotes} messages per day which must be processed by the operators of the COMLINK system. To manage this annoying but necessary task, an expert system named BMES was developed to diagnose the failures of information delivery.

  2. Aerosol assisted depositions of polymers using an atomiser delivery system.

    PubMed

    Crick, Colin R; Clausen-Thue, Victoria; Parkin, Ivan P

    2011-09-01

    The hydrophobicity, robustness and anti-microbial properties of Sylgard 184 polymer films deposited via AACVD were optimised by using aerosol droplets from an atomiser delivery system, polymer coating substrates and the swell encapsulation of methylene blue. By using an atomiser deposition system (average droplet size 0.35 microm) rather than a misting aerosol system (45 microm) lead to a surface with smaller surface features, which improved hydrophobicity (water contact angle 165 degrees) in addition to increasing the films transparency from ca 10 to 65%. Pre-treating the substrates with the same Sylgard 184 elastomer lead to a highly consistent surface hydrophobicity and an increase in average water contact angle measured (169 degrees). This paper shows the first example of dye incorporation in a CVD derived polymer film-these films have potential as antimicrobial surfaces. PMID:22097584

  3. Noble gas storage and delivery system for ion propulsion

    NASA Technical Reports Server (NTRS)

    Back, Dwight Douglas (Inventor); Ramos, Charlie (Inventor)

    2001-01-01

    A method and system for storing and delivering a noble gas for an ion propulsion system where an adsorbent bearing a noble gas is heated within a storage vessel to desorb the noble gas which is then flowed through a pressure reduction device to a thruster assembly. The pressure and flow is controlled using a flow restrictor and low wattage heater which heats an adsorbent bed containing the noble gas propellant at low pressures. Flow rates of 5-60 sccm can be controlled to within about 0.5% or less and the required input power is generally less than 50 W. This noble gas storage and delivery system and method can be used for earth orbit satellites, and lunar or planetary space missions.

  4. Aerosol assisted depositions of polymers using an atomiser delivery system.

    PubMed

    Crick, Colin R; Clausen-Thue, Victoria; Parkin, Ivan P

    2011-09-01

    The hydrophobicity, robustness and anti-microbial properties of Sylgard 184 polymer films deposited via AACVD were optimised by using aerosol droplets from an atomiser delivery system, polymer coating substrates and the swell encapsulation of methylene blue. By using an atomiser deposition system (average droplet size 0.35 microm) rather than a misting aerosol system (45 microm) lead to a surface with smaller surface features, which improved hydrophobicity (water contact angle 165 degrees) in addition to increasing the films transparency from ca 10 to 65%. Pre-treating the substrates with the same Sylgard 184 elastomer lead to a highly consistent surface hydrophobicity and an increase in average water contact angle measured (169 degrees). This paper shows the first example of dye incorporation in a CVD derived polymer film-these films have potential as antimicrobial surfaces.

  5. Interplay effects in proton scanning for lung: a 4D Monte Carlo study assessing the impact of tumor and beam delivery parameters

    NASA Astrophysics Data System (ADS)

    Dowdell, S.; Grassberger, C.; Sharp, G. C.; Paganetti, H.

    2013-06-01

    Relative motion between a tumor and a scanning proton beam results in a degradation of the dose distribution (interplay effect). This study investigates the relationship between beam scanning parameters and the interplay effect, with the goal of finding parameters that minimize interplay. 4D Monte Carlo simulations of pencil beam scanning proton therapy treatments were performed using the 4DCT geometry of five lung cancer patients of varying tumor size (50.4-167.1 cc) and motion amplitude (2.9-30.1 mm). Treatments were planned assuming delivery in 35 × 2.5 Gy(RBE) fractions. The spot size, time to change the beam energy (τes), time required for magnet settling (τss), initial breathing phase, spot spacing, scanning direction, scanning speed, beam current and patient breathing period were varied for each of the five patients. Simulations were performed for a single fraction and an approximation of conventional fractionation. For the patients considered, the interplay effect could not be predicted using the superior-inferior motion amplitude alone. Larger spot sizes (σ ˜ 9-16 mm) were less susceptible to interplay, giving an equivalent uniform dose (EUD) of 99.0 ± 4.4% (1 standard deviation) in a single fraction compared to 86.1 ± 13.1% for smaller spots (σ ˜ 2-4 mm). The smaller spot sizes gave EUD values as low as 65.3% of the prescription dose in a single fraction. Reducing the spot spacing improved the target dose homogeneity. The initial breathing phase can have a significant effect on the interplay, particularly for shorter delivery times. No clear benefit was evident when scanning either parallel or perpendicular to the predominant axis of motion. Longer breathing periods decreased the EUD. In general, longer delivery times led to lower interplay effects. Conventional fractionation showed significant improvement in terms of interplay, giving a EUD of at least 84.7% and 100.0% of the prescription dose for the small and larger spot sizes respectively

  6. Interplay effects in proton scanning for lung: a 4D Monte Carlo study assessing the impact of tumor and beam delivery parameters.

    PubMed

    Dowdell, S; Grassberger, C; Sharp, G C; Paganetti, H

    2013-06-21

    Relative motion between a tumor and a scanning proton beam results in a degradation of the dose distribution (interplay effect). This study investigates the relationship between beam scanning parameters and the interplay effect, with the goal of finding parameters that minimize interplay. 4D Monte Carlo simulations of pencil beam scanning proton therapy treatments were performed using the 4DCT geometry of five lung cancer patients of varying tumor size (50.4-167.1 cc) and motion amplitude (2.9-30.1 mm). Treatments were planned assuming delivery in 35 × 2.5 Gy(RBE) fractions. The spot size, time to change the beam energy (τes), time required for magnet settling (τss), initial breathing phase, spot spacing, scanning direction, scanning speed, beam current and patient breathing period were varied for each of the five patients. Simulations were performed for a single fraction and an approximation of conventional fractionation. For the patients considered, the interplay effect could not be predicted using the superior-inferior motion amplitude alone. Larger spot sizes (σ ~ 9-16 mm) were less susceptible to interplay, giving an equivalent uniform dose (EUD) of 99.0 ± 4.4% (1 standard deviation) in a single fraction compared to 86.1 ± 13.1% for smaller spots (σ ~ 2-4 mm). The smaller spot sizes gave EUD values as low as 65.3% of the prescription dose in a single fraction. Reducing the spot spacing improved the target dose homogeneity. The initial breathing phase can have a significant effect on the interplay, particularly for shorter delivery times. No clear benefit was evident when scanning either parallel or perpendicular to the predominant axis of motion. Longer breathing periods decreased the EUD. In general, longer delivery times led to lower interplay effects. Conventional fractionation showed significant improvement in terms of interplay, giving a EUD of at least 84.7% and 100.0% of the prescription dose for the small and larger spot sizes respectively. The

  7. Site-specific and compensatory mutations imply unexpected pathways for proton delivery to the QB binding site of the photosynthetic reaction center.

    PubMed Central

    Hanson, D K; Tiede, D M; Nance, S L; Chang, C H; Schiffer, M

    1993-01-01

    In photosynthetic reaction centers, a quinone molecule, QB, is the terminal acceptor in light-induced electron transfer. The protonatable residues Glu-L212 and Asp-L213 have been implicated in the binding of QB and in proton transfer to QB anions generated by electron transfer from the primary quinone QA. Here we report the details of the construction of the Ala-L212/Ala-L213 double mutant strain by site-specific mutagenesis and show that its photosynthetic incompetence is due to an inability to deliver protons to the QB anions. We also report the isolation and biophysical characterization of a collection of revertant and suppressor strains that have regained the photosynthetic phenotype. The compensatory mutations that restore function are diverse and show that neither Glu-L212 nor Asp-L213 is essential for efficient light-induced electron or proton transfer in Rhodobacter capsulatus. Second-site mutations, located within the QB binding pocket or at more distant sites, can compensate for mutations at L212 and L213 to restore photocompetence. Acquisition of a single negatively charged residue (at position L213, across the binding pocket at position L225, or outside the pocket at M43) or loss of a positively charged residue (at position M231) is sufficient to restore proton transfer activity to the complex. The proton transport pathways in the suppressor strains cannot, in principle, be identical to that of the wild type. The apparent mutability of this pathway suggests that the reaction center can serve as a model system to study the structural basis of protein-mediated proton transport. PMID:8105468

  8. Preliminary results, obtained by using a proton beam, for an active scanning system to installed on the KHIMA

    NASA Astrophysics Data System (ADS)

    Kim, Chang Hyeuk; Lee, Hwa-Ryun; Jang, Sea Duk; Kim, Hyunyong; Hahn, Garam; Kim, Jeong Hwan; Jang, Hong Suk; Park, Dong Wook; Hwang, Won Taek; Yang, Tae-Keun

    2015-08-01

    The active scanning technique is a pencil beam delivery method in particle therapy. The active scanning beam delivery system consists of a beam scanner, beam monitor, energy modulator, and related programs, such as the irradiation control and planning programs. A proposed prototype active scanning system was designed and installed on MC-50 at the Korea Institute of Radiological and Medical Science (KIRAMS) with a 45-MeV proton beam. The laminated magnetic yoke of the scanning magnet supported fast ramping. The beam intensity and the beam profile monitors were designed for measuring the beam's properties. Both the range shifter and the ridge filter modulate the incoming beam energy. The LabVIEW®-based beam-irradiation-control program operates the system in a sequential operation manner for use with the MC-50 cyclotron. In addition, an in-housecoded irradiation-planning program generates an optimal irradiation path. A scanning experiment was successfully completed to print the logo of the Korea Heavy Ion Medical Accelerator (KHIMA) on GaF film. Moreover, the beam's position accuracy was measured as 0.62 mm in the x-direction and as 0.83 mm in the y-direction.

  9. Niosomes as Nano-Delivery Systems in the Pharmaceutical Field.

    PubMed

    Cerqueira-Coutinho, Cristal; Dos Santos, Elisabete P; Mansur, Claudia Regina E

    2016-01-01

    Nanosystems used in the pharmaceutical field aim to guarantee a controlled release and efficacy boost with dose reduction of the drug. The same active ingredient could be vehiculated in different concentrations in distinct nanosystems. Among these nanostructures, the vesicular ones present a versatile delivery system that could be applied to encapsulate lipophilic, amphiphilic, and hydrophilic compounds. Liposomes are the most well-known vesicular nanosystems; however, there are others, such as niosomes, that are composed of nonionic surfactants that are polymeric or conventional. Niosomes could be prepared using the thin film hydration method, in which the active ingredient is solubilized in organic solvent with the surfactant or in aqueous solution depending on its polarity. In addition, co-surfactants could be used to improve stabilization and vesicle integrity because they occupy regions in the interface where the mainly surfactant could not reach. Vesicular nanosystems could be characterized by different techniques, such as microscopy, dynamic light scattering, nuclear magnetic resonance, and others. These nanostructures could be applied to drugs (administered by different routes) or to gene and cosmetic delivery systems. PMID:27651102

  10. The Smart Drug Delivery System and Its Clinical Potential.

    PubMed

    Liu, Dong; Yang, Fang; Xiong, Fei; Gu, Ning

    2016-01-01

    With the unprecedented progresses of biomedical nanotechnology during the past few decades, conventional drug delivery systems (DDSs) have been involved into smart DDSs with stimuli-responsive characteristics. Benefiting from the response to specific internal or external triggers, those well-defined nanoplatforms can increase the drug targeting efficacy, in the meantime, reduce side effects/toxicities of payloads, which are key factors for improving patient compliance. In academic field, variety of smart DDSs have been abundantly demonstrated for various intriguing systems, such as stimuli-responsive polymeric nanoparticles, liposomes, metals/metal oxides, and exosomes. However, these nanoplatforms are lack of standardized manufacturing method, toxicity assessment experience, and clear relevance between the pre-clinical and clinical studies, resulting in the huge difficulties to obtain regulatory and ethics approval. Therefore, such relatively complex stimulus-sensitive nano-DDSs are not currently approved for clinical use. In this review, we highlight the recent advances of smart nanoplatforms for targeting drug delivery. Furthermore, the clinical translation obstacles faced by these smart nanoplatforms have been reviewed and discussed. We also present the future directions and perspectives of stimuli-sensitive DDS in clinical applications. PMID:27375781

  11. Alginate Nanoparticles as a Promising Adjuvant and Vaccine Delivery System

    PubMed Central

    Sarei, F.; Dounighi, N. Mohammadpour; Zolfagharian, H.; Khaki, P.; Bidhendi, S. Moradi

    2013-01-01

    During last decades, diphtheria has remained as a serious disease that still outbreaks and can occur worldwide. Recently, new vaccine delivery systems have been developed by using the biodegradable and biocompatible polymers such as alginate. Alginate nanoparticles as a carrier with adjuvant and prolong release properties that enhance the immunogenicity of vaccines. In this study diphtheria toxoid loaded nanoparticles were prepared by ionic gelation technique and characterized with respect to size, zeta potential, morphology, encapsulation efficiency, release profile, and immunogenicity. Appropriate parameters (calcium chloride and sodium alginate concentration, homogenization rate and homogenization time) redounded to the formation of suitable nanoparticles with a mean diameter of 70±0.5 nm. The loading studies of the nanoparticles resulted in high loading capacities (>90%) and subsequent release studies showed prolong profile. The stability and antigenicity of toxoid were evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and ouchterlony test and proved that the encapsulation process did not affect the antigenic integrity and activity. Guinea pigs immunized with the diphtheria toxoid-loaded alginate nanoparticles showed highest humoral immune response than conventional vaccine. It is concluded that, with regard to the desirable properties of nanoparticles and high immunogenicity, alginate nanoparticles could be considered as a new promising vaccine delivery and adjuvant system. PMID:24302799

  12. Nanostructured lipid carriers: Promising drug delivery systems for future clinics.

    PubMed

    Beloqui, Ana; Solinís, María Ángeles; Rodríguez-Gascón, Alicia; Almeida, António J; Préat, Véronique

    2016-01-01

    During the past decade, the number of studies describing nanostructured lipid carriers (NLCs)-based formulations has been dramatically increased. The raise in NLC exploitation is essentially due to defeated barriers within the technological process of lipid-based nanoparticles' formulation and increased knowledge of the underlying mechanisms of transport of NLCs via different routes of administration. This review article aims to give an overview on the current state of the art of NLC as controlled drug delivery systems for future clinics through novel NLC applications providing examples of successfull outcomes. The reported data clearly illustrate the promise of these nanoparticles for novel treatments in the near future. From the Clinical Editor: The understanding of the nanostructured lipid carriers (NLC)-based formulations has improved with continuing research recently. The result has seen an increase in the use of these in the clinical setting. In this comprehensive review, the authors discussed the current state and major challenges in the use of nanostructured lipid carriers as controlled drug delivery systems. PMID:26410277

  13. Cubic and hexagonal liquid crystals as drug delivery systems.

    PubMed

    Chen, Yulin; Ma, Ping; Gui, Shuangying

    2014-01-01

    Lipids have been widely used as main constituents in various drug delivery systems, such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, and lipid-based lyotropic liquid crystals. Among them, lipid-based lyotropic liquid crystals have highly ordered, thermodynamically stable internal nanostructure, thereby offering the potential as a sustained drug release matrix. The intricate nanostructures of the cubic phase and hexagonal phase have been shown to provide diffusion controlled release of active pharmaceutical ingredients with a wide range of molecular weights and polarities. In addition, the biodegradable and biocompatible nature of lipids demonstrates the minimum toxicity and thus they are used for various routes of administration. Therefore, the research on lipid-based lyotropic liquid crystalline phases has attracted a lot of attention in recent years. This review will provide an overview of the lipids used to prepare cubic phase and hexagonal phase at physiological temperature, as well as the influencing factors on the phase transition of liquid crystals. In particular, the most current research progresses on cubic and hexagonal phases as drug delivery systems will be discussed. PMID:24995330

  14. Advanced drug delivery systems of curcumin for cancer chemoprevention.

    PubMed

    Bansal, Shyam S; Goel, Mehak; Aqil, Farrukh; Vadhanam, Manicka V; Gupta, Ramesh C

    2011-08-01

    Since ancient times, chemopreventive agents have been used to treat/prevent several diseases including cancer. They are found to elicit a spectrum of potent responses including anti-inflammatory, antioxidant, antiproliferative, anticarcinogenic, and antiangiogenic activity in various cell cultures and some animal studies. Research over the past 4 decades has shown that chemopreventives affect a number of proteins involved in various molecular pathways that regulate inflammatory and carcinogenic responses in a cell. Various enzymes, transcription factors, receptors, and adhesion proteins are also affected by chemopreventives. Although, these natural compounds have shown significant efficacy in cell culture studies, they elicited limited efficacy in various clinical studies. Their introduction into the clinical setting is hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Therefore, to circumvent these limitations and to ease their transition to clinics, alternate strategies should be explored. Drug delivery systems such as nanoparticles, liposomes, microemulsions, and polymeric implantable devices are emerging as one of the viable alternatives that have been shown to deliver therapeutic concentrations of various potent chemopreventives such as curcumin, ellagic acid, green tea polyphenols, and resveratrol into the systemic circulation. In this review article, we have attempted to provide a comprehensive outlook for these delivery approaches, using curcumin as a model agent, and discussed future strategies to enable the introduction of these highly potent chemopreventives into a physician's armamentarium. PMID:21546540

  15. Advanced Drug-Delivery Systems of Curcumin for Cancer Chemoprevention

    PubMed Central

    Bansal, Shyam S.; Goel, Mehak; Aqil, Farrukh; Vadhanam, Manicka V.; Gupta, Ramesh C.

    2011-01-01

    From ancient times, chemopreventive agents have been used to treat/prevent several diseases, including cancer. They are found to elicit a spectrum of potent responses including anti-inflammatory, anti-oxidant, anti-proliferative, anti-carcinogenic, and anti-angiogenic activity in various cell culture and some animal studies. Research over the past four decades has shown that chemopreventives affect a number of proteins involved in various molecular pathways that regulate inflammatory and carcinogenic responses in a cell. Various enzymes, transcription factors, receptors, and adhesion proteins are also affected by chemopreventives. Although, these natural compounds have shown significant efficacy in cell-culture studies, they elicited limited efficacy in various clinical studies. Their introduction into the clinical setting is hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Therefore, to circumvent these limitations and to ease their transition to clinics, alternate strategies should be explored. Drug delivery systems such as nanoparticles, liposomes, microemulsions, and polymeric implantable devices are emerging as one of the viable alternatives that have been demonstrated to deliver therapeutic concentrations of various potent chemopreventives such as curcumin, ellagic acid, green tea polyphenols, and resveratrol into the systemic circulation. In this review article, we have attempted to provide a comprehensive outlook for these delivery approaches, using curcumin as a model agent, and discussed future strategies to enable the introduction of these highly potent chemopreventives into a physician’s armamentarium. PMID:21546540

  16. Cubic and Hexagonal Liquid Crystals as Drug Delivery Systems

    PubMed Central

    Chen, Yulin; Ma, Ping; Gui, Shuangying

    2014-01-01

    Lipids have been widely used as main constituents in various drug delivery systems, such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, and lipid-based lyotropic liquid crystals. Among them, lipid-based lyotropic liquid crystals have highly ordered, thermodynamically stable internal nanostructure, thereby offering the potential as a sustained drug release matrix. The intricate nanostructures of the cubic phase and hexagonal phase have been shown to provide diffusion controlled release of active pharmaceutical ingredients with a wide range of molecular weights and polarities. In addition, the biodegradable and biocompatible nature of lipids demonstrates the minimum toxicity and thus they are used for various routes of administration. Therefore, the research on lipid-based lyotropic liquid crystalline phases has attracted a lot of attention in recent years. This review will provide an overview of the lipids used to prepare cubic phase and hexagonal phase at physiological temperature, as well as the influencing factors on the phase transition of liquid crystals. In particular, the most current research progresses on cubic and hexagonal phases as drug delivery systems will be discussed. PMID:24995330

  17. Regulatory considerations on new adjuvants and delivery systems.

    PubMed

    Sesardic, D

    2006-04-12

    New and improved vaccines and delivery systems are increasingly being developed for prevention, treatment and diagnosis of human diseases. Prior to their use in humans, all new biological products must undergo pre-clinical evaluation. These pre-clinical studies are important not only to establish the biological properties of the material and to evaluate its possible risk to the public, but also to plan protocols for subsequent clinical trials from which safety and efficacy can be evaluated. For vaccines, evaluation in pre-clinical studies is particularly important as information gained may also contribute to identifying the optimum composition and formulation process and provide an opportunity to develop suitable indicator tests for quality control. Data from pre-clinical and laboratory evaluation studies, which continue during clinical studies, is used to support an application for marketing authorisation. Addition of a new adjuvant and exploration of new delivery systems for vaccines presents challenges to both manufacturers and regulatory authorities. Because no adjuvant is licensed as a medicinal product in its own right, but only as a component of a particular vaccine, pre-clinical and appropriate toxicology studies need to be designed on a case-by-case basis to evaluate the safety profile of the adjuvant and adjuvant/vaccine combination. Current regulatory requirements for the pharmaceutical and pre-clinical safety assessment of vaccines are insufficient and initiatives are in place to develop more specific guidelines for evaluation of adjuvants in vaccines.

  18. The Smart Drug Delivery System and Its Clinical Potential

    PubMed Central

    Liu, Dong; Yang, Fang; Xiong, Fei; Gu, Ning

    2016-01-01

    With the unprecedented progresses of biomedical nanotechnology during the past few decades, conventional drug delivery systems (DDSs) have been involved into smart DDSs with stimuli-responsive characteristics. Benefiting from the response to specific internal or external triggers, those well-defined nanoplatforms can increase the drug targeting efficacy, in the meantime, reduce side effects/toxicities of payloads, which are key factors for improving patient compliance. In academic field, variety of smart DDSs have been abundantly demonstrated for various intriguing systems, such as stimuli-responsive polymeric nanoparticles, liposomes, metals/metal oxides, and exosomes. However, these nanoplatforms are lack of standardized manufacturing method, toxicity assessment experience, and clear relevance between the pre-clinical and clinical studies, resulting in the huge difficulties to obtain regulatory and ethics approval. Therefore, such relatively complex stimulus-sensitive nano-DDSs are not currently approved for clinical use. In this review, we highlight the recent advances of smart nanoplatforms for targeting drug delivery. Furthermore, the clinical translation obstacles faced by these smart nanoplatforms have been reviewed and discussed. We also present the future directions and perspectives of stimuli-sensitive DDS in clinical applications. PMID:27375781

  19. Spatiotemporal drug delivery using laser-generated-focused ultrasound system.

    PubMed

    Di, Jin; Kim, Jinwook; Hu, Quanyin; Jiang, Xiaoning; Gu, Zhen

    2015-12-28

    Laser-generated-focused ultrasound (LGFU) holds promise for the high-precision ultrasound therapy owing to its tight focal spot, broad frequency band, and stable excitation with minimal ultrasound-induced heating. We here report the development of the LGFU as a stimulus for promoted drug release from microgels integrated with drug-loaded polymeric nanoparticles. The pulsed waves of ultrasound, generated by a carbon black/polydimethylsiloxane (PDMS)-photoacoustic lens, were introduced to trigger the drug release from alginate microgels encapsulated with drug-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. We demonstrated the antibacterial capability of this drug delivery system against Escherichia coli by the disk diffusion method, and antitumor efficacy toward the HeLa cell-derived tumor spheroids in vitro. This novel LGFU-responsive drug delivery system provides a simple and remote approach to precisely control the release of therapeutics in a spatiotemporal manner and potentially suppress detrimental effects to the surrounding tissue, such as thermal ablation.

  20. Gastroretentive drug delivery systems for therapeutic management of peptic ulcer.

    PubMed

    Garg, Tarun; Kumar, Animesh; Rath, Goutam; Goyal, Amit K

    2014-01-01

    A peptic ulcer, stomach ulcer, or gastric ulcer, also known as peptic ulcer disease (PUD), is a very common chronic disorder of the stomach which is mainly caused by damage or impairment of the stomach lining. Various factors such as pepsin, gastric acid, H. pylori, NSAIDs, prostaglandins, mucus, bicarbonate, and blood flow to mucosa play an important role in causing peptic ulcers. In this review article, our main focus is on some important gastroretentive drug delivery systems (GRDDS) (floating, bioadhesive, high density, swellable, raft forming, superporous hydrogel, and magnetic systems) which will be helpful in gastroretention of different dosage forms for treatment of peptic ulcer. GRDDS provides a mean for controlled release of compounds that are absorbed by active transport in the upper intestine. It also enables controlled delivery for paracellularly absorbed drugs without a decrease in bioavailability. The above approaches are specific for targeting and leading to a marked improvement in the quality of life for a large number of patients. In the future, it is expected that they will become of growing significance, finally leading to improved efficiencies of various types of pharmacotherapies.

  1. Design of a Multiple Drug Delivery System Directed at Periodontitis

    PubMed Central

    Sundararaj, Sharath C.; Thomas, Mark V.; Peyyala, Rebecca; Dziubla, Thomas D.; Puleo, David A.

    2013-01-01

    Periodontal disease is highly prevalent, with 90% of the world population affected by either periodontitis or its preceding condition, gingivitis. These conditions are caused by bacterial biofilms on teeth, which stimulate a chronic inflammatory response that leads to loss of alveolar bone and, ultimately, the tooth. Current treatment methods for periodontitis address specific parts of the disease, with no individual treatment serving as a complete therapy. The present research sought to demonstrate development of a multiple drug delivery system for stepwise treatment of different stages of periodontal disease. More specifically, multilayered films were fabricated from an association polymer comprising cellulose acetate phthalate and Pluronic F-127 to achieve sequential release of drugs. The four types of drugs used were metronidazole, ketoprofen, doxycycline, and simvastatin to eliminate infection, inhibit inflammation, prevent tissue destruction, and aid bone regeneration, respectively. Different erosion times and adjustable sequential release profiles were achieved by modifying the number of layers or by inclusion of a slower-eroding polymer layer. Analysis of antibiotic and anti-inflammatory bioactivity showed that drugs released from the devices retained 100% bioactivity. The multilayered CAPP delivery system offers a versatile approach for releasing different drugs based on the pathogenesis of periodontitis and other conditions. PMID:23948165

  2. Microparticulate based topical delivery system of clobetasol propionate.

    PubMed

    Badıllı, Ulya; Sen, Tangül; Tarımcı, Nilüfer

    2011-09-01

    Psoriasis is a chronic, autoimmune skin disease affecting approximately 2% of the world's population. Clobetasol propionate which is a superpotent topical corticosteroid is widely used for topical treatment of psoriasis. Conventional dosage forms like creams and ointments are commonly prefered for the therapy. The purpose of this study was to develop a new topical delivery system in order to provide the prolonged release of clobetasol propionate and to reduce systemic absorption and side effects of the drug. Clobetasol propionate loaded-poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres were prepared by oil-in-water emulsion-solvent evaporation technique. Particle size analysis, morphological characterization, DSC and XRD analyses and in vitro drug release studies were performed on the microparticle formulations. Emulgel formulations were prepared as an alternative for topical delivery of clobetasol propionate. In vitro drug release studies were carried out from the emulgel formulations containing pure drug and drug-loaded microspheres. In addition, the same studies were performed to determine the drug release from the commercial cream product of clobetasol propionate. The release of clobetasol propionate from the emulgel formulations was significantly higher than the commercial product. In addition, the encapsulation of clobetasol propionate in the PLGA microspheres significantly delayed the drug release from the emulgel formulation. As a result, the decrease in the side effects of clobetasol propionate by the formulation containing PLGA microspheres is expected.

  3. Transdermal evaporation delivery system of praziquantel for schistosomiasis japonicum chemotherapy.

    PubMed

    Wang, Lei; Zheng, Xinsheng; Fang, Yan; Wang, Yi; Duan, Cunzheng; Yao, Baoan

    2011-07-01

    A transdermal evaporation delivery system (TEDS) of praziquantel (PZQ) was developed by selecting ethylene glycol monophenyl ether as a nonvolatile component solvent and ethanol as a volatile component solvent to control efficiently the transmission and morbidity of the global schistosomiasis, providing a convenient administration system of PZQ for both humans and domestic animals. The solubility of PZQ in TEDS was more than 400 mg/mL when the ethanol concentration was 50% (w/w) in the solvent mixture at 32 °C, enabling to adapt requirements for the treatment of schistosomiasis. The highest serum drug concentration reached 35.93 µg/mL after transdermal administration of TEDS of PZQ in rabbits, being 6.3-fold higher than that after oral administration at the same dose. The TEDS of PZQ achieved treatment efficacy with the worm reduction of 100% when it was applied in the experimental treatment of Schistosoma japonicum in rabbits. The TEDS of PZQ that provides passive and nonocclusive delivery, having the inexpensive cost, low skin irritation rates, and precise dose of administration, should find application in the transmission control and chemotherapy of global schistosomiasis.

  4. Proton transport in biological systems can be probed by two-dimensional infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Liang, Chungwen; Jansen, Thomas L. C.; Knoester, Jasper

    2011-01-01

    We propose a new method to determine the proton transfer (PT) rate in channel proteins by two-dimensional infrared (2DIR) spectroscopy. Proton transport processes in biological systems, such as proton channels, trigger numerous fundamental biochemical reactions. Due to the limitation in both spatial and time resolution of the traditional experimental approaches, describing the whole proton transport process and identifying the rate limiting steps at the molecular level is challenging. In the present paper, we focus on proton transport through the Gramicidin A channel. Using a kinetic PT model derived from all-atom molecular dynamics simulations, we model the amide I region of the 2DIR spectrum of the channel protein to examine its sensitivity to the proton transport process. We demonstrate that the 2DIR spectrum of the isotope-labeled channel contain information on the PT rate, which may be extracted by analyzing the antidiagonal linewidth of the spectral feature related to the labeled site. Such experiments in combination with detailed numerical simulations should allow the extraction of site dependent PT rates, providing a method for identifying possible rate limiting steps for proton channel transfer.

  5. Proton-Resistant Quantum Dots: Stability in Gastrointestinal Fluids and Implications for Oral Delivery of Nanoparticle Agents.

    PubMed

    Mohs, Aaron M; Duan, Hongwei; Kairdolf, Brad A; Smith, Andrew M; Nie, Shuming

    2009-06-01

    Semiconductor quantum dots (QDs) have shown great promise as fluorescent probes for molecular, cellular and in-vivo imaging. However, the fluorescence of traditional polymer-encapsulated QDs is often quenched by proton-induced etching in acidic environments. This is a major problem for QD applications in the gastrointestinal tract because the gastric (stomach) environment is strongly acidic (pH 1-2). Here we report the use of proton-resistant surface coatings to stabilize QD fluorescence under acidic conditions. Using both hyperbranched polyethylenimine (PEI) and its polyethylene glycol derivative (PEG grafted PEI), we show that the fluorescence of core-shell CdSe/CdS/ZnS QDs is effectively protected from quenching in simulated gastric fluids. In comparison, amphiphilic lipid or polymer coatings provide no protection under similarly acidic conditions. The proton-resistant QDs are found to cause moderate membrane damage to cultured epithelial cells, but PEGylation (PEG grafting) can be used to reduce cellular toxicity and to improved nanoparticle stability. PMID:20379372

  6. Intensity modulated proton therapy.

    PubMed

    Kooy, H M; Grassberger, C

    2015-07-01

    Intensity modulated proton therapy (IMPT) implies the electromagnetic spatial control of well-circumscribed "pencil beams" of protons of variable energy and intensity. Proton pencil beams take advantage of the charged-particle Bragg peak-the characteristic peak of dose at the end of range-combined with the modulation of pencil beam variables to create target-local modulations in dose that achieves the dose objectives. IMPT improves on X-ray intensity modulated beams (intensity modulated radiotherapy or volumetric modulated arc therapy) with dose modulation along the beam axis as well as lateral, in-field, dose modulation. The clinical practice of IMPT further improves the healthy tissue vs target dose differential in comparison with X-rays and thus allows increased target dose with dose reduction elsewhere. In addition, heavy-charged-particle beams allow for the modulation of biological effects, which is of active interest in combination with dose "painting" within a target. The clinical utilization of IMPT is actively pursued but technical, physical and clinical questions remain. Technical questions pertain to control processes for manipulating pencil beams from the creation of the proton beam to delivery within the patient within the accuracy requirement. Physical questions pertain to the interplay between the proton penetration and variations between planned and actual patient anatomical representation and the intrinsic uncertainty in tissue stopping powers (the measure of energy loss per unit distance). Clinical questions remain concerning the impact and management of the technical and physical questions within the context of the daily treatment delivery, the clinical benefit of IMPT and the biological response differential compared with X-rays against which clinical benefit will be judged. It is expected that IMPT will replace other modes of proton field delivery. Proton radiotherapy, since its first practice 50 years ago, always required the highest level of

  7. Intensity modulated proton therapy

    PubMed Central

    Grassberger, C

    2015-01-01

    Intensity modulated proton therapy (IMPT) implies the electromagnetic spatial control of well-circumscribed “pencil beams” of protons of variable energy and intensity. Proton pencil beams take advantage of the charged-particle Bragg peak—the characteristic peak of dose at the end of range—combined with the modulation of pencil beam variables to create target-local modulations in dose that achieves the dose objectives. IMPT improves on X-ray intensity modulated beams (intensity modulated radiotherapy or volumetric modulated arc therapy) with dose modulation along the beam axis as well as lateral, in-field, dose modulation. The clinical practice of IMPT further improves the healthy tissue vs target dose differential in comparison with X-rays and thus allows increased target dose with dose reduction elsewhere. In addition, heavy-charged-particle beams allow for the modulation of biological effects, which is of active interest in combination with dose “painting” within a target. The clinical utilization of IMPT is actively pursued but technical, physical and clinical questions remain. Technical questions pertain to control processes for manipulating pencil beams from the creation of the proton beam to delivery within the patient within the accuracy requirement. Physical questions pertain to the interplay between the proton penetration and variations between planned and actual patient anatomical representation and the intrinsic uncertainty in tissue stopping powers (the measure of energy loss per unit distance). Clinical questions remain concerning the impact and management of the technical and physical questions within the context of the daily treatment delivery, the clinical benefit of IMPT and the biological response differential compared with X-rays against which clinical benefit will be judged. It is expected that IMPT will replace other modes of proton field delivery. Proton radiotherapy, since its first practice 50 years ago, always required the

  8. Microneedle-based drug delivery systems: Microfabrication, drug delivery, and safety

    PubMed Central

    Donnelly, Ryan F.; Raj Singh, Thakur Raghu; Woolfson, A. David

    2010-01-01

    Many promising therapeutic agents are limited by their inability to reach the systemic circulation, due to the excellent barrier properties of biological membranes, such as the stratum corneum (SC) of the skin or the sclera/cornea of the eye and others. The outermost layer of the skin, the SC, is the principal barrier to topically-applied medications. The intact SC thus provides the main barrier to exogenous substances, including drugs. Only drugs with very specific physicochemical properties (molecular weight < 500 Da, adequate lipophilicity, and low melting point) can be successfully administered transdermally. Transdermal delivery of hydrophilic drugs and macromolecular agents of interest, including peptides, DNA, and small interfering RNA is problematic. Therefore, facilitation of drug penetration through the SC may involve by-pass or reversible disruption of SC molecular architecture. Microneedles (MNs), when used to puncture skin, will by-pass the SC and create transient aqueous transport pathways of micron dimensions and enhance the transdermal permeability. These micropores are orders of magnitude larger than molecular dimensions, and, therefore, should readily permit the transport of hydrophilic macromolecules. Various strategies have been employed by many research groups and pharmaceutical companies worldwide, for the fabrication of MNs. This review details various types of MNs, fabrication methods and, importantly, investigations of clinical safety of MN. PMID:20297904

  9. Preparing a health care delivery system for Space Station

    NASA Technical Reports Server (NTRS)

    Logan, J. S.; Stewart, G. R.

    1985-01-01

    NASA's Space Station is viewed as the beginning of man's permanent presence in space. This paper presents the guidelines being developed by NASA's medical community in preparing a quality, permanent health care delivery system for Space Station. The guidelines will be driven by unique Space Station requirements such as mission duration, crew size, orbit altitude and inclination, EVA frequency and rescue capability. The approach will emphasize developing a health care system that is modular and flexible. It will also incorporate NASA's requirements for growth capability, commonality, maintainability, and advanced technology development. Goals include preventing unnecessary rescue attempts, as well as maintaining the health and safety of the crew. Proper planning will determine the levels of prevention, diagnosis, and treatment necessary to achieve these goals.

  10. Gene gun delivery systems for cancer vaccine approaches.

    PubMed

    Aravindaram, Kandan; Yang, Ning Sun

    2009-01-01

    Gene-based immunization with transgenic DNA vectors expressing tumor-associated antigens (TAA), cytokines, or chemokines, alone or in combination, provides an attractive approach to increase the cytotoxic T cell immunity against various cancer diseases. With this consideration, particle-mediated or gene gun technology has been developed as a nonviral method for gene transfer into various mammalian tissues. It has been shown to induce both humoral and cell-mediated immune responses in both small and large experimental animals. A broad range of somatic cell types, including primary cultures and established cell lines, has been successfully transfected ex vivo or in vitro by gene gun technology, either as suspension or adherent cultures. Here, we show that protocols and techniques for use in gene gun-mediated transgene delivery system for skin vaccination against melanoma using tumor-associated antigen (TAA) human gpl00 and reporter gene assays as experimental systems.

  11. Polymeric nanoparticles for targeted drug delivery system for cancer therapy.

    PubMed

    Masood, Farha

    2016-03-01

    A targeted delivery system based on the polymeric nanoparticles as a drug carrier represents a marvelous avenue for cancer therapy. The pivotal characteristics of this system include biodegradability, biocompatibility, non-toxicity, prolonged circulation and a wide payload spectrum of a therapeutic agent. Other outstanding features are their distinctive size and shape properties for tissue penetration via an active and passive targeting, specific cellular/subcellular trafficking pathways and facile control of cargo release by sophisticated material engineering. In this review, the current implications of encapsulation of anticancer agents within polyhydroxyalkanoates, poly-(lactic-co-glycolic acid) and cyclodextrin based nanoparticles to precisely target the tumor site, i.e., cell, tissue and organ are highlighted. Furthermore, the promising perspectives in this emerging field are discussed.

  12. Spatial service delivery system for smart licensing & enforcement management

    NASA Astrophysics Data System (ADS)

    Wahap, N. A.; Ismail, N. M.; Nor, N. M.; Ahmad, N.; Omar, M. F.; Termizi, A. A. A.; Zainal, D.; Noordin, N. M.; Mansor, S.

    2016-06-01

    Spatial information has introduced a new sense of urgency for a better understanding of the public needs in term of what, when and where they need services and through which devices, platform or physical locations they need them. The objective of this project is to value- add existing license management process for business premises which comes under the responsibility of Local Authority (PBT). Manipulation of geospatial and tracing technology via mobile platform allows enforcement officers to work in real-time, use a standardized system, improve service delivery, and optimize operation management. This paper will augment the scope and capabilities of proposed concept namely, Smart Licensing/Enforcement Management (SLEm). It will review the current licensing and enforcement practice of selected PBT in comparison to the enhanced method. As a result, the new enhanced system is expected to offer a total solution for licensing/enforcement management whilst increasing efficiency and transparency for smart city management and governance.

  13. Polymeric nanoparticles for targeted drug delivery system for cancer therapy.

    PubMed

    Masood, Farha

    2016-03-01

    A targeted delivery system based on the polymeric nanoparticles as a drug carrier represents a marvelous avenue for cancer therapy. The pivotal characteristics of this system include biodegradability, biocompatibility, non-toxicity, prolonged circulation and a wide payload spectrum of a therapeutic agent. Other outstanding features are their distinctive size and shape properties for tissue penetration via an active and passive targeting, specific cellular/subcellular trafficking pathways and facile control of cargo release by sophisticated material engineering. In this review, the current implications of encapsulation of anticancer agents within polyhydroxyalkanoates, poly-(lactic-co-glycolic acid) and cyclodextrin based nanoparticles to precisely target the tumor site, i.e., cell, tissue and organ are highlighted. Furthermore, the promising perspectives in this emerging field are discussed. PMID:26706565

  14. Polarimeters and Energy Spectrometers for the ILC Beam Delivery System

    SciTech Connect

    Boogert, S.; Hildreth, M.; Kafer, D.; List, J.; Monig, K.; Moffeit, K.C.; Moortgat-Pick, G.; Riemann, S.; Schreiber, H.J.; Schuler, P.; Torrence, E.; Woods, M.; /SLAC

    2009-02-24

    This article gives an overview of current plans and issues for polarimeters and energy spectrometers in the Beam Delivery System of the ILC. It is meant to serve as a useful reference for the Detector Letter of Intent documents currently being prepared. Concepts for high precision polarization and energy measurements exist. These concepts have resulted in detailed system layouts that are included in the RDR description for the Beam Delivery System. The RDR includes both upstream and downstream polarimeters and energy spectrometers for both beams. This provides needed complementarity and redundancy for achieving the precision required, with adequate control and demonstration of systematic errors. The BDS polarimeters and energy spectrometers need to be a joint effort of the ILC BDS team and the Detector collaborations, with collaboration members responsible for the performance and accuracy of the measurements. Details for this collaboration and assigning of responsibilities remain to be worked out. There is also a demonstrated need for Detector physicists to play an active role in the design and evaluation of accelerator components that impact beam polarization and beam energy capabilities, including the polarized source and spin rotator systems. A workshop was held in 2008 on ILC Polarization and Energy measurements, which resulted in a set of recommendations for the ILC design and operation. Additional input and action is needed on these from the Detector collaborations, the Research Director and the GDE. Work is continuing during the ILC engineering design phase to further optimize the polarimeter and energy spectrometer concepts and fully implement them in the ILC. This includes consideration for alternative methods, detailed design and cost estimates, and prototype and test beam activities.

  15. Ternary particles for effective vaccine delivery to the pulmonary system

    NASA Astrophysics Data System (ADS)

    Terry, Treniece La'shay

    Progress in the fields of molecular biology and genomics has provided great insight into the pathogenesis of disease and the defense mechanisms of the immune system. This knowledge has lead to the classification of an array of abnormal genes, for which, treatment relies on cellular expression of proteins. The utility of DNA-based vaccines hold great promise for the treatment of genetically based and infectious diseases, which ranges from hemophilia, cystic fibrosis, and HIV. Synthetic delivery systems consisting of cationic polymers, such as polyethylenimine (PEI), are capable of condensing DNA into compact structures, maximizing cellular uptake of DNA and yielding high levels of protein expression. To date, short term expression is a major obstacle in the development of gene therapies and has halted their expansion in clinical applications. This study intends to develop a sustained release vaccine delivery system using PLA-PEG block copolymers encapsulating PEI:DNA polyplexes. To enhance the effectiveness of such DNA-based vaccines, resident antigen presenting cells, macrophages and dendritic cells, will be targeted within the alveoli regions of the lungs. Porous microspheres will be engineered with aerodynamic properties capable of achieving deep lung deposition. A fabrication technique using concentric nozzles will be developed to produce porous microspheres. It was observed that modifications in the dispersed to continuous phase ratios have the largest influence on particle size distributions, release rates and encapsulation efficiency which ranged form 80--95% with fourteen days of release. Amphiphilic block copolymers were also used to fabricate porous microspheres. The confirmation of PEG within the biodegradable polymer backbone was found to have a tremendous impact on the microsphere morphology and encapsulation efficiency which varied from 50--90%. Porous microspheres were capable of providing sustained gene expression when tested in vitro using the

  16. Evaluation of the range shifter model for proton pencil-beam scanning for the Eclipse v.11 treatment planning system.

    PubMed

    Matysiak, Witold; Yeung, Daniel; Slopsema, Roelf; Li, Zuofeng

    2016-03-08

    Existing proton therapy pencil-beam scanning (PBS) systems have limitations on the minimum range to which a patient can be treated. This limitation arises from practical considerations, such as beam current intensity, layer spacing, and delivery time. The range shifter (RS) - a slab of stopping material inserted between the nozzle and the patient - is used to reduce the residual range of the incident beam so that the treatment ranges can be extended to shallow depths. Accurate modeling of the RS allows one to calculate the beam spot size entering the patient, given the proton energy, for arbitrary positions and thicknesses of the RS in the beam path. The Eclipse version 11 (v11) treatment planning system (TPS) models RS-induced beam widening by incorporating the scattering properties of the RS material into the V-parameter. Monte Carlo simulations with Geant4 code and analytical calculations using the Fermi-Eyges (FE) theory with Highland approximation of multiple Coulomb scattering (MCS) were employed to calculate proton beam widening due to scattering in the RS. We demonstrated that both methods achieved consistent results and could be used as a benchmark for evaluating the Eclipse V-parameter model. In most cases, the V-parameter model correctly predicted the beam spot size after traversing the RS. However, Eclipse did not enforce the constraint for a nonnegative covariance matrix when fitting the spot sizes to derive the phase space parameters, which resulted in incorrect calculations under specific conditions. In addition, Eclipse v11 incorrectly imposed limits on the individual values of the phase space parameters, which could lead to incorrect spot size values in the air calculated for beams with spot sigmas <3.8 mm. Notably, the TPS supplier (Varian) and hardware vendor (Ion Beam Applications) inconsistently refer to the RS position, which may result in improper spot size calculations.

  17. Evaluation of the range shifter model for proton pencil-beam scanning for the Eclipse v.11 treatment planning system.

    PubMed

    Matysiak, Witold; Yeung, Daniel; Slopsema, Roelf; Li, Zuofeng

    2016-01-01

    Existing proton therapy pencil-beam scanning (PBS) systems have limitations on the minimum range to which a patient can be treated. This limitation arises from practical considerations, such as beam current intensity, layer spacing, and delivery time. The range shifter (RS) - a slab of stopping material inserted between the nozzle and the patient - is used to reduce the residual range of the incident beam so that the treatment ranges can be extended to shallow depths. Accurate modeling of the RS allows one to calculate the beam spot size entering the patient, given the proton energy, for arbitrary positions and thicknesses of the RS in the beam path. The Eclipse version 11 (v11) treatment planning system (TPS) models RS-induced beam widening by incorporating the scattering properties of the RS material into the V-parameter. Monte Carlo simulations with Geant4 code and analytical calculations using the Fermi-Eyges (FE) theory with Highland approximation of multiple Coulomb scattering (MCS) were employed to calculate proton beam widening due to scattering in the RS. We demonstrated that both methods achieved consistent results and could be used as a benchmark for evaluating the Eclipse V-parameter model. In most cases, the V-parameter model correctly predicted the beam spot size after traversing the RS. However, Eclipse did not enforce the constraint for a nonnegative covariance matrix when fitting the spot sizes to derive the phase space parameters, which resulted in incorrect calculations under specific conditions. In addition, Eclipse v11 incorrectly imposed limits on the individual values of the phase space parameters, which could lead to incorrect spot size values in the air calculated for beams with spot sigmas <3.8 mm. Notably, the TPS supplier (Varian) and hardware vendor (Ion Beam Applications) inconsistently refer to the RS position, which may result in improper spot size calculations. PMID:27074461

  18. Strategic workforce planning for a multihospital, integrated delivery system.

    PubMed

    Datz, David; Hallberg, Colleen; Harris, Kathy; Harrison, Lisa; Samples, Patience

    2012-01-01

    Banner Health has long recognized the need to anticipate, beyond the immediate operational realities or even the annual budgeting projection exercises, the necessary workforce needs of the future. Thus, in 2011, Banner implemented a workforce planning model that included structures, processes, and tools for predicting workforce needs, with particular focus on identified critical systemwide practice areas. The model represents the incorporation of labor management tools and processes with more strategic, broad-view, long-term assessment and planning mechanisms. The sequential tying of the workforce planning lifecycle with the organization's strategy and financial planning process supports alignment of goals, objectives, and resource allocation. Collaboration among strategy, finance, human resources, and operations has provided us with the ability to identify critical position groups based on 3-year strategic priorities. By engaging leaders from across the organization, focusing on activities at facility, regional, and system levels, and building in mechanisms for accountability, we are now engaged in continuous evaluations of our delivery models, the competencies and preparations necessary for the staff to effectively function within those delivery models, and developing and implementing action plans designed to ensure adequate numbers of the staff whose competencies will be suited to the work expected of them.

  19. Viral Vectors for Gene Delivery to the Central Nervous System

    PubMed Central

    Lentz, Thomas B.; Gray, Steven J.; Samulski, R. Jude

    2011-01-01

    The potential benefits of gene therapy for neurological diseases such as Parkinson’s, Amyotrophic Lateral Sclerosis (ALS), Epilepsy, and Alzheimer’s are enormous. Even a delay in the onset of severe symptoms would be invaluable to patients suffering from these and other diseases. Significant effort has been placed in developing vectors capable of delivering therapeutic genes to the CNS in order to treat neurological disorders. At the forefront of potential vectors, viral systems have evolved to efficiently deliver their genetic material to a cell. The biology of different viruses offers unique solutions to the challenges of gene therapy, such as cell targeting, transgene expression and vector production. It is important to consider the natural biology of a vector when deciding whether it will be the most effective for a specific therapeutic function. In this review, we outline desired features of the ideal vector for gene delivery to the CNS and discuss how well available viral vectors compare to this model. Adeno-associated virus, retrovirus, adenovirus and herpesvirus vectors are covered. Focus is placed on features of the natural biology that have made these viruses effective tools for gene delivery with emphasis on their application in the CNS. Our goal is to provide insight into features of the optimal vector and which viral vectors can provide these features. PMID:22001604

  20. Novel pluronic-chitosan micelle as an ocular delivery system.

    PubMed

    Lin, Hong-Ru; Chang, Pei-Csang

    2013-07-01

    Pluronic micelles were prepared for ophthalmic delivery by incorporation of ethyl acetate as a dispersion agent and their surfaces were modified by chitosan to improve their bioavailability. The micelles disperse well in the solution and have a core-shell like structure with a particle size ranging from 93 to 181 nm for drug unloaded, 123-232 nm for drug-loaded, and a zeta potential between 6.1 and 9.2 mV, indicating very suitable use as ophthalmic carrier. The in vitro serum stability tests indicate the particle size of the micelles was very stable during the serum absorption. The turbidity test reveals that the prepared micelles were very stable under phosphate buffered saline environment, which can prevent the blurred vision. The loading efficiency of metipranolol in micelles can be as high as 83%. Finally, the in vitro and in vivo studies indicate the pluronic micelles modified by chitosan have sustained release behavior and good pharmacological response. As the results, the pluroic-chitosan micelles system provides a potential opportunity in decreasing frequency of administration and improving patient compliance for ocular drug delivery.

  1. Strategic workforce planning for a multihospital, integrated delivery system.

    PubMed

    Datz, David; Hallberg, Colleen; Harris, Kathy; Harrison, Lisa; Samples, Patience

    2012-01-01

    Banner Health has long recognized the need to anticipate, beyond the immediate operational realities or even the annual budgeting projection exercises, the necessary workforce needs of the future. Thus, in 2011, Banner implemented a workforce planning model that included structures, processes, and tools for predicting workforce needs, with particular focus on identified critical systemwide practice areas. The model represents the incorporation of labor management tools and processes with more strategic, broad-view, long-term assessment and planning mechanisms. The sequential tying of the workforce planning lifecycle with the organization's strategy and financial planning process supports alignment of goals, objectives, and resource allocation. Collaboration among strategy, finance, human resources, and operations has provided us with the ability to identify critical position groups based on 3-year strategic priorities. By engaging leaders from across the organization, focusing on activities at facility, regional, and system levels, and building in mechanisms for accountability, we are now engaged in continuous evaluations of our delivery models, the competencies and preparations necessary for the staff to effectively function within those delivery models, and developing and implementing action plans designed to ensure adequate numbers of the staff whose competencies will be suited to the work expected of them. PMID:22955225

  2. Phase transition of an ice-proton system into a Bernal-Fowler state

    NASA Astrophysics Data System (ADS)

    Ryzhkin, Ivan A.; Petrenko, Victor F.

    2000-11-01

    We present a microscopic model of an ice-proton system. A mean-field approximation was used to study the disorder-partial order transition in the proton subsystem of ice. This analysis revealed that ice rules arise as a result of the second-order phase transition. From the theoretical point of view, above the phase-transition temperature the protons should be distributed over all possible positions without any restrictions. However, in real ice under zero pressure the disordering of the proton lattice apparently leads to ice melting. We also derived the Landau-Ginzburg equation suitable for the model under consideration and showed that the theories based on ice rules must be modified when one is working in the region of the critical temperature.

  3. Advances in the Applications of Polyhydroxyalkanoate Nanoparticles for Novel Drug Delivery System

    PubMed Central

    Shrivastav, Anupama; Kim, Hae-Yeong; Kim, Young-Rok

    2013-01-01

    Drug delivery technology is emerging as an interdisciplinary science aimed at improving human health. The controlled delivery of pharmacologically active agents to the specific site of action at the therapeutically optimal rate and dose regimen has been a major goal in designing drug delivery systems. Over the past few decades, there has been considerable interest in developing biodegradable drug carriers as effective drug delivery systems. Polymeric materials from natural sources play an important role in controlled release of drug at a particular site. Polyhydroxyalkanoates, due to their origin from natural sources, are given attention as candidates for drug delivery materials. Biodegradable and biocompatible polyhydroxyalkanoates are linear polyesters produced by microorganisms under unbalanced growth conditions, which have emerged as potential polymers for use as biomedical materials for drug delivery due to their unique physiochemical and mechanical properties. This review summarizes many of the key findings in the applications of polyhydroxyalkanoates and polyhydroxyalkanoate nanoparticles for drug delivery system. PMID:23984383

  4. SU-E-CAMPUS-J-03: Commissioning of the On-Board Cone-Beam CT System Equipped On the Rotating Gantry of a Proton Therapy System

    SciTech Connect

    Takao, S; Miyamoto, N; Matsuura, T; Toramatsu, C; Nihongi, H; Yamada, T; Umegaki, K; Shimizu, S; Shirato, H; Matsuda, K; Sasaki, T; Nagamine, Y; Baba, R; Umekawa, T

    2014-06-15

    Purpose: Proton therapy requires highly-precise image guidance in patient setup to ensure accurate dose delivery. Cone-beam CT (CBCT) is expected to play an important role to reduce uncertainties in patient setup. Hokkaido University has developed a new proton therapy system dedicated to spot-scanning under a collaborative work with Hitachi Ltd. In our system, an orthogonal X-ray imaging system is mounted on a full-rotating gantry. On-board CBCT imaging is therefore available. We have conducted commissioning of the CBCT system for clinical use in proton therapy. Methods: The orthogonal X-ray imaging system, which consists of two sets of X-ray tubes and flat panel detectors (FPDs), are equipped on the rotating gantry. The FPDs are mounted on the proton beam nozzle and can be retracted when not in use. The distance between the X-ray source and the FPD is about 2.1 m. The maximum rotation speed of the gantry is 1 rpm, so CBCT images can be acquired in approximately 1 minute. The maximum reconstruction volume is nearly 40 cm in diameter and 20 cm in axial length. For commissioning of the CBCT system, mechanical accuracy of the rotating gantry first was evaluated. Imaging performance was examined via quantitative evaluation of image quality. Results: Through the mechanical test, the isocentricity of the gantry was confirmed to be less than 1 mm. Moreover, it was improved to 0.5 mm with an appropriate correction. The accurate rotation of the gantry contributes to the CBCT image quality. In the image quality test, objects with 7 line-pairs per cm, which corresponds to a line spacing of 0.071 cm, could be discerned. Spatial linearity and uniformity were also sufficient. Conclusion: Clinical commissioning of the on-board CBCT system for proton therapy was conducted, and CBCT images with sufficient quality were successfully obtained. This research was supported by the Cabinet Office, Government of Japan and the Japan Society for the Promotion of Science (JSPS) through the

  5. Relative bioavailability of a new transdermal nitroglycerin delivery system.

    PubMed

    Noonan, P K; Gonzalez, M A; Ruggirello, D; Tomlinson, J; Babcock-Atkinson, E; Ray, M; Golub, A; Cohen, A

    1986-07-01

    The purpose of this study was to measure the bioavailability of nitroglycerin from a new transdermal delivery system, Nitro-Dur II, relative to that of Nitro-Dur. Twenty-four healthy male volunteers completed a two-way crossover study. Each subject randomly received Nitro-Dur (I) and Nitro-Dur II (II) for a 24-h period. Both transdermal systems had an active surface area of 20 cm2. Blood samples were collected immediately before treatment, at 0.5, 1, 2, 3, 4, 6, 8, 12, 18, and 24 h after topical application of the units, and 30 min after the units were removed. Nitroglycerin was determined with an analytical sensitivity of 50 pg/mL using gas chromatography with electron capture detection (GC-EC). Mean steady-state concentrations of nitroglycerin were 182 and 224 pg/mL for I and II, respectively. There were no statistical differences between I and II in the pharmacokinetic parameters measured (Css, AUC, Cmax, % fluctuation). Residual nitroglycerin content was measured in each transdermal unit after application to each of the 24 volunteers. The amounts of nitroglycerin delivered by I and II were 9.78 +/- 4.11 and 10.67 +/- 4.78 mg, respectively, or approximately 10 mg in 24 h. Statistical analysis of these data using an analysis of variance indicated no significant difference between these treatments (p = 0.27). Since there were also no differences in the plasma concentrations and pharmacokinetic parameters calculated after treatment with I and II, the bioequivalence of the two delivery systems was established. PMID:3093667

  6. Progress in Psoriasis Therapy via Novel Drug Delivery Systems

    PubMed Central

    Vincent, Nitha; Ramya, Devi D; Vedha, Hari BN

    2014-01-01

    Psoriasis is a lifelong condition which is caused by the negative signals produced by immune system, which leads to hyper proliferation and other inflammatory reactions on the skin. In this case, keratinocytes which are the outermost layer of skin possess shortened life cycle and results in the alteration of desquamation process where the cytokines will come out through lesions of affected patients and as a result, scaling marks appears on the skin. These conditions may negatively affect the patient’s quality of life and lead to psychosocial stress. Psoriasis can be categorized as mild, moderate and severe conditions. Mild psoriasis leads to the formation of rashes, and when it becomes moderate, the skin turns into scaly. In severe conditions, red patches may be present on skin surface and becomes itchy. Topical therapy continues to be one of the pillars for psoriasis management. Drug molecules with target effect on the skin tissues and other inflammations should be selected for the treatment of psoriasis. Most of the existing drugs lead to systemic intoxication and dryness when applied in higher dose. Different scientific approaches for topical delivery are being explored by researches including emollient, modified gelling system, transdermal delivery, spray, nanogels, hydrogels, micro/nano emulsion, liposomes, nano capsules etc. These topical dosage forms are evaluated for various physico chemical properties such as drug content, viscosity, pH, extrudability, spreadability, toxicity, irritancy, permeability and drug release mechanism. This review paper focus attention to the impact of these formulation approaches on various anti-psoriasis drugs for their successful treatment. PMID:25386329

  7. Systems approaches to design of targeted therapeutic delivery

    PubMed Central

    Myerson, Jacob W.; Brenner, Jacob S.; Greineder, Colin F.; Muzykantov, Vladimir R.

    2016-01-01

    Targeted drug delivery aims to improve therapeutic effects and enable mechanisms that are not feasible for untargeted agents (e.g., due to impermeable biological barriers). To achieve targeting, a drug or its carrier should possess properties providing specific accumulation from circulation at the desired site. There are several examples of systems-inspired approaches that have been applied to achieve this goal. First, proteomics analysis of plasma membrane fraction of the vascular endothelium has identified a series of target molecules and their ligands (e.g., antibodies) that deliver conjugated cargoes to well-defined vascular cells and subcellular compartments. Second, selection of ligands binding to cells of interest using phage display libraries in vitro and in vivo has provided peptides and polypeptides that bind to normal and pathologically altered cells. Finally, large-scale high-throughput combinatorial synthesis and selection of lipid- and polymer-based nanocarriers varying their chemical components has yielded a series of carriers accumulating in diverse organs and delivering RNA interference agents to diverse cells. Together, these approaches offer a basis for systems-based design and selection of targets, targeting molecules, and targeting vehicles. Current studies focus on expanding the arsenal of these and alternative targeting strategies, devising drug delivery systems capitalizing on these strategies and evaluation of their benefit/risk ratio in adequate animal models of human diseases. These efforts, combined with better understanding of mechanisms and unintended consequences of these targeted interventions, need to be ultimately translated into industrial development and the clinical domain. PMID:25946066

  8. A pinger system for the Los Alamos Proton Storage Ring

    SciTech Connect

    Hardek, T.W.; Thiessen, H.A.

    1991-01-01

    Developers at the Proton Storage Ring have long desired a modulator and electrode combination capable of kicking the 800-MeV proton beam enough to conduct tune measurements with full intensity beams. At present this has been accomplished by reducing the voltage on one extraction kicker modulator and turning the other off. This method requires that all of the accumulated beam be lost on the walls of the vacuum chamber. In addition to tune measurements a more recent desire is to sweep out beam that may have leaked into the area between bunches. A four-meter electrode has been designed and constructed for the purpose. The design is flexible in that the electrode may be split in the center and rotated in order to provide vertical and horizontal electrodes each 2 meters long. In addition two solid-state pulse modulators that can provide 10kV in burst mode at up to 700 KHz have been purchased. This hardware and its intended use are described. 3 refs., 2 figs., 1 tab.

  9. Systemic gene delivery to the central nervous system using Adeno-associated virus

    PubMed Central

    Bourdenx, Mathieu; Dutheil, Nathalie; Bezard, Erwan; Dehay, Benjamin

    2014-01-01

    Adeno-associated virus (AAV)-mediated gene delivery has emerged as an effective and safe tool for both preclinical and clinical studies of neurological disorders. The recent discovery that several serotypes are able to cross the blood–brain barrier when administered systemically has been a real breakthrough in the field of neurodegenerative diseases. Widespread transgene expression after systemic injection could spark interest as a therapeutic approach. Such strategy will avoid invasive brain surgery and allow non-focal gene therapy promising for CNS diseases affecting large portion of the brain. Here, we will review the recent results achieved through different systemic routes of injection generated in the last decade using systemic AAV-mediated delivery and propose a brief assessment of their values. In particular, we emphasize how the methods used for virus engineering could improve brain transduction after peripheral delivery. PMID:24917785

  10. Evaluation of metal nanoparticles for drug delivery systems.

    PubMed

    Adeyemi, Oluyomi S; Sulaiman, Faoziyat A

    2015-04-01

    Diminazene aceturate is a trypanocide with unwanted toxicity and limited efficacy. It was reasoned that conjugating diminazene aceturate to functionalized nanoparticle would lower untoward toxicity while improving selectivity and therapeutic efficacy. Silver and gold nanoparticles were evaluated for their capacities to serve as carriers for diminazene aceturate. The silver and gold nanoparticles were synthesized, functionalized and coupled to diminazene aceturate following established protocols. The nanoparticle conjugates were characterized. The free diminazene aceturate and drug conjugated nanoparticles were subsequently evaluated for cytotoxicity in vitro. The characterizations by transmission electron microscopy or UV/Vis spectroscopy revealed that conjugation of diminazene aceturate to silver or gold nanoparticles was successful. Evaluation for cytotoxic actions in vitro demonstrated no significance difference between free diminazene aceturate and the conjugates. Our data suggest that surface modified metal nanoparticles could be optimized for drug delivery systems.

  11. Multiple delivery cesium oven system for negative ion sources

    SciTech Connect

    Bansal, G.; Bhartiya, S.; Pandya, K.; Bandyopadhyay, M.; Singh, M. J.; Soni, J.; Gahlaut, A.; Parmar, K. G.; Chakraborty, A.

    2012-02-15

    Distribution of cesium in large negative ion beam sources to be operational in ITER, is presently based on the use of three or more cesium ovens, which operate simultaneously and are controlled remotely. However, use of multiple Cs ovens simultaneously is likely to pose difficulties in operation and maintenance of the ovens. An alternate method of Cs delivery, based on a single oven distribution system is proposed as one which could reduce the need of simultaneous operation of many ovens. A proof of principle experiment verifying the concept of a multinozzle distributor based Cs oven has been carried out at Institute for Plasma Research. It is also observed that the Cs flux is not controlled by Cs reservoir temperature after few hours of operation but by the temperature of the distributor which starts behaving as a Cs reservoir.

  12. Loading, Release, Biodegradation, and Biocompatibility of a Nanovector Delivery System

    NASA Technical Reports Server (NTRS)

    Ferrai, Mauro; Tasciotti, Ennio

    2012-01-01

    A nanovector multistage system has been created to overcome or bypass sequential barriers within the human body, in order to deliver a therapeutic or imaging agent to a specific location. This innovation consists of a composition that includes two or more stages of particles, such that smaller, later-stage particles are contained in the larger, early-stage particles. An active agent, such as a therapeutic agent or imaging agent, is preferentially delivered and/or localized to a particular target site in the body of a subject. The multistage composition overcomes multiple biological barriers in the body. The multistage composition also allows for simultaneous delivery and localization at the same or different target sites of multiple active agents.

  13. Cell or Cell Membrane-Based Drug Delivery Systems

    PubMed Central

    Tan, Songwei; Wu, Tingting; Zhang, Dan; Zhang, Zhiping

    2015-01-01

    Natural cells have been explored as drug carriers for a long period. They have received growing interest as a promising drug delivery system (DDS) until recently along with the development of biology and medical science. The synthetic materials, either organic or inorganic, are found to be with more or less immunogenicity and/or toxicity. The cells and extracellular vesicles (EVs), are endogenous and thought to be much safer and friendlier. Furthermore, in view of their host attributes, they may achieve different biological effects and/or targeting specificity, which can meet the needs of personalized medicine as the next generation of DDS. In this review, we summarized the recent progress in cell or cell membrane-based DDS and their fabrication processes, unique properties and applications, including the whole cells, EVs and cell membrane coated nanoparticles. We expect the continuing development of this cell or cell membrane-based DDS will promote their clinic applications. PMID:26000058

  14. Fenton-treated functionalized diamond nanoparticles as gene delivery system.

    PubMed

    Martín, Roberto; Alvaro, Mercedes; Herance, José Raúl; García, Hermenegildo

    2010-01-26

    When raw diamond nanoparticles (Dnp, 7 nm average particle size) obtained from detonation are submitted to harsh Fenton-treatment, the resulting material becomes free of amorphous soot matter and the process maintains the crystallinity, reduces the particle size (4 nm average particle size), increases the surface OH population, and increases water solubility. All these changes are beneficial for subsequent Dnp covalent functionalization and for the ability of Dnp to cross cell membranes. Fenton-treated Dnps have been functionalized with thionine and the resulting sample has been observed in HeLa cell nuclei. A triethylammonium-functionalized Dnp pairs electrostatically with a plasmid having the green fluorescent protein gene and acts as gene delivery system permitting the plasmid to cross HeLa cell membrane, something that does not occur for the plasmid alone without assistance of polycationic Dnp. PMID:20047335

  15. Current pharmaceutical design on adhesive based transdermal drug delivery systems.

    PubMed

    Ghosh, Animesh; Banerjee, Subham; Kaity, Santanu; Wong, Tin W

    2015-01-01

    Drug-in-adhesive transdermal drug delivery matrix exploits intimate contact of the carrier with stratum corneum, the principal skin barrier to drug transport, to deliver the actives across the skin and into the systemic circulation. The main application challenges of drug-in-adhesive matrix lie in the physicochemical properties of skin varying with age, gender, ethnicity, health and environmental condition of patients. This in turn poses difficulty to design a universal formulation to meet the intended adhesiveness, drug release and drug permeation performances. This review focuses on pressure-sensitive adhesives, and their adhesiveness and drug release/permeation modulation mechanisms as a function of adhesive molecular structure and formulation attributes. It discusses approaches to modulate adhesive tackiness, strength, elasticity, hydrophilicity, molecular suspension capability and swelling capacity, which contribute to the net effect of adhesive on skin bonding, drug release and drug permeation. PMID:25925119

  16. An overview of Ball Aerospace cryogen storage and delivery systems

    NASA Astrophysics Data System (ADS)

    Marquardt, J.; Keller, J.; Mills, G.; Schmidt, J.

    2015-12-01

    Starting on the Gemini program in the 1960s, Beech Aircraft (now Ball Aerospace) has been designing and manufacturing dewars for a variety of cryogens including liquid hydrogen and oxygen. These dewars flew on the Apollo, Skylab and Space Shuttle spacecraft providing fuel cell reactants resulting in over 150 manned spaceflights. Since Space Shuttle, Ball has also built the liquid hydrogen fuel tanks for the Boeing Phantom Eye unmanned aerial vehicle. Returning back to its fuel cell days, Ball has designed, built and tested a volume-constrained liquid hydrogen and oxygen tank system for reactant delivery to fuel cells on unmanned undersea vehicles (UUVs). Herein past history of Ball technology is described. Testing has been completed on the UUV specific design, which will be described.

  17. Rapid cycling medical synchrotron and beam delivery system

    DOEpatents

    Peggs, Stephen G.; Brennan, J. Michael; Tuozzolo, Joseph E.; Zaltsman, Alexander

    2008-10-07

    A medical synchrotron which cycles rapidly in order to accelerate particles for delivery in a beam therapy system. The synchrotron generally includes a radiofrequency (RF) cavity for accelerating the particles as a beam and a plurality of combined function magnets arranged in a ring. Each of the combined function magnets performs two functions. The first function of the combined function magnet is to bend the particle beam along an orbital path around the ring. The second function of the combined function magnet is to focus or defocus the particle beam as it travels around the path. The radiofrequency (RF) cavity is a ferrite loaded cavity adapted for high speed frequency swings for rapid cycling acceleration of the particles.

  18. Current pharmaceutical design on adhesive based transdermal drug delivery systems.

    PubMed

    Ghosh, Animesh; Banerjee, Subham; Kaity, Santanu; Wong, Tin W

    2015-01-01

    Drug-in-adhesive transdermal drug delivery matrix exploits intimate contact of the carrier with stratum corneum, the principal skin barrier to drug transport, to deliver the actives across the skin and into the systemic circulation. The main application challenges of drug-in-adhesive matrix lie in the physicochemical properties of skin varying with age, gender, ethnicity, health and environmental condition of patients. This in turn poses difficulty to design a universal formulation to meet the intended adhesiveness, drug release and drug permeation performances. This review focuses on pressure-sensitive adhesives, and their adhesiveness and drug release/permeation modulation mechanisms as a function of adhesive molecular structure and formulation attributes. It discusses approaches to modulate adhesive tackiness, strength, elasticity, hydrophilicity, molecular suspension capability and swelling capacity, which contribute to the net effect of adhesive on skin bonding, drug release and drug permeation.

  19. Processing of Polymer Nanofibers Through Electrospinning as Drug Delivery Systems

    NASA Astrophysics Data System (ADS)

    Kenawy, E.; Abdel-Hay, F. I.; El-Newehy, M. H.; Wnek, G. E.

    The use of electrospun fibers as drug carriers could be promising in the future for biomedical applications, especially postoperative local chemotherapy. In this research, electrospun fibers were developed as a new system for the delivery of ketoprofen as non-steroidal anti-inflammatory drug (NSAID). The fibers were made either from polycaprolactone (PCL) as a biodegradable polymer or polyurethane (PU) as a non-biodegradable polymer, or from the blends of the two. The release of the ketoprofen was followed by UV—VIS spectroscopy in phosphate buffer of pH 7.4 at 37°C and 20°C. The results showed that the release rates from the polycaprolactone, polyurethane and their blend were similar. However, the blend of the polycaprolactone with polyurethane improved its visual mechanical properties. Release profiles from the electrospun mats were compared to cast films of the various formulations.

  20. Pathogen-inspired drug delivery to the central nervous system.

    PubMed

    McCall, Rebecca L; Cacaccio, Joseph; Wrabel, Eileen; Schwartz, Mary E; Coleman, Timothy P; Sirianni, Rachael W

    2014-01-01

    For as long as the human blood-brain barrier (BBB) has been evolving to exclude bloodborne agents from the central nervous system (CNS), pathogens have adopted a multitude of strategies to bypass it. Some pathogens, notably viruses and certain bacteria, enter the CNS in whole form, achieving direct physical passage through endothelial or neuronal cells to infect the brain. Other pathogens, including bacteria and multicellular eukaryotic organisms, secrete toxins that preferentially interact with specific cell types to exert a broad range of biological effects on peripheral and central neurons. In this review, we will discuss the directed mechanisms that viruses, bacteria, and the toxins secreted by higher order organisms use to enter the CNS. Our goal is to identify ligand-mediated strategies that could be used to improve the brain-specific delivery of engineered nanocarriers, including polymers, lipids, biologically sourced materials, and imaging agents.

  1. PLGA-based nanoparticles as cancer drug delivery systems.

    PubMed

    Sadat Tabatabaei Mirakabad, Fatemeh; Nejati-Koshki, Kazem; Akbarzadeh, Abolfazl; Yamchi, Mohammad Rahmati; Milani, Mortaza; Zarghami, Nosratollah; Zeighamian, Vahideh; Rahimzadeh, Amirbahman; Alimohammadi, Somayeh; Hanifehpour, Younes; Joo, Sang Woo

    2014-01-01

    Poly (lactic-co-glycolic acid) (PLGA) is one of the most effective biodegradable polymeric nanoparticles (NPs). It has been approved by the US FDA to use in drug delivery systems due to controlled and sustained- release properties, low toxicity, and biocompatibility with tissue and cells. In the present review, the structure and properties of PLGA copolymers synthesized by ring-opening polymerization of DL-lactide and glicolide were characterized using 1H nuclear magnetic resonance spectroscopy, gel permeation chromatography, Fourier transform infrared spectroscopy and differential scanning calorimetry. Methods of preparation and characterization, various surface modifications, encapsulation of diverse anticancer drugs, active or passive tumor targeting and different release mechanisms of PLGA nanoparticles are discussed. Increasing experience in the application of PLGA nanoparticles has provided a promising future for use of these nanoparticles in cancer treatment, with high efficacy and few side effects. PMID:24568455

  2. Recent developments in retinal lasers and delivery systems.

    PubMed

    Yadav, Naresh Kumar; Jayadev, Chaitra; Rajendran, Anand; Nagpal, Manish

    2014-01-01

    Photocoagulation is the standard of care for several ocular disorders and in particular retinal conditions. Technology has offered us newer lasing mediums, wavelengths and delivery systems. Pattern scan laser in proliferative diabetic retinopathy and diabetic macular edema allows laser treatment that is less time consuming and less painful. Now, it is possible to deliver a subthreshold micropulse laser that is above the threshold of biochemical effect but below the threshold of a visible, destructive lesion thereby preventing collateral damage. The advent of solid-state diode yellow laser allows us to treat closer to the fovea, is more effective for vascular structures and offers a more uniform effect in patients with light or irregular fundus pigmentation. Newer retinal photocoagulation options along with their advantages is discussed in this review.

  3. Polybutylcyanoacrylate nanocarriers as promising targeted drug delivery systems.

    PubMed

    Gao, Shiya; Xu, Yurui; Asghar, Sajid; Chen, Minglei; Zou, Lang; Eltayeb, Sulieman; Huo, Meirong; Ping, Qineng; Xiao, Yanyu

    2015-01-01

    Among the materials for preparing the polymeric nanocarriers, poly(n-butylcyanoacrylate) (PBCA), a polymer with medium length alkyl side chain, is of lower toxicity and proper degradation time. Therefore, PBCA has recently been regarded as a kind of widely used, biocompatible, biodegradable, low-toxic drug carrier. This review highlights the use of PBCA-based nanocarriers (PBCA-NCs) as targeting drug delivery systems and presents the methods of preparation, the surface modification and the advantages and limitations of PBCA-NCs. The drugs loaded in PBCA-NCs are summarized according to the treatment of diseases, and the different therapeutic applications and the most recent developments of PBCA-NCs are also discussed, which provides useful guidance on the targeting research of PBCA-NCs.

  4. Single-wall carbon nanotubes based anticancer drug delivery system

    NASA Astrophysics Data System (ADS)

    Tripisciano, C.; Kraemer, K.; Taylor, A.; Borowiak-Palen, E.

    2009-08-01

    Conventional administration of chemotherapeutic agents is compromised by their lack of selectivity which is the cause of a lethal effect accomplishment on healthy tissues. Since therapeutic and diagnostic agents could functionalize the structure of carbon nanotubes (CNTs), the development of CNTs as drug containers would pave the way to their employment as nanovectors into the cells. Here a study on cisplatin (Cis-Diamminedichloroplatinum (CDDP) - a platinum-based chemotherapy drug) embedding to single-wall CNTs (SWCNTs) is shown.Being sure that the anticancer drug discharge occurred, in vitro analysis have been performed. The inhibition of prostate cancer cells (PC3 and DU145) viability from tubes encapsulating cisplatin proved the efficiency of the produced delivery system.

  5. Pathogen-inspired drug delivery to the central nervous system

    PubMed Central

    McCall, Rebecca L; Cacaccio, Joseph; Wrabel, Eileen; Schwartz, Mary E; Coleman, Timothy P; Sirianni, Rachael W

    2014-01-01

    For as long as the human blood-brain barrier (BBB) has been evolving to exclude bloodborne agents from the central nervous system (CNS), pathogens have adopted a multitude of strategies to bypass it. Some pathogens, notably viruses and certain bacteria, enter the CNS in whole form, achieving direct physical passage through endothelial or neuronal cells to infect the brain. Other pathogens, including bacteria and multicellular eukaryotic organisms, secrete toxins that preferentially interact with specific cell types to exert a broad range of biological effects on peripheral and central neurons. In this review, we will discuss the directed mechanisms that viruses, bacteria, and the toxins secreted by higher order organisms use to enter the CNS. Our goal is to identify ligand-mediated strategies that could be used to improve the brain-specific delivery of engineered nanocarriers, including polymers, lipids, biologically sourced materials, and imaging agents. PMID:25610755

  6. Development of an energy selector system for laser-driven proton beam applications

    NASA Astrophysics Data System (ADS)

    Scuderi, V.; Bijan Jia, S.; Carpinelli, M.; Cirrone, G. A. P.; Cuttone, G.; Korn, G.; Licciardello, T.; Maggiore, M.; Margarone, D.; Pisciotta, P.; Romano, F.; Schillaci, F.; Stancampiano, C.; Tramontana, A.

    2014-03-01

    Nowadays, laser-driven proton beams generated by the interaction of high power lasers with solid targets represent a fascinating attraction in the field of the new acceleration techniques. These beams can be potentially accelerated up to hundreds of MeV and, therefore, they can represent a promising opportunity for medical applications. Laser-accelerated proton beams typically show high flux (up to 1011 particles per bunch), very short temporal profile (ps), broad energy spectra and poor reproducibility. In order to overcome these limitations, these beams have be controlled and transported by means of a proper beam handling system. Furthermore, suitable dosimetric diagnostic systems must be developed and tested. In the framework of the ELIMED project, we started to design a dedicated beam transport line and we have developed a first prototype of a beam line key-element: an Energy Selector System (ESS). It is based on permanent dipoles, capable to control and select in energy laser-accelerated proton beams. Monte Carlo simulations and some preliminary experimental tests have been already performed to characterize the device. A calibration of the ESS system with a conventional proton beam will be performed in September at the LNS in Catania. Moreover, an experimental campaign with laser-driven proton beam at the Centre for Plasma Physics, Queens University in Belfast is already scheduled and will be completed within 2014.

  7. High Power Proton Accelerator Development at KAERI and its Vacuum System

    NASA Astrophysics Data System (ADS)

    Choi, Byung-Ho; Park, Mi Young; Kim, Kui Young; Kim, Kye Ryung; Kim, Jun Yeon; Cho, Yong-Sub

    The Proton Engineering Frontier Project (PEFP), approved and launched by the Korean government in July 2002, includes a 100 MeV proton linear accelerator (linac) development and programs for its utilization and application. The main goals in the first phase of the project, spanning from 2002 to 2005, were the design of a 100 MeV proton linac and the development of a 20 MeV linac consisting of a 50 keV proton injector, a 3 MeV radio frequency quadrupole (RFQ), and a 20 MeV drift tube linac (DTL). The 50 keV injector and 3 MeV RFQ have been installed and tested, and the 20 MeV DTL is being assembled, tuned and under a beam test. At the same time, the utilization programs using the proton beam have been planned, and some are now under way. The vacuum system of the 20 MeV proton linac and its related issues, especially in operation with a high duty, are discussed in detail.

  8. Proton Radiotherapy for Pediatric Central Nervous System Germ Cell Tumors: Early Clinical Outcomes

    SciTech Connect

    MacDonald, Shannon M.; Trofimov, Alexei; Safai, Sairos; Adams, Judith; Fullerton, Barbara; Ebb, David; Tarbell, Nancy J.; Yock, Torunn I.

    2011-01-01

    Purpose: To report early clinical outcomes for children with central nervous system (CNS) germ cell tumors treated with protons; to compare dose distributions for intensity-modulated photon radiotherapy (IMRT), three-dimensional conformal proton radiation (3D-CPT), and intensity-modulated proton therapy with pencil beam scanning (IMPT) for whole-ventricular irradiation with and without an involved-field boost. Methods and Materials: All children with CNS germinoma or nongerminomatous germ cell tumor who received treatment at the Massachusetts General Hospital between 1998 and 2007 were included in this study. The IMRT, 3D-CPT, and IMPT plans were generated and compared for a representative case. Results: Twenty-two patients were treated with 3D-CPT. At a median follow-up of 28 months, there were no CNS recurrences; 1 patient had a recurrence outside the CNS. Local control, progression-free survival, and overall survival rates were 100%, 95%, and 100%, respectively. Comparable tumor volume coverage was achieved with IMRT, 3D-CPT, and IMPT. Substantial normal tissue sparing was seen with any form of proton therapy as compared with IMRT. The use of IMPT may yield additional sparing of the brain and temporal lobes. Conclusions: Preliminary disease control with proton therapy compares favorably to the literature. Dosimetric comparisons demonstrate the advantage of proton radiation over IMRT for whole-ventricle radiation. Superior dose distributions were accomplished with fewer beam angles utilizing 3D-CPT and scanned protons. Intensity-modulated proton therapy with pencil beam scanning may improve dose distribution as compared with 3D-CPT for this treatment.

  9. Instructional Systems Development Model for Interactive Videodisc Training Delivery Systems. Volume I: Hardware, Software and Procedures.

    ERIC Educational Resources Information Center

    Bunderson, C. Victor; And Others

    Developed for use by army authors, this report provides information to assist in the step-by-step production of interactive videodisc training delivery systems (VTDS). The first of three volumes describes the hardware and software for VTDS, as well as videodisc authoring and production systems (VAPS). The range of capabilities of consumer-model…

  10. Tritium storage/delivery and associated cleanup systems for TFTR

    SciTech Connect

    Gill, J.T.; Anderson, B.E.; Watkins, R.A.; Pierce, C.W.

    1982-01-01

    The Tritium Storage and Delivery System (TSDS) will provide the tritium for high power plasmas in TFTR. TSDS will store tritium as solid uranium tritide at room temperature. At greater than or equal to 400/sup 0/C gas may be released from uranium and pumped through a metal bellows pump to a holding volume. Acceptably pure T/sub 2/ will be passed along a 40 m manifold into the storage volumes of three piezoelectric gas injection valves above the torus. Tests on several above components are described. Process components are contained within evacuable housings and three seismically qualified gloveboxes. Two of these boxes are serviced by catalytic oxidation/dessicant adsorption-based T/sub 2/ cleanup systems, one of which is dedicated and the other also detritiating torus and neutral beam exhaust gases. TSDS is located in a sealable vault, its air purifiable by a third such system. Emergency dehumidification of the torus test cell and its basement is also provided. TSDS and the cleanup systems will operate remotely under hardwired interlocks and operator-interactive computer control. Interlocks are safety-oriented and, e.g., prevent overheating of uranium, overpressurization of bellows pumps, and large glovebox pressure excursions. Tritium monitors are important to cleanup interlocks.

  11. Tritium storage/delivery and associated cleanup systems for TFTR

    SciTech Connect

    Gill, J.T.; Anderson, B.E.; Watkins, R.A.; Pierce, C.W.

    1983-04-01

    The tritium storage and delivery system (TSDS) will provide the tritium for high power plasmas in TFTR. TSDS will store tritium as solid uranium tritide at room temperature. At > or approx. =400 /sup 0/C gas may be released from uranium and pumped through a metal bellows pump to a holding volume. Acceptably pure T/sub 2/ will be passed along a approx.100-ft manifold into the storage volumes of three piezoelectric gas injection valves above the torus. Tests on several above components are described. Process components are contained within evacuable housings and three seismically qualified gloveboxes. Two of these boxes are serviced by catalytic oxidation/dessicant adsorption-based T/sub 2/ cleanup systems, one of which is dedicated and the other also detritiating torus and neutral beam exhaust gases. TSDS is located in a sealable vault, it is air purifiable by a third such system. Emergency dehumidification of the torus test cell and its basement is also provided. TSDS and the cleanup systems will operate remotely under hardwired interlocks and operator--interactive computer control. Interlocks are safety-oriented and, e.g., prevent overheating of uranium, overpressurization of bellows pumps, and large glovebox pressure excursions. Tritium monitors are important to cleanup interlocks.

  12. Intrathecal Drug Delivery (ITDD) systems for cancer pain

    PubMed Central

    Bhatia, Gaurav; Lau, Mary E; Koury, Katharine M; Gulur, Padma

    2014-01-01

    Intrathecal drug delivery is an effective pain management option for patients with chronic and cancer pain. The delivery of drugs into the intrathecal space provides superior analgesia with smaller doses of analgesics to minimize side effects while significantly improving quality of life. This article aims to provide a general overview of the use of intrathecal drug delivery to manage pain, dosing recommendations, potential risks and complications, and growing trends in the field. PMID:24555051

  13. New developments and opportunities in oral mucosal drug delivery for local and systemic disease.

    PubMed

    Hearnden, Vanessa; Sankar, Vidya; Hull, Katrusha; Juras, Danica Vidović; Greenberg, Martin; Kerr, A Ross; Lockhart, Peter B; Patton, Lauren L; Porter, Stephen; Thornhill, Martin H

    2012-01-01

    The oral mucosa's accessibility, excellent blood supply, by-pass of hepatic first-pass metabolism, rapid repair and permeability profile make it an attractive site for local and systemic drug delivery. Technological advances in mucoadhesives, sustained drug release, permeability enhancers and drug delivery vectors are increasing the efficient delivery of drugs to treat oral and systemic diseases. When treating oral diseases, these advances result in enhanced therapeutic efficacy, reduced drug wastage and the prospect of using biological agents such as genes, peptides and antibodies. These technologies are also increasing the repertoire of drugs that can be delivered across the oral mucosa to treat systemic diseases. Trans-mucosal delivery is now a favoured route for non-parenteral administration of emergency drugs and agents where a rapid onset of action is required. Furthermore, advances in drug delivery technology are bringing forward the likelihood of transmucosal systemic delivery of biological agents.

  14. A fast beam loss monitor system for the KEK proton synchrotron complex

    NASA Astrophysics Data System (ADS)

    Holt, J. A.; Kishiro, J.; Arakawa, D.; Hiramatsu, S.

    1991-06-01

    Efforts to increase the intensity of the KEK proton synchrotron have led to the need for a new fast response beam loss monitor system. The design and some prelimitary test results of a new beam loss monitor system are presented.(AIP)

  15. System-state and operating condition sensitive control method and apparatus for electric power delivery systems

    NASA Technical Reports Server (NTRS)

    Burns, III, William Wesley (Inventor); Wilson, Thomas George (Inventor)

    1978-01-01

    This invention provides a method and apparatus for determining a precise switching sequence for the power switching elements of electric power delivery systems of the on-off switching type and which enables extremely fast transient response, precise regulation and highly stable operation. The control utilizes the values of the power delivery system power handling network components, a desired output characteristic, a system timing parameter, and the externally imposed operating conditions to determine where steady state operations should be in order to yield desired output characteristics for the given system specifications. The actual state of the power delivery system is continuously monitored and compared to a state-space boundary which is derived from the desired equilibrium condition, and from the information obtained from this comparison, the system is moved to the desired equilibrium condition in one cycle of switching control. Since the controller continuously monitors the power delivery system's externally imposed operating conditions, a change in the conditions is immediately sensed and a new equilibrium condition is determined and achieved, again in a single cycle of switching control.

  16. SU-E-T-621: Analysis of Robustness of Proton Pencil Beam Scanning Technique for Delivery of Craniospinal Irradiation

    SciTech Connect

    Lin, H; Kirk, M; Zhai, H; Ding, X; Liu, H; Hill-Kayser, C; Lustig, R; Tochner, Z; McDonough, J; Both, S

    2014-06-15

    Purpose: To investigate the robustness and safety of craniospinal irradiation (CSI) planned with a proton pencil beam scanning (PBS) technique which overcomes the complexity of the planning associated with feathering match lines. Methods: Six CSI patients were planned with gradient-dose matching using PBS technique. Uniform dose coverage to the entire target volumes was achieved with averaged junction lengths of 6.9±0.3 cm. Robustness of the plans was evaluated by shifting the isocenter of each treatment field by ±3 mm in longitudinal direction and compared with the original non-shifted plan with metrics of conformity number (CN) and homogeneity index (HI). An anthropomorphic phantom study using film measurements was also carried out on a plan with 5 cm junction length. Results: For a given junction length, the dose errors were directly proportional to the setup errors. Setup errors of 3 mm from each field caused on average 3.5% lower CN and 2.1% higher HI. Minimal D95% to PTV and D98% to CTV were reduced by 2.2%±1.5% and 2.8%±1.7% respectively. A drop of maximal 6.8%±5.5% on the minimal dose to the cribriform plate was also observed. When the junction length was 5cm or longer, these 3mm setup errors from each field resulted in up to 12% dose errors. Consistent results were reached between film measurements and planned dose profiles in the junction area. Due to near-zero exit doses beyond the target volume, sparing of anterior organs such as heart, liver, lung and kidney were observed. Conclusions: Longitudinal setup errors directly reduce the dosimetric accuracy of the CSI treatment with matched proton fields. The reported technique creates a slow dose gradient in the junction area, which makes the treatment more robust and safe to longitudinal setup errors compared to conventional feathering methods.

  17. An injectable liquid crystal system for sustained delivery of entecavir.

    PubMed

    Lim, Jong-Lae; Ki, Min-Hyo; Joo, Min Kyung; An, Sung-Won; Hwang, Kyu-Mok; Park, Eun-Seok

    2015-07-25

    Liquid crystal (LC) technology has attracted much interest for new injectable sustained-release (SR) formulations. In this study, an injectable liquid crystal-forming system (LCFS) including entecavir was prepared for the treatment of hepatitis B. In particular, an anchoring effect was introduced because LCFSs are relatively hydrophobic while entecavir is a slightly charged drug. The physicochemical properties of LCFSs were investigated by cryo-transmission electron microscopy (cryo-TEM), polarized optical microscopy, and small-angle X-ray scattering (SAXS), showing typical characteristics of the liquid crystalline phase, which was classified as the hexagonal phase. A pharmacokinetic study in rats showed sustained release of entecavir for 3-5 days with a basic LCFS formulation composed of sorbitan monooleate (SMO), phosphatidyl choline (PC), and tocopherol acetate (TA) as the main LC components. 1,2-Dipalmitoyl-sn-glycero-3-phosphatidic acid (DPPA), an anionic phospholipid, was added to increase the anchoring effect between the cationic entecavir and the anionic DPPA, which resulted in a 1.5-times increase in half-life in rats. In addition, anchoring was strengthened by optimizing the pH to 2.5-4.5, increasing the half-life in the rat and dog. Also, due to the increasing terminal half-life from rat to dog resulting from species differences, LCFS produced one week delivery of entecavir in rat and two weeks delivery in dog. Therefore, LCFS injection using the anchoring effect for entecavir can potentially be used to deliver the drug over more than 2 weeks or even 1 month for the treatment of hepatitis B.

  18. Proton Delivery and Removal in [Ni(P R 2 N R' 2 ) 2 ] 2+ Hydrogen Production and Oxidation Catalysts

    SciTech Connect

    O’Hagan, Molly; Ho, Ming-Hsun; Yang, Jenny Y.; Appel, Aaron M.; DuBois, M. Rakowski; Raugei, Simone; Shaw, Wendy J.; DuBois, Daniel L.; Bullock, R. Morris

    2012-11-28

    To examine the role of proton delivery and removal in the electrocatalytic oxidation and production of hydrogen by [Ni(PR2NR´)2]2+ (where PR2NR´2 is 1,5-R´-3,7-R-1,5-diaza-3,7-diphosphacyclooctane), we report experimental and theoretical studies of the intermolecular proton exchange reactions underlying the isomerization of [Ni(PCy2NBn2H)2]2+ (Cy = cyclohexyl, Bn = benzyl) species formed during the stochiometric oxidation of H2 by [NiII(PCy2NBn2)2]2+ or the protonation of [Ni0(PCy2NBn2)2]. The three isomers formed differ by the position of the N-H bond with respect to the nickel (endo-endo, endo-exo, or exo-exo) and only the endo-endo isomer is catalytically active. We have found that the rate of isomerization is limited by proton removal from and delivery to the complex. In particular, steric hindrance disfavors the catalytically active protonation site (endo to the metal) in favor of inactive protonation (exo to the metal). The ramifications to catalysis of poor accessibility of the endo site and protonation at the exo site are discussed. In hydrogen oxidation, deprotonation of the sterically hindered endo position by an external base may lead to slow catalytic turnover. As for hydrogen production, the limited accessibility of the endo position can result in the formation of exo protonated species, which must undergo one or more isomerization steps to generate the catalytically active endo protonated species. These studies highlight the importance of precise proton delivery, and the mechanistic details described herein will guide future catalyst design. This research was carried out in the Center for Molecular Electrocatalysis, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science. WJS was funded by the DOE Office of Science Early Career Research Program through the Office of Basic Energy Sciences. Pacific Northwest National Laboratory is operated for the U.S. Department of Energy by Battelle. Computational resources

  19. A local proton irradiation model for isotopic anomalies in the solar system

    NASA Technical Reports Server (NTRS)

    Lee, T.

    1978-01-01

    An attempt is made to explain the O-16 and Al-26 anomalies observed in solar-system bodies in the framework of a local irradiation model wherein a small amount of solar system matter of normal isotopic composition was irradiated by energetic protons from the primeval sun. Several isotopic constraints are summarized with which the model should be consistent, and a proton energy distribution and fluence and a target elemental composition are chosen such that the extraordinary component produced by irradiation satisfies the constraints. Detailed attention is given to the relevant oxygen reactions, Al-26 production, and effects of proton irradiation on isotopes of Mg, Ca, and Ba. A scenario is outlined which satisfies all the constraints. Consequences of the model are discussed with respect to the isotopic anomalies observed in Allende inclusions.

  20. Initial Results From the 3D Hybrid Heliospheric Modeling System With Pickup Protons

    NASA Astrophysics Data System (ADS)

    Detman, T. R.; Intriligator, D.; Dryer, M.; Sun, W.; Deehr, C.; Intriligator, J.

    2008-12-01

    Interstellar neutral hydrogen flows into the heliosphere and becomes ionized by photoionization and by charge exchange with solar wind protons. These "pickup" protons cause a slowing and heating of the solar wind flow in the outer heliosphere. We are adding the physics of these processes to our time-dependent 3D Hybrid Heliospheric Modeling System. We plan to present initial results for the "Halloween" 2003 events, and to show comparisons with both ACE and Ulysses observations and with our previous results (without pickup protons). This work is sponsored by NASA Grant NNX08AE40G and by Carmel Research Center. Detman et al., 2006, A hybrid heliospheric modeling system: Background solar wind, J. Geophys. Res., V 111, doi:10.1029/2005JA011340

  1. Measurement of differential proton spectra onboard the Space Shuttle using a thermoluminescent dosimetry system.

    PubMed

    Richmond, R G; Badhwar, G D; Cash, B; Atwell, W

    1987-01-01

    An experimental technique that permits the extraction of orbit-averaged, differential energy spectra of trapped radiation belt protons using simple passive detectors is described. An inversion technique is used for the data analysis. The basic principle of the described system is measurement of the energy deposited in six thermoluminescent (TLD) detector assemblies behind various spherical absorbers. The technique has been applied to a detector assembly flown on four Shuttle flights. Although severe restraints were placed on the flight package, the differential energy spectra derived from these measurements are in good agreement with analytical results using a modified trapped proton environment model. The technique shows good promise for measuring the spectra in low inclination orbits where the flux of high energy galactic cosmic rays protons is small. Modifications to the detector assembly to improve the accuracy and to extend the range of the system to higher energies are suggested.

  2. Development of a pulmonary peptide delivery system using porous nanoparticle-aggregate particles for systemic application.

    PubMed

    Yang, Likai; Luo, Jing; Shi, Sanjun; Zhang, Qiang; Sun, Xun; Zhang, Zhirong; Gong, Tao

    2013-07-15

    As a non-invasive administration route, pulmonary peptide delivery for systemic application has shown great promise. However, many barriers exist that prevent effective peptide delivery. The use of porous nanoparticle-aggregate particles (PNAPs) is an excellent option because of their proper aerodynamic size and maximal deposition. However, in most cases, the spray drying heating process for PNAPs has been challenging in regard to maintaining peptide stability and activity. To overcome these issues, we developed a spray freeze-drying method for PNAP preparation. To solve the low entrapment efficiency problem of nanostructured lipid carriers, we used hydrophobic ion pair complexes to increase the lipophilicity of the peptide, thus increasing entrapment efficiency and drug loading. Here, we used a model peptide, octreotide acetate, for PNAP preparation, which has a high entrapment efficiency (>95%) and proper aerodynamic size (~3 μm). In addition, after intrapulmonary administration, we evaluated the pharmacokinetics and pharmacodynamics in a rat preventive hepatic ischemia-reperfusion injury model. Our in vivo data showed significantly increased area under the curve and improved plasma aspartate aminotransferase levels for our PNAP intrapulmonary delivery system vs. the clinically used octreotide acetate delivery via subcutaneous injection. Together, PNAPs may have great potential for carrying peptide drugs for pulmonary delivery.

  3. SU-E-T-594: Out-Of-Field Neutron and Gamma Dose Estimated Using TLD-600/700 Pairs in the Wobbling Proton Therapy System

    SciTech Connect

    Chen, Y; Lin, Y; Tsai, H

    2015-06-15

    Purpose: Secondary fast neutrons and gamma rays are mainly produced due to the interaction of the primary proton beam with the beam delivery nozzle. These secondary radiation dose to patients and radiation workers are unwanted. The purpose of this study is to estimate the neutron and gamma dose equivalent out of the treatment volume during the wobbling proton therapy system. Methods: Two types of thermoluminescent (TL) dosimeters, TLD-600 ({sup 6}LiF: Mg, Ti) and TLD-700 ({sup 7}LiF: Mg, Ti) were used in this study. They were calibrated in the standard neutron and gamma sources at National Standards Laboratory. Annealing procedure is 400°C for 1 hour, 100°C for 2 hours and spontaneously cooling down to the room temperature in a programmable oven. Two-peak method (a kind of glow curve analysis technique) was used to evaluate the TL response corresponding to the neutron and gamma dose. The TLD pairs were placed outside the treatment field at the neutron-gamma mixed field with 190-MeV proton beam produced by the wobbling system through the polyethylene plate phantom. The results of TLD measurement were compared to the Monte Carlo simulation. Results: The initial experiment results of calculated dose equivalents are 0.63, 0.38, 0.21 and 0.13 mSv per Gy outside the field at the distance of 50, 100, 150 and 200 cm. Conclusion: The TLD-600 and TLD-700 pairs are convenient to estimate neutron and gamma dosimetry during proton therapy. However, an accurate and suitable glow curve analysis technique is necessary. During the wobbling system proton therapy, our results showed that the neutron and gamma doses outside the treatment field are noticeable. This study was supported by the grants from the Chang Gung Memorial Hospital (CMRPD1C0682)

  4. Novel Nanostructured Solid Materials for Modulating Oral Drug Delivery from Solid-State Lipid-Based Drug Delivery Systems.

    PubMed

    Dening, Tahnee J; Rao, Shasha; Thomas, Nicky; Prestidge, Clive A

    2016-01-01

    Lipid-based drug delivery systems (LBDDS) have gained significant attention in recent times, owing to their ability to overcome the challenges limiting the oral delivery of poorly water-soluble drugs. Despite the successful commercialization of several LBDDS products over the years, a large discrepancy exists between the number of poorly water-soluble drugs displaying suboptimal in vivo performances and the application of LBDDS to mitigate their various delivery challenges. Conventional LBDDS, including lipid solutions and suspensions, emulsions, and self-emulsifying formulations, suffer from various drawbacks limiting their widespread use and commercialization. Accordingly, solid-state LBDDS, fabricated by adsorbing LBDDS onto a chemically inert solid carrier material, have attracted substantial interest as a viable means of stabilizing LBDDS whilst eliminating some of the various limitations. This review describes the impact of solid carrier choice on LBDDS performance and highlights the importance of appropriate solid carrier material selection when designing hybrid solid-state LBDDS. Specifically, emphasis is placed on discussing the ability of the specific solid carrier to modulate drug release, control lipase action and lipid digestion, and enhance biopharmaceutical performance above the original liquid-state LBDDS. To encourage the interested reader to consider their solid carrier choice on a higher level, various novel materials with the potential for future use as solid carriers for LBDDS are described. This review is highly significant in guiding future research directions in the solid-state LBDDS field and fostering the translation of these delivery systems to the pharmaceutical marketplace. PMID:26354801

  5. Novel Nanostructured Solid Materials for Modulating Oral Drug Delivery from Solid-State Lipid-Based Drug Delivery Systems.

    PubMed

    Dening, Tahnee J; Rao, Shasha; Thomas, Nicky; Prestidge, Clive A

    2016-01-01

    Lipid-based drug delivery systems (LBDDS) have gained significant attention in recent times, owing to their ability to overcome the challenges limiting the oral delivery of poorly water-soluble drugs. Despite the successful commercialization of several LBDDS products over the years, a large discrepancy exists between the number of poorly water-soluble drugs displaying suboptimal in vivo performances and the application of LBDDS to mitigate their various delivery challenges. Conventional LBDDS, including lipid solutions and suspensions, emulsions, and self-emulsifying formulations, suffer from various drawbacks limiting their widespread use and commercialization. Accordingly, solid-state LBDDS, fabricated by adsorbing LBDDS onto a chemically inert solid carrier material, have attracted substantial interest as a viable means of stabilizing LBDDS whilst eliminating some of the various limitations. This review describes the impact of solid carrier choice on LBDDS performance and highlights the importance of appropriate solid carrier material selection when designing hybrid solid-state LBDDS. Specifically, emphasis is placed on discussing the ability of the specific solid carrier to modulate drug release, control lipase action and lipid digestion, and enhance biopharmaceutical performance above the original liquid-state LBDDS. To encourage the interested reader to consider their solid carrier choice on a higher level, various novel materials with the potential for future use as solid carriers for LBDDS are described. This review is highly significant in guiding future research directions in the solid-state LBDDS field and fostering the translation of these delivery systems to the pharmaceutical marketplace.

  6. Systemic drug delivery systems for bone tissue regeneration- a mini review.

    PubMed

    Xinluan, Wang; Yuxiao, Lai; Helena, Ng HueiLeng; Zhijun, Yang; Ling, Qin

    2015-01-01

    Musculoskeletal metabolic diseases such as osteoporosis have become the major public health problems worldwide in our aging society. Pharmaceutical therapy is one of the approaches to prevent and treat related medical conditions. Most of the clinically used anti-osteoporotic drugs are administered systemically and have demonstrated some side effects in non-skeletal tissues. One of the innovative approaches to prevent potential adverse effects is the development of bone-targeting drug delivery technologies that not only minimizes the systemic toxicity but also improves the pharmacokinetic profile and therapeutic efficacy of chemical drugs. This paper reviews the currently available bone targeting drug delivery systems with emphasis as bone-targeting moieties, including the bonesurface- site-specific (bone formation dominant or bone resorption dominant) and cell-specific moieties. In addition, the connections of drug-bone-targeting moieties-carrier are also summarized, and the newly developed liposomes and nanoparticles are discussed for their potential use and main challenges in delivering therapeutic agents to bone tissue. As a rapid-developing biotechnology, systemic bonetargeting delivery system is promising but still in its infancy where challenges are ahead of us, including the stability and the toxicity issues, especially to fulfill the regulatory requirement to realize bench-to-bedside translation. Newly developed biomaterials and technologies with potential for safer and more effective drug delivery require multidisciplinary collaborations with preclinical and clinical scientists that are essential to facilitate their clinical applications.

  7. Key Considerations in Designing Oral Drug Delivery Systems for Dogs.

    PubMed

    Song, Yunmei; Peressin, Karl; Wong, Pooi Yin; Page, Stephen W; Garg, Sanjay

    2016-05-01

    The present review discusses the pharmaceutical impact of the anatomy and physiology of the canine gastrointestinal tract to provide a comprehensive guide to the theories and challenges associated with the development of oral drug delivery systems for dogs. Novel pharmaceutical technologies applied to veterinary drugs are discussed indicating the advantages and benefits for animals. There are currently immense research and development efforts being funneled into novel canine health products. Such products are being used to overcome limitations of drugs that display site-dependent absorption or possess poor biopharmaceutical properties. Techniques that are employed to increase bioavailability of the Biopharmaceutics Classification System class II drugs are discussed in this article. Furthermore, an overview of palatable oral formulations for dog care is provided as an approach to easy administration. In vitro and in vivo evaluation and correlation of oral drug formulations in dogs are also addressed. This article assesses the outlook of canine oral drug development recognizing substantial growth forecasts of the dog care market. PMID:27056627

  8. Wakefield Effects in the Beam Delivery System of the ILC

    SciTech Connect

    Bane, K.L.F.; Seryi, A.; /SLAC

    2007-06-27

    The main linac of the International Linear Collider (ILC) accelerates short, high peak current bunches into the Beam Delivery System (BDS) on the way to the interaction point. In the BDS wakefields, excited by the resistance of the beam pipe walls and by beam pipe transitions, will tend to degrade the emittance of the beam bunches. In this report we calculate the effect on single bunch emittance of incoming jitter or drift, and of misalignments of the beam pipes with respect to the beam axis, both analytically and through multi-particle tracking. As we want to keep emittance growth due to this effect small, we consider also mitigation measures of changing the metallic surface material and/or the beam pipe aperture. The wake effects are studied in that part of the BDS which includes the collimation and final focus systems. Typical ILC beam parameters are given in Table 1. Initially a stainless steel (SS) beam pipe is considered. Note that the ILC collimator wakes, though very important, are not included in this study; their effects have been studied elsewhere [1]. Note also that similar methods are presented in recent reports Refs. [2],[3].

  9. Chitosan in nasal delivery systems for therapeutic drugs.

    PubMed

    Casettari, Luca; Illum, Lisbeth

    2014-09-28

    There is an obvious need for efficient and safe nasal absorption enhancers for the development of therapeutically efficacious nasal products for small hydrophilic drugs, peptides, proteins, nucleic acids and polysaccharides, which do not easily cross mucosal membranes, including the nasal. Recent years have seen the development of a range of nasal absorption enhancer systems such as CriticalSorb (based on Solutol HS15) (Critical Pharmaceuticals Ltd), Chisys based on chitosan (Archimedes Pharma Ltd) and Intravail based on alkylsaccharides (Aegis Therapeutics Inc.), that is presently being tested in clinical trials for a range of drugs. So far, none of these absorption enhancers have been used in a marketed nasal product. The present review discusses the evaluation of chitosan and chitosan derivatives as nasal absorption enhancers, for a range of drugs and in a range of formulations such as solutions, gels and nanoparticles and finds that chitosan and its derivatives are able to efficiently improve the nasal bioavailability. The revirtew also questions whether chitosan nanoparticles for systemic drug delivery provide any real improvement over simpler chitosan formulations. Furthermore, the review also evaluates the use of chitosan formulations for the improvement of transport of drugs directly from the nasal cavity to the brain, based on its mucoadhesive characteristics and its ability to open tight junctions in the olfactory and respiratory epithelia. It is found that the use of chitosan nanoparticles greatly increases the transport of drugs from nose to brain over and above the effect of simpler chitosan formulations. PMID:24818769

  10. Healthcare Delivery Systems at Higher Educational Institutions in India

    PubMed Central

    Yeravdekar, Rajiv Chintaman; Yeravdekar, Vidya Rajiv

    2014-01-01

    Background: The interrelation between health and academic performance is well established. Academic institutions have a larger mandate, beyond academic instruction alone. The objective is to contribute holistically to student development through various paradigms, ultimately culminating in student success. To meet the global challenges of a changing educational system, educational institutions today are therefore vying to be Centers of Excellence, aiming to develop the overall personality of the student. Fundamental to this ideology and with student success as the common denominator, student Wellness assumes critical significance. Higher education institutions, especially universities offer varying levels of healthcare services. Health Promoting University (HPU) projects have therefore been implemented in the West. Unlike in the West, the concept of a Health Promoting University is nascent in India. Methods: A total of 1071 responses to a structured questionnaire administered to the students were studied. Results: In general, there appears to be a lack of awareness regarding the importance of addressing student healthcare issues. Consequently, the spectrum of healthcare services provided is varied and scattered. This encompasses infrastructure, manpower, resource allocation etc. Conclusions: The collective responses obtained could provide the basis for a policy formulation. The policy formulation in turn could be the basis of a national consensus for health care delivery systems operational at higher educational institutions in India. PMID:25317306

  11. Chitosan in nasal delivery systems for therapeutic drugs.

    PubMed

    Casettari, Luca; Illum, Lisbeth

    2014-09-28

    There is an obvious need for efficient and safe nasal absorption enhancers for the development of therapeutically efficacious nasal products for small hydrophilic drugs, peptides, proteins, nucleic acids and polysaccharides, which do not easily cross mucosal membranes, including the nasal. Recent years have seen the development of a range of nasal absorption enhancer systems such as CriticalSorb (based on Solutol HS15) (Critical Pharmaceuticals Ltd), Chisys based on chitosan (Archimedes Pharma Ltd) and Intravail based on alkylsaccharides (Aegis Therapeutics Inc.), that is presently being tested in clinical trials for a range of drugs. So far, none of these absorption enhancers have been used in a marketed nasal product. The present review discusses the evaluation of chitosan and chitosan derivatives as nasal absorption enhancers, for a range of drugs and in a range of formulations such as solutions, gels and nanoparticles and finds that chitosan and its derivatives are able to efficiently improve the nasal bioavailability. The revirtew also questions whether chitosan nanoparticles for systemic drug delivery provide any real improvement over simpler chitosan formulations. Furthermore, the review also evaluates the use of chitosan formulations for the improvement of transport of drugs directly from the nasal cavity to the brain, based on its mucoadhesive characteristics and its ability to open tight junctions in the olfactory and respiratory epithelia. It is found that the use of chitosan nanoparticles greatly increases the transport of drugs from nose to brain over and above the effect of simpler chitosan formulations.

  12. An experimental platform for systemic drug delivery to the retina.

    PubMed

    Campbell, Matthew; Nguyen, Anh T H; Kiang, Anna-Sophia; Tam, Lawrence C S; Gobbo, Oliviero L; Kerskens, Christian; Ni Dhubhghaill, Sorcha; Humphries, Marian M; Farrar, G-Jane; Kenna, Paul F; Humphries, Peter

    2009-10-20

    Degenerative retinopathies, including age-related macular degeneration, diabetic retinopathy, and hereditary retinal disorders--major causes of world blindness--are potentially treatable by using low-molecular weight neuroprotective, antiapoptotic, or antineovascular drugs. These agents are, however, not in current systemic use owing to, among other factors, their inability to passively diffuse across the microvasculature of the retina because of the presence of the inner blood-retina barrier (iBRB). Moreover, preclinical assessment of the efficacies of new formulations in the treatment of such conditions is similarly compromised. We describe here an experimental process for RNAi-mediated, size-selective, transient, and reversible modulation of the iBRB in mice to molecules up to 800 Da by suppression of transcripts encoding claudin-5, a protein component of the tight junctions of the inner retinal vasculature. MRI produced no evidence indicative of brain or retinal edema, and the process resulted in minimal disturbance of global transcriptional patterns analyzed in neuronal tissue. We show that visual function can be improved in IMPDH1(-/-) mice, a model of autosomal recessive retinitis pigmentosa, and that the rate of photoreceptor cell death can be reduced in a model of light-induced retinal degeneration by systemic drug delivery after reversible barrier opening. These findings provide a platform for high-throughput drug screening in models of retinal degeneration, and they ultimately could result in the development of a novel "humanized" approach to therapy for conditions with little or no current forms of treatment.

  13. Fast range measurement of spot scanning proton beams using a volumetric liquid scintillator detector

    PubMed Central

    Hui, CheukKai; Robertson, Daniel; Alsanea, Fahed; Beddar, Sam

    2016-01-01

    Accurate confirmation and verification of the range of spot scanning proton beams is crucial for correct dose delivery. Current methods to measure proton beam range using ionization chambers are either time-consuming or result in measurements with poor spatial resolution. The large-volume liquid scintillator detector allows real-time measurements of the entire dose profile of a spot scanning proton beam. Thus, liquid scintillator detectors are an ideal tool for measuring the proton beam range for commissioning and quality assurance. However, optical artefacts may decrease the accuracy of measuring the proton beam range within the scintillator tank. The purpose of the current study was to 1) develop a geometric calibration system to accurately calculate physical distances within the liquid scintillator detector, taking into account optical artefacts; and 2) assess the accuracy, consistency, and robustness of proton beam range measurement using the liquid scintillator detector with our geometric calibration system. The range of the proton beam was measured with the calibrated liquid scintillator system and was compared to the nominal range. Measurements were made on three different days to evaluate the setup robustness from day to day, and three sets of measurements were made for each day to evaluate the consistency from delivery to delivery. All proton beam ranges measured using the liquid scintillator system were within half a millimeter of the nominal range. The delivery-to-delivery standard deviation of the range measurement was 0.04 mm, and the day-to-day standard deviation was 0.10 mm. In addition to the accuracy and robustness demonstrated by these results when our geometric calibration system was used, the liquid scintillator system allowed the range of all 94 proton beams to be measured in just two deliveries, making the liquid scintillator detector a perfect tool for range measurement of spot scanning proton beams. PMID:27274863

  14. Assessment of Alternative Student Aid Delivery Systems. The General Assessment Model.

    ERIC Educational Resources Information Center

    Advanced Technology, Inc., Reston, VA.

    An evaluation model for the student aid delivery system is described, and extensive tables that make up the model are presented. The model can be used to evaluate the effects of specific activities and subsystems of the delivery system for major participants, as well as to estimate the likely effects of activity changes. A conceptual model for…

  15. Educational Audiology: A Comparison of Service Delivery Systems Utilized by Missouri Schools.

    ERIC Educational Resources Information Center

    Allard, J. Brad; Golden, Diane Cordry

    1991-01-01

    Comparison of three audiology service delivery systems--(1) school-based audiology within the district, (2) non-school-based audiology in the community, and (3) school-based audiology in a remote community--found the local school-based delivery system superior on various quality indicators. (Author/DB)

  16. Social Influence for Perceived Usefulness and Ease-of-Use of Course Delivery Systems

    ERIC Educational Resources Information Center

    Shen, Demei; Laffey, James; Lin, Yimei; Huang, Xinxin

    2006-01-01

    This study explores the extent to which subjective norm beliefs of online learners shape perceptions of ease-of-use and usefulness for the use of course delivery systems. Subjective norm beliefs represent the influence that instructors, mentors, and peers have on students to use the course delivery system. The results show that instructor and…

  17. Current Faculty Development Practices for Alternative Delivery Systems in Christian Higher Education Institutions: A Qualitative Study

    ERIC Educational Resources Information Center

    Yates, Steven Lowell

    2009-01-01

    This research study was an investigation of current faculty development practices for alternative delivery systems. Attention was given to faculty development in general as well as specific facets of faculty development for alternative delivery systems. Future or intended faculty development practices were pursued, along with factors that…

  18. 41 CFR 60-300.84 - Responsibilities of appropriate employment service delivery system.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... appropriate employment service delivery system. 60-300.84 Section 60-300.84 Public Contracts and Property... of appropriate employment service delivery system. By statute, appropriate employment service... protected veterans, and Armed Forces service medal veterans to fill employment openings listed...

  19. 41 CFR 60-300.84 - Responsibilities of appropriate employment service delivery system.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... appropriate employment service delivery system. 60-300.84 Section 60-300.84 Public Contracts and Property... of appropriate employment service delivery system. By statute, appropriate employment service... protected veterans, and Armed Forces service medal veterans to fill employment openings listed...

  20. Development of a polymeric nanoparticulate delivery system for indocyanine green

    NASA Astrophysics Data System (ADS)

    Saxena, Vishal

    Purpose. The objective of this project was to develop an intravenously administrable poly(dl-lactic-co-glycolic acid) (PLGA) nanoparticulate delivery system for Indocyanine Green (ICG), to enhance the potential for ICG use in tumor imaging and therapy. Methods. For this purpose PLGA nanoparticles entrapping ICG were engineered by spontaneous emulsification solvent diffusion method. ICG entrapment in nanoparticles was determined and physicochemical characterization of nanoparticles was performed. The stability of ICG in nanoparticles formulation under various conditions was determined. The intracellular uptake of ICG in nanoparticles by B16-F10 and C-33A cancer cell lines was studied in comparison with the free ICG solution. Anti-proliferation studies against cancer cells were performed to prove the photodynamic activity of ICG in nanoparticles. Biodistribution of ICG when delivered through nanoparticles and solution were evaluated in mice after tail vein injection. Results. PLGA nanoparticles with a mean diameter of 350 nm and 74% ICG entrapment were obtained. The nanoparticles were nearly spherical in shape with zeta potential of -16 mV. The nanoparticles formulation provided overall stability to ICG with degradation half-lives of 2.5--3.5 days as compared to 10--20 hr of free ICG solutions. The intracellular uptake of ICG through nanoparticles was directly proportional to time and extracellular nanoparticle concentration. The intracellular uptake of ICG was enhanced about 100-fold by nanoparticles formulation as compared to the free ICG solution. Nanoparticles formulation showed significant photodynamic effect at nano-molar ICG concentrations and very low light dose (fluence: 0.22 W/cm2 and energy density: 1.1 J/cm2). In-vivo, the blood circulation-time and retention-time of ICG in various organs was enhanced 2--5 times by nanoparticles formulation as compared to the free ICG solution. Conclusions. A PLGA nanoparticlute delivery system was developed for ICG